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Pan Y, Jia Z, Yu X, Lv H, Zhang Y, Wu Y, Jiang J. Study on SARS-CoV-2 infection in middle-aged and elderly population infected with hepatitis virus: a cohort study in a rural area of northeast China. PeerJ 2025; 13:e19021. [PMID: 39995984 PMCID: PMC11849502 DOI: 10.7717/peerj.19021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/28/2025] [Indexed: 02/26/2025] Open
Abstract
Background To investigate the symptoms, the level of antibody, the progression of liver disease after SARS-CoV-2 infection in middle-aged and elderly population infected with hepatitis virus. Methods The study was based on a cohort of high-risk liver cancer and the participants was recruited in April 2023. Blood sample were collected and information was obtained through questionnaires. Data on reinfection was obtained by follow-up until July 31, 2023. The SARS-CoV-2-specific neutralizing antibody and IgG were measured. Results A total of 599 participants infected with hepatitis virus were included and the mean age was 61.3 ± 7.4 years. The SARS-CoV-2 infection rate was 94.7%. Among the infected, 132 were asymptomatic, 435 were symptomatic, no severe cases occurred. Four months after infection, no difference was in liver function and aMAP score between the infected and uninfected. The infected had higher seropositivity rates of both antibodies than the uninfected (neutralizing antibody: uninfected: 93.7%, infected: 99.6%; IgG: uninfected: 59.4%, infected: 98.9%). The levels of both antibodies in the symptomatic were higher than those the asymptomatic and the uninfected (neutralizing antibody: uninfected: 0.75 AU/mL, asymptomatic: 15.46 AU/mL, symptomatic: 24.76 AU/mL; IgG: uninfected: 15.10 AU/mL, asymptomatic: 263.84 AU/mL, symptomatic: 291.83 AU/mL). By July 31, 2023, the incidence of reinfection was 17.5%. Conclusions Although the infection rate of SARS-CoV-2 was high, no severe cases occurred. Omicron infection may not aggravate progression of hepatitis. Four months after infection, the population showed high positivity rate in neutralizing antibody and IgG. Monitoring of virus mutations and targeted prevention and care strategies is crucial for vulnerable populations.
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Affiliation(s)
- Yuchen Pan
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
- Center of Infectious Diseases and Pathogen Biology, the First Hospital of Jilin University, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health Jilin University, Changchun, China
| | - Zhifang Jia
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
| | - Xinyi Yu
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
| | - Haiyong Lv
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
| | - Yangyu Zhang
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
| | - Yanhua Wu
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
| | - Jing Jiang
- Department of Clinical Epidemiology, the First Hospital of Jilin University, Changchun, China
- Center of Infectious Diseases and Pathogen Biology, the First Hospital of Jilin University, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health Jilin University, Changchun, China
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Song XD, Gao HX, Tan H, Xie YY, Zhang X, Zhang CM, Wang YL, Dai EH. Prevalence of infection and reinfection among health care workers in a hospital of Northern China between BA.5/BF.7 and XBB.1.5 wave. Am J Infect Control 2025; 53:228-238. [PMID: 39151826 DOI: 10.1016/j.ajic.2024.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 08/06/2024] [Accepted: 08/09/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND To analyze the epidemiological characteristics of the SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in Healthcare workers (HCWs). METHODS We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions. RESULTS Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs 60.1%), cough (78.8% vs 58.0%), and sore throat (75.4% vs 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms, with a higher prevalence among female HCWs. CONCLUSIONS HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Strengthen infection prevention and control is crucial to mitigating infection risk and improving health services.
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Affiliation(s)
- Xue-Dong Song
- Department of Clinical Laboratory Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Department of Laboratory Medicine, Handan Central Hospital, Hebei Medical University, Handan, Hebei, China
| | - Hui-Xia Gao
- Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hao Tan
- Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yan-Yan Xie
- Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Xin Zhang
- Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Chen-Min Zhang
- Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yu-Ling Wang
- Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China.
| | - Er-Hei Dai
- Department of Clinical Laboratory Medicine, Hebei Medical University, Shijiazhuang, Hebei, China; Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, China.
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Li L, Guan Y, Du Y, Chen Z, Xie H, Lu K, Kang J, Jin P. Exploiting omic-based approaches to decipher Traditional Chinese Medicine. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118936. [PMID: 39413937 DOI: 10.1016/j.jep.2024.118936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 10/10/2024] [Accepted: 10/12/2024] [Indexed: 10/18/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese Medicine (TCM), an ancient health system, faces significant research challenges due to the complexity of its active components and targets, as well as a historical lack of detailed annotation. However, recent advances in omics technologies have begun to unravel these complexities, providing a more informed and nuanced understanding of TCM's therapeutic potential in contemporary healthcare. AIM OF THE REVIEW This review summarizes the application of omics technologies in TCM modernization, emphasizing components analysis, quality control, biomarker discovery, target identification, and treatment optimization. In addition, future perspectives on using omics for precision TCM treatment are also discussed. MATERIALS AND METHODS We have explored several databases (including PubMed, ClinicalTrials, Google Scholar, and Web of Science) to review related articles, focusing on Traditional Chinese Medicine, Omics Strategy, Precision Medicine, Biomarkers, Quality Control, and Molecular Mechanisms. Paper selection criteria involved English grammar, publication date, high citations, and broad applicability, exclusion criteria included low credibility, non-English publications, and those full-text inaccessible ones. RESULTS TCM and the popularity of Chinese herbal medicines (CHMs) are gaining increasing attention worldwide. This is driven, in part, by a large number of technologies, especially omics strategy, which are aiding the modernization of TCM. They contribute to the quality control of CHMs, the identification of cellular targets, discovery of new drugs and, most importantly, the understanding of their mechanisms of action. CONCLUSION To fully integrate TCM into modern medicine, further development of robust omics strategies is essential. This vision includes personalized medicine, backed by advanced computational power and secure data infrastructure, to facilitate global acceptance and seamless integration of TCM practices.
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Affiliation(s)
- Lei Li
- Department of anorectal Surgery, Hospital of Chengdu University of Traditional Chinese Medicine and Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
| | - Yueyue Guan
- Department of Encephalopathy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China.
| | - Yongjun Du
- Department of anorectal Surgery, Hospital of Chengdu University of Traditional Chinese Medicine and Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
| | - Zhen Chen
- School of Clinical Medicine of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Haoyang Xie
- School of Clinical Medicine of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Kejin Lu
- Yunnan Yunke Cheracteristic Plant Extraction Laboratory, Kunming, Yunnan, 650106, China.
| | - Jian Kang
- Department of anorectal Surgery, Hospital of Chengdu University of Traditional Chinese Medicine and Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
| | - Ping Jin
- State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China.
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Li B, Zhou Y, Zhang T, Ma A, Hao W. Effectiveness of a scenario-based, community-based intervention in containing COVID-19 in China. Front Public Health 2024; 12:1449305. [PMID: 39664544 PMCID: PMC11631882 DOI: 10.3389/fpubh.2024.1449305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 11/06/2024] [Indexed: 12/13/2024] Open
Abstract
Background Given the significant impact of the more than three-year-long COVID-19 pandemic on people's health, social order, and economic performance, as well as the potential re-emergence of a new variant and the epidemic "Disease X," it is crucial to examine its developmental trends and suggest countermeasures to address community epidemics of severe respiratory infectious diseases. Methods The epidemiological characterization of various strains of COVID-19 was modeled using an improved Susceptible-Exposed-Infectious-Recovered (SEIR) model to simulate the infections of different strains of COVID-19 under different scenarios, taking as an example an urban area of a prefecture-level city in Shandong Province, China, with a resident population of 2 million. Scenarios 1-5 are scenario-based simulations the Omicron strain, and 6-8 simulate the original COVID-19 strain, with different parameters for each scenario. Scenarios 1 and 6 do not consider community NPIs and represent natural epidemic scenarios. Scenarios 2-4 assess the impact of different NPIs on the original COVID-19 strain. Scenarios 1-4 and 6-8 compare the effects of the same measures on different strains. Scenario 5 simulates the effects of implementing NPIs after an outbreak has spread widely. Compare scenarios 4 and 9 to analyze the effect of high grades versus dynamic clearing of NPIs. By analyzing the time at which the peak number of cases was reached and the maximum number of cases, we were able to calculate the effectiveness of urban community control measures (NPIs) and the impact of vaccination on disease trends. Based on our research into the degree of restriction of social activities in different levels of control areas during real-world epidemics, we categorized the NPIs into three levels, with controls becoming increasingly stringent from levels 1 to 3 as low-, medium-, and high-risk areas are, respectively, controlled. Results In simulation scenarios 1-5 and 9, where the epidemic strain is Omicron and the susceptible population receives three doses of vaccine, it was found that the real-time peak number of cases in scenario 2, which implemented level 1 controls, was reduced by 18.19%, and in scenario 3, which implemented level 2 controls, it was reduced by 38.94%, compared with scenario 1, where no control measures were taken. Level 1 and level 2 controls do not block transmission but significantly reduce peak incidence and delay the peak time. In scenario 5, even with a high number of initial cases, the implementation of level 3 controls can still control the outbreak quickly, but it requires a longer period of time. However, Omicron has a low rate of severe illness, and the existing beds in City A could largely cope even if the control measures had not been implemented. Analyzing scenarios 4 and 9, level 3 community control and dynamic zeroing of the three zones were similarly successful in interrupting the spread of the epidemic. In simulation scenarios 6-8, where the prevalent strain was the original COVID-19 strain, only level 3 community control was able to rapidly extinguish the outbreak. Unchecked, the outbreak is severe, characterized by high peaks and substantial medical stress. Although level 2 controls reduced real-time incidence and peak new infections by 39.81 and 61.33%, and delayed the peaks by 55 and 52 days, respectively, the high rate of severe illnesses may still overwhelm the medical system. Conclusion Control effects are related to the level, timing and virus characteristics. Level 3 and dynamic zeroing measures can interrupt community transmission in the early stages of an outbreak. During a pandemic, different NPIs must be implemented, considering the virus's status and cost of control, and ensuring that medical resources are sufficient to maintain medical order.
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Affiliation(s)
- Binghang Li
- Weifang People’s Hospital, Shandong Second Medical University, Weifang, China
| | - Yalin Zhou
- School of Public Health, Shandong Second Medical University, Weifang, China
| | - Ting Zhang
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Anning Ma
- School of Public Health, Shandong Second Medical University, Weifang, China
| | - Wenhao Hao
- Weifang People’s Hospital, Shandong Second Medical University, Weifang, China
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Meltzer HC, Goodwin JL, Fowler LA, Britt TW, Pirrallo RG, Grier JT. Severe acute respiratory syndrome coronavirus 2-reactive salivary antibody detection in South Carolina emergency healthcare workers, September 2019-March 2020. Epidemiol Infect 2024; 152:e102. [PMID: 39320488 PMCID: PMC11427973 DOI: 10.1017/s0950268824000967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2024] Open
Abstract
On 19 January 2020, the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was identified in the United States, with the first cases in South Carolina confirmed on 06 March 2020. Due to initial limited testing capabilities and potential for asymptomatic transmission, it is possible that SARS-CoV-2 may have been present earlier than previously thought, while the immune status of at-risk populations was unknown. Saliva from 55 South Carolina emergency healthcare workers (EHCWs) was collected from September 2019 to March 2020, pre- and post-healthcare shifts, and stored frozen. To determine the presence of SARS-CoV-2-reactive antibodies, saliva-acquired post-shift was analysed by enzyme-linked immunosorbent assay (ELISA) with a repeat of positive or inconclusive results and follow-up testing of pre-shift samples. Two participants were positive for SARS-CoV-2 N/S1-reactive IgG, confirmed by follow-up testing, with S1 receptor binding domain (RBD)-specific IgG present in one individual. Positive samples were collected from medical students working in emergency medical services (EMSs) in October or November 2019. The presence of detectable anti-SARS-CoV-2 antibodies in 2019 suggests that immune responses to the virus existed in South Carolina, and the United States, in a small percentage of EHCWs prior to the earliest documented coronavirus disease 2019 (COVID-19) cases. These findings suggest the feasibility of saliva as a noninvasive tool for surveillance of emerging outbreaks, and EHCWs represent a high-risk population that should be the focus of infectious disease surveillance.
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Affiliation(s)
- Haley C Meltzer
- Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC, USA
| | - Jane L Goodwin
- Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC, USA
| | - Lauren A Fowler
- Department of Physiology and Pharmacology, Wake Forest School of Medicine, Charlotte, NC, USA
| | - Thomas W Britt
- Department of Psychology, Clemson University, Clemson, SC, USA
| | - Ronald G Pirrallo
- Department of Emergency Medicine, University of South Carolina School of Medicine Greenville, Greenville, SC, USA
| | - Jennifer T Grier
- Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC, USA
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Yao D, Patel RS, Lam A, Glover Q, Srinivasan C, Herchen A, Ritchie B, Agrawal B. Antibody Responses in SARS-CoV-2-Exposed and/or Vaccinated Individuals Target Conserved Epitopes from Multiple CoV-2 Antigens. Int J Mol Sci 2024; 25:9814. [PMID: 39337303 PMCID: PMC11432605 DOI: 10.3390/ijms25189814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), short-lived immunity, and susceptibility to immune imprinting due to frequent boosting practices. In this study, we examined the specificity of cross-reactive IgG antibody responses in mRNA-vaccinated, AstraZeneca-vaccinated, and unvaccinated donors to identify potentially conserved, cross-reactive epitopes to target in order to create a broadly protective SARS-CoV-2 vaccine. Our study provides evidence for cross-reactive IgG antibodies specific to eight different spike (S) variants. Furthermore, the specificities of these cross-variant IgG antibody titers were associated to some extent with spike S1- and S2-subunit-derived epitopes P1 and P2, respectively. In addition, nucleocapsid (N)- and membrane (M)-specific IgG antibody titers correlated with N- and M-derived epitopes conserved across beta-CoVs, P3-7. This study reveals conserved epitopes of viral antigens, targeted by natural and/or vaccine-induced human immunity, for future designs of next-generation COVID-19 vaccines.
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Affiliation(s)
- David Yao
- Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (D.Y.); (R.S.P.); (A.L.)
| | - Raj S. Patel
- Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (D.Y.); (R.S.P.); (A.L.)
| | - Adrien Lam
- Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (D.Y.); (R.S.P.); (A.L.)
| | - Quarshie Glover
- Department of Medicine, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (Q.G.); (C.S.); (A.H.); (B.R.)
| | - Cindy Srinivasan
- Department of Medicine, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (Q.G.); (C.S.); (A.H.); (B.R.)
| | - Alex Herchen
- Department of Medicine, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (Q.G.); (C.S.); (A.H.); (B.R.)
| | - Bruce Ritchie
- Department of Medicine, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (Q.G.); (C.S.); (A.H.); (B.R.)
| | - Babita Agrawal
- Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; (D.Y.); (R.S.P.); (A.L.)
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D’Amato M, Grignano MA, Iadarola P, Rampino T, Gregorini M, Viglio S. The Impact of Serum/Plasma Proteomics on SARS-CoV-2 Diagnosis and Prognosis. Int J Mol Sci 2024; 25:8633. [PMID: 39201322 PMCID: PMC11354567 DOI: 10.3390/ijms25168633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/19/2024] [Accepted: 08/05/2024] [Indexed: 09/02/2024] Open
Abstract
While COVID-19's urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneity. Mass spectrometry-based proteomics of patient serum/plasma emerges as a promising complementary approach to traditional diagnostic methods, offering insights into SARS-CoV-2 protein dynamics and enhancing understanding of the disease and its long-term consequences. This article highlights key findings from three years of pandemic-era proteomics research. It delves into biomarker discovery, diagnostic advancements, and drug development efforts aimed at monitoring COVID-19 onset and progression and exploring treatment options. Additionally, it examines global protein abundance and post-translational modification profiling to elucidate signaling pathway alterations and protein-protein interactions during infection. Finally, it explores the potential of emerging multi-omics analytic strategies in combatting SARS-CoV-2.
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Affiliation(s)
- Maura D’Amato
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy; (M.D.); (S.V.)
| | - Maria Antonietta Grignano
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy; (M.A.G.); (T.R.); (M.G.)
| | - Paolo Iadarola
- Department of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
| | - Teresa Rampino
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy; (M.A.G.); (T.R.); (M.G.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Marilena Gregorini
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy; (M.A.G.); (T.R.); (M.G.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Simona Viglio
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy; (M.D.); (S.V.)
- Lung Transplantation Unit, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
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Qiu C, Peng B, Xiao C, Chen P, Mao L, Shi X, Zhang Z, Lv Z, Lv Q, Zhang X, Li J, Huang Y, Hu Q, Chen G, Zou X, Liang X. A novel method for identifying SARS-CoV-2 infection mutants via an epitope-specific CD8 + T cell test. BIOSAFETY AND HEALTH 2024; 6:143-152. [PMID: 40078724 PMCID: PMC11894948 DOI: 10.1016/j.bsheal.2024.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 03/07/2024] [Accepted: 03/14/2024] [Indexed: 03/14/2025] Open
Abstract
Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8+ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8+ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8+ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8+ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a "method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8+ T cells in the peripheral blood of subjects", covering up to 46 % of the population, including HLA-A2+ and HLA-A24+ donors, providing a novel method for SARS-CoV-2 infected case tracing.
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Affiliation(s)
- Congling Qiu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Kangtai Biological Vaccine Industry Research Institute/Disease Prevention and Control Institute of Jinan University, Guangzhou 510632, China
| | - Bo Peng
- Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Chanchan Xiao
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- The Sixth Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Pengfei Chen
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Lipeng Mao
- Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Xiaolu Shi
- Microbiology Laboratory, Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Zhen Zhang
- Department of Communicable Diseases Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Ziquan Lv
- Central Laboratory, Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Qiuying Lv
- Department of Communicable Diseases Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Xiaomin Zhang
- Microbiology Laboratory, Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Jiaxin Li
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Kangtai Biological Vaccine Industry Research Institute/Disease Prevention and Control Institute of Jinan University, Guangzhou 510632, China
| | - Yanhao Huang
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Qinghua Hu
- Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Guobing Chen
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- The Sixth Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Xuan Zou
- Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
| | - Xiaofeng Liang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Kangtai Biological Vaccine Industry Research Institute/Disease Prevention and Control Institute of Jinan University, Guangzhou 510632, China
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Clever S, Limpinsel L, Meyer zu Natrup C, Schünemann LM, Beythien G, Rosiak M, Hülskötter K, Gregor KM, Tuchel T, Kalodimou G, Freudenstein A, Kumar S, Baumgärtner W, Sutter G, Tscherne A, Volz A. Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection. Viruses 2024; 16:417. [PMID: 38543782 PMCID: PMC10974247 DOI: 10.3390/v16030417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 05/23/2024] Open
Abstract
The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens.
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Affiliation(s)
- Sabrina Clever
- Institute of Virology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (S.C.); (C.M.z.N.); (L.-M.S.)
| | - Leonard Limpinsel
- Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; (L.L.); (G.K.); (A.F.); (S.K.); (G.S.); (A.T.)
| | - Christian Meyer zu Natrup
- Institute of Virology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (S.C.); (C.M.z.N.); (L.-M.S.)
| | - Lisa-Marie Schünemann
- Institute of Virology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (S.C.); (C.M.z.N.); (L.-M.S.)
| | - Georg Beythien
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (G.B.); (M.R.); (K.H.); (K.M.G.); (W.B.)
| | - Malgorzata Rosiak
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (G.B.); (M.R.); (K.H.); (K.M.G.); (W.B.)
| | - Kirsten Hülskötter
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (G.B.); (M.R.); (K.H.); (K.M.G.); (W.B.)
| | - Katharina Manuela Gregor
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (G.B.); (M.R.); (K.H.); (K.M.G.); (W.B.)
| | - Tamara Tuchel
- Institute of Virology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (S.C.); (C.M.z.N.); (L.-M.S.)
| | - Georgia Kalodimou
- Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; (L.L.); (G.K.); (A.F.); (S.K.); (G.S.); (A.T.)
| | - Astrid Freudenstein
- Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; (L.L.); (G.K.); (A.F.); (S.K.); (G.S.); (A.T.)
| | - Satendra Kumar
- Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; (L.L.); (G.K.); (A.F.); (S.K.); (G.S.); (A.T.)
| | - Wolfgang Baumgärtner
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (G.B.); (M.R.); (K.H.); (K.M.G.); (W.B.)
| | - Gerd Sutter
- Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; (L.L.); (G.K.); (A.F.); (S.K.); (G.S.); (A.T.)
| | - Alina Tscherne
- Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; (L.L.); (G.K.); (A.F.); (S.K.); (G.S.); (A.T.)
| | - Asisa Volz
- Institute of Virology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hanover, Germany; (S.C.); (C.M.z.N.); (L.-M.S.)
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10
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Gao M, Xing X, Hao W, Zhang X, Zhong K, Lu C, Deng X, Yu L. Diverse immune responses in vaccinated individuals with and without symptoms after omicron exposure during the recent outbreak in Guangzhou, China. Heliyon 2024; 10:e24030. [PMID: 38293451 PMCID: PMC10827461 DOI: 10.1016/j.heliyon.2024.e24030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 12/17/2023] [Accepted: 01/02/2024] [Indexed: 02/01/2024] Open
Abstract
Objectives During the recent wave of coronavirus disease 2019 (COVID-19) infections in China, most individuals have been vaccinated and exposed to the omicron variant. In the present study, two cohorts were observed in the vaccinated population: vaccinated individuals with symptoms (VIWS) and those without symptoms (VIWOS). Our study aimed to characterize the antibody response in two cohorts: VIWS and VIWOS. Methods A questionnaire survey was conducted in the community. Blood and saliva samples were collected from 124 individuals in the VIWS and VIWOS cohorts. Capture enzyme-linked immunosorbent assay (ELISA) was performed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies. Results The questionnaire survey revealed that 30.0 % (302/1005) of individuals in the older adult group (≥65 years) experienced no symptoms, whereas the rate of individuals without symptoms in the younger group (<65 years) was 17.8 % (166/932). Nucleocapsid (N)-specific IgM (N-IgM) was detected in the blood samples at a rate of 69.2 % (54/78) in the VIWS cohort. The positivity rate for N-specific IgA (N-IgA) was 93.6 % (73/78). In addition, the positivity rates of spike (S)-specific IgA (S-IgA) and N-IgA detected in saliva samples were 42 % (21/50) and 54 % (27/50), respectively. Both N-IgA positivity and negativity were observed in the VIWOS cohort. The detection rate of N-IgM positivity was 57.1 % (12/21) in the N-IgA-positive group. In addition, 54.3 % (25/46) of the vaccinated individuals without symptoms were IgA-negative. Conclusions Our study indicates that substantial N-specific antibodies were induced during omicron infection and that testing for N-IgA in both blood and saliva may aid in the diagnosis of SARS-CoV-2 infection in vaccinated populations.
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Affiliation(s)
- Ming Gao
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Xiaomin Xing
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Wenbiao Hao
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Xulei Zhang
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Kexin Zhong
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Canhui Lu
- Jiahe Community Health Service Center of Baiyun District, Guangzhou 510440, China
| | - Xilong Deng
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Lei Yu
- Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
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11
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Filimonova I, Innocenti G, Vogl T. Phage Immunoprecipitation Sequencing (PhIP-Seq) for Analyzing Antibody Epitope Repertoires Against Food Antigens. Methods Mol Biol 2024; 2717:101-122. [PMID: 37737980 DOI: 10.1007/978-1-0716-3453-0_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/23/2023]
Abstract
While thousands of food and environmental allergens have been reported, conventional methods for allergy testing typically rely on measuring immunoglobulin E (IgE) binding against panels of dozens to hundreds of antigens. Beyond IgE, also the specificity of other Ig (sub-)classes such as IgG4, has gained interest because of a potential protective role toward allergy.Phage immunoprecipitation sequencing (PhIP-Seq) allows to study hundreds of thousands of rationally selected peptide antigens and to resolve binding specificities of different Ig classes. This technology combines synthetic DNA libraries encoding antigens, with the display on the surface of T7 bacteriophages and next-generation sequencing (NGS) for quantitative readouts. Thereby binding of entire Ig repertoires can be measured to detect the exact epitopes of food allergens and to study potential cross-reactivity.In this chapter, we provide a summary of both the key experimental steps and various strategies for analyzing PhIP-Seq datasets, as well as comparing the advantages and disadvantages of this methodology for measuring antibody responses against food antigens.
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Affiliation(s)
- Ioanna Filimonova
- Medical University of Vienna, Center for Cancer Research, Vienna, Austria
| | - Gabriel Innocenti
- Medical University of Vienna, Center for Cancer Research, Vienna, Austria
| | - Thomas Vogl
- Medical University of Vienna, Center for Cancer Research, Vienna, Austria.
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12
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Brown JA, Hauser A, Abela IA, Pasin C, Epp S, Mohloanyane T, Nsakala BL, Trkola A, Labhardt ND, Kouyos RD, Günthard HF. Seroprofiling of Antibodies Against Endemic Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 in a Human Immunodeficiency Virus Cohort in Lesotho: Correlates of Antibody Response and Seropositivity. J Infect Dis 2023; 228:1042-1054. [PMID: 37261930 PMCID: PMC10582919 DOI: 10.1093/infdis/jiad197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 05/18/2023] [Accepted: 05/27/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND Serological data on endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Africa are scarce. Here, we report on (1) endemic HCoV seasonality, (2) SARS-CoV-2 seroprevalence, and (3) correlates of SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and endemic HCoV serological responses among adults living with human immunodeficiency virus (HIV). METHODS Plasma samples were collected from February 2020 to July 2021 within an HIV cohort in Lesotho. We used the AntiBody CORonavirus Assay (ABCORA) multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS Results for 3173 samples from 1403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter and spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex, obesity, working outside the home, and recent tiredness or fever. Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2 and between older age or obesity and the immunoglobulin G response to SARS-CoV-2. CONCLUSIONS These results add to our understanding of the impact of biological, clinical, and social/behavioral factors on serological responses to coronaviruses in southern Africa.
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Affiliation(s)
- Jennifer A Brown
- Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland
- Division of Clinical Epidemiology, Department of Clinical Research, University of Basel, Basel, Switzerland
| | - Anthony Hauser
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Irene A Abela
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Chloé Pasin
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Selina Epp
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | | | | | - Alexandra Trkola
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Niklaus D Labhardt
- Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland
- Division of Clinical Epidemiology, Department of Clinical Research, University of Basel, Basel, Switzerland
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Roger D Kouyos
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Huldrych F Günthard
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
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13
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Peterhoff D, Wiegrebe S, Einhauser S, Patt AJ, Beileke S, Günther F, Steininger P, Niller HH, Burkhardt R, Küchenhoff H, Gefeller O, Überla K, Heid IM, Wagner R. Population-based study of the durability of humoral immunity after SARS-CoV-2 infection. Front Immunol 2023; 14:1242536. [PMID: 37868969 PMCID: PMC10585261 DOI: 10.3389/fimmu.2023.1242536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
SARS-CoV-2 antibody quantity and quality are key markers of humoral immunity. However, there is substantial uncertainty about their durability. We investigated levels and temporal change of SARS-CoV-2 antibody quantity and quality. We analyzed sera (8 binding, 4 avidity assays for spike-(S-)protein and nucleocapsid-(N-)protein; neutralization) from 211 seropositive unvaccinated participants, from the population-based longitudinal TiKoCo study, at three time points within one year after infection with the ancestral SARS-CoV-2 virus. We found a significant decline of neutralization titers and binding antibody levels in most assays (linear mixed regression model, p<0.01). S-specific serum avidity increased markedly over time, in contrast to N-specific. Binding antibody levels were higher in older versus younger participants - a difference that disappeared for the asymptomatic-infected. We found stronger antibody decline in men versus women and lower binding and avidity levels in current versus never-smokers. Our comprehensive longitudinal analyses across 13 antibody assays suggest decreased neutralization-based protection and prolonged affinity maturation within one year after infection.
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Affiliation(s)
- David Peterhoff
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Simon Wiegrebe
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
- Statistical Consulting Unit StaBLab, Department of Statistics, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
| | - Sebastian Einhauser
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
| | - Arisha J. Patt
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Stephanie Beileke
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Felix Günther
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
- Statistical Consulting Unit StaBLab, Department of Statistics, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
| | - Philipp Steininger
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Hans H. Niller
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
| | - Ralph Burkhardt
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany
| | - Helmut Küchenhoff
- Statistical Consulting Unit StaBLab, Department of Statistics, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
| | - Olaf Gefeller
- Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Klaus Überla
- Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Iris M. Heid
- Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
| | - Ralf Wagner
- Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Regensburg, Germany
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
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14
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Wu M, Liu J, Wang X, Zhang X, Liang T, Chen L, Huang T, Li Y, Zheng C, Yang Y, Wang J, Yu X, Guo L, Yang J, Ren L. Profiling of SARS-CoV-2 neutralizing antibody-associated antigenic peptides signature using proteome microarray. MedComm (Beijing) 2023; 4:e361. [PMID: 37667740 PMCID: PMC10475218 DOI: 10.1002/mco2.361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 08/02/2023] [Accepted: 08/06/2023] [Indexed: 09/06/2023] Open
Abstract
The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS-CoV-2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID-19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S-82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10-3), were closely associated with the presence of SARS-CoV-2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID-19 cases in 2020, S82-IgG titers were higher in NAbs-positive samples (p = 0.002) than in NAbs-negative samples using enzyme-linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82-IgG titers, NAb titers were significantly higher in the samples with higher S82-IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay-associated signatures of SARS-CoV-2 NAbs.
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Affiliation(s)
- Mingkun Wu
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Jiangfeng Liu
- State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Xinming Wang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Xiaomei Zhang
- State Key Laboratory of Proteomics, Beijing Proteome Research CenterNational Center for Protein Sciences‐Beijing (PHOENIX Center)Beijing Institute of LifeomicsBeijingChina
| | - Te Liang
- State Key Laboratory of Proteomics, Beijing Proteome Research CenterNational Center for Protein Sciences‐Beijing (PHOENIX Center)Beijing Institute of LifeomicsBeijingChina
| | - Lan Chen
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Tingxuan Huang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Yanan Li
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Chang Zheng
- State Key Laboratory of Proteomics, Beijing Proteome Research CenterNational Center for Protein Sciences‐Beijing (PHOENIX Center)Beijing Institute of LifeomicsBeijingChina
| | - Yehong Yang
- State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Jianwei Wang
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
- Key Laboratory of Respiratory Disease PathogenomicsChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xiaobo Yu
- State Key Laboratory of Proteomics, Beijing Proteome Research CenterNational Center for Protein Sciences‐Beijing (PHOENIX Center)Beijing Institute of LifeomicsBeijingChina
| | - Li Guo
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
- Key Laboratory of Respiratory Disease PathogenomicsChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Juntao Yang
- State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
| | - Lili Ren
- National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux LaboratoryInstitute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
- Key Laboratory of Respiratory Disease PathogenomicsChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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15
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Jensen S, Traugott M, Ramazanova D, Haslacher H, Mucher P, Perkmann T, Jeleff M, Kutalek R, Wenisch C, Crevenna R, Jordakieva G. SARS-CoV-2 infections in "less visible" hospital staff: The roles and safety of environmental services and allied health professionals. J Infect Public Health 2023; 16:1379-1385. [PMID: 37437431 PMCID: PMC10238113 DOI: 10.1016/j.jiph.2023.05.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/18/2023] [Accepted: 05/31/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND During the early SARS-CoV-2 pandemic, all healthcare workers had specific and essential functions. However, environmental services (e.g., cleaning staff) and allied health professionals (e.g., physiotherapists) are often less recognised inpatient care. The aim of our study was to evaluate SARS-CoV-2-infection rates and describe risk factors relevant to workplace transmission and occupational safety amongst healthcare workers in COVID-19 hospitals before the introduction of SARS-CoV-2-specific vaccines. METHODS This cross-sectional study (from May 2020 to March 2021, standardised WHO early-investigation protocol) is evaluating workplace or health-related data, COVID-19-patient proximity, personal protective equipment (PPE) use, and adherence to infection prevention and control (IPC) measures, anti-SARS-CoV-2-antibody status, and transmission pathways. RESULTS Out of n = 221 HCW (n = 189 cleaning/service staff; n = 32 allied health professionals), n = 17 (7.7 %) were seropositive. While even SARS-CoV-2-naïve HCW reported SARS-CoV-2-related symptoms, airway symptoms, loss of smell or taste, and appetite were the most specific for a SARS-CoV-2-infection. Adherence to IPC (98.6 %) and recommended PPE use (98.2 %) were high and not associated with seropositivity. In 70.6 %, transmission occurred in private settings; in 23.5 %, at the workplace (by interaction with SARS-CoV-2-positive colleagues [17.6 %] or patient contact [5.9 %]), or remained unclear (one case). CONCLUSIONS Infection rates were higher in all assessed 'less visible' healthcare-worker groups compared to the general population. Our data indicates that, while IPC measures and PPE may have contributed to the prevention of patient-to-healthcare-worker transmissions, infections were commonly acquired outside of work and transmitted between healthcare workers within the hospital. This finding emphasises the importance of ongoing education on transmission prevention and regular infection screenings at work.
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Affiliation(s)
- Sebastian Jensen
- Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, Vienna, Austria
| | - Marianna Traugott
- 4th Medical Department, Department of Infectious Diseases and Tropical Medicine, Kaiser-Franz-Josef Hospital, Vienna, Austria
| | - Dariga Ramazanova
- Center for Medical Statistics, Informatics and Intelligent Systems CeMSIIS, Medical University of Vienna, Vienna, Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Patrick Mucher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Maren Jeleff
- Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Austria
| | - Ruth Kutalek
- Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Austria
| | - Christoph Wenisch
- 4th Medical Department, Department of Infectious Diseases and Tropical Medicine, Kaiser-Franz-Josef Hospital, Vienna, Austria
| | - Richard Crevenna
- Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, Vienna, Austria
| | - Galateja Jordakieva
- Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, Vienna, Austria.
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16
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Ódor G, Vuckovic J, Ndoye MAS, Thiran P. Source identification via contact tracing in the presence of asymptomatic patients. APPLIED NETWORK SCIENCE 2023; 8:53. [PMID: 37614376 PMCID: PMC10442312 DOI: 10.1007/s41109-023-00566-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 06/26/2023] [Indexed: 08/25/2023]
Abstract
Inferring the source of a diffusion in a large network of agents is a difficult but feasible task, if a few agents act as sensors revealing the time at which they got hit by the diffusion. One of the main limitations of current source identification algorithms is that they assume full knowledge of the contact network, which is rarely the case, especially for epidemics, where the source is called patient zero. Inspired by recent implementations of contact tracing algorithms, we propose a new framework, which we call Source Identification via Contact Tracing Framework (SICTF). In the SICTF, the source identification task starts at the time of the first hospitalization, and initially we have no knowledge about the contact network other than the identity of the first hospitalized agent. We may then explore the network by contact queries, and obtain symptom onset times by test queries in an adaptive way, i.e., both contact and test queries can depend on the outcome of previous queries. We also assume that some of the agents may be asymptomatic, and therefore cannot reveal their symptom onset time. Our goal is to find patient zero with as few contact and test queries as possible. We implement two local search algorithms for the SICTF: the LS algorithm, which has recently been proposed by Waniek et al. in a similar framework, is more data-efficient, but can fail to find the true source if many asymptomatic agents are present, whereas the LS+ algorithm is more robust to asymptomatic agents. By simulations we show that both LS and LS+ outperform previously proposed adaptive and non-adaptive source identification algorithms adapted to the SICTF, even though these baseline algorithms have full access to the contact network. Extending the theory of random exponential trees, we analytically approximate the source identification probability of the LS/ LS+ algorithms, and we show that our analytic results match the simulations. Finally, we benchmark our algorithms on the Data-driven COVID-19 Simulator (DCS) developed by Lorch et al., which is the first time source identification algorithms are tested on such a complex dataset.
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Amellal H, Assaid N, Charoute H, Akarid K, Maaroufi A, Ezzikouri S, Sarih M. Kinetics of specific anti-SARS-CoV-2 IgM, IgA, and IgG responses during the first 12 months after SARS-CoV-2 infection: A prospective longitudinal study. PLoS One 2023; 18:e0288557. [PMID: 37437051 DOI: 10.1371/journal.pone.0288557] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/29/2023] [Indexed: 07/14/2023] Open
Abstract
Coronavirus 2019 (COVID-19) is a global health threat. The kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be assessed, as the long-term duration of these immunoglobulins remains largely controversial. The aim of this study was to assess the longitudinal dynamics of anti-SARS-CoV-2 antibodies against the nucleocapsid (N) protein and the receptor-binding domain (RBD) of the spike protein up to one year in a cohort of 190 COVID-19 patients. Between March and September 2021, we enrolled patients from two regional hospitals in Casablanca, Morocco. Blood samples were collected and analyzed for antibody levels. We used the commercial Euroimmun ELISA for the determination of anti-N IgM, the Abbott Architect™ SARS-CoV-2 IgG test for the detection of anti-RBD IgG, and an in-house kit for the assay of anti-N IgG and anti-N IgA. IgM and IgA antibodies were assessed 2-5, 9-12, 17-20 and 32-37 days after symptom onset. IgG antibodies were also assessed 60, 90, 120 and 360 days after symptom onset. One-third of patients developed IgM (32%), while two-thirds developed IgA (61%). One month of symptom onset, most patients developed IgG, with 97% and 93% positivity for anti-RBD IgG and anti-N IgG, respectively. The anti-RBD IgG positivity rate remained high up to one year of follow-up. However, the anti-N IgG positivity rate decreased over time, with only 41% of patients testing positive after one year's follow-up. IgG levels were significantly higher in older people (over 50 years) than in other study participants. We also found that patients who had received two doses of ChAdOx1 nCoV-19 vaccine prior to infection had a lower IgM response than unvaccinated patients. This difference was statistically significant two weeks after the onset of symptoms. We present the first study in Africa to measure the kinetics of antibody response (IgA, IgM and IgG) to SARS-CoV-2 over one year. Most participants remained seropositive for anti-RBD IgG after one year but showed a significant decline in antibody titers.
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Affiliation(s)
- Houda Amellal
- Department of Parasitology and Vector-Borne Diseases, Institut Pasteur du Maroc, Casablanca, Morocco
- Aïn Chock Faculty of Sciences, Health and Environment Laboratory, Biochemistry, Biotechnology and Immunophysiopathology Research Team, Hassan II University of Casablanca, Casablanca, Morocco
| | - Najlaa Assaid
- Department of Parasitology and Vector-Borne Diseases, Institut Pasteur du Maroc, Casablanca, Morocco
| | - Hicham Charoute
- Institut Pasteur du Maroc, Research Unit of Epidemiology, Biostatistics and Bioinformatics, Casablanca, Morocco
| | - Khadija Akarid
- Aïn Chock Faculty of Sciences, Health and Environment Laboratory, Biochemistry, Biotechnology and Immunophysiopathology Research Team, Hassan II University of Casablanca, Casablanca, Morocco
| | - Abderrahmane Maaroufi
- Department of Parasitology and Vector-Borne Diseases, Institut Pasteur du Maroc, Casablanca, Morocco
| | - Sayeh Ezzikouri
- Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Virology Unit, Casablanca, Morocco
| | - M'hammed Sarih
- Department of Parasitology and Vector-Borne Diseases, Institut Pasteur du Maroc, Casablanca, Morocco
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18
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Boumar I, Deliorman M, Sukumar P, Qasaimeh MA. Spike- and nucleocapsid-based gold colloid assay toward the development of an adhesive bandage for rapid SARS-CoV-2 immune response detection and screening. MICROSYSTEMS & NANOENGINEERING 2023; 9:82. [PMID: 37351273 PMCID: PMC10281977 DOI: 10.1038/s41378-023-00554-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 05/02/2023] [Accepted: 05/14/2023] [Indexed: 06/24/2023]
Abstract
Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are important biomarkers used for the diagnosis and screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in both symptomatic and asymptomatic individuals. These antibodies are highly specific to the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus. This paper outlines the development steps of a novel hybrid (vertical-lateral-vertical) flow assay in the form of a finger-stick point-of-care device, similar to an adhesive bandage, designed for the timely detection and screening of IgM and IgG immune responses to SARS-CoV-2 infections. The assay, comprising a vertically stacked plasma/serum separation membrane, conjugate pad, and detection (readout) zone, utilizes gold nanoparticles (AuNPs) conjugated with SARS-CoV-2 S and N proteins to effectively capture IgM and IgG antibodies from a pinprick (~15 µL) of blood in just one step and provides results of no immune IgM-/IgG-, early immune IgM+/IgG-, active immune IgM+/IgG+ or immune IgM-/IgG+ in a short amount of time (minutes). The adhesive bandage-like construction is an example of the design of rapid, low-cost, disposable, and easy-to-use tests for large-scale detection and screening in households. Furthermore, the bandage can be easily adjusted and optimized to detect different viral infections as they arise by simply selecting appropriate antigens related to pandemics and outbreaks.
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Affiliation(s)
- Imen Boumar
- Division of Engineering, New York University Abu Dhabi (NYUAD), Abu Dhabi, UAE
| | | | - Pavithra Sukumar
- Division of Engineering, New York University Abu Dhabi (NYUAD), Abu Dhabi, UAE
| | - Mohammad A. Qasaimeh
- Division of Engineering, New York University Abu Dhabi (NYUAD), Abu Dhabi, UAE
- NYU Tandon School of Engineering, New York University, New York, USA
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19
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Radion EI, Mukhin VE, Kholodova AV, Vladimirov IS, Alsaeva DY, Zhdanova AS, Ulasova NY, Bulanova NV, Makarov VV, Keskinov AA, Yudin SM. Functional Characteristics of Serum Anti-SARS-CoV-2 Antibodies against Delta and Omicron Variants after Vaccination with Sputnik V. Viruses 2023; 15:1349. [PMID: 37376648 DOI: 10.3390/v15061349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/05/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Anti-SARS-CoV-2 vaccination leads to the production of neutralizing as well as non-neutralizing antibodies. In the current study, we investigated the temporal dynamics of both sides of immunity after vaccination with two doses of Sputnik V against SARS-CoV-2 variants Wuhan-Hu-1 SARS-CoV-2 G614-variant (D614G), B.1.617.2 (Delta), and BA.1 (Omicron). First, we constructed a SARS-CoV-2 pseudovirus assay to assess the neutralization activity of vaccine sera. We show that serum neutralization activity against BA.1 compared to D614G is decreased by 8.16-, 11.05-, and 11.16- fold in 1, 4, and 6 months after vaccination, respectively. Moreover, previous vaccination did not increase serum neutralization activity against BA.1 in recovered patients. Next, we used the ADMP assay to evaluate the Fc-mediated function of vaccine-induced serum antibodies. Our results show that the antibody-dependent phagocytosis triggered by S-proteins of the D614G, B.1.617.2 and BA.1 variants did not differ significantly in vaccinated individuals. Moreover, the ADMP efficacy was retained over up to 6 months in vaccine sera. Our results demonstrate differences in the temporal dynamics of neutralizing and non-neutralizing antibody functions after vaccination with Sputnik V.
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Affiliation(s)
- Elizaveta I Radion
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Vladimir E Mukhin
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Alyona V Kholodova
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Ivan S Vladimirov
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Darya Y Alsaeva
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Anastasia S Zhdanova
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Natalya Y Ulasova
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Natalya V Bulanova
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Valentin V Makarov
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Anton A Keskinov
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
| | - Sergey M Yudin
- Federal State Budgetary Institution, Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Schukinskaya 5, Building 1, Moscow 123182, Russia
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20
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Özkaya E, Yazıcı M, Baran I, Çetin NS, Tosun İ, Buruk CK, Kaklıkkaya N, Aydın F, Doymaz MZ. Neutralization of Wild-Type and Alpha SARS-CoV-2 Variant by CoronaVac® Vaccine and Natural Infection- Induced Antibodies. Curr Microbiol 2023; 80:162. [PMID: 37004596 PMCID: PMC10066983 DOI: 10.1007/s00284-023-03248-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 02/27/2023] [Indexed: 04/04/2023]
Abstract
One of the immune responses desired to be achieved by SARS-CoV-2 vaccination is to create neutralizing antibodies (nAbs), thus preventing the development and spread of infection. The aim of this study was to investigate the seropositivity rate, anti-spike antibody levels, and neutralizing capacity of these antibodies against wild type (WT) and alpha variants in serum samples of individuals who had been naturally infected or vaccinated with CoronaVac®. Total anti-spike antibody levels were determined in all samples. Neutralization assays were performed by the reduction of the cytopathic effect in Vero-E6 cells with infectious WT and alpha SARS-CoV-2 variants. Although both naturally infected and vaccinated individuals were all seropositive for antispike antibodies, 84.8% of the vaccinated group, and 89.3% of the naturally infected group had detectable nAbs. The nAbs titers were significantly higher in the naturally infected group for both WT and alfa variant of the virus as compared to the vaccinated individuals. In this study, it was observed that all individuals became seropositive six weeks after exposure to the vaccine or the virus. Moreover, naturally infected individuals had higher levels of nAbs than those vaccinated. The presence of nAbs against the alpha variant in both naturally infected and vaccinated individuals suggests that these antibodies may also be protective against infections, which may be caused by other variants, such as delta and omicron.
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Affiliation(s)
- Esra Özkaya
- Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.
| | - Merve Yazıcı
- Department of Medical Microbiology, Bezmialem Vakıf University Faculty of Medicine, Istanbul, Turkey
- Beykoz Institute of Life Sciences and Technology, Bezmialem Vakıf University, Istanbul, Turkey
| | - Irmak Baran
- Medical Microbiology Laboratory, Ankara Training and Research Hospital, Ankara, Turkey
| | - Nesibe Selma Çetin
- Department of Medical Microbiology, Bezmialem Vakıf University Faculty of Medicine, Istanbul, Turkey
| | - İlknur Tosun
- Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Celal Kurtuluş Buruk
- Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Neşe Kaklıkkaya
- Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Faruk Aydın
- Department of Medical Microbiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
- Department of Medical Microbiology, Atlas University Faculty of Medicine, Istanbul, Turkey
| | - Mehmet Ziya Doymaz
- Department of Medical Microbiology, Bezmialem Vakıf University Faculty of Medicine, Istanbul, Turkey
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21
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Fraser R, Orta-Resendiz A, Dockrell D, Müller-Trutwin M, Mazein A. Severe COVID-19 versus multisystem inflammatory syndrome: comparing two critical outcomes of SARS-CoV-2 infection. Eur Respir Rev 2023; 32:32/167/220197. [PMID: 36889788 PMCID: PMC10032586 DOI: 10.1183/16000617.0197-2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 12/31/2022] [Indexed: 03/10/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with diverse host response immunodynamics and variable inflammatory manifestations. Several immune-modulating risk factors can contribute to a more severe coronavirus disease 2019 (COVID-19) course with increased morbidity and mortality. The comparatively rare post-infectious multisystem inflammatory syndrome (MIS) can develop in formerly healthy individuals, with accelerated progression to life-threatening illness. A common trajectory of immune dysregulation forms a continuum of the COVID-19 spectrum and MIS; however, severity of COVID-19 or the development of MIS is dependent on distinct aetiological factors that produce variable host inflammatory responses to infection with different spatiotemporal manifestations, a comprehensive understanding of which is necessary to set better targeted therapeutic and preventative strategies for both.
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Affiliation(s)
- Rupsha Fraser
- The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| | - Aurelio Orta-Resendiz
- Institut Pasteur, Université Paris Cité, HIV, Inflammation and Persistence Unit, Paris, France
| | - David Dockrell
- The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| | - Michaela Müller-Trutwin
- Institut Pasteur, Université Paris Cité, HIV, Inflammation and Persistence Unit, Paris, France
| | - Alexander Mazein
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
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22
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Pilati Campos IM, Marques M, Peiter GC, Brandalize APC, dos Santos MB, de Melo FF, Teixeira KN. Temporal pattern of humoral immune response in mild cases of COVID-19. World J Biol Chem 2023; 14:40-51. [PMID: 37034134 PMCID: PMC10080547 DOI: 10.4331/wjbc.v14.i2.40] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/08/2022] [Accepted: 02/02/2023] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019 (COVID-19) is one of the essential factors to better characterize the immune memory of patients, which allows understanding the temporality of reinfection, provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consequently helps in global public health and vaccination strategy. Among the patients who became infected with SARS-CoV-2, the majority who did not progress to death were those who developed the mild COVID-19, so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.
AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G (IgG) in mild cases of COVID-19.
METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction (RT-qPCR)-positive volunteers from the municipality of Toledo/ Paraná/Brazil, underwent two distinct serological tests, enzyme-linked immunosorbent assay, and detection of anti-nucleocapsid IgG. Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021. All assays were performed in duplicate and the manufacturers' recommendations were strictly followed. The data were statistically analyzed using multiple logistic regression; the variables were selected by applying the P < 0.05 criterion.
RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo. The time periods when the highest number of participants with detectable IgG was observed were 1, 2 and 3 mo. It was observed that 9.42% of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57% were also IgG negative at less than 1 mo. At 5 mo, 3.14% of volunteers were IgG negative, and at 6 or 7 mo, 1 volunteer (0.52%) had no detectable IgG. During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study, no statistical significance was observed for any association analyzed. Moreover, considering the age category between 31 and 59 years as the exposed group, the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older, showing that in both age categories there was no association between the pair of variables analyzed. Regarding chronic disease, the exposure group consisted of the participants without any comorbidity, so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.
CONCLUSION A temporal pattern of IgG response was not observed, but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.
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Affiliation(s)
| | - Milena Marques
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
| | | | | | | | - Fabrício Freire de Melo
- Campus Anísio Teixeira, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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23
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Projection of COVID-19 Positive Cases Considering Hybrid Immunity: Case Study in Tokyo. Vaccines (Basel) 2023; 11:vaccines11030633. [PMID: 36992217 DOI: 10.3390/vaccines11030633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/27/2023] [Accepted: 03/10/2023] [Indexed: 03/16/2023] Open
Abstract
Since the emergence of COVID-19, the forecasting of new daily positive cases and deaths has been one of the essential elements in policy setting and medical resource management worldwide. An essential factor in forecasting is the modeling of susceptible populations and vaccination effectiveness (VE) at the population level. Owing to the widespread viral transmission and wide vaccination campaign coverage, it becomes challenging to model the VE in an efficient and realistic manner, while also including hybrid immunity which is acquired through full vaccination combined with infection. Here, the VE model of hybrid immunity was developed based on an in vitro study and publicly available data. Computational replication of daily positive cases demonstrates a high consistency between the replicated and observed values when considering the effect of hybrid immunity. The estimated positive cases were relatively larger than the observed value without considering hybrid immunity. Replication of the daily positive cases and its comparison would provide useful information of immunity at the population level and thus serve as useful guidance for nationwide policy setting and vaccination strategies.
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24
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Al-Tamimi M, Tarifi AA, Qaqish A, Abbas MM, Albalawi H, Abu-Raideh J, Salameh M, Khasawneh AI. Immunoglobulins response of COVID-19 patients, COVID-19 vaccine recipients, and random individuals. PLoS One 2023; 18:e0281689. [PMID: 36787317 PMCID: PMC9928079 DOI: 10.1371/journal.pone.0281689] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 01/29/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND The development of specific immunoglobulins to COVID-19 after natural infection or vaccination has been proposed. The efficacy and dynamics of this response are not clear yet. AIM This study aims to analyze the immunoglobulins response among COVID-19 patients, COVID-19 vaccine recipients and random individuals. METHODS A total of 665 participants including 233 COVID-19 patients, 288 COVID-19 vaccine recipients, and 144 random individuals were investigated for anti-COVID-19 immunoglobulins (IgA, IgG, IgM). RESULTS Among COVID-19 patients, 22.7% had detectable IgA antibodies with a mean of 27.3±57.1 ng/ml, 29.6% had IgM antibodies with a mean of 188.4±666.0 BAU/ml, while 59.2% had IgG antibodies with a mean of 101.7±139.7 BAU/ml. Pfizer-BioNTech vaccine recipients had positive IgG in 99.3% with a mean of 515.5±1143.5 BAU/ml while 85.7% of Sinopharm vaccine recipients had positive IgG with a mean of 170.0±230.0 BAU/ml. Regarding random individuals, 54.9% had positive IgG with a mean of 164.3±214 BAU/ml. The peak IgM response in COVID-19 patients was detected early at 15-22 days, followed by IgG peak at 16-30 days, and IgA peak at 0-60 days. IgM antibodies disappeared at 61-90 days, while IgG and IgA antibodies decreased slowly after the peak and remained detectable up to 300 days. The frequency of IgG positivity among patients was significantly affected by increased age, admission department (inpatient or outpatient), symptoms, need for oxygen therapy, and increased duration between positive COVID-19 RT PCR test and serum sampling (p˂0.05). Positive correlations were noted between different types of immunoglobulins (IgG, IgM, and IgA) among patients. CONCLUSIONS Natural infection and COIVD-19 vaccines provide IgG-mediated immunity. The class, positivity, mean, efficacy, and duration of immunoglobulins response are affected by the mechanism of immunity and host related variables. Random community individuals had detectable COVID-19 IgG at ~55%, far from reaching herd immunity levels.
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Affiliation(s)
- Mohammad Al-Tamimi
- Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | - Amjed A. Tarifi
- Department of Specialized Surgery, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | - Arwa Qaqish
- Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa, Jordan
| | - Manal M. Abbas
- Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan
- Pharmacological and Diagnostic Research Lab, Al-Ahliyya Amman University, Amman, Jordan
| | - Hadeel Albalawi
- Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | - Jumanah Abu-Raideh
- Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | - Muna Salameh
- Department of Basic Medical Sciences, Faculty of Medicine, AlBalqa Applied University, Alsalt, Jordan
| | - Ashraf I. Khasawneh
- Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
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25
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Sanada T, Kohara M. Response to the Letter to the Editor Regarding "Serologic Survey of IgG Against SARS-CoV-2 Among Hospital Visitors Without a History of SARS-CoV-2 Infection in Tokyo, 2020-2021". J Epidemiol 2023; 33:109. [PMID: 35908936 PMCID: PMC9794450 DOI: 10.2188/jea.je20220202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Takahiro Sanada
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
| | - Michinori Kohara
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
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26
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Zhang Y, Ndzouboukou JB, Lin X, Hou H, Wang F, Yuan L, Gan M, Yao Z, Fu H, Cao J, Fan X. SARS-CoV-2 evolves to reduce but not abolish neutralizing action. J Med Virol 2023; 95:e28207. [PMID: 36217880 PMCID: PMC9874811 DOI: 10.1002/jmv.28207] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/25/2022] [Accepted: 10/02/2022] [Indexed: 01/27/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.
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Affiliation(s)
- Yandi Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Jo‐Lewis B. Ndzouboukou
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiaosong Lin
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Hongyan Hou
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Feng Wang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Leyong Yuan
- Department of Clinical LaboratorySouthern University of Science and Technology HospitalShenzhenChina
| | - Mengze Gan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Zongjie Yao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Hui Fu
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Jinge Cao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xionglin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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Cui SJ, Zhang Y, Gao WJ, Wang XL, Yang P, Wang QY, Pang XH, Zeng XP, Li LM. Symptomatic and Asymptomatic SARS-CoV-2 Infection and Follow-up of Neutralizing Antibody Levels. BIOMEDICAL AND ENVIRONMENTAL SCIENCES : BES 2022; 35:1100-1105. [PMID: 36597289 PMCID: PMC9850449 DOI: 10.3967/bes2022.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 10/08/2022] [Indexed: 06/17/2023]
Abstract
OBJECTIVE To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019 (COVID-19) at 6 and 10 months after disease onset. METHODS Blood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed. RESULTS The symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1-2 months post polymerase chain reaction confirmation, respectively. However, neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation. CONCLUSION Continued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.
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Affiliation(s)
- Shu Juan Cui
- Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Yi Zhang
- General Administration of Customs (Beijing) International Travel Health Care Center, Beijing 100013, China
| | - Wen Jing Gao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China
| | - Xiao Li Wang
- Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Peng Yang
- Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Quan Yi Wang
- Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Xing Huo Pang
- Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Xiao Peng Zeng
- Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing 100013, China
| | - Li Ming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China
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28
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Fox T, Geppert J, Dinnes J, Scandrett K, Bigio J, Sulis G, Hettiarachchi D, Mathangasinghe Y, Weeratunga P, Wickramasinghe D, Bergman H, Buckley BS, Probyn K, Sguassero Y, Davenport C, Cunningham J, Dittrich S, Emperador D, Hooft L, Leeflang MM, McInnes MD, Spijker R, Struyf T, Van den Bruel A, Verbakel JY, Takwoingi Y, Taylor-Phillips S, Deeks JJ. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev 2022; 11:CD013652. [PMID: 36394900 PMCID: PMC9671206 DOI: 10.1002/14651858.cd013652.pub2] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND The diagnostic challenges associated with the COVID-19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS-CoV-2 infection. Serology tests to detect the presence of antibodies to SARS-CoV-2 enable detection of past infection and may detect cases of SARS-CoV-2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS-CoV-2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS-CoV-2 epidemiology. OBJECTIVES To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS-CoV-2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS-CoV-2. Sources of heterogeneity investigated included: timing of test, test method, SARS-CoV-2 antigen used, test brand, and reference standard for non-SARS-CoV-2 cases. SEARCH METHODS The COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) 'COVID-19: Living map of the evidence' and the Norwegian Institute of Public Health 'NIPH systematic and living map on COVID-19 evidence'. We did not apply language restrictions. SELECTION CRITERIA We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT-PCR test. Small studies with fewer than 25 SARS-CoV-2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR), clinical diagnostic criteria, and pre-pandemic samples). DATA COLLECTION AND ANALYSIS We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS-2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta-analysis, we fitted univariate random-effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria. MAIN RESULTS We included 178 separate studies (described in 177 study reports, with 45 as pre-prints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARS-CoV-2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARS-CoV-2 infection were most commonly hospital inpatients (78/178, 44%), and pre-pandemic samples were used by 45% (81/178) to estimate specificity. Over two-thirds of studies recruited participants based on known SARS-CoV-2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARS-CoV-2 vaccines and present data for naturally acquired antibody responses. Seventy-nine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzyme-linked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%). Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies. Average sensitivities for current SARS-CoV-2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot. Average specificities were consistently high and precise, particularly for pre-pandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies). Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescent-phase infection) and specific (pre-pandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spike-protein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescent-phase infection. Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity. In a low-prevalence (2%) setting, where antibody testing is used to diagnose COVID-19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARS-CoV-2 infection. In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days post-symptom onset or post-positive PCR) of SARS-CoV-2 infection. AUTHORS' CONCLUSIONS Some antibody tests could be a useful diagnostic tool for those in whom molecular- or antigen-based tests have failed to detect the SARS-CoV-2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post-acute sequelae of COVID-19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero-epidemiological purposes. The applicability of results for detection of vaccination-induced antibodies is uncertain.
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Affiliation(s)
- Tilly Fox
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Julia Geppert
- Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK
| | - Jacqueline Dinnes
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Katie Scandrett
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Jacob Bigio
- Research Institute of the McGill University Health Centre, Montreal, Canada
- McGill International TB Centre, Montreal, Canada
| | - Giorgia Sulis
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
| | - Dineshani Hettiarachchi
- Department of Anatomy Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Yasith Mathangasinghe
- Department of Anatomy Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
- Australian Regenerative Medicine Institute, Monash University, Clayton, Australia
| | - Praveen Weeratunga
- Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | | | | | - Brian S Buckley
- Cochrane Response, Cochrane, London, UK
- Department of Surgery, University of the Philippines, Manila, Philippines
| | | | | | - Clare Davenport
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Jane Cunningham
- Global Malaria Programme, World Health Organization, Geneva, Switzerland
| | | | | | - Lotty Hooft
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht , Netherlands
| | - Mariska Mg Leeflang
- Epidemiology and Data Science, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Public Health, Amsterdam, Netherlands
| | | | - René Spijker
- Medical Library, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Amsterdam, Netherlands
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Thomas Struyf
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Ann Van den Bruel
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Jan Y Verbakel
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Yemisi Takwoingi
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Sian Taylor-Phillips
- Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Jonathan J Deeks
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
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Atti A, Insalata F, Carr EJ, Otter AD, Castillo-Olivares J, Wu M, Harvey R, Howell M, Chan A, Lyall J, Temperton N, Cantoni D, da Costa K, Nadesalingam A, Taylor-Kerr A, Hettiarachchi N, Tranquillini C, Hewson J, Cole MJ, Foulkes S, Munro K, Monk EJM, Milligan ID, Linley E, Chand MA, Brown CS, Islam J, Semper A, Charlett A, Heeney JL, Beale R, Zambon M, Hopkins S, Brooks T, Hall V. Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study. J Infect 2022; 85:545-556. [PMID: 36089104 PMCID: PMC9458758 DOI: 10.1016/j.jinf.2022.09.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/05/2022] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER ISRCTN11041050.
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Affiliation(s)
- Ana Atti
- UK Health Security Agency, Smith Square, London SW1P, UK.
| | | | - Edward J Carr
- The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
| | - Ashley D Otter
- UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK
| | - Javier Castillo-Olivares
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge University, Madingley Road, Cambridge CB3 0ES, UK
| | - Mary Wu
- The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
| | - Ruth Harvey
- The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
| | - Michael Howell
- The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
| | - Andrew Chan
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge University, Madingley Road, Cambridge CB3 0ES, UK
| | - Jonathan Lyall
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge University, Madingley Road, Cambridge CB3 0ES, UK
| | - Nigel Temperton
- Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Greenwich and Kent at Medway, Central Ave, Gillingham, Chatham ME4 4BF, UK
| | - Diego Cantoni
- Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Greenwich and Kent at Medway, Central Ave, Gillingham, Chatham ME4 4BF, UK
| | - Kelly da Costa
- Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Greenwich and Kent at Medway, Central Ave, Gillingham, Chatham ME4 4BF, UK
| | - Angalee Nadesalingam
- Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge University, Madingley Road, Cambridge CB3 0ES, UK
| | | | | | | | | | | | - Sarah Foulkes
- UK Health Security Agency, Smith Square, London SW1P, UK
| | - Katie Munro
- UK Health Security Agency, Smith Square, London SW1P, UK
| | | | | | - Ezra Linley
- Manchester Royal Infirmary, UK Health Security Agency, Oxford Road, Manchester M139WL, UK
| | - Meera A Chand
- UK Health Security Agency, Smith Square, London SW1P, UK
| | - Colin S Brown
- UK Health Security Agency, Smith Square, London SW1P, UK; The National Institute for Health Research Health Protection Research (NIHR) Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Old Road Campus, Headington, Oxford OX3 7BN, UK
| | - Jasmin Islam
- UK Health Security Agency, Smith Square, London SW1P, UK
| | - Amanda Semper
- UK Health Security Agency, Smith Square, London SW1P, UK
| | - Andre Charlett
- UK Health Security Agency, Smith Square, London SW1P, UK; NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol in partnership with Public Health England, Queens Road, Bristol BS8 1QU, UK; NIHR Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England, Keppel St, London WC1E 7HT, UK
| | | | - Rupert Beale
- The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
| | - Maria Zambon
- UK Health Security Agency, Smith Square, London SW1P, UK
| | - Susan Hopkins
- UK Health Security Agency, Smith Square, London SW1P, UK; The National Institute for Health Research Health Protection Research (NIHR) Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Old Road Campus, Headington, Oxford OX3 7BN, UK
| | - Tim Brooks
- UK Health Security Agency, Smith Square, London SW1P, UK
| | - Victoria Hall
- UK Health Security Agency, Smith Square, London SW1P, UK; The National Institute for Health Research Health Protection Research (NIHR) Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Old Road Campus, Headington, Oxford OX3 7BN, UK
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30
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Qi H, Xue JB, Lai DY, Li A, Tao SC. Current advances in antibody-based serum biomarker studies: From protein microarray to phage display. Proteomics Clin Appl 2022; 16:e2100098. [PMID: 36071670 DOI: 10.1002/prca.202100098] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 08/16/2022] [Accepted: 09/05/2022] [Indexed: 12/30/2022]
Abstract
PURPOSE This review aims to summarize the technological advances in the field of antibody-based biomarker studies by proteome microarray and phage display. In addition, the possible development directions of this field are also discussed. EXPERIMENTAL DESIGN We have focused on the antibody profiling by proteome microarray and phage display, including the technological advances, the tools/resources constructed, and the characteristics of both platforms. RESULTS With the help of tools/resources and technological advances in proteome microarray and phage display, the efficiency of profiling antibody-based biomarkers in serum samples has been greatly improved. CONCLUSIONS In the past few years, proteome microarray and phage display, especially the latter one, have already demonstrated their capacity and efficiency for biomarker identification. In the near future, we believe that more antibody-based biomarkers could be identified, and some of them could eventually be developed into real clinical applications.
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Affiliation(s)
- Huan Qi
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
| | - Jun-Biao Xue
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
| | - Dan-Yun Lai
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
| | - Ang Li
- College of Life Sciences, Shanghai Normal University, Shanghai, China
| | - Sheng-Ce Tao
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
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31
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Zhang D, Guo Y, Zhang L, Wang Y, Peng S, Duan S, Geng L, Zhang X, Wang W, Yang M, Wu G, Chen J, Feng Z, Wang X, Wu Y, Jiang H, Zhang Q, Sun J, Li S, He Y, Xiao M, Xu Y, Wang H, Liu P, Zhou Q, Luo H. Integrated System for On-Site Rapid and Safe Screening of COVID-19. Anal Chem 2022; 94:13810-13819. [PMID: 36184789 PMCID: PMC9578365 DOI: 10.1021/acs.analchem.2c02337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 09/22/2022] [Indexed: 12/04/2022]
Abstract
Since the outbreak of coronavirus disease 2019 (COVID-19), the epidemic has been spreading around the world for more than 2 years. Rapid, safe, and on-site detection methods of COVID-19 are in urgent demand for the control of the epidemic. Here, we established an integrated system, which incorporates a machine-learning-based Fourier transform infrared spectroscopy technique for rapid COVID-19 screening and air-plasma-based disinfection modules to prevent potential secondary infections. A partial least-squares discrimination analysis and a convolutional neural network model were built using the collected infrared spectral dataset containing 857 training serum samples. Furthermore, the sensitivity, specificity, and prediction accuracy could all reach over 94% from the results of the field test regarding 968 blind testing samples. Additionally, the disinfection modules achieved an inactivation efficiency of 99.9% for surface and airborne tested bacteria. The proposed system is conducive and promising for point-of-care and on-site COVID-19 screening in the mass population.
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Affiliation(s)
- Dongheyu Zhang
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Yuntao Guo
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Liyang Zhang
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Yao Wang
- Department
of Clinical Laboratory, Peking Union Medical
College Hospital, Chinese Academy of Medical Sciences, Beijing100730, China
| | - Siqi Peng
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Simeng Duan
- Department
of Clinical Laboratory, Peking Union Medical
College Hospital, Chinese Academy of Medical Sciences, Beijing100730, China
| | - Lin Geng
- JINSP
Co., Ltd., Beijing100083, China
| | | | - Wei Wang
- Shanghai
Customs Port Clinic, Shanghai International
Travel Healthcare Center, Shanghai200335, China
| | - Mengjie Yang
- Chinese
Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing102206, China
| | - Guizhen Wu
- Chinese
Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing102206, China
| | - Jiayi Chen
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Zihao Feng
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Xinyuan Wang
- Holy-shine
Technology Co., Ltd., Beijing100045, China
| | - Yue Wu
- Holy-shine
Technology Co., Ltd., Beijing100045, China
| | - Haotian Jiang
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Qikang Zhang
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Jingjun Sun
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
| | - Shenwei Li
- Shanghai
Customs Port Clinic, Shanghai International
Travel Healthcare Center, Shanghai200335, China
| | - Yuping He
- Shanghai
Customs Port Clinic, Shanghai International
Travel Healthcare Center, Shanghai200335, China
| | - Meng Xiao
- Department
of Clinical Laboratory, Peking Union Medical
College Hospital, Chinese Academy of Medical Sciences, Beijing100730, China
| | - Yingchun Xu
- Department
of Clinical Laboratory, Peking Union Medical
College Hospital, Chinese Academy of Medical Sciences, Beijing100730, China
| | | | - Peipei Liu
- Chinese
Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing102206, China
| | - Qun Zhou
- Department
of Chemistry, Tsinghua University, Beijing100084, China
| | - Haiyun Luo
- Department
of Electrical Engineering, Tsinghua University, Beijing100084, China
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32
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Hartley GE, Edwards ESJ, O’Hehir RE, van Zelm MC. New insights into human immune memory from SARS-CoV-2 infection and vaccination. Allergy 2022; 77:3553-3566. [PMID: 36048132 PMCID: PMC9538469 DOI: 10.1111/all.15502] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/13/2022] [Accepted: 08/29/2022] [Indexed: 01/28/2023]
Abstract
Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS-CoV-2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS-CoV-2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan-based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.
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Affiliation(s)
- Gemma E. Hartley
- Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical SchoolMonash UniversityMelbourneVictoriaAustralia
| | - Emily S. J. Edwards
- Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical SchoolMonash UniversityMelbourneVictoriaAustralia
| | - Robyn E. O’Hehir
- Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical SchoolMonash UniversityMelbourneVictoriaAustralia,Allergy, Asthma and Clinical Immunology ServiceAlfred HospitalMelbourneVictoriaAustralia
| | - Menno C. van Zelm
- Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical SchoolMonash UniversityMelbourneVictoriaAustralia,Allergy, Asthma and Clinical Immunology ServiceAlfred HospitalMelbourneVictoriaAustralia
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Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations. Immunol Lett 2022; 249:23-32. [PMID: 36055412 PMCID: PMC9428335 DOI: 10.1016/j.imlet.2022.08.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 08/07/2022] [Accepted: 08/30/2022] [Indexed: 01/13/2023]
Abstract
B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3-7 and IGKV2-24 enriched in the asymptomatic subjects, whereas IGHV3-13, IGHV3-23-IGHJ4, IGHV1-18-IGLV3-19, IGHV1-18-IGLV3-21, and IGHV1-18-IGLV3-25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3-23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3-13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections.
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Menges D, Zens KD, Ballouz T, Caduff N, Llanas-Cornejo D, Aschmann HE, Domenghino A, Pellaton C, Perreau M, Fenwick C, Pantaleo G, Kahlert CR, Münz C, Puhan MA, Fehr JS. Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort. Nat Commun 2022; 13:4855. [PMID: 35982045 PMCID: PMC9386650 DOI: 10.1038/s41467-022-32573-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 08/06/2022] [Indexed: 12/14/2022] Open
Abstract
To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection. The persistence of the immune response to SARS-CoV-2 after recovery from infection is an indicator for subsequent protection against infection. Here the authors follow recovered patients and measure antibody and T cell responses and find that these two parts of the immune response may have different longevity.
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Affiliation(s)
- Dominik Menges
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland
| | - Kyra D Zens
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland.,Institute for Experimental Immunology, University of Zurich (UZH), Zurich, Switzerland
| | - Tala Ballouz
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland
| | - Nicole Caduff
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland.,Institute for Experimental Immunology, University of Zurich (UZH), Zurich, Switzerland
| | - Daniel Llanas-Cornejo
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland
| | - Hélène E Aschmann
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland.,Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
| | - Anja Domenghino
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland.,Department of Visceral and Transplantation Surgery, University Hospital Zurich (USZ), University of Zurich (UZH), Zurich, Switzerland
| | - Céline Pellaton
- Service of Immunology and Allergy, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Matthieu Perreau
- Service of Immunology and Allergy, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Craig Fenwick
- Service of Immunology and Allergy, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Giuseppe Pantaleo
- Service of Immunology and Allergy, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Christian R Kahlert
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,Division of Infectious Diseases and Hospital Epidemiology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland
| | - Christian Münz
- Institute for Experimental Immunology, University of Zurich (UZH), Zurich, Switzerland
| | - Milo A Puhan
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland.
| | - Jan S Fehr
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland
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Torres-Ruiz J, Lomelín-Gascón J, Vargas-Castro AS, Lira-Luna J, Pérez-Fragoso A, Tapia-Conyer R, Nuñez-Aguirre M, Alcalá-Carmona B, Absalón-Aguilar A, Maravillas-Montero JL, Mejía-Domínguez NR, Núñez-Álvarez C, Rull-Gabayet M, Llorente L, Romero-Ramírez S, Sosa-Hernández VA, Cervantes-Díaz R, Juárez-Vega G, Meza-Sánchez DE, Martínez-Juárez LA, Morales-Juárez L, López-López LN, Negrete-Trujillo JA, Falcón-Lezama JA, Valdez-Vázquez RR, Gallardo-Rincón H, Gómez-Martín D. Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study. Front Immunol 2022; 13:943563. [PMID: 36045688 PMCID: PMC9421299 DOI: 10.3389/fimmu.2022.943563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/29/2022] [Indexed: 11/28/2022] Open
Abstract
Background Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.
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Affiliation(s)
- Jiram Torres-Ruiz
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - Ana Sofía Vargas-Castro
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jaquelin Lira-Luna
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina-Instituto Politécnico Nacional (IPN), Mexico City, Mexico
| | - Alfredo Pérez-Fragoso
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Laboratorio de Inmunoquimica 1, Posgrado en Ciencias Químicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Roberto Tapia-Conyer
- Operative Solutions, Carlos Slim Foundation, Mexico City, Mexico
- Universidad Nacional Autónoma de México, Facultad de Medicina, Mexico City, Mexico
| | - Miroslava Nuñez-Aguirre
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Laboratorio de Inmunoquimica 1, Posgrado en Ciencias Químicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Beatriz Alcalá-Carmona
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Laboratorio de Inmunoquimica 1, Posgrado en Ciencias Químicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Abdiel Absalón-Aguilar
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Internal Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José Luis Maravillas-Montero
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Nancy Raquel Mejía-Domínguez
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Carlos Núñez-Álvarez
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Marina Rull-Gabayet
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Luis Llorente
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Sandra Romero-Ramírez
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Victor Andrés Sosa-Hernández
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Rodrigo Cervantes-Díaz
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Guillermo Juárez-Vega
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - David Eduardo Meza-Sánchez
- Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Luis Alberto Martínez-Juárez
- Operative Solutions, Carlos Slim Foundation, Mexico City, Mexico
- Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Linda Morales-Juárez
- Operative Solutions, Carlos Slim Foundation, Mexico City, Mexico
- Temporary COVID-19 Hospital, Hipódromo de las Américas, Mexico City, Mexico
| | | | | | - Jorge Abelardo Falcón-Lezama
- Operative Solutions, Carlos Slim Foundation, Mexico City, Mexico
- Division of Health Sciences, Juárez Autonomous University of Tabasco, Tabasco, Mexico
| | | | - Héctor Gallardo-Rincón
- Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Mexico
- *Correspondence: Diana Gómez-Martín, ; Héctor Gallardo-Rincón,
| | - Diana Gómez-Martín
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- *Correspondence: Diana Gómez-Martín, ; Héctor Gallardo-Rincón,
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Ravera F, Borea R, Cirmena G, Dameri M, Ferrando L, Gallo M, Casini C, Fallani N, Stabile M, Barbero V, Murialdo R, Tixi L, Cappuccio M, Cuboni A, Sivieri I, Fornarini G, De Maria A, Ballestrero A, Zoppoli G. Incidence and immunomic features of apyretic COVID-19 in patients affected by solid tumors: a prospective cohort study. J Transl Med 2022; 20:230. [PMID: 35568887 PMCID: PMC9107211 DOI: 10.1186/s12967-022-03429-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 05/05/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND RATIONALE Little is known about SARS-CoV-2 seroconversion in asymptomatic patients affected by solid cancer, and whether it is associated with specific transcriptomics changes in peripheral blood mononuclear cells (PBMC). METHODS Patients affected by solid cancer treated in a top comprehensive cancer center in Italy during the first COVID-19 pandemic wave, and negative for COVID-19-symptoms since the first detection of COVID-19 in Italy, were prospectively evaluated by SARS-CoV-2 serology in the period between April 14th and June 23rd 2020. Follow-up serologies were performed, every 21-28 days, until August 23rd 2020. All SARS-CoV-2 IgM + patients underwent confirmatory nasopharyngeal swab (NPS). PBMCs from a subset of SARS-CoV-2 IgM + patients were collected at baseline, at 2 months, and at 7 months for transcriptome sequencing. RESULTS SARS-CoV-2 serology was performed on 446 of the 466 recruited patients. A total of 14 patients (3.14%) tested positive for at least one SARS-CoV-2 immunoglobulin in the period between April 14th and August 23rd 2020. Incidence of SARS-CoV-2 IgM decreased from 1.48% in the first month of the accrual to 0% in the last month. Viral RNA could not be detected in any of the NPS. PBMC serial transcriptomic analysis showed progressive downregulation of interleukin 6 upregulated signatures, chemokine-mediated signaling and chemokine-chemokine receptor KEGG pathways. B- and T-cell receptor pathways (p-values = 0.0002 and 0.017 respectively) were progressively upregulated. CONCLUSIONS SARS-CoV-2 seroconversion rate in asymptomatic patients affected by solid cancer is consistent with that of asymptomatic COVID-19 assessed in the general population through NPS at the peak of the first wave. Transcriptomic features over time in IgM + asymptomatic cases are suggestive of previous viral exposure.
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Affiliation(s)
- Francesco Ravera
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | - Roberto Borea
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | | | - Martina Dameri
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | | | - Maurizio Gallo
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | - Cecilia Casini
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | - Neri Fallani
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | - Mario Stabile
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | | | | | - Lucia Tixi
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | | | - Andrea Cuboni
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Irene Sivieri
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
| | | | - Andrea De Maria
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Department of Health Sciences (DISSAL), Università Degli Studi Di Genova, Genoa, Italy
| | - Alberto Ballestrero
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gabriele Zoppoli
- Department of Internal Medicine (DiMI), Università Degli Studi Di Genova, Genoa, Italy.
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
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Yan H, Ding Y, Guo W. Epidemiological, Radiographical, and Laboratorial Characteristics of Chinese Asymptomatic Cases With COVID-19: A Systematic Review and Meta-Analysis. Front Public Health 2022; 10:808471. [PMID: 35433622 PMCID: PMC9008196 DOI: 10.3389/fpubh.2022.808471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 03/11/2022] [Indexed: 12/23/2022] Open
Abstract
The comprehensive understanding of the characteristics of asymptomatic cases are helpful for the identification and management of patients with asymptomatic COVID-19 infection. Four electronic databases were searched from December 1, 2019 to February 8, 2022 for relevant articles. Data synthesis, subgroup analysis, and sensitivity analysis were performed on the included studies. I2 and Q tests were applied to evaluate heterogeneity across studies. The risk of publication bias was assessed and visualized using a funnel plot. A total of 45 studies consisting of 2,655 patients with no symptoms at the screening point were included. Pooled results showed that in China, 65% of initial no-symptoms COVID-19 patients did not present any COVID-19-related symptom during follow-up or by end of disease course (asymptomatic infections). High proportions of initial no-symptoms COVID-19 patients (76%) and patients with asymptomatic infection (55%) had abnormal CT features at the screening point. High proportion of patients with asymptomatic infection had been detected Ig G+ (72%) and/or Ig M+ (57%) at the screening point. The chest CT scan and SARS-CoV-2-specific antibody testing could serve as effective supplementary methods to identify asymptomatic cases in the early stage of SARS-CoV-2 infection. However, the chest CT scan and the SARS-CoV-2-specific IgM and IgG testing should not replace reverse transcription–polymerase chain reaction (RT-PCR) for screening in asymptomatic patients. The combination of repeated RT-PCR, chest CT scans, and the SARS-CoV-2-specific IgM and IgG testing should be performed for those highly suspected SARS-CoV-2 infections.
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Affiliation(s)
- Haohao Yan
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yudan Ding
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Wenbin Guo
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.,Department of Psychiatry, The Third People's Hospital of Foshan, Foshan, China
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He G, Chuai X, Liang D, Chen C, Hu C, Ke C, Ke B, Zhen P, Zhang H. Case report: Long-term asymptomatic SARS-CoV-2 infection associated with deficiency on multiple immune cells. BIOSAFETY AND HEALTH 2022; 4:205-208. [PMID: 35434596 PMCID: PMC9004222 DOI: 10.1016/j.bsheal.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 03/21/2022] [Accepted: 04/11/2022] [Indexed: 11/19/2022] Open
Abstract
The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cases, especially in immuno-compromised individuals, remain largely unknown. Here we present a case of asymptomatic SARS-CoV-2 infection that lasted for at least 67 days. The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70, plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57. Throughout the infection, no anti-SARS-CoV-2 specific IgM or IgG antibodies were detected. Instead, the patient showed either a low percentage or an absolute number of non-classical monocytes, dendritic cells (DCs), CD4+ T cells, and regulatory T cells (Tregs), which may account for the clinical feature and absence of antibody response. This case may shed new light on the outbreak management related to control/prevention, treatment, and vaccination of SARS-CoV-2 and other virus infections in immunocompromised individuals.
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Affiliation(s)
- Gang He
- Jiangmen Central Hospital affiliated with Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529000, China
| | - Xia Chuai
- Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Dan Liang
- Guangdong Center for Disease Control and Prevention, Guangzhou 511430, China
| | - Chunyu Chen
- Jiangmen Central Hospital affiliated with Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529000, China
| | - Changzheng Hu
- Jiangmen Central Hospital affiliated with Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529000, China
| | - Changwen Ke
- Guangdong Center for Disease Control and Prevention, Guangzhou 511430, China
| | - Bixia Ke
- Guangdong Center for Disease Control and Prevention, Guangzhou 511430, China
| | - Peilin Zhen
- Jiangmen Central Hospital affiliated with Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529000, China
| | - Huajun Zhang
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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A cohort study measuring SARS-CoV-2 seroconversion and serial viral testing in university students. BMC Infect Dis 2022; 22:314. [PMID: 35361140 PMCID: PMC8968700 DOI: 10.1186/s12879-022-07314-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 03/23/2022] [Indexed: 11/13/2022] Open
Abstract
Background To improve understanding of the antibody response to SARS-CoV-2 infection, we examined seroprevalence, incidence of infection, and seroconversion among a cohort of young adults living on university campuses during the fall of 2020. Methods At the beginning (semester start) and end (semester end) of an 11-week period, serum collected from 107 students was tested using the qualitative Abbott Architect SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Results were matched to interim weekly surveillance viral testing and symptom data. Results With the SARS-CoV-2 IgG assay, 15 (14.0%) students were seropositive at semester start; 29 (27.1%) students were seropositive at semester end; 10 (9.3%) were seropositive at both times. With the AdviseDx SARS-CoV-2 IgG II assay, 17 (16.3%) students were seropositive at semester start, 37 (35.6%) were seropositive at semester end, and 16 (15.3%) were seropositive at both times. Overall, 23 students (21.5%) had positive viral tests during the semester. Infection was identified by serial testing in a large majority of individuals who seroconverted using both assays. Those seropositive at semester end more frequently reported symptomatic infections (56.5%) than asymptomatic infections (30.4%). Conclusion Differences between antibody targets were observed, with more declines in antibody index values below the threshold of positivity with the anti-nucleocapsid assay compared to the anti-spike assay. Serology testing, combined with serial viral testing, can detect seroconversions, and help understand the potential correlates of protection provided by antibodies to SARS-CoV-2. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07314-5.
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Yan LN, Liu PP, Li XG, Zhou SJ, Li H, Wang ZY, Shen F, Lu BC, Long Y, Xiao X, Wang ZD, Li D, Han HJ, Yu H, Zhou SH, Lv WL, Yu XJ. Neutralizing Antibodies and Cellular Immune Responses Against SARS-CoV-2 Sustained One and a Half Years After Natural Infection. Front Microbiol 2022; 12:803031. [PMID: 35310397 PMCID: PMC8928406 DOI: 10.3389/fmicb.2021.803031] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/20/2021] [Indexed: 12/23/2022] Open
Abstract
Background COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population. Methods We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays. Results We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age. Conclusions We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.
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Affiliation(s)
- Li-Na Yan
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Pan-Pan Liu
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Xu-Gui Li
- The Department of Clinical Laboratory Medicine, Hubei 672 Orthopaedics Hospital, Wuhan, China
| | - Shi-Jing Zhou
- The Department of Clinical Laboratory Medicine, Hubei 672 Orthopaedics Hospital, Wuhan, China
| | - Hao Li
- The First School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Zhi-Yin Wang
- Department of Clinical Laboratory Medicine, Hubei University of Chinese Medicine Huangjiahu Hospital, Wuhan, China
| | - Feng Shen
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China
| | - Bi-Chao Lu
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Yu Long
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Xiao Xiao
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Zhen-Dong Wang
- School of Public Health, Xi'an Medical University, Xi'an, China
| | - Dan Li
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Hui-Ju Han
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
| | - Hao Yu
- Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston, TX, United States
| | - Shu-Han Zhou
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Wen-Liang Lv
- Clinical College, Hubei University of Chinese Medicine, Wuhan, China
| | - Xue-Jie Yu
- State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China
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Nair S, Chen X. Biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the humoral immunoresponse: a systematic review of evidence to support global policy-level actions and research. GLOBAL HEALTH JOURNAL 2022; 6:38-43. [PMID: 34840854 PMCID: PMC8603838 DOI: 10.1016/j.glohj.2021.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/12/2021] [Accepted: 11/14/2021] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019 (COVID-19) pandemic. Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a paucity of systemized data on this subject. OBJECTIVE In this review, we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies. We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity, transmission potential, and prognosis. DATA SOURCES AND METHODS Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications. Search terms included: "Novel Coronavirus" OR "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Immunity" OR "Immune Response" OR "Antibody Response" OR "Immunologic Response". Studies published from December 31, 2019 to December 31, 2020 were included. To ensure validity, papers in pre-print were excluded. RESULTS Of 2 889 identified papers, 36 were included. Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2. Antibody titers appear to markedly increase two weeks after infection, followed by a plateau. A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations. This trend persists with regard to the length of antibody maintenance. However, overall immunity appears to wane within two to three months post-infection. CONCLUSION Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection. Immunity generated through natural infection appears to be short, suggesting a need for long-term efforts to control the pandemic. Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention. Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.
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Kopanja S, Gattinger P, Schmidthaler K, Sieber J, Niepodziana K, Schlederer T, Weseslindtner L, Stiasny K, Götzinger F, Pickl WF, Frischer T, Valenta R, Szépfalusi Z. Characterization of the antibody response to SARS-CoV-2 in a mildly affected pediatric population. Pediatr Allergy Immunol 2022; 33:e13737. [PMID: 35212039 PMCID: PMC9115525 DOI: 10.1111/pai.13737] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/21/2022] [Accepted: 01/24/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND While children usually experience a mild course of COVID-19, and a severe disease is more common in adults, the features, specificities, and functionality of the SARS-CoV-2-specific antibody response in the pediatric population are of interest. METHODS We performed a detailed analysis of IgG antibodies specific for SARS-CoV-2-derived antigens S and RBD by ELISA in 26 SARS-CoV-2 seropositive schoolchildren with mild or asymptomatic disease course, and in an equally sized, age- and gender-matched control group. Furthermore, a detailed mapping of IgG reactivity to a panel of microarrayed SARS-CoV-2 proteins and S-derived peptides was performed by microarray technology. The capacity of the antibody response to block RBD-ACE2 binding and virus neutralization were assessed. Results were compared with those obtained in an adult COVID-19 convalescent population. RESULTS After mild COVID-19, anti-S and RBD-specific IgG antibodies were developed by 100% and 84.6% of pediatric subjects, respectively. No difference was observed in regards to symptoms and gender. Mounted antibodies recognized conformational epitopes of the spike protein and were capable to neutralize the virus up to a titer of ≥80 and to inhibit the ACE2-RBD interaction by up to 65%. SARS-CoV-2-specific IgG responses in children were comparable to mildly affected adult patients. CONCLUSION SARS-CoV-2 asymptomatic and mildly affected pediatric patients develop a SARS-CoV-2-specific antibody response, which is comparable regarding antigen, epitope recognition, and the ability to inhibit the RBD-ACE2 interaction to that observed in adult patients after mild COVID-19.
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Affiliation(s)
- Sonja Kopanja
- Division of Pediatric Pulmonology, Allergy and EndocrinologyDepartment of Pediatrics and Adolescent MedicineComprehensive Centre of PediatricsMedical University of ViennaViennaAustria
| | - Pia Gattinger
- Department of Pathophysiology and Allergy ResearchDivision of ImmunopathologyCentre for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Klara Schmidthaler
- Division of Pediatric Pulmonology, Allergy and EndocrinologyDepartment of Pediatrics and Adolescent MedicineComprehensive Centre of PediatricsMedical University of ViennaViennaAustria
| | - Justyna Sieber
- Division of Pediatric Pulmonology, Allergy and EndocrinologyDepartment of Pediatrics and Adolescent MedicineComprehensive Centre of PediatricsMedical University of ViennaViennaAustria
- Department of Clinical ImmunologyWroclaw Medical UniversityWroclawPoland
| | - Katarzyna Niepodziana
- Department of Pathophysiology and Allergy ResearchDivision of ImmunopathologyCentre for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Thomas Schlederer
- Department of Pathophysiology and Allergy ResearchDivision of ImmunopathologyCentre for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | | | - Karin Stiasny
- Centre for VirologyMedical University of ViennaViennaAustria
| | - Florian Götzinger
- Department of Pediatrics and Adolescent MedicineKlinik OttakringViennaAustria
| | - Winfried F. Pickl
- Institute of ImmunologyCenter for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- Karl Landsteiner University of Health SciencesKremsAustria
| | - Thomas Frischer
- Department of Pediatrics and Adolescent MedicineKlinik OttakringViennaAustria
- Sigmund Freud Private UniversityViennaAustria
| | - Rudolf Valenta
- Department of Pathophysiology and Allergy ResearchDivision of ImmunopathologyCentre for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- Karl Landsteiner University of Health SciencesKremsAustria
- Laboratory for ImmunopathologyDepartment of Clinical Immunology and AllergologySechenov First Moscow State Medical UniversityMoscowRussia
- NRC Institute of Immunology FMBA of RussiaMoscowRussia
| | - Zsolt Szépfalusi
- Division of Pediatric Pulmonology, Allergy and EndocrinologyDepartment of Pediatrics and Adolescent MedicineComprehensive Centre of PediatricsMedical University of ViennaViennaAustria
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Does infection with or vaccination against SARS-CoV-2 lead to lasting immunity? THE LANCET. RESPIRATORY MEDICINE 2021; 9:1450-1466. [PMID: 34688434 PMCID: PMC8530467 DOI: 10.1016/s2213-2600(21)00407-0] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/26/2021] [Accepted: 08/21/2021] [Indexed: 12/17/2022]
Abstract
Many nations are pursuing the rollout of SARS-CoV-2 vaccines as an exit strategy from unprecedented COVID-19-related restrictions. However, the success of this strategy relies critically on the duration of protective immunity resulting from both natural infection and vaccination. SARS-CoV-2 infection elicits an adaptive immune response against a large breadth of viral epitopes, although the duration of the response varies with age and disease severity. Current evidence from case studies and large observational studies suggests that, consistent with research on other common respiratory viruses, a protective immunological response lasts for approximately 5-12 months from primary infection, with reinfection being more likely given an insufficiently robust primary humoral response. Markers of humoral and cell-mediated immune memory can persist over many months, and might help to mitigate against severe disease upon reinfection. Emerging data, including evidence of breakthrough infections, suggest that vaccine effectiveness might be reduced significantly against emerging variants of concern, and hence secondary vaccines will need to be developed to maintain population-level protective immunity. Nonetheless, other interventions will also be required, with further outbreaks likely to occur due to antigenic drift, selective pressures for novel variants, and global population mobility.
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Rockstroh A, Wolf J, Fertey J, Kalbitz S, Schroth S, Lübbert C, Ulbert S, Borte S. Correlation of humoral immune responses to different SARS-CoV-2 antigens with virus neutralizing antibodies and symptomatic severity in a German COVID-19 cohort. Emerg Microbes Infect 2021; 10:774-781. [PMID: 33830901 PMCID: PMC8079054 DOI: 10.1080/22221751.2021.1913973] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/11/2021] [Accepted: 04/04/2021] [Indexed: 01/03/2023]
Abstract
Monitoring the humoral protective immune response and its durability after SARS-CoV-2 infections is essential for risk assessment of reinfections, the improvement of diagnostic methods and the evaluation of vaccine trials. We have analyzed neutralizing antibodies and IgG responses specific to different antigens, including the inactivated whole-virion of SARS-CoV-2, the spike subunit 1 protein and its receptor binding domain, as well as the nucleocapsid protein. We show the dynamic developments of the responses from the early convalescent stages up to 9 months post symptoms onset in follow-up samples from 57 COVID-19 patients with varying clinical severity. By correlating antibody signals to neutralizing titres, valid diagnostic markers for the estimation of neutralizing protection could be identified.
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Affiliation(s)
| | - Johannes Wolf
- Department of Laboratory Medicine, Hospital St. Georg, Leipzig, Germany
- ImmunoDeficiencyCenter Leipzig (IDCL) at Hospital St. Georg Leipzig, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Diseases, Leipzig, Germany
| | - Jasmin Fertey
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Sven Kalbitz
- Department of Infectious Diseases/Tropical Medicine, Nephrology and Rheumatology, Hospital St. Georg, Leipzig, Germany
| | - Stefanie Schroth
- Department of Infectious Diseases/Tropical Medicine, Nephrology and Rheumatology, Hospital St. Georg, Leipzig, Germany
| | - Christoph Lübbert
- Department of Infectious Diseases/Tropical Medicine, Nephrology and Rheumatology, Hospital St. Georg, Leipzig, Germany
- Interdisciplinary Center for Infectious Diseases, Leipzig University Hospital, Leipzig, Germany
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine II, Leipzig University Hospital, Leipzig, Germany
| | - Sebastian Ulbert
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Stephan Borte
- Department of Laboratory Medicine, Hospital St. Georg, Leipzig, Germany
- ImmunoDeficiencyCenter Leipzig (IDCL) at Hospital St. Georg Leipzig, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Diseases, Leipzig, Germany
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Seroprevalence of Antibodies to SARS-CoV-2 in Guangdong Province, China between March to June 2020. Pathogens 2021; 10:pathogens10111505. [PMID: 34832661 PMCID: PMC8619097 DOI: 10.3390/pathogens10111505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 11/17/2022] Open
Abstract
Guangdong province, located in South China, is an important economic hub with a large domestic migrant population and was among the earliest areas to report COVID-19 cases outside of Wuhan. We conducted a cross-sectional, age-stratified serosurvey to determine the seroprevalence of antibodies against SARS-CoV-2 after the emergence of COVID-19 in Guangdong. We tested 14,629 residual serum samples that were submitted for clinical testing from 21 prefectures between March and June 2020 for SARS-CoV-2 antibodies using a magnetic particle based chemiluminescent enzyme immunoassay and validated the results using a pseudovirus neutralization assay. We found 21 samples positive for SARS-CoV-2 IgG, resulting in an estimated age- and sex-weighted seroprevalence of 0.15% (95% CI: 0.06–0.24%). The overall age-specific seroprevalence was 0.07% (95% CI: 0.01–0.24%) in persons up to 9 years old, 0.22% (95% CI: 0.03–0.79%) in persons aged 10–19, 0.16% (95% CI: 0.07–0.33%) in persons aged 20–39, 0.13% (95% CI: 0.03–0.33%) in persons aged 40–59 and 0.18% (95% CI: 0.07–0.40%) in persons ≥60 years old. Fourteen (67%) samples had pseudovirus neutralization titers to S-protein, suggesting most of the IgG-positive samples were true-positives. Seroprevalence of antibodies to SARS-CoV-2 was low, indicating that there were no hidden epidemics during this period. Vaccination is urgently needed to increase population immunity to SARS-CoV-2.
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Xu Z, Li Y, Lei Q, Huang L, Lai DY, Guo SJ, Jiang HW, Hou H, Zheng YX, Wang XN, Wu J, Ma ML, Zhang B, Chen H, Yu C, Xue JB, Zhang HN, Qi H, Yu S, Lin M, Zhang Y, Lin X, Yao Z, Sheng H, Sun Z, Wang F, Fan X, Tao SC. COVID-ONE-hi: The One-stop Database for COVID-19 Specific Humoral Immunity and Clinical Parameters. GENOMICS PROTEOMICS & BIOINFORMATICS 2021; 19:669-678. [PMID: 34748989 PMCID: PMC8570443 DOI: 10.1016/j.gpb.2021.09.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 08/26/2021] [Accepted: 10/11/2021] [Indexed: 12/29/2022]
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (named COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database. Furthermore, COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-hi is freely available at www.COVID-ONE.cn.
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Affiliation(s)
- Zhaowei Xu
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
| | - Yang Li
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qing Lei
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Likun Huang
- Fujian Key Laboratory of Crop Breeding by Design, Key Laboratory of Genetics, Breeding and Multiple Utilization of Crops, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou 350028, China
| | - Dan-Yun Lai
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Shu-Juan Guo
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - He-Wei Jiang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hongyan Hou
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Yun-Xiao Zheng
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xue-Ning Wang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jiaoxiang Wu
- Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ming-Liang Ma
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Bo Zhang
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Hong Chen
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Caizheng Yu
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Jun-Biao Xue
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hai-Nan Zhang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Huan Qi
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Siqi Yu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
| | - Mingxi Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
| | - Yandi Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Xiaosong Lin
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Zongjie Yao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Huiming Sheng
- Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ziyong Sun
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Feng Wang
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
| | - Xionglin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
| | - Sheng-Ce Tao
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
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Lei Q, Yu CZ, Li Y, Hou HY, Xu ZW, Yao ZJ, Zhang YD, Lai DY, Ndzouboukou JLB, Zhang B, Chen H, Ouyang ZQ, Xue JB, Lin XS, Zheng YX, Wang XN, Jiang HW, Zhang HN, Qi H, Guo SJ, He MA, Sun ZY, Wang F, Tao SC, Fan XL. Anti-SARS-CoV-2 IgG responses are powerful predicting signatures for the outcome of COVID-19 patients. J Adv Res 2021; 36:133-145. [PMID: 35116173 PMCID: PMC8641215 DOI: 10.1016/j.jare.2021.11.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/10/2021] [Accepted: 11/23/2021] [Indexed: 12/14/2022] Open
Affiliation(s)
- Qing Lei
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cai-zheng Yu
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Li
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hong-yan Hou
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhao-wei Xu
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Zong-jie Yao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan-di Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dan-yun Lai
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jo-Lewis Banga Ndzouboukou
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Zhang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Chen
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Zhu-qing Ouyang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun-biao Xue
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xiao-song Lin
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yun-xiao Zheng
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xue-ning Wang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - He-wei Jiang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hai-nan Zhang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Huan Qi
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Shu-juan Guo
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
| | - Mei-an He
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental and Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zi-yong Sun
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Wang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Corresponding authors at: No.13, Hangkong Rd., Wuhan 430030, China (X. Fan).
| | - Sheng-ce Tao
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
- Corresponding authors at: No.13, Hangkong Rd., Wuhan 430030, China (X. Fan).
| | - Xiong-lin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Corresponding authors at: No.13, Hangkong Rd., Wuhan 430030, China (X. Fan).
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48
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Deutsch EW, Omenn GS, Sun Z, Maes M, Pernemalm M, Palaniappan KK, Letunica N, Vandenbrouck Y, Brun V, Tao SC, Yu X, Geyer PE, Ignjatovic V, Moritz RL, Schwenk JM. Advances and Utility of the Human Plasma Proteome. J Proteome Res 2021; 20:5241-5263. [PMID: 34672606 PMCID: PMC9469506 DOI: 10.1021/acs.jproteome.1c00657] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The study of proteins circulating in blood offers tremendous opportunities to diagnose, stratify, or possibly prevent diseases. With recent technological advances and the urgent need to understand the effects of COVID-19, the proteomic analysis of blood-derived serum and plasma has become even more important for studying human biology and pathophysiology. Here we provide views and perspectives about technological developments and possible clinical applications that use mass-spectrometry(MS)- or affinity-based methods. We discuss examples where plasma proteomics contributed valuable insights into SARS-CoV-2 infections, aging, and hemostasis and the opportunities offered by combining proteomics with genetic data. As a contribution to the Human Proteome Organization (HUPO) Human Plasma Proteome Project (HPPP), we present the Human Plasma PeptideAtlas build 2021-07 that comprises 4395 canonical and 1482 additional nonredundant human proteins detected in 240 MS-based experiments. In addition, we report the new Human Extracellular Vesicle PeptideAtlas 2021-06, which comprises five studies and 2757 canonical proteins detected in extracellular vesicles circulating in blood, of which 74% (2047) are in common with the plasma PeptideAtlas. Our overview summarizes the recent advances, impactful applications, and ongoing challenges for translating plasma proteomics into utility for precision medicine.
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Affiliation(s)
- Eric W Deutsch
- Institute for Systems Biology, Seattle, Washington 98109, United States
| | - Gilbert S Omenn
- Institute for Systems Biology, Seattle, Washington 98109, United States.,Departments of Computational Medicine & Bioinformatics, Internal Medicine, and Human Genetics and School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-2218, United States
| | - Zhi Sun
- Institute for Systems Biology, Seattle, Washington 98109, United States
| | - Michal Maes
- Institute for Systems Biology, Seattle, Washington 98109, United States
| | - Maria Pernemalm
- Department of Oncology and Pathology/Science for Life Laboratory, Karolinska Institutet, 171 65 Stockholm, Sweden
| | | | - Natasha Letunica
- Murdoch Children's Research Institute, 50 Flemington Road, Parkville 3052, Victoria, Australia
| | - Yves Vandenbrouck
- Université Grenoble Alpes, CEA, Inserm U1292, Grenoble 38000, France
| | - Virginie Brun
- Université Grenoble Alpes, CEA, Inserm U1292, Grenoble 38000, France
| | - Sheng-Ce Tao
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, B207 SCSB Building, 800 Dongchuan Road, Shanghai 200240, China
| | - Xiaobo Yu
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing 102206, China
| | - Philipp E Geyer
- OmicEra Diagnostics GmbH, Behringstr. 6, 82152 Planegg, Germany
| | - Vera Ignjatovic
- Murdoch Children's Research Institute, 50 Flemington Road, Parkville 3052, Victoria, Australia.,Department of Paediatrics, The University of Melbourne, 50 Flemington Road, Parkville 3052, Victoria, Australia
| | - Robert L Moritz
- Institute for Systems Biology, Seattle, Washington 98109, United States
| | - Jochen M Schwenk
- Affinity Proteomics, Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Tomtebodavägen 23, SE-171 65 Solna, Sweden
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49
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Herzberg J, Vollmer T, Fischer B, Becher H, Becker AK, Sahly H, Honarpisheh H, Guraya SY, Strate T, Knabbe C. Half-Year Longitudinal Seroprevalence of SARS-CoV-2-Antibodies and Rule Compliance in German Hospital Employees. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182010972. [PMID: 34682719 PMCID: PMC8535494 DOI: 10.3390/ijerph182010972] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 10/05/2021] [Accepted: 10/13/2021] [Indexed: 01/02/2023]
Abstract
COVID-19, which is caused by SARS-CoV-2, is an occupational health risk, especially for healthcare employees due to their higher exposure and consequently higher risk of symptomatic and asymptomatic infections. This study was designed to determine the longitudinal seroprevalence of specific immunoglobulin-G (IgG) antibodies in employees in a hospital setting. All employees in a secondary care hospital, including healthcare and non-healthcare workers, were invited to participate in this single-center study. After an initial screening, a 6-month follow-up was carried out, which included serological examination for SARS-CoV-2 IgG antibodies and a questionnaire for self-reported symptoms, self-perception, and thoughts about local and national hygiene and pandemic plans. The seroprevalence of SARS-CoV-2 IgG antibodies was 0.74% among 406 hospital employees (0.75% in healthcare workers, 0.72% in non-healthcare workers), initially recruited in April 2020, in their follow-up blood specimens in October 2020. In this study, 30.54% of the participants reported using the official German coronavirus mobile application and the majority were content with the local and national rules in relation to coronavirus-related restrictions. At the 6-month follow-up, the 0.74% seroprevalence was below the reported seroprevalence of 1.35% in the general German population. The prevalence in healthcare workers in direct patient care compared with that in workers without direct patient contact did not differ significantly. Further follow-up to monitor the seroprevalence in the high-risk healthcare sector during the ongoing global pandemic is essential.
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Affiliation(s)
- Jonas Herzberg
- Department of Surgery, Krankenhaus Reinbek St. Adolf-Stift, Hamburger Strasse 41, 21465 Reinbek, Germany; (H.H.); (T.S.)
- Correspondence: ; Tel.: +49-40-7280-5375
| | - Tanja Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany; (T.V.); (B.F.); (C.K.)
| | - Bastian Fischer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany; (T.V.); (B.F.); (C.K.)
| | - Heiko Becher
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany;
| | - Ann-Kristin Becker
- Asklepios Klinik Harburg Abteilung für Psychiatrie und Psychotherapie, Eißendorfer Pferdeweg 52, 21075 Hamburg, Germany;
| | - Hany Sahly
- Labor Lademannbogen MVZ Hamburg, Lademannbogen 61, 22339 Hamburg, Germany;
| | - Human Honarpisheh
- Department of Surgery, Krankenhaus Reinbek St. Adolf-Stift, Hamburger Strasse 41, 21465 Reinbek, Germany; (H.H.); (T.S.)
| | - Salman Yousuf Guraya
- Clinical Sciences Department, College of Medicine, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates;
| | - Tim Strate
- Department of Surgery, Krankenhaus Reinbek St. Adolf-Stift, Hamburger Strasse 41, 21465 Reinbek, Germany; (H.H.); (T.S.)
| | - Cornelius Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany; (T.V.); (B.F.); (C.K.)
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50
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Lei Q, Hou H, Yu C, Zhang Y, Ndzouboukou JLB, Lin X, Yao Z, Fu H, Sun Z, Wang F, Fan X. Kinetics of Neutralizing Antibody Response Underscores Clinical COVID-19 Progression. J Immunol Res 2021; 2021:9822706. [PMID: 34712742 PMCID: PMC8548120 DOI: 10.1155/2021/9822706] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/22/2021] [Accepted: 09/20/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Neutralizing antibody (nAb) response is generated following infection or immunization and plays an important role in the protection against a broad of viral infections. The role of nAb during clinical progression of coronavirus disease 2019 (COVID-19) remains little known. METHODS 123 COVID-19 patients during hospitalization in Tongji Hospital were involved in this retrospective study. The patients were grouped based on the severity and outcome. The nAb responses of 194 serum samples were collected from these patients within an investigation period of 60 days after the onset of symptoms and detected by a pseudotyped virus neutralization assay. The detail data about onset time, disease severity and laboratory biomarkers, treatment, and clinical outcome of these participants were obtained from electronic medical records. The relationship of longitudinal nAb changes with each clinical data was further assessed. RESULTS The nAb response in COVID-19 patients evidently experienced three consecutive stages, namely, rising, stationary, and declining periods. Patients with different severity and outcome showed differential dynamics of the nAb response over the course of disease. During the stationary phase (from 20 to 40 days after symptoms onset), all patients evolved nAb responses. In particular, high levels of nAb were elicited in severe and critical patients and older patients (≥60 years old). More importantly, critical but deceased COVID-19 patients showed high levels of several proinflammation cytokines, such as IL-2R, IL-8, and IL-6, and anti-inflammatory cytokine IL-10 in vivo, which resulted in lymphopenia, multiple organ failure, and the rapidly decreased nAb response. CONCLUSION Our results indicate that nAb plays a crucial role in preventing the progression and deterioration of COVID-19, which has important implications for improving clinical management and developing effective interventions.
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Affiliation(s)
- Qing Lei
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongyan Hou
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Caizheng Yu
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yandi Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jo-Lewis Banga Ndzouboukou
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaosong Lin
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zongjie Yao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Fu
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ziyong Sun
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Wang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xionglin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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