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Shohan M, Mahmoudian-Sani MR, Saeedi-Boroujeni A, Iranparast S, Nashibi R, Abolnezhadian F, Yousefi F, Alavi SM, Cheraghian B, Khodadadi A. The Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19. J Interferon Cytokine Res 2024; 44:316-324. [PMID: 38738802 DOI: 10.1089/jir.2024.0018] [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: 05/14/2024] Open
Abstract
As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.
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Affiliation(s)
- Mojtaba Shohan
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Reza Mahmoudian-Sani
- Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Saeedi-Boroujeni
- Department of Basic Medical Sciences, Faculty of Medicine, Abadan University of Medical Sciences, Abadan, Iran
| | - Sara Iranparast
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Roohangiz Nashibi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farhad Abolnezhadian
- Department of Pediatrics, Abuzar children's hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farid Yousefi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Mohammad Alavi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Bahman Cheraghian
- Department of Biostatistics and Epidemiology, School of Public Health, Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Khodadadi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cancer, Petroleum, and Environmental pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Maličev E, Žiberna K, Jazbec K, Kolenc A, Mali P, Potokar UR, Rožman P. Cytokine, Anti-SARS-CoV-2 Antibody, and Neutralizing Antibody Levels in Conventional Blood Donors Who Have Recovered from COVID-19. Transfus Med Hemother 2024; 51:175-184. [PMID: 38867805 PMCID: PMC11166906 DOI: 10.1159/000531942] [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: 01/20/2023] [Accepted: 07/02/2023] [Indexed: 06/14/2024] Open
Abstract
Background At the beginning of the pandemic, COVID-19 convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies was suggested as a source of therapy. In the last 3 years, many trials have demonstrated the limited usefulness of CCP therapy. This led us to the hypothesis that CCP could contain other elements, along with the desired neutralizing antibodies, which could potentially prevent it from having a therapeutic effect, among them cytokines, chemokines, growth factors, clotting factors, and autoantibodies. Methods In total, 39 cytokines were analyzed in the plasma of 190 blood donors, and further research focused on the levels of 23 different cytokines in CCP (sCD40L, eotaxin, FGF-2, FLT-3L, ractalkine, GRO-α, IFNα2, IL-1β, IL-1RA, IL-5, IL-6, IL-8, IL-12, IL-13, IL-15, IL-17E, IP-10, MCP-1, MIP-1b, PDGF-AA, TGFα, TNFα, and TRAIL). Anti-SARS-CoV-2 antibodies and neutralizing antibodies were detected in CCP. Results We found no significant differences between CCP taken within a maximum of 180 days from the onset of the first COVID-19 symptoms and the controls. We also made a comparison of the cytokine levels between the low neutralizing antibodies (<160) group and the high neutralizing antibodies (≥160) group and found there were no differences between the groups. Our research also showed no correlation either to levels of anti-SARS-CoV-2 IgG Ab or to the levels of neutralizing antibodies. There were also no significant changes in cytokine levels based on the period after the start of COVID-19 symptoms. Conclusions No elements which could potentially be responsible for preventing CCP from having a therapeutic effect were found.
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Affiliation(s)
- Elvira Maličev
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
- Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Klemen Žiberna
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | | | - Ana Kolenc
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | - Polonca Mali
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | | | - Primož Rožman
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
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Wagner C, Hirsch C, Siemens W, Kapp P, Iannizzi C. Experience report of two living systematic Cochrane reviews on COVID-19. ZEITSCHRIFT FUR EVIDENZ, FORTBILDUNG UND QUALITAT IM GESUNDHEITSWESEN 2024; 184:90-95. [PMID: 38220533 DOI: 10.1016/j.zefq.2023.11.004] [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: 03/02/2023] [Revised: 10/23/2023] [Accepted: 11/08/2023] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Up-to-date systematic reviews (SRs) are essential for making evidence-based decisions. During the 2019 coronavirus (COVID-19) pandemic, there was a particular need for up-to-date evidence, making the living systematic review (LSR) approach an appropriate review type. However, this approach poses certain challenges. OBJECTIVE AND OUTLINE We aim to provide practice insights and report challenges that we faced while conducting two Cochrane LSRs on COVID-19 treatments with (i) convalescent plasma and (ii) systemic corticosteroids. We address our objective with an experience report and share challenges of the following components based on Iannizzi et al. (2022): study design, publication types, intervention/comparator, outcomes, search strategy, review updates and transparent reporting of differences between review updates. RESULTS Regarding the study design, the plasma LSR included different study designs because RCT data were not available at the beginning of the pandemic, whereas for the corticosteroids LSR, which started several months later, RCT data were already available. The challenges in both LSRs included the publication types (preprints were included with caution) and the intervention/comparator, for instance the unavailability of standard of care for either LSR, or SARS-CoV-2 variants occurrence. Further challenges in both LSRs occurred in the components "outcome sets" (which had to be adjusted) and "literature search". The decision criteria for updating were based on important studies and available resources in both LSRs and policy relevance in the plasma LSR. Transparent reporting of the differences between the various update versions were discussed for both LSRs. DISCUSSION AND CONCLUSION In summary, there are similarities and differences regarding challenges of review components for both LSRs. It is important to keep in mind that the two LSR examples presented here were conducted in the wake of the COVID-19 pandemic. Therefore, many of the challenges are attributable to the pandemic and are not specific to LSRs, such as constant adjustments of the outcome sets or changes in the database search. Nevertheless, we believe that some of these aspects are helpful for LSR authors and are applicable to other LSRs outside the pandemic context, particularly in areas where new evidence is rapidly emerging.
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Affiliation(s)
- Carina Wagner
- Department I of Internal Medicine, Evidence-based Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany
| | - Caroline Hirsch
- Department I of Internal Medicine, Evidence-based Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany
| | - Waldemar Siemens
- Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany; Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
| | - Philipp Kapp
- Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
| | - Claire Iannizzi
- Department I of Internal Medicine, Evidence-based Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
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Mia ME, Howlader M, Akter F, Hossain MM. Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2024; 17:2632010X241263054. [PMID: 39070952 PMCID: PMC11282570 DOI: 10.1177/2632010x241263054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 06/03/2024] [Indexed: 07/30/2024]
Abstract
The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.
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Affiliation(s)
- Md. Easin Mia
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Mithu Howlader
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Farzana Akter
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Md. Murad Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
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Terada M, Saito S, Kutsuna S, Kinoshita-Iwamoto N, Togano T, Hangaishi A, Shiratori K, Takamatsu Y, Maeda K, Ishizaka Y, Ohtsu H, Satake M, Mitsuya H, Ohmagari N. Efficacy and Safety of Treatment with Plasma from COVID-19-Recovered Individuals. Life (Basel) 2023; 13:2184. [PMID: 38004324 PMCID: PMC10671928 DOI: 10.3390/life13112184] [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: 08/29/2023] [Revised: 10/14/2023] [Accepted: 10/31/2023] [Indexed: 11/26/2023] Open
Abstract
Convalescent plasma therapy, which involves administering plasma from recovered coronavirus disease 2019 (COVID-19) patients to infected individuals, is being explored as a potential treatment for severe cases of COVID-19. This study aims to evaluate the efficacy and safety of convalescent plasma therapy in COVID-19 patients with moderate to severe illness. An open-label, single-arm intervention study was conducted without a control group. Plasma collected from recovered COVID-19 patients was administered to eligible participants. The primary endpoint was the proportion of patients who were placed on artificial ventilation or died within 14 days of transfusion. Secondary endpoints included clinical improvement, viral load measurements, and adverse event monitoring. A total of 59 cases were included in the study. The primary endpoint was evaluated by comparing the rate obtained in the study to an existing rate of 25%. The study also assessed clinical improvement, viral load changes, and safety endpoints through adverse event monitoring. Convalescent plasma therapy shows potential as a treatment option for COVID-19. This study aimed to provide evidence for the efficacy and safety of this therapy and may contribute to its future use in treating severe cases of COVID-19.
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Affiliation(s)
- Mari Terada
- Center for Clinical Sciences, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Sho Saito
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Satoshi Kutsuna
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Noriko Kinoshita-Iwamoto
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Tomiteru Togano
- Department of Hematology, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Akira Hangaishi
- Department of Hematology, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Katsuyuki Shiratori
- Laboratory Testing Department, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Yuki Takamatsu
- Department of Refractory Viral Infections, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Kenji Maeda
- Division of Antiviral Therapy Joint Research Center for Human Retrovirus Infection, Kagoshima University, Sakuragaoka, Kagoshima 890-8544, Japan
| | - Yukihito Ishizaka
- Department of Intractable Diseases, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Hiroshi Ohtsu
- Faculty of Health Data Science, Juntendo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Masahiro Satake
- Central Blood Institute, Japanese Red Cross, Tatsumi, Koto-ku, Tokyo 135-8521, Japan
| | - Hiroaki Mitsuya
- Department of Intractable Diseases, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
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Sevdi MS, Erkalp K, Ozalp A, Ozcan FG, Demirgan S, Akyol O, Guneyli HC, Tunali MC, Selcan A. Convalescent plasma therapy in critically İll COVID-19 patients: A retrospective cohort study. Niger J Clin Pract 2023; 26:1410-1422. [PMID: 37929515 DOI: 10.4103/njcp.njcp_552_20] [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: 11/07/2023]
Abstract
Background Convalescent plasma (CP) therapy can be defined as a passive immunity transfer approach involving the administration of plasma for therapeutic purposes to inpatients hospitalized due to an active virus infection. Passive immunity antibodies can reduce target organ damage and directly neutralize the responsible pathogens. A limited number of studies on the use of CP have reported that critically ill patients can benefit from CP therapy. Aim We aimed in this study as the outcomes of CP therapy in critically ill coronavirus disease 2019 (COVID-19) patients in intensive care unit (ICU) and determine the differences between the recovery and mortality groups. Patients and Methods This retrospective design study involved critically ill patients who were diagnosed with COVID-19 pneumonia or who were suspected of having COVID-19 in the ICU between April 1, 2020, and June 1, 2020. Comorbidity of patients, respiratory findings, hemodynamic data, laboratory data, and poor prognostic measures were compared between mortality and recovery group. Results Convalescent plasma (CP) therapy was supplied for 41 (13.58%) patients in total of 302 COVID-19 patients. Twenty-nine patients were died in total of 41 COVID-19 patients who supplied CP therapy. The mortality rate is 70.73% in CP therapy. There was a significantly higher incidence (P < 0.021) of invasive mechanical ventilation (IMV) and significantly lower mean arterial pressure (MAP) values in mortality group (P < 0.05). There were significantly higher NLR values (P < 0.05), lower platelet count (P < 0.05), lower of glomerular filtration rate (GFR) level (P < 0.05), higher creatinine values (P < 0.05), higher lactate dehydrogenase (LDH) levels (P < 0.05), higher D-dimer levels (P < 0.05), higher level of pro-brain natriuretic peptide (BNP) (P = 0.000), rate of fever (P = 0.031), arrythmia (P = 0.024), and transfusion-associated circulatory overload (TACO) (P = 0.008) were more often in mortality group. Conclusion Convalescent plasma therapy seems not useful in critically ill COVID-19 patients.
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Affiliation(s)
- M S Sevdi
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - K Erkalp
- Anesthesiology and Reanimation, Istanbul University-Cerrahpasa Institute of Cardiology, Istanbul, Turkey
| | - A Ozalp
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - F G Ozcan
- Anesthesiology and Reanimation, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - S Demirgan
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - O Akyol
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - H C Guneyli
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - M C Tunali
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - A Selcan
- Anesthesiology and Reanimation, Istanbul Bagcilar Research and Training Hospital, Istanbul, Turkey
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Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev 2023; 5:CD013600. [PMID: 37162745 PMCID: PMC10171886 DOI: 10.1002/14651858.cd013600.pub6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
BACKGROUND Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required. OBJECTIVES To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence. AUTHORS' CONCLUSIONS For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have very-low to low certainty evidence for most primary outcomes and moderate certainty for hospital admission or death. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.
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Affiliation(s)
- Claire Iannizzi
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Khai Li Chai
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Vanessa Piechotta
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Sarah J Valk
- Jon J van Rood Center for Clinical Transfusion Research, Sanquin/Leiden University Medical Center, Leiden, Netherlands
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - Catherine Kimber
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Ina Monsef
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Erica M Wood
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | | | - David J Roberts
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Zoe McQuilten
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Cynthia So-Osman
- Sanquin Blood Bank, Amsterdam, Netherlands
- Erasmus Medical Centre, Rotterdam, Netherlands
| | - Aikaj Jindal
- Department of Transfusion Medicine, SPS Hospitals, Ludhiana (Punjab), India
| | - Nora Cryns
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Lise J Estcourt
- Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK
| | - Nina Kreuzberger
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Nicole Skoetz
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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8
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Moon Y. Gut distress and intervention via communications of SARS-CoV-2 with mucosal exposome. Front Public Health 2023; 11:1098774. [PMID: 37139365 PMCID: PMC10150023 DOI: 10.3389/fpubh.2023.1098774] [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: 11/15/2022] [Accepted: 03/27/2023] [Indexed: 05/05/2023] Open
Abstract
Acute coronavirus disease 2019 (COVID-19) has been associated with prevalent gastrointestinal distress, characterized by fecal shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA or persistent antigen presence in the gut. Using a meta-analysis, the present review addressed gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and diarrhea. Despite limited data on the gut-lung axis, viral transmission to the gut and its influence on gut mucosa and microbial community were found to be associated by means of various biochemical mechanisms. Notably, the prolonged presence of viral antigens and disrupted mucosal immunity may increase gut microbial and inflammatory risks, leading to acute pathological outcomes or post-acute COVID-19 symptoms. Patients with COVID-19 exhibit lower bacterial diversity and a higher relative abundance of opportunistic pathogens in their gut microbiota than healthy controls. Considering the dysbiotic changes during infection, remodeling or supplementation with beneficial microbial communities may counteract adverse outcomes in the gut and other organs in patients with COVID-19. Moreover, nutritional status, such as vitamin D deficiency, has been associated with disease severity in patients with COVID-19 via the regulation of the gut microbial community and host immunity. The nutritional and microbiological interventions improve the gut exposome including the host immunity, gut microbiota, and nutritional status, contributing to defense against acute or post-acute COVID-19 in the gut-lung axis.
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Affiliation(s)
- Yuseok Moon
- Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences, Pusan National University, Yangsan-si, Republic of Korea
- Biomedical Research Institute, Pusan National University, Busan, Republic of Korea
- Graduate Program of Genomic Data Sciences, Pusan National University, Yangsan-si, Republic of Korea
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9
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Nagoba B, Gavkare A, Rayate A. Exploring the Possibility of Use of SARS-CoV-2 Antiserum as an Alternative
for Plasma Therapy. CORONAVIRUSES 2023; 4. [DOI: 10.2174/2666796704666230329101950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 01/04/2023] [Accepted: 01/26/2023] [Indexed: 01/13/2025]
Affiliation(s)
- Basavraj Nagoba
- Department of Microbiology, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur, India
| | - Ajay Gavkare
- Department of Physiology, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur, India
| | - Abhijit Rayate
- Department of Surgery, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur, India
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10
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Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev 2023; 2:CD013600. [PMID: 36734509 PMCID: PMC9891348 DOI: 10.1002/14651858.cd013600.pub5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required. OBJECTIVES To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence. AUTHORS' CONCLUSIONS For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have low certainty evidence for our primary outcomes. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.
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Affiliation(s)
- Claire Iannizzi
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Khai Li Chai
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Vanessa Piechotta
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Sarah J Valk
- Jon J van Rood Center for Clinical Transfusion Research, Sanquin/Leiden University Medical Center, Leiden, Netherlands
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - Catherine Kimber
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Ina Monsef
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Erica M Wood
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | | | - David J Roberts
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Zoe McQuilten
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Cynthia So-Osman
- Sanquin Blood Bank, Amsterdam, Netherlands
- Erasmus Medical Centre, Rotterdam, Netherlands
| | - Aikaj Jindal
- Department of Transfusion Medicine, SPS Hospitals, Ludhiana (Punjab), India
| | - Nora Cryns
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Lise J Estcourt
- Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK
| | - Nina Kreuzberger
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Nicole Skoetz
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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11
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Abebe EC, Dejenie TA. Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications. Front Immunol 2023; 14:1055457. [PMID: 36742320 PMCID: PMC9892939 DOI: 10.3389/fimmu.2023.1055457] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 01/03/2023] [Indexed: 01/20/2023] Open
Abstract
Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.
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Affiliation(s)
- Endeshaw Chekol Abebe
- Department of Medical Biochemistry, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Tadesse Asmamaw Dejenie
- Department of Medical Biochemistry, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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12
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Clinical nursing care protocol for convalescent plasma transfusion in patients with COVID-19. INTERNATIONAL JOURNAL OF AFRICA NURSING SCIENCES 2023; 18:100518. [PMID: 36530550 PMCID: PMC9745971 DOI: 10.1016/j.ijans.2022.100518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 08/10/2022] [Accepted: 12/12/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction The treatment of COVID-19 is still challenge. So convalescent plasma can be an important alternative of treatment. Protocols with nursing care during infusion is very important to guide an effective and safety care. Objective to analyze the evidence in the literature on the action of convalescent plasma, of the use of protocols with nursing care to use convalescent plasma and build a nursing care protocol for transfusion in patients with COVID-19. Methods Methodological study carried out in two stages: scoping review. The search was done using the descriptors: convalescent plasma transfusion, convalescent plasma, and acute respiratory syndromes or COVID-19, to found protocols and effectiveness of convalescent plasm. Beside was done a specialist panel to build the protocol. Results Low-evidence studies have shown improvement in the clinical signs of COVID-19 using Convalescent Plasma, reduction or elimination of viral load, benefits in the production of lymphocytes, decreases C-reactive protein, increases titers of anti-SARS-CoV-2 antibodies, positive evolution in lung involvement identified by X-rays, decrease in hospitalization. No studies were found in the databases on the protocol for clinical nursing care in plasma transfusion. Therefore, a protocol was developed with the description of clinical nursing care to be performed before, during and after the transfusion by plasma: checking of vital signs and indicative signs of transfusion reaction, measurement of oxygen saturation, assessment of venous access and checking of the level of consciousness. Conclusion There are no evidence studies to support the use of plasma, nor anything related to bundles.
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13
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Kazempour-Dizaji M, Zare A, Varahram M, Abedini A, Kiani A, Roozbahani R. Time-Dependent Changes in COVID-19 Severity Based on the Information of Patients Referring to Masih Daneshvari Hospital, Tehran, Iran. TANAFFOS 2023; 22:70-74. [PMID: 37920323 PMCID: PMC10618582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 11/07/2022] [Indexed: 11/04/2023]
Abstract
Background Coronavirus disease 2019 (COVID-19) is a newly emerged disease with many unknown facets, so both the treatment and the cause of spreading this disease have remained mysterious so far. Materials and Methods Based on the information of 4372 patients with COVID-19 referring to Dr. Masih Daneshvari Hospital in Tehran, the time-dependent changes in COVID-19 severity were investigated in this study using correlation analysis. Results According to the results of this study, on average 154.80 patients were infected with mild to moderate COVID-19, and 39.06 were infected with severe COVID-19. The results of this study also indicated a descending trend in the number of patients with mild to moderate COVID-19 (r=-0.40, P-value=0.004) and an ascending trend in the number of patients with severe COVID-19 (r=0.43, P-value=0.003) overtime on a daily basis so that almost two patients were removed from those with mild to moderate COVID-19 and one was added to the patients with severe COVID-19 on average per day. Conclusion Based on the current study results, it is concluded that COVID-19 severity will not be constant over time, and there is a probability of COVID-19 becoming more aggressive. Therefore, by the lack of timely control of the disease over time, we will witness an increased number of patients with severe COVID-19 and an increased number of hospitalizations in the intensive care unit (ICU) ward.
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Affiliation(s)
- Mehdi Kazempour-Dizaji
- Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Biostatistics, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Zare
- Department of Biostatistics, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Varahram
- Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Abedini
- Chronic Respiratory Diseases Research Center (CRDRC), NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arda Kiani
- Tracheal Diseases Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rahim Roozbahani
- Clinical Tuberculosis and Epidemiology Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran
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14
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Abullais SS, Arora S, Wahab S, Grover V, Alshahrani MY, Shamsudeen SM, Mohammed Asif S, Faragalla AI, Elagib MF. Convalescent Plasma Therapy against COVID-19: An Update on the Changing Facets of the ongoing Pandemic. Curr Pharm Biotechnol 2023; 24:1515-1523. [PMID: 36733203 DOI: 10.2174/1389201024666230202144314] [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: 06/01/2022] [Revised: 10/01/2022] [Accepted: 11/01/2022] [Indexed: 02/04/2023]
Abstract
The severe respiratory infections in the current pandemic coronavirus disease-19 (COVID-19) have influenced more or less every human life. The first person to get infected with this virus was reported in the capital of Hubei province (Wuhan), China, in late December 2019. Since the disease has been declared a pandemic, research scholars and experts have been manufacturing new vaccines or targeted therapies to curb the spread of SARS-CoV-2. However, only limited options have emerged so far, which yet require complete scientific validation by long-term data collection regarding safety and efficacy. In the wake of the recent emerging wave of the pandemic viz omicron variant, changing facets of the viral genome and dearth of preventative and therapeutic possibilities for the management of COVID-19, the usage of Convalescent Plasma Therapy (CPT) may be looked at as a potentially viable option of treatment in the existing situation. Earlier, immune plasma has been used with success in the management of H1N1 influenza virus, MERS-CoV, and SARS-CoV-1 epidemics. In the present unpredictable situation created by the COVID-19 pandemic, the CPT is used with a positive outcome amongst many infected individuals in different parts of the world with acceptable efficacy. This article aimed to present an up-to-date evaluation of existing literature on the efficacy of convalescent plasma as a potential therapy, its safety and effectiveness and the challenges in treating COVID-19.
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Affiliation(s)
- Saquib Shahabe Abullais
- Department of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, Abha, KSA
| | - Suraj Arora
- Department of Restorative Dental Sciences, College of Dentistry, King Khalid University, Abha, KSA
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, KSA
| | - Vishakha Grover
- Department of Periodontology, Dr. H. S. J. Institute of Dental Sciences, Punjab University, Chandigarh, India
| | - Mohammed Yahya Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, KSA
| | - Shaik Mohamed Shamsudeen
- Department of Diagnostic Science and Oral Biology, College of Dentistry, King Khalid University, Abha, KSA
| | - Shaik Mohammed Asif
- Department of Diagnostic Science and Oral Biology, College of Dentistry, King Khalid University, Abha, KSA
| | - Amel Ibrahim Faragalla
- Department of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, Abha, KSA
| | - Mohamed Fadul Elagib
- Department of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University, Abha, KSA
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15
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Rahman MM, Islam MR, Akash S, Mim SA, Rahaman MS, Emran TB, Akkol EK, Sharma R, Alhumaydhi FA, Sweilam SH, Hossain ME, Ray TK, Sultana S, Ahmed M, Sobarzo-Sánchez E, Wilairatana P. In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective. Front Cell Infect Microbiol 2022; 12:929430. [PMID: 36072227 PMCID: PMC9441699 DOI: 10.3389/fcimb.2022.929430] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/03/2022] [Indexed: 12/07/2022] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.
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Affiliation(s)
- Md. Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Shopnil Akash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Sadia Afsana Mim
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Saidur Rahaman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh
| | - Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey
| | - Rohit Sharma
- Department of Rasashastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Sherouk Hussein Sweilam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Badr City, Egypt
| | - Md. Emon Hossain
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Tanmay Kumar Ray
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Sharifa Sultana
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Muniruddin Ahmed
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Eduardo Sobarzo-Sánchez
- Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago, Chile
- Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Weisser M, Khanna N, Hedstueck A, Tschudin Sutter S, Roesch S, Stehle G, Sava M, Deigendesch N, Battegay M, Infanti L, Holbro A, Bassetti S, Pargger H, Hirsch HH, Leuzinger K, Kaiser L, Vu D, Baur K, Massaro N, Busch MP, Simmons G, Stone M, Felgner PL, de Assis RR, Khan S, Tsai C, Robinson PV, Seftel D, Irsch J, Bagri A, Buser AS, Corash L. Characterization of Pathogen Inactivated
COVID
‐19 Convalescent Plasma and Responses in Transfused Patients. Transfusion 2022; 62:1997-2011. [PMID: 36054476 PMCID: PMC9538076 DOI: 10.1111/trf.17083] [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: 04/11/2022] [Revised: 07/31/2022] [Accepted: 07/31/2022] [Indexed: 12/15/2022]
Abstract
Background Efficacy of donated COVID‐19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. Study Design and Methods In a single‐center hypothesis‐generating prospective case–control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID‐19 pneumonia received 2 × 200 ml pathogen‐reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies in COVID‐19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28‐day mortality, and dCCP ‐related adverse events in recipients. Results Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP‐related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV‐2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS‐CoV‐2 antigens over 14–21 days post dCCP in all except 4 immunosuppressed recipients. Discussion PRT did not impact dCCP anti‐virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post‐transfusion antibody responses indicate the need for controlled trials using well‐characterized dCCP with informative assays.
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Affiliation(s)
- Maja Weisser
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Nina Khanna
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Anemone Hedstueck
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
| | - Sarah Tschudin Sutter
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Sandra Roesch
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
| | - Gregor Stehle
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Mihaela Sava
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
| | | | - Manuel Battegay
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Laura Infanti
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Andreas Holbro
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Stefano Bassetti
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Department of Internal Medicine University Hospital Basel Basel Switzerland
| | - Hans Pargger
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Department of Intensive Care University Hospital Basel Basel Switzerland
| | - Hans H. Hirsch
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Transplantation & Clinical Virology, Department of Biomedicine University of Basel Basel Switzerland
| | - Karoline Leuzinger
- Transplantation & Clinical Virology, Department of Biomedicine University of Basel Basel Switzerland
| | - Laurent Kaiser
- Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, 1205 Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals & Faculty of Medicine University of Geneva Geneva Switzerland
| | - Diem‐Lan Vu
- Division of Infectious Diseases Geneva University Hospitals Geneva Switzerland
| | - Katharina Baur
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Nadine Massaro
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Michael Paul Busch
- Department of Laboratory Medicine University of California, San Francisco San Francisco CA USA
- Vitalant Research Institute San Francisco CA
| | - Graham Simmons
- Department of Laboratory Medicine University of California, San Francisco San Francisco CA USA
- Vitalant Research Institute San Francisco CA
| | - Mars Stone
- Department of Laboratory Medicine University of California, San Francisco San Francisco CA USA
- Vitalant Research Institute San Francisco CA
| | - Philip L. Felgner
- Department of Physiology and Biophysics, Vaccine Research and Development Laboratory University of California, Irvine Irvine CA USA
| | - Rafael R. de Assis
- Department of Physiology and Biophysics, Vaccine Research and Development Laboratory University of California, Irvine Irvine CA USA
| | - Saahir Khan
- Division of Infectious Diseases, Department of Medicine, Keck School of Medicine University of Southern California Los Angeles CA USA
| | | | | | | | | | | | - Andreas S. Buser
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
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Vaccines platforms and COVID-19: what you need to know. Trop Dis Travel Med Vaccines 2022; 8:20. [PMID: 35965345 PMCID: PMC9537331 DOI: 10.1186/s40794-022-00176-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 06/22/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The novel SARS-CoV-2, responsible for the COVID-19 pandemic, is the third zoonotic coronavirus since the beginning of the 21 first century, and it has taken more than 6 million human lives because of the lack of immunity causing global economic losses. Consequently, developing a vaccine against the virus represents the fastest way to finish the threat and regain some "normality." OBJECTIVE Here, we provide information about the main features of the most important vaccine platforms, some of them already approved, to clear common doubts fostered by widespread misinformation and to reassure the public of the safety of the vaccination process and the different alternatives presented. METHODS Articles published in open access databases until January 2022 were identified using the search terms "SARS-CoV-2," "COVID-19," "Coronavirus," "COVID-19 Vaccines," "Pandemic," COVID-19, and LMICs or their combinations. DISCUSSION Traditional first-generation vaccine platforms, such as whole virus vaccines (live attenuated and inactivated virus vaccines), as well as second-generation vaccines, like protein-based vaccines (subunit and viral vector vaccines), and third-generation vaccines, such as nanoparticle and genetic vaccines (mRNA vaccines), are described. CONCLUSIONS SARS-CoV-2 sequence information obtained in a record time provided the basis for the fast development of a COVID-19 vaccine. The adaptability characteristic of the new generation of vaccines is changing our capability to react to emerging threats to future pandemics. Nevertheless, the slow and unfair distribution of vaccines to low- and middle-income countries and the spread of misinformation are a menace to global health since the unvaccinated will increase the chances for resurgences and the surge of new variants that can escape the current vaccines.
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18
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Nagoba BS, Abhijit R. Science in the Times of COVID-19. MEDICAL JOURNAL OF DR. D.Y. PATIL VIDYAPEETH 2022; 15:466-467. [DOI: 10.4103/mjdrdypu.mjdrdypu_96_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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19
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Dawadi P, Syangtan G, Lama B, Kanel SR, Raj Joshi D, Pokhrel LR, Adhikari R, Joshi HR, Pavel I. Understanding COVID-19 Situation in Nepal and Implications for SARS-CoV-2 Transmission and Management. ENVIRONMENTAL HEALTH INSIGHTS 2022; 16:11786302221104348. [PMID: 35694428 PMCID: PMC9178984 DOI: 10.1177/11786302221104348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 05/14/2022] [Indexed: 06/15/2023]
Abstract
Background The pandemic of Coronavirus Disease 2019 (COVID-19), one of the most infectious diseases in the modern history, is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and has had a profound health and economic toll, globally. This paper identifies the overall health status associated with COVID-19 pandemic in all 7 provinces of Nepal, a developing country in South Asia, analyzing data from January 2020 to February 2022. It focuses on the SARS-CoV-2 prevalence, transmission through wastewater and other routes, diagnostics, treatment options, and alternative medicines, thereby offering key perspectives for its management. Materials and Methods Studies regarding coronavirus spanning the 2017 to 2022 period were searched on the web, Nepalese database, and Web of Science. Refined criteria included SARS-CoV-2 in wastewater of Nepal or worldwide. Demographic data (sex, age-group, and geographic location) were also obtained from websites and relevant reports of the Ministry of Health and Population (MOHP) of Nepal, ranging from January 2020 to February 2022. Moreover, trends concerning lockdown, business, and border activities in Nepal between February 2020 and October 2020 were evaluated. The viral dissemination pathways, diagnosis, and available treatment options, including the Ayurvedic medicine, were also examined. Results Aerosols generated during the hospital, industrial, recreational, and household activities were found to contribute to the propagation of SARS-CoV-2 into environmental wastewater, thereby putting the surrounding communities at risk of infection. When lockdown ended and businesses opened in October 2020, the number of active cases of COVID-19 increased exponentially. Bagmati Province had the highest number of cases (53.84%), while the remaining 6 provinces tallied 46.16%. Kathmandu district had the highest number of COVID-19 cases (138, 319 cases), while Manang district had the smallest number of infections (81 cases). The male population was found to be predominantly infected (58.7%). The most affected age groups were the 31 to 40 years old males (25.92%) and the 21 to 30 years old females (26.85%). Conclusion The pandemic impacted the public health and economic growth in our study duration. SARS-CoV-2 was prevalent in the wastewater of Nepal. The Terai districts and the megacities were mostly affected by SARS-CoV-2 infections. Working-age groups and males were identified as the highest risk groups. More investigations on the therapeutic and alternative cures are recommended. These findings may guide the researchers and professionals with handling the COVID-19 challenges in developing countries such as Nepal and better prepare for future pandemics.
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Affiliation(s)
- Prabin Dawadi
- Biological Resources Unit, Nepal Academy of Science and Technology, Lalitpur, Bagmati, Nepal
- Central Department of Microbiology, Tribhuvan University, Kathmandu, Bagmati, Nepal
| | - Gopiram Syangtan
- Central Department of Microbiology, Tribhuvan University, Kathmandu, Bagmati, Nepal
- Shi-Gan International College of Science and Technology, Tribhuvan University, Kathmandu, Bagmati, Nepal
| | - Bhupendra Lama
- Central Department of Microbiology, Tribhuvan University, Kathmandu, Bagmati, Nepal
| | - Sushil R. Kanel
- Department of Chemistry, Wright State University, Dayton, OH, USA
| | - Dev Raj Joshi
- Central Department of Microbiology, Tribhuvan University, Kathmandu, Bagmati, Nepal
| | - Lok R. Pokhrel
- Department of Public Health, The Brody School of Medicine, East Carolina University, Greenville, NC, USA
| | - Rameshwar Adhikari
- Research Center for Applied Science and Technology, Tribhuvan University, Kathmandu, Nepal
| | - Hem R. Joshi
- Department of Mathematics, Xavier University, Cincinnati, OH, USA
| | - Ioana Pavel
- Department of Physical and Environmental Sciences, Texas A&M University at Corpus Christi, Corpus Christi, TX, USA
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20
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Lee B, Ko JH, Park J, Moon HW, Baek JY, Jung S, Lim HY, Kim KC, Huh K, Cho SY, Kang CI, Chung DR, Huh HJ, Chung CR, Kim YJ, Joo EJ, Kang ES, Peck KR. Estimating the Neutralizing Effect and Titer Correlation of Semi-Quantitative Anti-SARS-CoV-2 Antibody Immunoassays. Front Cell Infect Microbiol 2022; 12:822599. [PMID: 35493733 PMCID: PMC9046723 DOI: 10.3389/fcimb.2022.822599] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 03/10/2022] [Indexed: 11/18/2022] Open
Abstract
For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50 ≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.
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Affiliation(s)
- Beomki Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jae-Hoon Ko
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jiho Park
- Division of Infectious Diseases, Department of Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Hee-Won Moon
- Department of Laboratory Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea
| | - Jin Yang Baek
- Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, South Korea
| | - Sunhee Jung
- Division of Emerging Virus and Vector Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea
| | - Hee-Young Lim
- Division of Emerging Virus and Vector Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea
| | - Kyung-Chang Kim
- Division of Emerging Virus and Vector Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea
| | - Kyungmin Huh
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sun Young Cho
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Cheol-In Kang
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Doo Ryeon Chung
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hee Jae Huh
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Chi Ryang Chung
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yae-Jean Kim
- Division of Infectious Diseases and Immunodeficiency, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eun-Jeong Joo
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
- *Correspondence: Eun-Jeong Joo, ; Eun-Suk Kang, ; Kyong Ran Peck,
| | - Eun-Suk Kang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- *Correspondence: Eun-Jeong Joo, ; Eun-Suk Kang, ; Kyong Ran Peck,
| | - Kyong Ran Peck
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- *Correspondence: Eun-Jeong Joo, ; Eun-Suk Kang, ; Kyong Ran Peck,
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21
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Ioannidis JP. High-cited favorable studies for COVID-19 treatments ineffective in large trials. J Clin Epidemiol 2022; 148:1-9. [PMID: 35398190 PMCID: PMC8986133 DOI: 10.1016/j.jclinepi.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: 02/27/2022] [Revised: 03/27/2022] [Accepted: 04/01/2022] [Indexed: 12/15/2022]
Abstract
Objectives Study Design and Setting Results Conclusion
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22
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Elahi R, Karami P, Heidary AH, Esmaeilzadeh A. An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19). Int Immunopharmacol 2022; 105:108536. [PMID: 35074571 PMCID: PMC8747952 DOI: 10.1016/j.intimp.2022.108536] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/01/2022] [Accepted: 01/07/2022] [Indexed: 02/07/2023]
Abstract
Since 2019, COVID-19 has become the most important health dilemma around the world. The dysregulated immune response which results in ARDS and cytokine storm has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through induction of pro-inflammatory chemokines and cytokines, is the pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, IL-6 pathway blockade is considered an emerging approach with high efficacy to reduce lung damage in COVID-19. This article aims to review the pleiotropic roles of the IL-6 pathway in lung damage and ARDS in severe COVID-19, and the rationale for IL-6 signaling blockade at different levels, including IL-6 soluble and membrane receptor pathways, IL-6 downstream signaling (such as JAK-STAT) inhibition, and non-specific anti-inflammatory therapeutic approaches. Recent clinical data of each method, with specific concentration on tocilizumab, along with other new drugs, such as sarilumab and siltuximab, have been discussed. Challenges of IL-6 signaling inhibition, such as the risk of superinfection and hepatic injury, and possible solutions have also been explained. Moreover, to achieve the highest efficacy, ongoing clinical trials and special clinical considerations of using different IL-6 inhibitors have been discussed in detail. Special considerations, including the appropriate timing and dosage, monotherapy or combination therapy, and proper side effect managment must be noticed regarding the clinical administration of these drugs. Future studies are still necessary to improve the productivity and unknown aspects of IL-6 signaling blockade for personalized treatment of severe COVID-19.
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Affiliation(s)
- Reza Elahi
- Zanjan University of Medical Sciences, Zanjan, Iran
| | - Parsa Karami
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Abdolreza Esmaeilzadeh
- Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran.
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23
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Khan MA, Bin Islam S, Rakib MU, Alam D, Hossen MM, Tania M, Asad A. Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Validation
and Current Progress in Trials. CORONAVIRUSES 2022; 3. [DOI: 10.2174/2666796701999201204122819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 11/16/2020] [Accepted: 11/11/2020] [Indexed: 07/28/2024]
Abstract
Background:
Currently, the present world is facing a new deadly challenge against a pandemic disease called
COVID-19, which is caused by a coronavirus, named SARS-CoV-2. To date, there is no drug or vaccine that can treat
COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This
review article discussed and compared those drugs which are running ahead in COVID-19 treatments.
Methods:
We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press release of WHO, NIH and FDA for
articles about COVID-19, and reviewed them.
Results:
Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin,
corticosteroids and interferons have been found effective in some extents, and partially approved by FDA and WHO to treat
COVID-19 at different phases of pandemic. However, some of these drugs have been disapproved later, although clinical
trials are going on. In parallel, plasma therapy has been found fruitful in some extents too, and a number of vaccine trails are
going on.
Conclusions:
This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how
drugs could act on this virus with the comparative discussion on progress and backwards of major drugs used till date,
which might be beneficial for choosing therapies against COVID-19 in different countries.
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Affiliation(s)
- Md. Asaduzzaman Khan
- The Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical
University, Luzhou, Sichuan 646000, China
| | - Shad Bin Islam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Mejbah Uddin Rakib
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Didarul Alam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Md. Munnaf Hossen
- Department of Immunology, Health Science Center, Shenzhen,
University, Shenzhen, Guangdong 518060, China
| | - Mousumi Tania
- Division of Molecular Cancer, Red Green Research Center,
Dhaka, Bangladesh
| | - Asaduzzaman Asad
- Department of Biochemistry and Molecular Biology, Jahangirnagar University; and International
Center for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
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24
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Iannizzi C, Dorando E, Burns J, Weibel S, Dooley C, Wakeford H, Estcourt LJ, Skoetz N, Piechotta V. Methodological challenges for living systematic reviews conducted during the COVID-19 pandemic: A concept paper. J Clin Epidemiol 2022; 141:82-89. [PMID: 34525406 PMCID: PMC8435072 DOI: 10.1016/j.jclinepi.2021.09.013] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/30/2021] [Accepted: 09/08/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND A living systematic review (LSR) is an emerging review type that makes use of continual updating. In the COVID-19 pandemic, we were confronted with a shifting epidemiological landscape, clinical uncertainties and evolving evidence. These unexpected challenges compelled us to amend standard LSR methodology. OBJECTIVE AND OUTLINE Our primary objective is to discuss some challenges faced when conducting LSRs in the context of the COVID-19 pandemic, and to provide methodological guidance for others doing similar work. Based on our experience and lessons learned from two Cochrane LSRs and challenges identified in several non-Cochrane LSRs, we highlight methodological considerations, particularly with regards to the study design, interventions and comparators, changes in outcome measure, and the search strategy. We discuss when to update, or rather when not to update the review, and the importance of transparency when reporting changes. LESSONS LEARNED AND CONCLUSION We learned that a LSR is a very suitable review type for the pandemic context, even in the face of new methodological and clinical challenges. Our experience showed that the decision for updating a LSR depends not only on the evolving disease or emerging evidence, but also on the individual review question and the review teams' resources.
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Affiliation(s)
- Claire Iannizzi
- Department I of Internal Medicine, Evidence-based Oncology Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
| | - Elena Dorando
- Department I of Internal Medicine, Evidence-based Oncology Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
| | - Jacob Burns
- Biometry and Epidemiology - IBE, LMU Munich , Institute for Medical Information Processing, Marchioninistr. 17, 81377, Munich, Germany; Pettenkofer School of Public Health, Munich, Germany
| | - Stephanie Weibel
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Germany
| | - Clare Dooley
- Department of Editorial and Methods, Cochrane Central Executive, London, UK
| | - Helen Wakeford
- Department of Editorial and Methods, Cochrane Central Executive, London, UK
| | - Lise J Estcourt
- Haematology/Transfusion Medicine, NHS Blood and Transplant, John Radcliffe Hospital, Oxford UK, OX3 9BQ
| | - Nicole Skoetz
- Department I of Internal Medicine, Evidence-based Oncology Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
| | - Vanessa Piechotta
- Department I of Internal Medicine, Evidence-based Oncology Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
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25
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Nagoba B, Gavkare A, Rayate A, Mumbre S. Positive Aspects, Negative Aspects and Challenges Associated with Stem Cell Therapy for COVID - 19: A Mini-review. Curr Stem Cell Res Ther 2022; 17:720-726. [PMID: 34727866 DOI: 10.2174/1574888x16666211102092039] [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: 07/13/2021] [Revised: 09/10/2021] [Accepted: 09/18/2021] [Indexed: 12/15/2022]
Abstract
Like any other pandemic, Covid-19 scenario has also demanded effective treatment options. The circumstances demand to utilize all the possible weapons in the armamentarium. There have been many issues regarding the short-term and long-term safety and efficacy of these options. Some options are like uncharted seas and these need a detailed and critical review with respect to safety, efficacy, feasibility and financial constraints. Mesenchymal stem cells (MSCs) therapy has been studied for many years for its potential role in diseases with complex pathogenesis. Its efficacy in controlling cytokine imbalance and immuno-modulatory properties is well proven. These effects are being extensively studied for potential extension of the benefits for an effective option for management of COVID-19 patients with severe respiratory involvement. In this mini-review, an attempt has been made to review positive aspects, negative aspects, and challenges influencing MSCs therapy in the management of COVID-19 disease. The results of various studies and literature reviews show that MSCs therapy can be considered as one of the potential options. This article reviews the role of Mesenchymal Stem Cell (MSC) transplantation in critically ill SARS-COV-19 patients with lung involvement. The MSCs counteract the cytokine storm, regulate the immune responses, facilitate the expression of essential growth factors, and eventually improve the local milieu and promote the restoration of pulmonary vascular and alveolar linings for early healing. As with all new therapeutic options, MSC therapy will also have to stand the test of time with respect to safety, specificity, and constraints like mass production and "available for all" at "affordable cost."
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Affiliation(s)
- Basavraj Nagoba
- Maharashtra Institute of Medical Sciences & Research, Latur - 413531, India
| | - Ajay Gavkare
- Maharashtra Institute of Medical Sciences & Research, Latur - 413531, India
| | - Abhijit Rayate
- Maharashtra Institute of Medical Sciences & Research, Latur - 413531, India
| | - Sachin Mumbre
- Ashwini Rural Medical College, Solapur- 413006, India
- Dean, Faculty of Medicine, Maharashtra University of Health Sciences, Nashik India
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Farooq M, Kutikuppala LVS, Deka N, Gaffar AA, Jose A. Convalescent plasma for coronavirus disease 2019: A boon or bane. JOURNAL OF THE SCIENTIFIC SOCIETY 2022. [DOI: 10.4103/jss.jss_138_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Dhawan M, Priyanka, Parmar M, Angural S, Choudhary OP. Convalescent plasma therapy against the emerging SARS-CoV-2 variants: Delineation of the potentialities and risks. Int J Surg 2022; 97:106204. [PMID: 34974199 PMCID: PMC8717699 DOI: 10.1016/j.ijsu.2021.106204] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 12/21/2021] [Accepted: 12/23/2021] [Indexed: 12/12/2022]
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a catastrophic pandemic and severely impacted people's livelihoods worldwide. In addition, the emergence of SARS-CoV-2 variants has posed a severe threat to humankind. Due to the dearth of therapeutic options during the commencement of the pandemic, convalescent plasma therapy (CPT) played a significant part in the management of patients with severe form of COVID-19. Several recent studies have proposed various protective effects of CPT, such as antiviral, anti-inflammatory, anti-thrombotic, and immunomodulatory actions, curtailing the devastating consequences of the SARS-CoV-2 infection. On the contrary, several clinical studies have raised some serious concerns about the effectiveness and reliability of CPT in the management of patients with COVID-19. The protective effects of CPT in severely ill patients are yet to be proved. Moreover, the emergence of SARS-CoV-2 variants has raised concerns about the effectiveness of CPT against COVID-19. Therefore, to establish concrete evidence of the efficacy of CPT and adjudicate its inclusion in the management of COVID-19, an updated review of present literature is required, which could help in the development of an efficient therapeutic regimen to treat COVID-19 amid the emergence of new viral variants.
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Affiliation(s)
- Manish Dhawan
- Department of Microbiology, Punjab Agricultural University, Ludhiana, 141004, Punjab, India,The Trafford Group of Colleges, Manchester, WA14 5PQ, UK
| | - Priyanka
- Independent Researcher, 07, Type IV Quarter, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl, 796015, Mizoram, India
| | - Manisha Parmar
- Department of Veterinary Microbiology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, 141004, Punjab, India
| | - Steffy Angural
- Department of Medical Lab Technology, Faculty of Applied Health Sciences, GNA University, Phagwara-Hoshiarpur Road, Sri Hargobindgarh, 144401, Punjab, India,Corresponding author
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl, 796015, Mizoram, India,Corresponding author
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Mehraeen E, Najafi Z, Hayati B, Javaherian M, Rahimi S, Dadras O, SeyedAlinaghi S, Ghadimi M, Sabatier JM. Current Treatments and Therapeutic Options for COVID-19 Patients: A Systematic Review. Infect Disord Drug Targets 2022; 22:e260721194968. [PMID: 34313204 DOI: 10.2174/1871526521666210726150435] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/09/2021] [Accepted: 05/19/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION COVID-19 is the third rising epidemic in the 21st century that quickly turned into a worldwide pandemic. Many clinical studies have been achieved to investigate treatments to confront COVID-19. Therefore, we conducted a systematic review to describe the recent treatment strategies to treat COVID-19 patients. METHODS A systematic search was performed in the databases of PubMed, Scopus, Embase, Science direct, Up to date, and Web of Science using the keywords of Coronavirus, COVID-19, SARS-CoV-2, Novel Coronavirus, 2019-nCoV, Treatment, Medicine, Therapy, Intervention, Drug, Medications, and Cure. All the relevant articles were collected from December 2019 to July 2020. RESULTS We included 58 studies including 38 articles (eleven reviews, ten editorial documents, three case reports, one mix method, one cohort study), and 19 published clinical trials. Review of studies showed that Lopinavir/Ritonavir (n=16), Remdesivir (n=13), Convalescent plasma (n=11), Chloroquine (n=11), Ribavirin (n=9), Hydroxychloroquine sulfate (n=8), Traditional Chinese Medicine (TCM) (n=8), and Arbidol (n=7), were the most frequently therapies used to treat COVID-19 patients. CONCLUSION In the absence of definitive treatment protocols, recently proposed approaches have appeared to be an effective therapy for accelerating the recovery of COVID-19 patients. Some of these treatments may have been in the early stages of testing. However, future preclinical and clinical trials are warranted to validate findings.
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Affiliation(s)
- Esmaeil Mehraeen
- Department of Health Information Technology, Khalkhal University of Medical Sciences, Khalkhal, Iran
| | - Zeinab Najafi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Hayati
- Department of Environmental Health, Khalkhal University of Medical Sciences, Khalkhal, Iran
| | - Mohammad Javaherian
- Department of Physiotherapy, Tehran University of Medical Sciences, Tehran, Iran
| | - Sajad Rahimi
- Department of Environmental Health, Khalkhal University of Medical Sciences, Khalkhal, Iran
| | - Omid Dadras
- School of Public Health, Walailak University 222 Thaiburi Thasala, Nakhon Si Thammarat, Thailand
| | - SeyedAhmad SeyedAlinaghi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Ghadimi
- Postdoctoral Fellow, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jean-Marc Sabatier
- Institut de Neuro-physiopathologie (INP), Faculté de Pharmacie, Université Aix-Marseille, UMR 7051, 27 Bd Jean Moulin, 13385 Marseille Cedex, France
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Senderovich H, Vinoraj D, Stever M, Waicus S. Efficacy of COVID-19 treatments among geriatric patients: a systematic review. Ther Adv Infect Dis 2022; 9:20499361221095666. [PMID: 35677110 PMCID: PMC9168946 DOI: 10.1177/20499361221095666] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 03/29/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction A majority of the fatalities due to COVID-19 have been observed in those over the age of 60. There is no approved and universally accepted treatment for geriatric patients. The aim of this review is to assess the current literature on efficacy of COVID-19 treatments in geriatric populations. Methods A systematic review search was conducted in PubMed, MedRxiv, and JAMA databases with the keywords COVID-19, geriatric, hydroxychloroquine, dexamethasone, budesonide, remdesivir, favipiravir, ritonavir, molnupiravir, tocilizumab, bamlanivimab, baricitinib, sotrovimab, fluvoxamine, convalescent plasma, prone position, or anticoagulation. Articles published from January 2019 to January 2022 with a population greater than or equal to 60 years of age were included. Interventions examined included hydroxychloroquine, remdesivir, favipiravir, dexamethasone, budesonide, tocilizumab, bamlanivimab, baricitinib, sotrovimab, convalescent plasma, prone position, and anticoagulation therapy. Outcome measures included viral load, viral markers, ventilator-free days, or clinical improvement. Results The search revealed 302 articles, 52 met inclusion criteria. Hydroxychloroquine, dexamethasone, and remdesivir revealed greater side effects or inefficiency in geriatric patients with COVID-19. Favipiravir, bamlanivimab, baricitinib, and supportive therapy showed a decrease in viral load and improvement of clinical symptoms. There is conflicting evidence with tocilizumab, convalescent plasma, and anticoagulant therapy in reducing mortality, ventilator-free days, and clinical improvements. In addition, there was limited evidence and lack of data due to ongoing trials for treatments with sotrovimab and budesonide. Conclusion No agent is known to be effective for preventing COVID-19 after exposure to the virus. Further research is needed to ensure safety and efficacy of each of the reviewed interventions for older adults.
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Affiliation(s)
- Helen Senderovich
- Baycrest, 3560 Bathurst Street, Toronto, ON M6A
2E1, Canada
- Department of Family and Community Medicine,
University of Toronto, Toronto, ON, Canada
- Division of Palliative Care, University of
Toronto, Toronto, ON, Canada
| | - Danusha Vinoraj
- Department of Psychiatry, Faculty of Medicine,
University of Ottawa, Ottawa, ON, Canada
| | | | - Sarah Waicus
- School of Medicine, Trinity College Dublin, The
University of Dublin, Dublin, Ireland
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Baek AR, Choo EJ, Kim JY, Ha TS, Park SW, Shin HB, Park SK, Park JH, Kim T. A Transient Effect of Convalescent Plasma Therapy in a Patient with Severe Covonavirus Disease 2019: A Case Report. Infect Chemother 2022; 54:553-558. [PMID: 35920265 PMCID: PMC9533158 DOI: 10.3947/ic.2020.0089] [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: 08/13/2020] [Accepted: 09/28/2020] [Indexed: 11/28/2022] Open
Abstract
A 65-year-old male patient with an end-stage renal disease was diagnosed with coronavirus disease 2019 (COVID-19) by reverse transcription polymerase chain reaction. The patient complained of cough, sputum, and respiratory distress that worsened three days ago. The patient required mechanical ventilation and extracorporeal mentrane oxygenation. On day 9, convalescent plasma collected from a 34-year old man who recovered from COVID-19 45 days ago was administered. The patient showed immediate clinical improvement. However, on day 14, the patient’s clinical course worsened again. On day 19 and day 24, vancomycin-resistant Enterococcus faecium bacteremia and methicillin-resistant Staphylococcus aureus pneumonia were found. After long-term supportive care, he slowly recovered. He was discharged on day 91 without any oxygen requirement. This case report suggests that convalescent plasma therapy might just provide a short-term relief and that persistent effort for critical care is necessary to save patients from severe COVID-19.
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Affiliation(s)
- Ae-Rin Baek
- Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Eun Ju Choo
- Division of Infectious Disease, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Ji-Yeon Kim
- Division of Infectious Diseases, Department of Internal Medicine, Seongnam Citizens’ Medical Center, Seongnam, Korea
| | - Tae Sun Ha
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Sung Woo Park
- Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Hee Bong Shin
- Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Seong Kyu Park
- Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Joo Hyun Park
- Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea
| | - Tark Kim
- Division of Infectious Disease, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
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Agarwal N, Mishra S, Ayub A. Convalescent plasma therapy in COVID-19 and discharge status: A systematic review. J Family Med Prim Care 2021; 10:3876-3881. [PMID: 34934695 PMCID: PMC8653454 DOI: 10.4103/jfmpc.jfmpc_2429_20] [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: 12/09/2020] [Revised: 02/21/2021] [Accepted: 03/12/2021] [Indexed: 01/08/2023] Open
Abstract
Objective: Covid19 has emerged as a greatest threat of the decade worldwide. At present there is no certain treatment for treating coronavirus diseases, while some antiviral drugs (Remdesivir , Lopinavir and Ritonavir) are under investigation. Many countries including India have adopted the convalescent plasma therapy in the treatment of moderate to severely ill patients. Despite the treatment being given ,there are no such evidences on the utility and efficacy of convalescent plasma. Hence this study tries to find out the impact on the discharge status from hospital of the patients receiving the very therapy. Design: Systematic review and meta analysis. Setting: An extensive search was made, following PRISMA guidelines on online databases such as Pubmed, Google scholar and Science direct. Studies those fulfilled the inclusion and exclusion criteria ,were included and reviewed and analyzed for a common outcome(discharge status). Participants: A total of 6 eligible studies were analyzed qualitatively and quantitatively which included three case control, two case series and one case report. Results: The overall pooled discharge rate from the above studies was 75.7% after the CP therapy. When analyzed for relative risk , it showed CP therapy having a lower risk of staying in hospital (not getting discharged) when compared to Standard therapy ,overall RR (relative risk) being 0.946. Conclusion: Our study shows that there is always a higher rate of discharge and low risk of prolonged hospital stay in those patients who receive plasma therapy. CP therapy being a low cost and easy to administer therapy with very less adverse events, requires more focus on further research as it has a potential to become an ideal effective treatment option for COVID-19.
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Affiliation(s)
- Neeraj Agarwal
- Professor & Head, Department of Community and Family Medicine, AIIMS-Bibinagar, India
| | - Shradha Mishra
- Asst. Professor, Department of Community Medicine, BRD Medical College, Gorakhpur, Patna, India
| | - Arshad Ayub
- Asst. Professor,Department of Community Medicine, ESIC Medical College & Hospital, Bihta-Patna, India India
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Kim JM, Yoo JH, Cho HK, Hong ST. Analysis of PubMed and KoreaMed Indexed Korean Publications on COVID-19. J Korean Med Sci 2021; 36:e345. [PMID: 34931501 PMCID: PMC8688342 DOI: 10.3346/jkms.2021.36.e345] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 12/14/2021] [Indexed: 11/24/2022] Open
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, publications on the disease have exploded globally. The present study analyzed PubMed and KoreaMed indexed COVID-19 publications by Korean researchers from January 1, 2020 to August 19, 2021. A total of 83,549 COVID-19 articles were recorded in PubMed and 1,875 of these were published by Korean authors in 673 journals (67 Korean and 606 overseas journals). The KoreaMed platform covered 766 articles on COVID-19, including 612 by Korean authors. Among the Journal of Korean Medical Science (JKMS) articles on COVID-19, PubMed covered 176 and KoreaMed 141 documents. Korean researchers contributed to 2.2% of global publications on COVID-19 in PubMed. The JKMS has published most articles on COVID-19 in Korea.
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Affiliation(s)
- Jong-Min Kim
- Department of Neurology, Seoul National University College of Medicine & Associate Editor, Journal of Korean Medical Science, Seoul, Korea
| | - Jin-Hong Yoo
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea & Associate Editor, Journal of Korean Medical Science, Seoul, Korea
| | - Hae Kyung Cho
- Editorial Researcher, Journal of Korean Medical Science, Seoul, Korea
| | - Sung-Tae Hong
- Department of Tropical Medicine and Parasitology, Seoul National University College of Medicine & Editor-in-Chief, Journal of Korean Medical Science, Seoul, Korea.
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Dillner J, Ursing J. Convalescent plasma for treatment of COVID-19: study protocol for an open randomised controlled trial in Sweden. BMJ Open 2021; 11:e048337. [PMID: 34880010 PMCID: PMC8655340 DOI: 10.1136/bmjopen-2020-048337] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 11/19/2021] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Although there are many studies on the use of convalescent plasma (CP) for treatment of COVID-19, it is not clear (1) which groups of patients may benefit, (2) what dose of plasma to give, or (3) which antibody levels the plasma should contain. Previous phase I/II studies and literature review suggest that CP should only be given to patients with viraemia, that a daily infusion should be given until the patient becomes virus free and that the neutralising antibody titre should preferably be >1:640 METHODS AND ANALYSIS: An open randomised controlled trial enrolling patients with COVID-19, who must be SARS-CoV-2 positive in both airway and blood samples and admitted to a study hospital. Block randomisation 2:1 is to either 200 mL CP (preferably titre ≥1/640) daily for up to 10 days (until virus negative in blood) plus standard care or standard care only (control arm). The primary endpoint is mortality by day 28 after study inclusion. Secondary endpoints include mortality by day 60 and doses of plasma needed to clear viraemia. Assuming a reduced mortality of approximately 30% by the CP therapy and 85%-88% survival in the control arm, approximately 600 participants will be enrolled to the CP therapy arm and 300 participants to the control arm. ETHICS AND DISSEMINATION Ethical approval has been granted by the Swedish Ethical Review Authority (reference: 2020-06277). Results from this trial will be compiled in a clinical study report, disseminated via journal articles and communicated to stakeholders. TRIAL REGISTRATION NUMBER NCT04649879.
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Affiliation(s)
- Joakim Dillner
- Medical Diagnostics Karolinska, Karolinska University Hospital, Stockholm, Sweden
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Johan Ursing
- Department of Infectious Diseases, Danderyd University Hospital, Stockholm, Sweden
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Focosi D, Franchini M, Pirofski LA, Maggi F, Casadevall A. Is SARS-CoV-2 viral clearance in nasopharyngeal swabs an appropriate surrogate marker for clinical efficacy of neutralising antibody-based therapeutics? Rev Med Virol 2021; 32:e2314. [PMID: 34861088 DOI: 10.1002/rmv.2314] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/12/2021] [Accepted: 11/17/2021] [Indexed: 12/15/2022]
Abstract
Viral clearance is likely the best way to assess the efficacy of antibody-based therapies. Although antibodies can mediate a variety of effects that include modulation of inflammation, the demonstration of viral clearance provides an accessible and measurable parameter that can be used to evaluate efficacy and determine dosing. Therefore, it is important to ascertain the ability of monoclonal antibodies and convalescent plasma to effect viral clearance. For COVID-19, which is caused by the respiratory virus SARS-CoV-2, the most common assay to assess viral clearance is via a nasopharyngeal swab (NPS). However, assessment of antibody efficacy by sampling this site may be misleading because it may not be as accessible to serum antibodies as respiratory secretions or circulating blood. Adding to the complexity of assessing the efficacy of administered antibody, particularly in randomised controlled trials (RCTs) that enroled patients at different times after the onset of COVID-19 symptoms, viral clearance may also be mediated by endogenous antibody. In this article we critically review available data on viral clearance in RCTs, matched control studies, case series and case reports of antibody therapies in an attempt to identify variables that contribute to antibody efficacy and suggest optimal strategies for future studies.
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Affiliation(s)
- Daniele Focosi
- North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy
| | - Massimo Franchini
- Division of Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
| | - Liise-Anne Pirofski
- Division of Infectious Diseases, Departments of Medicine, Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, New York City, New York, USA
| | - Fabrizio Maggi
- Department of Medicine and Surgery, University of Insubria, Varese, Italy.,Laboratory of Microbiology, ASST Sette Laghi, Varese, Italy
| | - Arturo Casadevall
- Department of Medicine, Johns Hopkins School of Public Health and School of Medicine, Baltimore, Maryland, USA
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Bassetti M, Giacobbe DR, Bruzzi P, Barisione E, Centanni S, Castaldo N, Corcione S, De Rosa FG, Di Marco F, Gori A, Gramegna A, Granata G, Gratarola A, Maraolo AE, Mikulska M, Lombardi A, Pea F, Petrosillo N, Radovanovic D, Santus P, Signori A, Sozio E, Tagliabue E, Tascini C, Vancheri C, Vena A, Viale P, Blasi F. Clinical Management of Adult Patients with COVID-19 Outside Intensive Care Units: Guidelines from the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP). Infect Dis Ther 2021; 10:1837-1885. [PMID: 34328629 PMCID: PMC8323092 DOI: 10.1007/s40121-021-00487-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/15/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) constituted an expert panel for developing evidence-based guidance for the clinical management of adult patients with coronavirus disease 2019 (COVID-19) outside intensive care units. METHODS Ten systematic literature searches were performed to answer ten different key questions. The retrieved evidence was graded according to the Grading of Recommendations Assessment, Development, and Evaluation methodology (GRADE). RESULTS AND CONCLUSION The literature searches mostly assessed the available evidence on the management of COVID-19 patients in terms of antiviral, anticoagulant, anti-inflammatory, immunomodulatory, and continuous positive airway pressure (CPAP)/non-invasive ventilation (NIV) treatment. Most evidence was deemed as of low certainty, and in some cases, recommendations could not be developed according to the GRADE system (best practice recommendations were provided in similar situations). The use of neutralizing monoclonal antibodies may be considered for outpatients at risk of disease progression. For inpatients, favorable recommendations were provided for anticoagulant prophylaxis and systemic steroids administration, although with low certainty of evidence. Favorable recommendations, with very low/low certainty of evidence, were also provided for, in specific situations, remdesivir, alone or in combination with baricitinib, and tocilizumab. The presence of many best practice recommendations testified to the need for further investigations by means of randomized controlled trials, whenever possible, with some possible future research directions stemming from the results of the ten systematic reviews.
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Affiliation(s)
- Matteo Bassetti
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, L.go R. Benzi, 10, 16132, Genoa, Italy.
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
| | - Daniele Roberto Giacobbe
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, L.go R. Benzi, 10, 16132, Genoa, Italy.
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
| | - Paolo Bruzzi
- Clinical Epidemiology Unit, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
| | - Emanuela Barisione
- Interventional Pulmonology, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
| | - Stefano Centanni
- Department of Health Sciences, University of Milan, Respiratory Unit, ASST Santi Paolo e Carlo, Milan, Italy
| | - Nadia Castaldo
- Infectious Diseases Clinic, Santa Maria Misericordia Hospital, Udine, Italy
| | - Silvia Corcione
- Department of Medical Sciences, Infectious Diseases, University of Turin, Turin, Italy
- Tufts University School of Medicine, Boston, MA, USA
| | | | - Fabiano Di Marco
- Department of Health Sciences, University of Milan, Respiratory Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Andrea Gori
- Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Centre for Multidisciplinary Research in Health Science (MACH), University of Milan, Milan, Italy
| | - Andrea Gramegna
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
| | - Guido Granata
- Clinical and Research Department for Infectious Diseases, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy
| | - Angelo Gratarola
- Department of Emergency and Urgency, San Martino Policlinico Hospital, IRCCS, Genoa, Italy
| | | | - Malgorzata Mikulska
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, L.go R. Benzi, 10, 16132, Genoa, Italy
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
| | - Andrea Lombardi
- Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Federico Pea
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
- SSD Clinical Pharmacology Unit, University Hospital, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Nicola Petrosillo
- Clinical and Research Department for Infectious Diseases, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy
- Infection Control and Infectious Disease Service, University Hospital "Campus-Biomedico", Rome, Italy
| | - Dejan Radovanovic
- Division of Respiratory Diseases, Ospedale L. Sacco, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Pierachille Santus
- Division of Respiratory Diseases, Ospedale L. Sacco, ASST Fatebenefratelli-Sacco, Milan, Italy
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan, Italy
| | - Alessio Signori
- Department of Health Sciences, Section of Biostatistics, University of Genoa, Genoa, Italy
| | - Emanuela Sozio
- Infectious Diseases Clinic, Santa Maria Misericordia Hospital, Udine, Italy
| | - Elena Tagliabue
- Interventional Pulmonology, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
| | - Carlo Tascini
- Infectious Diseases Clinic, Santa Maria Misericordia Hospital, Udine, Italy
| | - Carlo Vancheri
- Regional Referral Centre for Rare Lung Diseases-University Hospital "Policlinico G. Rodolico", Catania, Italy
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Antonio Vena
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, L.go R. Benzi, 10, 16132, Genoa, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
- Infectious Diseases Unit, University Hospital IRCCS Policlinico Sant'Orsola, Bologna, Italy
| | - Francesco Blasi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
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Han F, Liu Y, Mo M, Chen J, Wang C, Yang Y, Wu J. Current treatment strategies for COVID‑19 (Review). Mol Med Rep 2021; 24:858. [PMID: 34664677 PMCID: PMC8548951 DOI: 10.3892/mmr.2021.12498] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/25/2021] [Indexed: 12/17/2022] Open
Abstract
The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID‑19). To date, there is no specific therapy established to treat COVID‑19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS‑CoV‑2 in humans. For the present review, >100 publications on therapeutic agents for COVID‑19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta‑analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS‑CoV‑2 infection were highlighted. Since the outbreak of COVID‑19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID‑19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID‑19. The molecular mechanisms of these therapeutic agents against SARS‑CoV2 have been investigated, including inhibition of viral interactions with angiotensin‑converting enzyme 2 receptors in human cells, viral RNA‑dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID‑19 were acknowledged.
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Affiliation(s)
- Fabin Han
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
- Laboratory for Stem Cell and Regenerative Medicine, Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital/Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Yanming Liu
- Laboratory for Stem Cell and Regenerative Medicine, Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital/Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Mei Mo
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Juanli Chen
- Laboratory for Stem Cell and Regenerative Medicine, Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital/Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Cheng Wang
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
- Department of Research and Development, Shandong Meijia Therapeutic Biotechnology Co., Ltd., Jinan, Shandong 250100, P.R. China
| | - Yong Yang
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Jibiao Wu
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
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Farag EA, Islam MM, Enan K, El-Hussein ARM, Bansal D, Haroun M. SARS-CoV-2 at the human-animal interphase: A review. Heliyon 2021; 7:e08496. [PMID: 34869934 PMCID: PMC8626158 DOI: 10.1016/j.heliyon.2021.e08496] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 09/29/2021] [Accepted: 11/24/2021] [Indexed: 12/15/2022] Open
Abstract
Since its emergence in China in December 2019, COVID-19 remains the recent leading disease of concern drawing the public health attention globally. The disease is known of viral origin and zoonotic nature originating from animals. However, to date neither the source of the spillover nor the intermediate hosts are identified. Moreover, the public health situation is intermittently aggravated by identification of new animals susceptible to the SARS-CoV-2 infection, potentially replicating the virus and maintaining intra and interspecies spread of the disease. Although the role of a given animal and/or its produce is important to map the disease pattern, continuous efforts should be undertaken to further understand the epidemiology of SARS-CoV-2, a vital step to establish effective disease prevention and control strategy. This manuscript attempted to review updates regarding SARS-CoV-2 infection at the human-animal interface with consideration to postulations on the genetic relatedness and origin of the different SARS-CoV-2 variants isolated from different animal species. Also, the review addresses the possible role of different animal species and their produce in transmission of the disease. Also, the manuscript discussed the contamination potentiality of the virus and its environmental stability. Finally, we reviewed the currently instituted measures to prevent and manage the spread of SARS-CoV-2 infection. The manuscript suggested the One Health based control measures that could prove of value for the near future.
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Affiliation(s)
| | - Md Mazharul Islam
- Department of Animal Resources, Ministry of Municipality and Environment, Doha, Qatar
| | - Khalid Enan
- Department of Animal Resources, Ministry of Municipality and Environment, Doha, Qatar
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Kumar S, Çalışkan DM, Janowski J, Faist A, Conrad BCG, Lange J, Ludwig S, Brunotte L. Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics. Front Immunol 2021; 12:752227. [PMID: 34659259 PMCID: PMC8519339 DOI: 10.3389/fimmu.2021.752227] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 09/14/2021] [Indexed: 12/15/2022] Open
Abstract
Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper the availability of vaccines in many countries. In addition, due to the emergency of SARS-CoV-2 variants with immune escape properties towards the vaccines the global numbers of new infections as well as patients developing severe COVID-19, remains high. New studies reported that about 8% of infected individuals develop long term symptoms with strong personal restrictions on private as well as professional level, which contributes to the long socioeconomic problems caused by this pandemic. Until today, emergency use-approved treatment options for COVID-19 are limited to the antiviral Remdesivir, a nucleoside analogue targeting the viral polymerase, the glucocorticosteroide Dexamethasone as well as neutralizing antibodies. The therapeutic benefits of these treatments are under ongoing debate and clinical studies assessing the efficiency of these treatments are still underway. To identify new therapeutic treatments for COVID-19, now and by the post-pandemic era, diverse experimental approaches are under scientific evaluation in companies and scientific research teams all over the world. To accelerate clinical translation of promising candidates, repurposing approaches of known approved drugs are specifically fostered but also novel technologies are being developed and are under investigation. This review summarizes the recent developments from the lab bench as well as the clinical status of emerging therapeutic candidates and discusses possible therapeutic entry points for the treatment strategies with regard to the biology of SARS-CoV-2 and the clinical course of COVID-19.
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Affiliation(s)
- Sriram Kumar
- Institute of Virology, University of Münster, Münster, Germany
- EvoPAD Research Training Group 2220, University of Münster, Münster, Germany
| | - Duygu Merve Çalışkan
- Institute of Virology, University of Münster, Münster, Germany
- EvoPAD Research Training Group 2220, University of Münster, Münster, Germany
| | - Josua Janowski
- Institute of Virology, University of Münster, Münster, Germany
- SP BioSciences Graduate Program, University of Münster, Münster, Germany
| | - Aileen Faist
- Institute of Virology, University of Münster, Münster, Germany
- CiM-IMPRS Graduate Program, University of Münster, Münster, Germany
| | | | - Julius Lange
- Institute of Virology, University of Münster, Münster, Germany
| | - Stephan Ludwig
- Institute of Virology, University of Münster, Münster, Germany
- EvoPAD Research Training Group 2220, University of Münster, Münster, Germany
- CiM-IMPRS Graduate Program, University of Münster, Münster, Germany
- Interdisciplinary Centre for Medical Research, University of Münster, Münster, Germany
| | - Linda Brunotte
- Institute of Virology, University of Münster, Münster, Germany
- Interdisciplinary Centre for Medical Research, University of Münster, Münster, Germany
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Zaky ZA, Moustafa B, Aly AH. Plasma cell sensor using photonic crystal cavity. OPTICAL AND QUANTUM ELECTRONICS 2021; 53:591. [PMID: 34602711 PMCID: PMC8475417 DOI: 10.1007/s11082-021-03201-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 08/18/2021] [Indexed: 06/13/2023]
Abstract
The performance of one-dimensional photonic crystal for plasma cell application is studied theoretically. The geometry of the structure can detect the change in the refractive index of the plasma cells in a sample that infiltrated through the defect layer. We have obtained a variation on the resonant peak positions using the analyte defect layer with different refractive indices. The defect peak of the optimized structure is red-shifted from 2195 to 2322 nm when the refractive index of the defect layer changes from 1.3246 to 1.3634. This indicates a high sensitivity of the device (S = 3300 nm/RIU) as well as a high Q-factor (Q = 103). The proposed sensor has a great potential for biosensing applications and the detection of convalescent plasma.
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Affiliation(s)
- Zaky A. Zaky
- TH-PPM Group, Physics Department, Faculty of Sciences, Beni-Suef University, Beni-Suef, Egypt
| | - Basma Moustafa
- TH-PPM Group, Physics Department, Faculty of Sciences, Beni-Suef University, Beni-Suef, Egypt
| | - Arafa H. Aly
- TH-PPM Group, Physics Department, Faculty of Sciences, Beni-Suef University, Beni-Suef, Egypt
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Baral PK, Yin J, James MNG. Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2. Int J Biol Macromol 2021; 186:490-500. [PMID: 34237371 PMCID: PMC8256663 DOI: 10.1016/j.ijbiomac.2021.07.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/02/2021] [Accepted: 07/02/2021] [Indexed: 12/19/2022]
Abstract
Researchers from the world over are working to create prophylactic and therapeutic interventions to combat the COVID-19 global healthcare crisis. The current therapeutic options against the COVID-19 include repurposed drugs aimed at targets other than virus-specific proteins. Antibody-based therapeutics carry a lot of promise, and there are several of these candidates for COVID-19 treatment currently being investigated in the preclinical and clinical research stages around the world. The viral spike protein (S protein) appears to be the main target of antibody development candidates, with the majority being monoclonal antibodies. Several antibody candidates targeting the SARS-CoV-2 S protein include LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. These neutralizing antibodies will treat COVID-19 and possibly future coronavirus infections. Future studies should focus on effective immune-therapeutics and immunomodulators with the purpose of developing specific, affordable, and cost-effective prophylactic and treatment regimens to fight the COVID-19 globally.
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Affiliation(s)
- Pravas Kumar Baral
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Jiang Yin
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Michael N G James
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
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Cho Y, Sohn Y, Hyun J, Baek Y, Kim M, Kim J, Ahn J, Jeong S, Ku N, Yeom JS, Ahn M, Oh D, Choi J, Kim S, Lee K, Song Y, Choi J. Effectiveness of Convalescent Plasma Therapy in Severe or Critically Ill COVID-19 Patients: A Retrospective Cohort Study. Yonsei Med J 2021; 62:799-805. [PMID: 34427065 PMCID: PMC8382726 DOI: 10.3349/ymj.2021.62.9.799] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/15/2021] [Accepted: 06/20/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. MATERIALS AND METHODS This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or life-threatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. RESULTS Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002). No transfusion-related side effects were observed. CONCLUSION CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.
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Affiliation(s)
- YunSuk Cho
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - YuJin Sohn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - JongHoon Hyun
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - YaeJee Baek
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - MooHyun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - JungHo Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - JinYoung Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - SuJin Jeong
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - NamSu Ku
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Sup Yeom
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - MiYoung Ahn
- Department of Internal Medicine, Seoul Medical Center, Seoul, Korea
| | - DongHyun Oh
- Department of Internal Medicine, Seoul Medical Center, Seoul, Korea
| | - JaePhil Choi
- Department of Internal Medicine, Seoul Medical Center, Seoul, Korea
| | - SinYoung Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - KyoungHwa Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - YoungGoo Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - JunYong Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea.
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Khamis F, Al Arimi Z, Al Naamani H, Al Bahrani M, Pandak N, Al Bolushi Z, Deenadayalan SS, Al Lawati A, Al Salmi I, Al-Zakwani I. Convalescent Plasma Therapy in Critically Ill COVID-19 Patients: An Open Label Trial. Oman Med J 2021; 36:e296. [PMID: 34631155 PMCID: PMC8491110 DOI: 10.5001/omj.2021.105] [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: 12/05/2020] [Accepted: 01/25/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES The novel severe acute respiratory syndrome coronavirus 2 pandemic continues to spread globally without an effective treatment. In search of the cure, convalescent plasma (CP) containing protective antibodies from survivors of coronavirus disease 2019 (COVID-19) infection has shown potential benefit in a non-intensive care unit setting. We sought to evaluate the effectiveness of CP therapy for patients with COVID-19 on mechanical ventilation (MV) and/or acute respiratory distress syndrome (ARDS). METHODS We conducted an open-label trial in a single center, Royal Hospital, in Oman. The study was conducted from 17 April to 20 June 2020. The trial included 94 participants with laboratory-confirmed COVID-19. The primary outcomes included extubation rates, discharges from the hospital and overall mortality, while secondary outcomes were the length of stay and improvement in respiratory and laboratory parameters. Analyses were performed using univariate statistics. RESULTS The overall mean age of the cohort was 50.0±15.0 years, and 90.4% (n = 85) were males. A total of 77.7% (n = 73) of patients received CP. Those on CP were associated with a higher extubation rate (35.6% vs. 76.2%; p < 0.001), higher extubation/home discharges rate (64.4% vs. 23.8%; p =0.001), and tendency towards lower overall mortality (19.2% vs. 28.6%; p =0.354; study power = 11.0%) when compared to COVID-19 patients that did not receive CP. CONCLUSIONS CP was associated with higher extubation/home discharges and a tendency towards lower overall mortality when compared to those that did not receive CP in COVID-19 patients on MV or in those with ARDS. Further studies are warranted to corroborate our findings.
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Affiliation(s)
- Faryal Khamis
- Infectious Diseases Unit, Department of Internal Medicine, Royal Hospital, Muscat, Oman
| | - Zainab Al Arimi
- Department of Blood Bank Services, Ministry of Health, Muscat, Oman
| | | | - Maher Al Bahrani
- Department of Anesthesia and Critical Care, Royal Hospital, Muscat, Oman
| | - Nenad Pandak
- Infectious Diseases Unit, Department of Internal Medicine, Royal Hospital, Muscat, Oman
| | - Zakaryia Al Bolushi
- Infectious Diseases Unit, Department of Internal Medicine, Royal Hospital, Muscat, Oman
| | | | - Adil Al Lawati
- Acute Medicine Unit, Department of Medicine, Royal Hospital Muscat, Oman
| | - Issa Al Salmi
- Department of Nephrology, Royal Hospital, Muscat, Oman
| | - Ibrahim Al-Zakwani
- Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
- Gulf Health Research, Muscat, Oman
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Gurugubelli KR, Bhat BV. Coronavirus Disease 2019 Infection among Children: Pathogenesis, Treatment, and Outcome. J Pediatr Intensive Care 2021; 10:167-173. [PMID: 34395033 PMCID: PMC8354362 DOI: 10.1055/s-0040-1718417] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 09/02/2020] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a contagious disease that may lead to respiratory distress syndrome and even death. Neonates and children are most vulnerable population to COVID-19 infection; however, the infection is usually milder and has a better prognosis in pediatric patients compared with adults. It remains unclear why pediatric population is less symptomatic than adults. Children frequently experience respiratory infections and their immune system is in developing stage. However, large proportion of the asymptomatic pediatric population may contribute to transmission. This review explored several aspects of COVID-19 infection such as its epidemiology, its molecular pathogenesis with respect to angiotensin-converting enzyme 2 receptor and inflammatory mediators, intrauterine vertical transmission, imaging findings, and complications like cytokine release syndrome (multisystem inflammatory syndrome in children). We also looked at prognostic factors and treatment modalities like corticosteroids, RNA replicate inhibitors, protease inhibitors, Bruton tyrosine kinase inhibitor, that is, acalabrutinib and convalescent plasma therapy. Since there is no strong evidence for the intrauterine transmission, early isolation should be performed to protect a neonate from a COVID-19 infected mother. Development of vaccine and an effective antiviral drug are the need of the hour.
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Affiliation(s)
- Krishna Rao Gurugubelli
- Department of Biochemistry, All India Institute of Medical Sciences, Mangalagiri, Andhra Pradesh, India
| | - Ballambattu Vishnu Bhat
- Department of Pediatrics and Neonatology, Aarupadai Veedu Medical College and Hospital, Kirumambakkam, Puducherry, India
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Huang L, Zhang C, Zhou X, Zhao Z, Wang W, Leng W, Su X, Lian Q. Convalescent plasma is of limited clinical benefit in critically ill patients with coronavirus disease-2019: a cohort study. J Transl Med 2021; 19:365. [PMID: 34446049 PMCID: PMC8390032 DOI: 10.1186/s12967-021-03028-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 08/06/2021] [Indexed: 01/08/2023] Open
Abstract
Background Recently, convalescent plasma (CP) transfusion was employed for severe or critically ill patients with coronavirus disease-2019. However, the benefits of CP for patients with different conditions are still in debate. To contribute clinical evidence of CP on critically ill patients, we analyze the characteristics and outcomes of patients with or without CP transfusion. Methods In this cohort study, 14 patients received CP transfusion based on the standard treatments, whereas the other 10 patients received standard treatments as control. Clinical characteristics and outcomes were analyzed. The cumulative survival rate was calculated by Kaplan–Meier survival analysis. Results Data analysis was performed on 24 patients (male/female: 15/9) with a median age of 64.0 (44.5–74.5) years. Transient fever was reported in one patient. The cumulative mortality was 21% (3/14) in patients receiving CP transfusion during a 28-day observation, whereas one dead case (1/10) was reported in the control group. No significant difference was detected between groups in 28-day mortality (P = 0.615) and radiological alleviation of lung lesions (P = 0.085). Conclusion In our current study, CP transfusion was clinically safe based on the safety profile; however, the clinical benefit was not significant in critically ill patients with more comorbidities at the late stage of disease during a 28-day observation. Graphic abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-03028-5.
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Affiliation(s)
- Li Huang
- The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China; Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai, 200031, China.,Clinical Research Centre, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Che Zhang
- Clinical Research Centre, Taihe Hospital, Hubei University of Medicine, Shiyan, China.,Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xihui Zhou
- Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhou Zhao
- Intensive Care Unit, Shiyan People Hospital, Shiyan, China
| | - Weiping Wang
- Department of Respiratory Medicine, Shiyan Xiyuan Hospital, Shiyan, China
| | - Weidong Leng
- Clinical Research Centre, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiao Su
- The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China; Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai, 200031, China.
| | - Qizhou Lian
- The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China; Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai, 200031, China. .,Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. .,HKUMed Laboratory of Cellular Therapeutics, The University of Hong Kong, Hong Kong, China.
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Leber W, Lammel O, Redlberger-Fritz M, Mustafa-Korninger ME, Glehr RC, Camp J, Agerer B, Lercher A, Popa A, Genger JW, Penz T, Aberle S, Bock C, Bergthaler A, Stiasny K, Hochstrasser EM, Hoellinger C, Siebenhofer A, Griffiths C, Panovska-Griffiths J. Rapid, early and accurate SARS-CoV-2 detection using RT-qPCR in primary care: a prospective cohort study (REAP-1). BMJ Open 2021; 11:e045225. [PMID: 34341034 PMCID: PMC8331320 DOI: 10.1136/bmjopen-2020-045225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 06/24/2021] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES We explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria. DESIGN Prospective cohort study. SETTING A single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein. PARTICIPANTS All 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020. INTERVENTION Nasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR). OUTCOME MEASURES We compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present. RESULTS Twenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1-4) among early acute, 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified. CONCLUSIONS RT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.
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Affiliation(s)
- Werner Leber
- Wolfson Institute of Population Health, Centre for Primary Care, Queen Mary University of London, London, UK
| | | | | | | | - Reingard Christina Glehr
- Institute of General Practice and Evidence-based Health Services Research, Medical University of Graz, Graz, Austria
| | - Jeremy Camp
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | - Benedikt Agerer
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Alexander Lercher
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Alexandra Popa
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Jakob-Wendelin Genger
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Thomas Penz
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Stephan Aberle
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | - Christoph Bock
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Andreas Bergthaler
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Karin Stiasny
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | | | | | - Andrea Siebenhofer
- Institute of General Practice and Evidence-based Health Services Research, Medical University of Graz, Graz, Austria
- Goethe University Frankfurt, Institute for General Practice, Frankfurt, Germany
| | - Chris Griffiths
- Wolfson Institute of Population Health, Centre for Primary Care, Queen Mary University of London, London, UK
| | - Jasmina Panovska-Griffiths
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- The Queen's College, University of Oxford, Oxford, UK
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46
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Fatehi F, Bingham RJ, Dykeman EC, Stockley PG, Twarock R. Comparing antiviral strategies against COVID-19 via multiscale within-host modelling. ROYAL SOCIETY OPEN SCIENCE 2021; 8:210082. [PMID: 34430042 PMCID: PMC8355669 DOI: 10.1098/rsos.210082] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 07/23/2021] [Indexed: 05/06/2023]
Abstract
Within-host models of COVID-19 infection dynamics enable the merits of different forms of antiviral therapy to be assessed in individual patients. A stochastic agent-based model of COVID-19 intracellular dynamics is introduced here, that incorporates essential steps of the viral life cycle targeted by treatment options. Integration of model predictions with an intercellular ODE model of within-host infection dynamics, fitted to patient data, generates a generic profile of disease progression in patients that have recovered in the absence of treatment. This is contrasted with the profiles obtained after variation of model parameters pertinent to the immune response, such as effector cell and antibody proliferation rates, mimicking disease progression in immunocompromised patients. These profiles are then compared with disease progression in the presence of antiviral and convalescent plasma therapy against COVID-19 infections. The model reveals that using both therapies in combination can be very effective in reducing the length of infection, but these synergistic effects decline with a delayed treatment start. Conversely, early treatment with either therapy alone can actually increase the duration of infection, with infectious virions still present after the decline of other markers of infection. This suggests that usage of these treatments should remain carefully controlled in a clinical environment.
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Affiliation(s)
- F. Fatehi
- Department of Mathematics, University of York, York YO10 5DD, UK
- York Cross-disciplinary Centre for Systems Analysis, University of York, York YO10 5DD, UK
| | - R. J. Bingham
- Department of Mathematics, University of York, York YO10 5DD, UK
- York Cross-disciplinary Centre for Systems Analysis, University of York, York YO10 5DD, UK
- Department of Biology, University of York, York YO10 5DD, UK
| | - E. C. Dykeman
- Department of Mathematics, University of York, York YO10 5DD, UK
- York Cross-disciplinary Centre for Systems Analysis, University of York, York YO10 5DD, UK
| | - P. G. Stockley
- Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - R. Twarock
- Department of Mathematics, University of York, York YO10 5DD, UK
- York Cross-disciplinary Centre for Systems Analysis, University of York, York YO10 5DD, UK
- Department of Biology, University of York, York YO10 5DD, UK
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47
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Herstein JJ, Lowe JJ, Wolf T, Vasoo S, Leo YS, Chin B, Shen Y, Hewlett AL, Lawler JV. Leveraging a preexisting global infectious disease network for local decision-making during a pandemic. Clin Infect Dis 2021; 74:729-733. [PMID: 34318871 PMCID: PMC8406886 DOI: 10.1093/cid/ciab660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Indexed: 12/15/2022] Open
Abstract
Emerging infectious disease epidemics require a rapid response from health systems; however, evidence-based consensus guidelines are generally absent early in the course of events. Formed in 2017 by five high-level isolation units spanning three continents, the experience of the Global Infectious Disease Preparedness Network (GIDPN) early in the course of COVID-19 provides a model for accelerating best practice development and improving decision-making in health emergencies. The network served as a platform for real-time, open and transparent information-sharing during unknowns of an active outbreak by clinicians caring for patients, by researchers conducting clinical trials and transmission and infection prevention studies, and by teams advising local and national policymakers. Shared knowledge led to earlier adoption of some treatment modalities as compared to most peer institutions and to implementation of protocols prior to incorporation into national guidelines. GIDPN and similar networks are integral in enhancing preparedness for and response to future epidemics/pandemics.
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Affiliation(s)
- Jocelyn J Herstein
- Department of Environmental, Agricultural, and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - John J Lowe
- Department of Environmental, Agricultural, and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Timo Wolf
- Department of Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Shawn Vasoo
- National Centre for Infectious Diseases, Singapore.,Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
| | - Yee Sin Leo
- National Centre for Infectious Diseases, Singapore.,Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
| | - BumSik Chin
- Division of Infectious Diseases, Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea
| | - Yinzhong Shen
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Angela L Hewlett
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - James V Lawler
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
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48
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Giardino G, Romano R, Coppola E, Cillo F, Borzachiello C, De Luca M, Palamaro L, Toriell E, Prencipe R, Cirillo E, Pignata C. SARS-CoV-2 infection in the immunodeficient host: necessary and dispensable immune pathways. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2021; 9:3237-3248. [PMID: 34273582 PMCID: PMC8279920 DOI: 10.1016/j.jaip.2021.06.045] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 06/29/2021] [Accepted: 06/30/2021] [Indexed: 12/15/2022]
Abstract
Since its outbreak in late December 2019 in Wuhan, coronavirus disease 2019 pandemic has posed a therapeutic challenge for the world population, with a plenty of clinical pictures and a broad spectrum of severity of the manifestations. In spite of initial speculations on a direct role of primary or acquired immune deficiency in determining a worse disease outcome, recent studies have provided evidence that specific immune defects may either serve as an experimentum naturae entailing this risk or may not be relevant enough to impact the host defense against the virus. Taken together, these observations may help unveil pathogenetic mechanisms of the infection and suggest new therapeutic strategies. Thus, in this review, we summarize current knowledge regarding the mechanisms of immune response against severe acute respiratory syndrome coronavirus 2 infection and clinical manifestations with a special focus on children and patients presenting with congenital or acquired immune deficiency.
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Affiliation(s)
- Giuliana Giardino
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Roberta Romano
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Emma Coppola
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Francesca Cillo
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Carla Borzachiello
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Martina De Luca
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Loredana Palamaro
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Elisabetta Toriell
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Rosaria Prencipe
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Emilia Cirillo
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy
| | - Claudio Pignata
- Department of Translational Medical Sciences, Pediatric Section, Federico II University of Naples, Naples, Italy;.
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49
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Iqbal Yatoo M, Hamid Z, Rather I, Nazir QUA, Bhat RA, Ul Haq A, Magray SN, Haq Z, Sah R, Tiwari R, Natesan S, Bilal M, Harapan H, Dhama K. Immunotherapies and immunomodulatory approaches in clinical trials - a mini review. Hum Vaccin Immunother 2021; 17:1897-1909. [PMID: 33577374 PMCID: PMC7885722 DOI: 10.1080/21645515.2020.1871295] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 12/28/2020] [Indexed: 12/13/2022] Open
Abstract
The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created havoc worldwide. Due to the non-availability of any vaccine or drugs against COVID-19, immunotherapies involving convalescent plasma, immunoglobulins, antibodies (monoclonal or polyclonal), and the use of immunomodulatory agents to enhance immunity are valuable alternative options. Cell-based therapies including natural killer cells, T cells, stem cells along with cytokines and toll-like receptors (TLRs) based therapies are also being exploited potentially against COVID-19. Future research need to strengthen the field of developing effective immunotherapeutics and immunomodulators with a thrust of providing appropriate, affordable, convenient, and cost-effective prophylactic and treatment regimens to combat global COVID-19 crisis that has led to a state of medical emergency enforcing entire countries of the world to devote their research infrastructure and manpower in tackling this pandemic.
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Affiliation(s)
- Mohd. Iqbal Yatoo
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Zeenat Hamid
- Department of Biotechnology, University of Kashmir, Jammu and Kashmir, India
| | - Izhar Rather
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Qurat Ul Ain Nazir
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Riyaz Ahmed Bhat
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Abrar Ul Haq
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Suhail Nabi Magray
- Division of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Zulfqar Haq
- ICAR-Centre for Research on Poultry, Division of Livestock Production and Management, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Ranjit Sah
- Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan (DUVASU), Mathura, Uttar Pradesh, India
| | - SenthilKumar Natesan
- Department of Infectious Diseases, Indian Institute of Public Health Gandhinagar, Gandhinagar, Gujarat, India
| | - Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, China
| | - Harapan Harapan
- Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
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50
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Liu L, Chen HG, Li Y, Li H, Li J, Wang Y, Yao S, Qin C, Tong S, Yuan X, Luo X, Miao X, Pan A, Liu Z, Cheng L. Temporal Profiles of Antibody Responses, Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort. ENGINEERING (BEIJING, CHINA) 2021; 7:958-965. [PMID: 34026297 PMCID: PMC8129785 DOI: 10.1016/j.eng.2021.04.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 04/15/2021] [Accepted: 04/21/2021] [Indexed: 05/08/2023]
Abstract
The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL-1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL-1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1β, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.
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Affiliation(s)
- Li Liu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Heng-Gui Chen
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Ying Li
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Huijun Li
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jiaoyuan Li
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yi Wang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Shuang Yao
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chuan Qin
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Shutao Tong
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xu Yuan
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xia Luo
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xiaoping Miao
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - An Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Liming Cheng
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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