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Le Stang V, Bastard P, Langouet E, Pineton de Chambrun M, Chommeloux J, Gervais A, Bizien L, Puel A, Cobat A, Mayaux J, Demoule A, Casanova JL, Boutolleau D, Combes A, Burrel S, Luyt CE. Similar Kinetics of Pulmonary SARS-CoV-2 Load in Intensive Care Unit Patients with COVID-19 Pneumonia with or Without Autoantibodies Neutralizing Type I Interferons. J Clin Immunol 2024; 45:45. [PMID: 39565497 PMCID: PMC11843546 DOI: 10.1007/s10875-024-01839-x] [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: 02/06/2024] [Accepted: 11/07/2024] [Indexed: 11/21/2024]
Abstract
PURPOSE The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear. METHODS We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020. LRT SARS-CoV-2 load (intensity and duration) was analyzed according to the presence or not of circulating auto-Abs neutralizing type I IFNs. RESULTS Among the 99 included patients, 38 (38%) were positive for auto-Abs neutralizing type I IFNs, with 5 (5%) harboring auto-Abs neutralizing IFN-α2 at any concentration, while 33 (33%) had auto-Abs neutralizing only IFN-ω at the lower concentration. SARS-CoV-2 load in the LRT and duration of viral shedding, were similar in patients with or without auto-Abs neutralizing type I IFNs. Patients with auto-Abs had the same mortality than those without auto-Abs, despite greater occurrence of renal failure and ECMO support, and longer duration of mechanical ventilation and ICU stay. CONCLUSION In summary, 5% of patients with critical COVID-19 pneumonia carried auto-Abs neutralizing IFN-α2, while about 1/3 harbored auto-Abs neutralizing low concentrations of IFN-ω. The detection of either type of auto-Abs did not impact LRT viral clearance and mortality, although it was associated with greater morbidity and a longer hospitalization. These findings suggest that similar albeit hitherto unknown mechanisms of disease drive critical COVID-19 pneumonia in patients without auto-Abs against type I IFNs.
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Affiliation(s)
- Valentine Le Stang
- Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France
| | - Paul Bastard
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
- Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistante Publique-Hôpitaux de Paris (AP-HP), Paris, EU, France
| | - Elise Langouet
- Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France
| | - Marc Pineton de Chambrun
- Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France
| | - Juliette Chommeloux
- Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France
| | - Adrian Gervais
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
| | - Lucy Bizien
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
| | - Anne Puel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
| | - Aurélie Cobat
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
| | - Julien Mayaux
- Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique- Hôpitaux de Paris, Médecine Intensive Réanimation (Département "R3S") and Sorbonne Université, INSERM, UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, Paris, France
| | - Alexandre Demoule
- Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique- Hôpitaux de Paris, Médecine Intensive Réanimation (Département "R3S") and Sorbonne Université, INSERM, UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, Paris, France
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
- Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France
- Howard Hughes Medical Institute, New York, NY, USA
| | - David Boutolleau
- Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Virologie, Centre National de Référence Herpèsvirus (laboratoire associé), Sorbonne Université, INSERM U1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France
| | - Alain Combes
- Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France
- INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Sonia Burrel
- Université de Bordeaux, CNRS UMR 5234, Fundamental Microbiology and Pathogenicity, Hôpital Universitaire de Bordeaux, Service de Virologie, Bordeaux, France
| | - Charles-Edouard Luyt
- Médecine Intensive Réanimation, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.
- INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Paris, France.
- Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, Paris Cedex 13, 75651, France.
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Pena NM, Santana LC, Hunter JR, Blum VF, Vergara T, Gouvea C, Leal E, Bellei N, Schechter M, Diaz RS. T cell-mediated Immune response and correlates of inflammation and their relationship with COVID-19 clinical severity: not an intuitive guess. BMC Infect Dis 2024; 24:612. [PMID: 38902613 PMCID: PMC11191252 DOI: 10.1186/s12879-024-09490-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 06/10/2024] [Indexed: 06/22/2024] Open
Abstract
BACKGROUND Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19. METHODS For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology. FINDINGS CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033). INTERPRETATION Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.
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Affiliation(s)
- Nathalia Mantovani Pena
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
- Weill Cornell Medicine, New York, United States of America
| | - Luiz Claudio Santana
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
| | - James R Hunter
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
| | - Vinicius Fontanesi Blum
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
| | - Tania Vergara
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
- Oncohiv, Rio de Janeiro, Brazil
| | - Celso Gouvea
- Centro de Hematologia e Hemoterapia do Ceará, Fortaleza, CE, Brazil
| | - Elcio Leal
- Laboratório de Diversidade Viral, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem, Pará, Brazil
| | - Nancy Bellei
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
| | - Mauro Schechter
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil
- Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Ricardo Sobhie Diaz
- Infectious Diseases Division, Federal University of São Paulo (UNIFESP), Pedro de Toledo, 669, Vila Clementino, Sao Paulo, SP, 04039-032, Brazil.
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Poleti ML, Gregório D, Bistaffa AGI, Vilhena FV, Simão ANC, Mori MTE, Stadtlober NP, Lozovoy MAB, da Silva Santos PS, Tatibana BT, Fernandes TMF. Can toothbrushing reduce the intraoral viral load of SARS-CoV-2? A pilot study with a dentifrice containing an antimicrobial phthalocyanine derivative. GMS HYGIENE AND INFECTION CONTROL 2024; 19:Doc32. [PMID: 38993377 PMCID: PMC11238404 DOI: 10.3205/dgkh000487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Figures] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
The aim of this study was to assess whether toothbrushing with a dentifrice containing an antimicrobial phthalocyanine derivative (APD) can reduce the intraoral viral load of SARS-CoV-2. Twenty COVID-19-positive dentate patients aged ≥18 years were selected instructed to brush their teeth for 2 min with a dentifrice containing APD. Self-collected samples of unstimulated saliva were carried out three times: T0 (baseline), T5 (5 min after toothbrushing), and T30 (30 min after toothbrushing). The analysis of viral RNA was performed by RT-qPCR for detection of three viral genes (ORF1ab, N and S genes). Results were statistically tested using Friedman's test and pairwise comparison with Bonferroni corrections, with a significance level of 5%. There was an increase in the cycle threshold (Ct) value from T0 to T5 in 13 patients (72.2%), and from T0 to T30 in 14 patients (77.8%). In two patients (11.1%) no SARS-CoV-2 was detected at T5 and five patients (27.8%) at T30. The Ct values were statistically significantly higher (p=0.020) at T30 in comparison to T0 and T5. This pilot study suggests that toothbrushing with a dentifrice containing APD could reduce the SARS-CoV-2 viral load in the oral cavity. However, further studies are needed to confirm this possible beneficial effect against SARS-CoV-2.
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Affiliation(s)
| | - Danielle Gregório
- Postgraduate Program in Dentistry, School of Dentistry, University of North Paraná – UNOPAR/UNIDERP, Londrina, Brazil
| | | | | | - Andréa Name Colado Simão
- Research Laboratory in Applied Immunology, Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Londrina, Brazil
| | - Mayara Tiemi Enokida Mori
- Research Laboratory in Applied Immunology, Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Londrina, Brazil
| | - Nicole Perugini Stadtlober
- Research Laboratory in Applied Immunology, Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Londrina, Brazil
| | - Marcell Alysson Batisti Lozovoy
- Research Laboratory in Applied Immunology, Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Londrina, Brazil
| | - Paulo Sérgio da Silva Santos
- Department of Surgery, Stomatology, Pathology, and Radiology, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | | | - Thais Maria Freire Fernandes
- Postgraduate Program in Dentistry, School of Dentistry, University of North Paraná – UNOPAR/UNIDERP, Londrina, Brazil
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Iam-Arunthai K, Chamnanchanunt S, Thungthong P, Chinapha A, Nakhahes C, Suwanban T, Umemura T. COVID-19 with high-sensitivity CRP associated with worse dynamic clinical parameters and outcomes. Front Med (Lausanne) 2024; 11:1346646. [PMID: 38711780 PMCID: PMC11073493 DOI: 10.3389/fmed.2024.1346646] [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: 11/29/2023] [Accepted: 03/26/2024] [Indexed: 05/08/2024] Open
Abstract
Objective This study aimed to evaluate the relationship between high-sensitivity C-reactive protein (hsCRP) in hospitalized COVID-19 patients and their clinical outcomes, including trajectory of hsCRP changes during hospitalization. Method and results Patients with positive COVID-19 tests between 2021 and 2023 were admitted to two hospitals. Among 184 adult patients, approximately half (47.3%) had elevated hsCRP levels upon admission, which defined as exceeding the laboratory-specific upper limit of test (> 5.0 mg/L). Clinical outcomes included critical illness, acute kidney injury, thrombotic events, intensive care unit (ICU) requirement, and death during hospitalization. Elevated hsCRP levels had a higher risk of ICU requirement than those with normal, 39.1% versus 16.5%; adjusted odds ratio (aOR), 2.3 [95% CI, 1.05-5.01]; p = 0.036. Patients with extremely high (≥2 times) hsCRP levels had aOR, 2.65 [95% CI, 1.09-6.45]; p < 0.001. On the fifth day hospitalization, patients with high hsCRP levels associated with acute kidney injury (aOR, 4.13 [95% CI, 1.30-13.08]; p = 0.016), ICU requirement (aOR, 2.67 [95%CI, 1.02-6.99]; p = 0.044), or death (aOR, 4.24 [95% CI, 1.38-12.99]; p = 0.011). The likelihood of worse clinical outcomes increased as hsCRP levels rose; patients with elevated hsCRP had lower overall survival rate than those with normal (p = 0.02). The subset of high hsCRP patients with high viral load also had a shorter half-life compared to those with normal hsCRP level (p = 0.003). Conclusion Elevated hsCRP levels were found to be a significant predictor of ICU requirement, acute kidney injury, or death within 5 days after hospitalization in COVID-19 patients. This emphasized the importance of providing more intensive care management to patients with elevated hsCRP.
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Affiliation(s)
- Kunapa Iam-Arunthai
- Division of Hematology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Supat Chamnanchanunt
- Division of Hematology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Pravinwan Thungthong
- Division of Hematology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Anongnart Chinapha
- Division of Infectious Diseases, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Chajchawan Nakhahes
- Division of Hematology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Tawatchai Suwanban
- Division of Hematology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Tsukuru Umemura
- Department of Medical Technology and Sciences, International University of Health and Welfare, Okawa, Japan
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Drouin A, Plumb ID, McCullough M, James Gist J, Liu S, Theberge M, Katz J, Moreida M, Flaherty S, Chatwani B, Briggs Hagen M, Midgley CM, Fusco D. Clinical and laboratory characteristics of patients hospitalized with severe COVID-19 in New Orleans, August 2020 to September 2021. Sci Rep 2024; 14:6539. [PMID: 38503862 PMCID: PMC10951213 DOI: 10.1038/s41598-024-57306-5] [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: 12/18/2023] [Accepted: 03/17/2024] [Indexed: 03/21/2024] Open
Abstract
Louisiana experienced high morbidity and mortality from COVID-19. To assess possible explanatory factors, we conducted a cohort study (ClinSeqSer) of patients hospitalized with COVID-19 in New Orleans during August 2020-September 2021. Following enrollment, we reviewed medical charts, and performed SARS-CoV-2 RT-PCR testing on nasal and saliva specimens. We used multivariable logistic regression to assess associations between patient characteristics and severe illness, defined as ≥ 6 L/min oxygen or intubation. Among 456 patients, median age was 56 years, 277 (60.5%) were Black non-Hispanic, 436 (95.2%) had underlying health conditions, and 358 were unvaccinated (92.0% of 389 verified). Overall, 187 patients (40.1%) had severe illness; 60 (13.1%) died during admission. In multivariable models, severe illness was associated with age ≥ 65 years (OR 2.08, 95% CI 1.22-3.56), hospitalization > 5 days after illness onset (OR 1.49, 95% CI 1.01-2.21), and SARS CoV-2 cycle threshold (Ct) result of < 32 in saliva (OR 4.79, 95% CI 1.22-18.77). Among patients who were predominantly Black non-Hispanic, unvaccinated and with underlying health conditions, approximately 1 in 3 patients had severe COVID-19. Older age and delayed time to admission might have contributed to high case-severity. An association between case-severity and low Ct value in saliva warrants further investigation.
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Affiliation(s)
- Arnaud Drouin
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70130, USA
- University Medical Center, New Orleans, LA, USA
| | - Ian D Plumb
- Applied Epidemiology Studies Team, Epidemiology Branch, and on detail to the Global Respiratory Viruses Branch Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control, Atlanta, GA, USA
| | | | | | - Sharon Liu
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70130, USA
| | - Marc Theberge
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70130, USA
| | - Joshua Katz
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70130, USA
| | - Matthew Moreida
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70130, USA
| | - Shelby Flaherty
- School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
| | - Bhoomija Chatwani
- School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
| | - Melissa Briggs Hagen
- Applied Epidemiology Studies Team, Epidemiology Branch, and on detail to the Global Respiratory Viruses Branch Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control, Atlanta, GA, USA
| | - Claire M Midgley
- Applied Epidemiology Studies Team, Epidemiology Branch, and on detail to the Global Respiratory Viruses Branch Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control, Atlanta, GA, USA
| | - Dahlene Fusco
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70130, USA.
- University Medical Center, New Orleans, LA, USA.
- School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
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de Nooijer AH, Pickkers P, Netea MG, Kox M. Inflammatory biomarkers to predict the prognosis of acute bacterial and viral infections. J Crit Care 2023; 78:154360. [PMID: 37343422 DOI: 10.1016/j.jcrc.2023.154360] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/07/2023] [Indexed: 06/23/2023]
Abstract
Mortality in acute infections is mostly associated with sepsis, defined as 'life-threatening organ dysfunction caused by a dysregulated host response to infection'. It remains challenging to identify the patients with increased mortality risk due to the high heterogeneity in the dysregulated host immune response and disease progression. Biomarkers reflecting different pathways involved in the inflammatory response might improve prediction of mortality risk (prognostic enrichment) among patients with acute infections by reducing heterogeneity of the host response, as well as suggest novel strategies for patient stratification and treatment (predictive enrichment) through precision medicine approaches. The predictive value of inflammatory biomarkers has been extensively investigated in bacterial infections and the recent COVID-19 pandemic caused an increased interest in inflammatory biomarkers in this viral infection. However, limited research investigated whether the prognostic potential of these biomarkers differs between bacterial and viral infections. In this narrative review, we provide an overview of the value of various inflammatory biomarkers for the prediction of mortality in bacterial and viral infections.
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Affiliation(s)
- Aline H de Nooijer
- Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Intensive Care Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands
| | - Mihai G Netea
- Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany
| | - Matthijs Kox
- Department of Intensive Care Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
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Harrison RE, Hamada A, Haswell N, Groves A, Vihta KD, Cella K, Garner S, Walker AS, Seale AC. Cycle Threshold Values as Indication of Increasing SARS-CoV-2 New Variants, England, 2020-2022. Emerg Infect Dis 2023; 29:2024-2031. [PMID: 37678158 PMCID: PMC10521603 DOI: 10.3201/eid2910.230030] [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] [Indexed: 09/09/2023] Open
Abstract
Early detection of increased infections or new variants of SARS-CoV-2 is critical for public health response. To determine whether cycle threshold (Ct) data from PCR tests for SARS-CoV-2 could serve as an early indicator of epidemic growth, we analyzed daily mean Ct values in England, UK, by gene target and used iterative sequential regression to detect break points in mean Ct values (and positive test counts). To monitor the epidemic in England, we continued those analyses in real time. During September 2020-January 2022, a total of 7,611,153 positive SARS-CoV-2 PCR test results with Ct data were reported. Spike (S) gene target (S+/S-)-specific mean Ct values decreased 6-29 days before positive test counts increased, and S-gene Ct values provided early indication of increasing new variants (Delta and Omicron). Our approach was beneficial in the context of the first waves of the COVID-19 pandemic and can be used to support future infectious disease monitoring.
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Zhou Z, Li D, Zhao Z, Shi S, Wu J, Li J, Zhang J, Gui K, Zhang Y, Ouyang Q, Mei H, Hu Y, Li F. Dynamical modelling of viral infection and cooperative immune protection in COVID-19 patients. PLoS Comput Biol 2023; 19:e1011383. [PMID: 37656752 PMCID: PMC10501599 DOI: 10.1371/journal.pcbi.1011383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 09/14/2023] [Accepted: 07/24/2023] [Indexed: 09/03/2023] Open
Abstract
Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.
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Affiliation(s)
- Zhengqing Zhou
- School of Physics, Center for Quantitative Biology, Peking University, Beijing, China
| | - Dianjie Li
- School of Physics, Center for Quantitative Biology, Peking University, Beijing, China
| | - Ziheng Zhao
- Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
| | - Shuyu Shi
- Peking University Third Hospital, Peking University, Beijing, China
| | - Jianghua Wu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianwei Li
- School of Physics, Center for Quantitative Biology, Peking University, Beijing, China
| | - Jingpeng Zhang
- School of Physics, Center for Quantitative Biology, Peking University, Beijing, China
| | - Ke Gui
- Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
| | - Yu Zhang
- Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
| | - Qi Ouyang
- School of Physics, Center for Quantitative Biology, Peking University, Beijing, China
| | - Heng Mei
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Hu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fangting Li
- School of Physics, Center for Quantitative Biology, Peking University, Beijing, China
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Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19. Viruses 2023; 15:v15020485. [PMID: 36851699 PMCID: PMC9959293 DOI: 10.3390/v15020485] [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: 11/23/2022] [Revised: 01/27/2023] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
Emerging evidence shows that individuals with COVID-19 who survive the acute phase of illness may experience lingering symptoms in the following months. There is no clear indication as to whether these symptoms persist for a short time before resolving or if they persist for a long time. In this review, we will describe the symptoms that persist over time and possible predictors in the acute phase that indicate long-term persistence. Based on the literature available to date, fatigue/weakness, dyspnea, arthromyalgia, depression, anxiety, memory loss, slowing down, difficulty concentrating and insomnia are the most commonly reported persistent long-term symptoms. The extent and persistence of these in long-term follow-up is not clear as there are still no quality studies available. The evidence available today indicates that female subjects and those with a more severe initial disease are more likely to suffer permanent sequelae one year after the acute phase. To understand these complications, and to experiment with interventions and treatments for those at greater risk, we must first understand the physio-pathological mechanisms that sustain them.
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10
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Hastie E, Amogan H, Looney D, Mehta SR. Association between SARS-CoV-2 Viral Load and Patient Symptoms and Clinical Outcomes Using Droplet Digital PCR. Viruses 2023; 15:446. [PMID: 36851660 PMCID: PMC9961727 DOI: 10.3390/v15020446] [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: 12/06/2022] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open
Abstract
The association between nasopharyngeal (NP) SARS-CoV-2 viral loads and clinical outcomes remains debated. Here, we examined the factors that might predict the NP viral load and the role of the viral load as a predictor of clinical outcomes. A convenience sample of 955 positive remnant NP swab eluent samples collected during routine care between 18 November 2020 and 26 September 2021 was cataloged and a chart review was performed. For non-duplicate samples with available demographic and clinical data (i.e., non-employees), an aliquot of eluent was sent for a droplet digital PCR quantification of the SARS-CoV-2 viral load. Univariate and multivariate analyses were performed to identify the clinical predictors of NP viral loads and the predictors of COVID-19-related clinical outcomes. Samples and data from 698 individuals were included in the final analysis. The sample cohort had a mean age of 50 years (range: 19-91); 86.6% were male and 76.3% were unvaccinated. The NP viral load was higher in people with respiratory symptoms (p = 0.0004) and fevers (p = 0.0006). In the predictive models for the clinical outcomes, the NP viral load approached a significance as a predictor for in-hospital mortality. In conclusion, the NP viral load did not appear to be a strong predictor of moderate-to-severe disease in the pre-Delta and Delta phases of the pandemic, but was predictive of symptomatic diseases and approached a significance for in-hospital mortality, providing support to the thesis that early viral control prevents the progression of disease.
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Affiliation(s)
- Elizabeth Hastie
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92039, USA
| | - Harold Amogan
- Veterans Medical Research Foundation, San Diego, CA 92161, USA
| | - David Looney
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92039, USA
- San Diego Veterans Affairs Medical Center, Department of Medicine, San Diego, CA 92161, USA
| | - Sanjay R. Mehta
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92039, USA
- San Diego Veterans Affairs Medical Center, Department of Medicine, San Diego, CA 92161, USA
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11
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Ontiveros N, Del Bosque-Aguirre A, Gonzalez-Urquijo M, Hinojosa Gonzalez DE, Martinez-Resendez MF, Schang L, Fabiani MA. Nasopharyngeal viral load at admission is not an independent predictor of thromboembolic complications in unvaccinated COVID-19 hospitalized patients. J Thromb Thrombolysis 2023; 55:282-288. [PMID: 36564590 PMCID: PMC9789302 DOI: 10.1007/s11239-022-02762-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2022] [Indexed: 12/25/2022]
Abstract
COVID-19 patients may develop thrombotic complications, and data regarding an association between nasopharyngeal viral load and thrombosis is scarce. The aim of our study was to evaluate whether SARS-CoV-2 nasopharyngeal viral load upon admission is a useful prognostic marker for the development of thromboembolic events in patients hospitalized for SARS-CoV-2 infection. We performed a retrospective study of all hospitalized patients with a positive PCR test for SARS-CoV2 who had deep vein thrombosis (DVT), pulmonary embolization (PE), or arterial thrombosis diagnosed during their clinical course in a single academic center. The study population was divided according to the cycle threshold (Ct) value upon admission in patients with high viral load (Ct < 25), intermediate/medium viral load (Ct 25-30), and low viral load (Ct > 30). A regression model for propensity was performed matching in a 1:3 ratio those patients who had a thrombotic complication to those who did not. Among 2,000 hospitalized COVID-19 patients, 41 (2.0%) developed thrombotic complications. Of these, 21 (51.2%) were diagnosed with PE, eight (19.5%) were diagnosed with DVT, and 12 (29.2%) were diagnosed with arterial thrombosis. Thrombotic complications occurred as frequently among the nasopharyngeal viral load or severity stratification groups with no statistically significant differences. Univariate logistic regression revealed increased odds for thrombosis only in mechanically ventilated patients OR 3.10 [1.37, 7.03] (p = 0.007). Admission SARS-CoV-2 nasopharyngeal viral loads, as determined by Ct values, were not independently associated with thromboembolic complications among hospitalized patients with COVID-19.
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Affiliation(s)
- Narda Ontiveros
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Dr. Ignacio Morones Prieto O 3000, 64710 Monterrey, Nuevo León México
| | - Adolfo Del Bosque-Aguirre
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Dr. Ignacio Morones Prieto O 3000, 64710 Monterrey, Nuevo León México
| | - Mauricio Gonzalez-Urquijo
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Dr. Ignacio Morones Prieto O 3000, 64710 Monterrey, Nuevo León México
| | - David E. Hinojosa Gonzalez
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Dr. Ignacio Morones Prieto O 3000, 64710 Monterrey, Nuevo León México
| | - Michel Fernando Martinez-Resendez
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Dr. Ignacio Morones Prieto O 3000, 64710 Monterrey, Nuevo León México
| | - Luis Schang
- Department of Microbiology and Immunology, Baker Institute for Animal Health, Cornell Universit, 235 Hungerford Hill Road, Ithaca, NY 14853 USA
| | - Mario Alejandro Fabiani
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Dr. Ignacio Morones Prieto O 3000, 64710 Monterrey, Nuevo León México
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12
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Papan C, Argentiero A, Adams O, Porwoll M, Hakim U, Farinelli E, Testa I, Pasticci MB, Mezzetti D, Perruccio K, Simon A, Liese JG, Knuf M, Stein M, Yacobov R, Bamberger E, Schneider S, Esposito S, Tenenbaum T. Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study. J Med Virol 2023; 95:e28113. [PMID: 36043485 DOI: 10.1002/jmv.28113] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.
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Affiliation(s)
- Cihan Papan
- Paediatric Infectious Diseases, Department of Paediatrics, University Children's Hospital Mannheim, Heidelberg University, Mannheim, Germany.,Centre for Infectious Diseases, Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany
| | - Alberto Argentiero
- Department of Surgical and Biomedical Sciences, Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy
| | - Ortwin Adams
- Institute of Virology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Marian Porwoll
- Paediatric Infectious Diseases, Department of Paediatrics, University Children's Hospital Mannheim, Heidelberg University, Mannheim, Germany
| | - Ummaya Hakim
- Paediatric Infectious Diseases, Department of Paediatrics, University Children's Hospital Mannheim, Heidelberg University, Mannheim, Germany
| | - Edoardo Farinelli
- Department of Surgical and Biomedical Sciences, Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy
| | - Ilaria Testa
- Department of Surgical and Biomedical Sciences, Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy
| | - Maria B Pasticci
- Department of Surgical and Biomedical Sciences, Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy
| | - Daniele Mezzetti
- Department of Surgical and Biomedical Sciences, Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy
| | - Katia Perruccio
- Department of Surgical and Biomedical Sciences, Santa Maria della Misericordia Hospital, Università degli Studi di Perugia, Perugia, Italy
| | - Arne Simon
- Department of Paediatric Oncology and Haematology, Saarland University Hospital, Homburg, Germany
| | - Johannes G Liese
- Department of Paediatrics, University of Würzburg, Würzburg, Germany
| | - Markus Knuf
- Department of Paediatrics, Children's Hospital, Helios Dr. Horst Schmidt Klinik, Wiesbaden, Germany.,Department of Paediatrics, University Medicine, Mainz, Germany
| | | | | | - Ellen Bamberger
- Technion-Israel Institute of Technology, Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.,Department of Paediatrics, Bnai-Zion Medical Center, Haifa, Israel
| | - Sven Schneider
- Institute for Clinical Chemistry, University of Heidelberg, Mannheim, Germany
| | - Susanna Esposito
- Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
| | - Tobias Tenenbaum
- Paediatric Infectious Diseases, Department of Paediatrics, University Children's Hospital Mannheim, Heidelberg University, Mannheim, Germany.,Clinic for Child and Adolescent Medicine, Sana Klinikum Lichtenberg, Academic Teaching Hospital, Charité-Universitätsmedizin, Berlin, Germany
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13
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Sturmberg J, Paul E, Van Damme W, Ridde V, Brown GW, Kalk A. The danger of the single storyline obfuscating the complexities of managing SARS-CoV-2/COVID-19. J Eval Clin Pract 2022; 28:1173-1186. [PMID: 34825442 DOI: 10.1111/jep.13640] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/11/2021] [Accepted: 11/12/2021] [Indexed: 12/15/2022]
Abstract
Chimamanda Ngozi Adichie showed how a single story is limited and thereby distorts the true nature of an issue. During this COVID-19 pandemic there have been, at least, three consecutive single stories-the 'lethal threat' story, followed by the 'economic threat' story, and finally the 'vaccine miracle' story. None of these single stories can convincingly and permanently capture the dynamics of the pandemic. This is because countries experienced different morbidity and mortality patterns, different socioeconomic disadvantage, age and vulnerability of population, timing and level of lockdown with economic variability, and, despite heavy promotion, vaccines were beset with a significant and variable degree of hesitancy. Lack of transparency, coherence and consistency of pandemic management-arising from holding on to single storylines-showed the global deficiency of public health policy and planning, an underfunding of (public) health and social services, and a growing distrust in governments' ability to manage crises effectively. Indeed, the global management has increased already large inequities, and little has been learnt to address the growing crises of more infectious and potentially more lethal virus mutations. Holding onto single stories prevents the necessary learnings to understand and manage the complexities of 'wicked' problems, whereas listening to the many stories provides insights and pathways to do so effectively as well as efficiently.
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Affiliation(s)
- Joachim Sturmberg
- Discipline of General Practice, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, New South Wales, Australia.,Foundation President-International Society for Systems and Complexity Sciences for Health
| | - Elisabeth Paul
- School of Public Health, Université Libre de Bruxelles, Brussels, Belgium
| | - Wim Van Damme
- Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
| | - Valery Ridde
- CEPED, Institute for Research on Sustainable Development (IRD), ERL INSERM SAGESUD, IRD-Université de Paris, Paris, France
| | - Garrett W Brown
- Colead-Global Health, School of Politics and International Studies (POLIS), University of Leeds, Leeds, UK
| | - Andreas Kalk
- Kinshasa Country Office, Deutsche Gesellschaft für Internationale Zusammenarbeit, Kinshasa, Democratic Republic of the Congo
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14
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Dos Santos PG, Vieira HCVS, Wietholter V, Gallina JP, Andrade TR, Marinowic DR, Zanirati GG, da Costa JC. When to test for COVID-19 using real-time reverse transcriptase polymerase chain reaction: a systematic review. Int J Infect Dis 2022; 123:58-69. [PMID: 35760382 PMCID: PMC9233872 DOI: 10.1016/j.ijid.2022.06.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/18/2022] [Accepted: 06/21/2022] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The aim of this study was to evaluate the time in days between symptom onset and first positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) result for COVID-19. METHODS This systematic review was conducted in the MEDLINE (PubMed), Embase, and Scopus databases using the following descriptors: "COVID-19", "SARS-CoV-2", "coronavirus", "RT-PCR", "real time PCR", and "diagnosis". RESULTS The included studies were conducted in 31 different countries and reported on a total of 6831 patients. The median age of the participants was 49.95 years. The three most common symptoms were fever, cough, and dyspnea, which affected 4012 (58.68%), 3192 (46.69%), and 2009 patients (29.38%), respectively. Among the 90 included studies, 13 were prospective cohorts, 15 were retrospective cohorts, 36 were case reports, 20 were case series, and six were cross-sectional studies. The overall mean time between symptom onset and positive test result was 6.72 days. Fourteen articles were analyzed separately for the temporal profile of RT-PCR test results; the best performance was on days 22-24, when 98% of test results were positive. CONCLUSION These findings corroborate the RT-PCR COVID-19 testing practices of some health units. In addition, the most frequently described symptoms of these patients can be considered the initial symptoms of infection and used in decision-making about RT-PCR testing.
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Affiliation(s)
- Paula Gabrielli Dos Santos
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Biomedical Gerontology, Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil
| | - Helena Cristina Valentini Speggiorin Vieira
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Vinícius Wietholter
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - João Pedro Gallina
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Thomás Ranquetat Andrade
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Daniel Rodrigo Marinowic
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Biomedical Gerontology, Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil
| | - Gabriele Goulart Zanirati
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil
| | - Jaderson Costa da Costa
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Biomedical Gerontology, Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil.
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15
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Wick KD, Leligdowicz A, Willmore A, Carrillo SA, Ghale R, Jauregui A, Chak SS, Nguyen V, Lee D, Jones C, Dewar R, Lane HC, Kangelaris KN, Hendrickson CM, Liu KD, Sinha P, Erle DJ, Langelier CR, Krummell MF, Woodruff PG, Calfee CS, Matthay MA. Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19. Crit Care 2022; 26:278. [PMID: 36104754 PMCID: PMC9472195 DOI: 10.1186/s13054-022-04153-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 08/22/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. METHODS SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived "high antigen" cutoff of N-antigen ≥ 1000 pg/mL was also tested. RESULTS N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03-1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. CONCLUSIONS Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.
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Affiliation(s)
- Katherine D Wick
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
| | - Aleksandra Leligdowicz
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Division of Critical Care, Departments of Medicine and Microbiology and Immunology, Western University, London, ON, Canada
- Robarts Research Institute, Western University, London, ON, Canada
| | - Andrew Willmore
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Sidney A Carrillo
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Rajani Ghale
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Alejandra Jauregui
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Suzanna S Chak
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Viet Nguyen
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, USA
| | - Deanna Lee
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, USA
| | - Chayse Jones
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Robin Dewar
- Virus Isolation and Serology Laboratory, Applied and Developmental Directorate, Frederick National Laboratory, Frederick, MD, USA
| | - H Clifford Lane
- Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Kirsten N Kangelaris
- Department of Hospital Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Carolyn M Hendrickson
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, USA
| | - Kathleen D Liu
- Division of Nephrology, Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA
- Division of Critical Care Medicine, Department of Anesthesia, University of California San Francisco School of Medicine, San Francisco, CA, USA
| | - Pratik Sinha
- Department of Anesthesia, Division of Critical Care, Washington University, St. Louis, MO, USA
- Division of Clinical and Translational Research, Washington University School of Medicine, St. Louis, MO, USA
| | - David J Erle
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Lung Biology Center, University of California San Francisco, San Francisco, CA, USA
- ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA
- UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA
| | - Charles R Langelier
- Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA
- Chan Zuckerberg Biohub, University of California San Francisco, San Francisco, CA, USA
| | - Matthew F Krummell
- ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA
- Departments of Medicine and Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Prescott G Woodruff
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Carolyn S Calfee
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Michael A Matthay
- Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA
- Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA, USA
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16
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Leowattana W, Leowattana T, Leowattana P. SARS-CoV-2 viral load in the upper respiratory tract and disease severity in COVID-19 patients. World J Meta-Anal 2022; 10:195-205. [DOI: 10.13105/wjma.v10.i4.195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/23/2022] [Accepted: 07/27/2022] [Indexed: 02/05/2023] Open
Abstract
Due to the disease's broad clinical spectrum, it is currently unclear how to predict the future prognosis of patients at the time of diagnosis of coronavirus disease 2019 (COVID-19). Real-time reverse transcription-polymerase chain reaction (RT-PCR) is the gold standard molecular technique for diagnosing COVID-19. The number of amplification cycles necessary for the target genes to surpass a threshold level is represented by the RT-PCR cycle threshold (Ct) values. Ct values were thought to be an adequate proxy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load. A body of evidence suggests that SARS-CoV-2 viral load is a possible predictor of COVID-19 severity. The link between SARS-CoV-2 viral load and the likelihood of severe disease development in COVID-19 patients is not clearly elucidated. In this review, we describe the scientific data as well as the important findings from many clinical studies globally, emphasizing how viral load may be related to disease severity in COVID-19 patients. Most of the evidence points to the association of SARS-CoV-2 viral load and disease severity in these patients, and early anti-viral treatment will reduce the severe clinical outcomes.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand
| | - Pathomthep Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
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17
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Duan R, Mao Q, Ding X, Qiu Q, Wang P. Immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults. Immun Inflamm Dis 2022; 10:e670. [PMID: 35759224 PMCID: PMC9210569 DOI: 10.1002/iid3.670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 05/23/2022] [Accepted: 06/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Asymptomatic infections may play an important role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Delta variant transmissions. However, the immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults remain to be defined. METHODS A retrospective study involving 36 vaccinated adults infected with the SARS-CoV-2 Delta variant was performed. Their demographic and laboratory data were collected and analyzed in The First People's Hospital of Jingmen from August 4 to 20, 2021. RESULTS Of the 36 adults, 6 persons had an asymptomatic infection. The severity of the SARS-CoV-2 infections was highly correlated with the doses of vaccinations (p = 0.019). The symptomatic and asymptomatic infected SARS-CoV-2 adults showed normal levels of leukocytes and lymphocytes. The C-reactive protein (CRP) and interleukin-6 (IL-6) levels were elevated in the symptomatic groups. The period between the last vaccination to the time of infection in the asymptomatic group was longer than that in the mild and moderate groups (73 vs. 61 vs. 50 days; p = 0.047). The percentage of suppressor T-cells in the asymptomatic group was the highest (32.2 ± 4.0% vs. 22.0 ± 7.2% vs. 29.3 ± 8.0%; p = 0.004). The signal-to-cutoff ratio value of total antibody against SARS-CoV-2 in the asymptomatic group was lower than that in the other two groups (383 vs. 703 vs. 1792; p < 0.001) and much lower than that in the moderate group. The multivariate ordinal logistic analysis after adjusting for gender, vaccination date, and vaccination dose indicated that CRP at Days 4-7 and 8-14, IL-6 on Days 4-7, and total antibody were risk factors for coronavirus disease 2019 severity. CONCLUSIONS Asymptomatic postvaccination infections with the Delta variant of SARS-CoV-2 in adults tend to infect persons vaccinated twice. The immunophenotype profile for asymptomatic postvaccination infections is less inflammatory and accompanied by relatively lower antibody titers.
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Affiliation(s)
- Rui Duan
- Department of Laboratory Medicine and Blood TransfusionThe First People's Hospital of JingmenHubeiChina
| | - Qiang Mao
- Department of Medical Records and StatisticsThe First People's Hospital of JingmenHubeiChina
| | - Xu Ding
- Department of Laboratory Medicine and Blood TransfusionThe First People's Hospital of JingmenHubeiChina
| | - Qiwu Qiu
- Department of Infectious DiseasesThe First People's Hospital of JingmenHubeiChina
| | - Pei Wang
- Department of Laboratory Medicine and Blood TransfusionThe First People's Hospital of JingmenHubeiChina
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18
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Ernest CS, Chien JY, Patel DR, Chigutsa E. PK/PD modeling links accelerated resolution of COVID‐19‐related clinical symptoms to SARS‐CoV‐2 viral load reduction in patients following treatment with Bamlanivimab alone or Bamlanivimab and Etesevimab together. CPT Pharmacometrics Syst Pharmacol 2022; 11:721-730. [PMID: 35289125 PMCID: PMC9111027 DOI: 10.1002/psp4.12784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 12/03/2022] Open
Abstract
The relationship between severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral load reduction and disease symptom resolution remains largely undefined for coronavirus disease 2019 (COVID‐19). While the vaccine‐derived immunity takes time to develop, neutralizing monoclonal antibodies offer immediate, passive immunity to patients with COVID‐19. Bamlanivimab and etesevimab are two potent neutralizing monoclonal antibodies directed to the receptor binding domain of the spike protein of SARS‐CoV‐2. This study aims to describe the relationship between viral load and resolution of eight common COVID‐19‐related symptoms in patients following treatment with neutralizing monoclonal antibodies (bamlanivimab alone or bamlanivimab and etesevimab together), in a phase II clinical trial. Corresponding pharmacokinetics (PKs), viral load, and COVID‐19‐related symptom data were modeled using Nonlinear Mixed Effects Modeling to describe the time‐course of eight COVID‐19‐related symptoms in an ordered categorical manner (none, mild, moderate, and severe), following administration of bamlanivimab or bamlanivimab and etesevimab together to participants with COVID‐19. The PK/pharmacodynamic (PD) models characterized the exposure‐viral load‐symptom time course of the eight preselected COVID‐19‐related symptoms. Baseline viral load (BVL), change in viral load from baseline, and time since the onset of symptoms, demonstrated statistically significant effects on symptom score probabilities. Higher BVL generally indicated an increased probability of symptom severity. The severity of symptoms decreased over time, partially driven by the decrease in viral load. The effect of increasing time resulting in decreased severity of symptoms was over and above the effect of decreasing viral load. Administration of bamlanivimab alone or together with etesevimab results in a faster time to resolution of COVID‐19‐related symptoms compared to placebo.
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19
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Dadras O, Afsahi AM, Pashaei Z, Mojdeganlou H, Karimi A, Habibi P, Barzegary A, Fakhfouri A, Mirzapour P, Janfaza N, Dehghani S, Afroughi F, Dashti M, Khodaei S, Mehraeen E, Voltarelli F, Sabatier J, SeyedAlinaghi S. The relationship between COVID-19 viral load and disease severity: A systematic review. Immun Inflamm Dis 2022; 10:e580. [PMID: 34904379 PMCID: PMC8926507 DOI: 10.1002/iid3.580] [Citation(s) in RCA: 93] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/14/2021] [Accepted: 11/22/2021] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Patients with COVID-19 may present different viral loads levels. However, the relationship between viral load and disease severity in COVID-19 is still unknown. Therefore, this study aimed to systematically review the association between SARS-CoV-2 viral load and COVID-19 severity. METHODS The relevant studies using the keywords of "COVID-19" and "viral load" were searched in the databases of PubMed, Scopus, Google Scholar, and Web of Science. A two-step title/abstract screening process was carried out and the eligible studies were included in the study. RESULTS Thirty-four studies were included from the initial 1015 records. The vast majority of studies have utilized real-time reverse transcription-polymerase chain reaction of the nasopharyngeal/respiratory swabs to report viral load. Viral loads were commonly reported either as cycle threshold (Ct ) or log10 RNA copies/ml. CONCLUSION The results were inconclusive about the relationship between COVID-19 severity and viral load, as a similar number of studies either approved or opposed this hypothesis. However, the studies denote the direct relationship between older age and higher SARS-CoV-2 viral load, which is a known risk factor for COVID-19 mortality. The higher viral load in older patients may serve as a mechanism for any possible relationships between COVID-19 viral load and disease severity. There was a positive correlation between SARS-CoV-2 viral load and its transmissibility. Nonetheless, further studies are recommended to precisely characterize this matter.
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Affiliation(s)
- Omid Dadras
- The Excellent Center for Dengue and Community Public Health (EC for DACH), School of Public HealthWalailak UniversityNakhon Si ThammaratThailand
| | - Amir M. Afsahi
- Department of Radiology, School of MedicineUniversity of California, San Diego (UCSD)La JollaCaliforniaUSA
| | - Zahra Pashaei
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High‐Risk BehaviorsTehran University of Medical SciencesTehranIran
| | | | - Amirali Karimi
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Pedram Habibi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High‐Risk BehaviorsTehran University of Medical SciencesTehranIran
| | | | | | - Pegah Mirzapour
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High‐Risk BehaviorsTehran University of Medical SciencesTehranIran
| | - Nazanin Janfaza
- Internal Medicine Department, Imam Khomeini Hospital Complex, School of MedicineTehran University of Medical SciencesTehranIran
| | - Soheil Dehghani
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Fatemeh Afroughi
- School of MedicineIslamic Azad UniversityTehranIran
- Pars HospitalIran University of Medical SciencesTehranIran
| | - Mohsen Dashti
- Department of RadiologyTabriz University of Medical SciencesTabrizIran
| | - Sepideh Khodaei
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High‐Risk BehaviorsTehran University of Medical SciencesTehranIran
| | - Esmaeil Mehraeen
- Department of Health Information TechnologyKhalkhal University of Medical SciencesKhalkhalIran
| | - Fabricio Voltarelli
- Graduation Program of Health Sciences, Faculty of MedicineFederal University of Mato GrossoCuiabáBrazil
| | - Jean‐Marc Sabatier
- Université Aix‐MarseilleInstitut deNeuro‐physiopathologie (INP)UMR 7051, Faculté de PharmacieMarseilleFrance
| | - SeyedAhmad SeyedAlinaghi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High‐Risk BehaviorsTehran University of Medical SciencesTehranIran
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20
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Kim M, Linstadt RTH, Ahn Ando K, Ahn J. Gemini-Mediated Self-Disinfecting Surfaces to Address the Contact Transmission of Infectious Diseases. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2022; 38:2162-2173. [PMID: 35108488 DOI: 10.1021/acs.langmuir.1c03401] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
According to both the Center for Disease Control and the World Health Organization, contact transmission is the primary transmission route of infectious diseases worldwide. Usually, this is mitigated by a schedule of repeated regular sanitization, yet surfaces are easily re-contaminated in the interim between cleanings. One solution to this problem is to generate self-disinfecting surfaces that can display sustained virucidal/antimicrobial properties against pathogens that settle upon them. Quaternary ammonium organosilicon compounds are ideal candidates to achieve this; cationic surfactants are safe and well-established surface disinfectants, while organosilanes are used broadly to form durable coatings with altered surface properties on many different materials. Despite their potential to circumvent the disadvantages of traditional disinfection methods, extant commercially available quaternary ammonium silanes do not display comparable efficacy to the standard surface disinfectants, nor have their respective coatings been demonstrated to meet the Environmental Protection Agency's guidelines for residual/extended efficacy. Inspired by the powerful surface activity of double-headed "gemini" surfactants, here, we present gemini-diquaternary silanes (GQs) with robust residual germicidal efficacy on various surfaces by incorporating a second cationic "head" to the structure of a conventional monoquaternary ammonium silane (MQ). Aqueous solutions of GQs were tested in suspension- and surface-antimicrobial assays against an array of pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). GQ performance was benchmarked against the common disinfectants, ethanol, hydrogen peroxide, hypochlorite, as well as MQ. Solutions of GQs were efficacious when used for immediate disinfection (>106-fold reduction in 15 s). Additionally, GQs were demonstrated to impart durable self-disinfecting properties to a variety of porous and nonporous surfaces, effective after repeated cycles of abrasion and repeated contaminations, and with superior coating ability and activity (>108 higher activity) than that of MQs. GQs as surface treatments show great promise to overcome the limitations of traditional disinfectants in preventing the spread of infectious diseases.
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Affiliation(s)
- MinJu Kim
- Dental Research Institute and Department of Dental Biomaterials Science, Seoul National University School of Dentistry, Seoul 03080, South Korea
| | - Roscoe T H Linstadt
- Marine Science Institute, University of California, Santa Barbara, California 93106, United States
- ACatechol, Inc., Santa Barbara, California 93103, United States
| | - Kollbe Ahn Ando
- Marine Science Institute, University of California, Santa Barbara, California 93106, United States
- ACatechol, Inc., Santa Barbara, California 93103, United States
| | - Jinsoo Ahn
- Dental Research Institute and Department of Dental Biomaterials Science, Seoul National University School of Dentistry, Seoul 03080, South Korea
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21
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da Silva SJR, de Lima SC, da Silva RC, Kohl A, Pena L. Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants. Front Med (Lausanne) 2022; 8:836826. [PMID: 35174189 PMCID: PMC8841511 DOI: 10.3389/fmed.2021.836826] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 12/29/2021] [Indexed: 12/14/2022] Open
Abstract
The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented public health crisis in the 21st century. As the pandemic evolves, the emergence of SARS-CoV-2 has been characterized by the emergence of new variants of concern (VOCs), which resulted in a catastrophic impact on SARS-CoV-2 infection. In light of this, research groups around the world are unraveling key aspects of the associated illness, coronavirus disease 2019 (COVID-19). A cumulative body of data has indicated that the SARS-CoV-2 viral load may be a determinant of the COVID-19 severity. Here we summarize the main characteristics of the emerging variants of SARS-CoV-2, discussing their impact on viral transmissibility, viral load, disease severity, vaccine breakthrough, and lethality among COVID-19 patients. We also provide a rundown of the rapidly expanding scientific evidence from clinical studies and animal models that indicate how viral load could be linked to COVID-19 prognosis and vaccine efficacy among vaccinated individuals, highlighting the differences compared to unvaccinated individuals.
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Affiliation(s)
- Severino Jefferson Ribeiro da Silva
- Laboratory of Virology and Experimental Therapy (LAVITE), Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
| | - Suelen Cristina de Lima
- Laboratory of Virology and Experimental Therapy (LAVITE), Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil
| | - Ronaldo Celerino da Silva
- Laboratory of Virology and Experimental Therapy (LAVITE), Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil
| | - Alain Kohl
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
| | - Lindomar Pena
- Laboratory of Virology and Experimental Therapy (LAVITE), Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil
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22
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Kawasuji H, Morinaga Y, Tani H, Yoshida Y, Takegoshi Y, Kaneda M, Murai Y, Kimoto K, Ueno A, Miyajima Y, Fukui Y, Kimura M, Yamada H, Sakamaki I, Yamamoto Y. SARS-CoV-2 RNAemia with a higher nasopharyngeal viral load is strongly associated with disease severity and mortality in patients with COVID-19. J Med Virol 2022; 94:147-153. [PMID: 34411312 PMCID: PMC8426802 DOI: 10.1002/jmv.27282] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 08/14/2021] [Indexed: 12/15/2022]
Abstract
This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/μl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/μl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/μl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/μl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.
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Affiliation(s)
- Hitoshi Kawasuji
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Yoshitomo Morinaga
- Department of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Hideki Tani
- Department of VirologyToyama Institute of HealthToyamaJapan
| | - Yoshihiro Yoshida
- Department of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Yusuke Takegoshi
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Makito Kaneda
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Yushi Murai
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Kou Kimoto
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Akitoshi Ueno
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Yuki Miyajima
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Yasutaka Fukui
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Miyuki Kimura
- Department of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Hiroshi Yamada
- Department of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Ippei Sakamaki
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Yoshihiro Yamamoto
- Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
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23
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Satlin MJ, Zucker J, Baer BR, Rajan M, Hupert N, Schang LM, Pinheiro LC, Shen Y, Sobieszczyk ME, Westblade LF, Goyal P, Wells MT, Sepulveda JL, Safford MM. Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City. PLoS One 2021; 16:e0257979. [PMID: 34797838 PMCID: PMC8604305 DOI: 10.1371/journal.pone.0257979] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/14/2021] [Indexed: 12/15/2022] Open
Abstract
Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.
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Affiliation(s)
- Michael J. Satlin
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, United States of America
- * E-mail:
| | - Jason Zucker
- Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, United States of America
| | - Benjamin R. Baer
- Department of Statistics and Data Science, Cornell University, Ithaca, New York, United States of America
| | - Mangala Rajan
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
| | - Nathaniel Hupert
- Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, United States of America
- Cornell Institute for Disease and Disaster Preparedness, New York, New York, United States of America
| | - Luis M. Schang
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Laura C. Pinheiro
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
| | - Yanhan Shen
- Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, United States of America
- Department of Epidemiology and Biostatistics, CUNY Graduate School of Public Health and Health Policy, New York, New York, United States of America
| | - Magdalena E. Sobieszczyk
- Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, United States of America
| | - Lars F. Westblade
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, United States of America
| | - Parag Goyal
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
- Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
| | - Martin T. Wells
- Department of Statistics and Data Science, Cornell University, Ithaca, New York, United States of America
- Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, New York, United States of America
| | - Jorge L. Sepulveda
- Department of Pathology, George Washington University, Washington, DC, United States of America
| | - Monika M. Safford
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
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24
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Soria ME, Cortón M, Martínez-González B, Lobo-Vega R, Vázquez-Sirvent L, López-Rodríguez R, Almoguera B, Mahillo I, Mínguez P, Herrero A, Taracido JC, Macías-Valcayo A, Esteban J, Fernandez-Roblas R, Gadea I, Ruíz-Hornillos J, Ayuso C, Perales C. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease. Access Microbiol 2021; 3:000259. [PMID: 34712904 PMCID: PMC8549390 DOI: 10.1099/acmi.0.000259] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 07/15/2021] [Indexed: 01/01/2023] Open
Abstract
COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.
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Affiliation(s)
- María Eugenia Soria
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain
| | - Marta Cortón
- Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Brenda Martínez-González
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Rebeca Lobo-Vega
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Lucía Vázquez-Sirvent
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Rosario López-Rodríguez
- Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Berta Almoguera
- Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Ignacio Mahillo
- Department of Statistics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Pablo Mínguez
- Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Antonio Herrero
- Data Analysis Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Juan Carlos Taracido
- Data Analysis Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Alicia Macías-Valcayo
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Jaime Esteban
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Ricardo Fernandez-Roblas
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Ignacio Gadea
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain
| | - Javier Ruíz-Hornillos
- Allergy Unit, Hospital Infanta Elena, Valdemoro, Madrid, Spain.,Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, Spain
| | - Carmen Ayuso
- Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Celia Perales
- Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Av. Reyes Católicos 2, 28040 Madrid, Spain.,Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029, Madrid, Spain
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25
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Tanner AR, Phan H, Brendish NJ, Borca F, Beard KR, Poole S, W Clark T. SARS-CoV-2 viral load at presentation to hospital is independently associated with the risk of death. J Infect 2021; 83:458-466. [PMID: 34363885 PMCID: PMC8339449 DOI: 10.1016/j.jinf.2021.08.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 07/30/2021] [Accepted: 08/01/2021] [Indexed: 01/09/2023]
Abstract
Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.
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Affiliation(s)
- Alex R Tanner
- Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
| | - Hang Phan
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,Clinical Informatics Research Unit, University of Southampton, Southampton, United Kingdom
| | - Nathan J Brendish
- Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Florina Borca
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,Clinical Informatics Research Unit, University of Southampton, Southampton, United Kingdom
| | - Kate R Beard
- Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Stephen Poole
- Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Tristan W Clark
- Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom,School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom,NIHR Post Doctoral Research Fellowship Programme, LF101, South Academic block, Southampton General Hospital, Southampton SO16 6YD, United Kingdom,Corresponding author at: LF101, South Academic block, Southampton General Hospital, Southampton SO16 6YD, United Kingdom
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26
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Shah VP, Farah WH, Hill JC, Hassett LC, Binnicker MJ, Yao JD, Murad MH. Association Between SARS-CoV-2 Cycle Threshold Values and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. Open Forum Infect Dis 2021; 8:ofab453. [PMID: 34584900 PMCID: PMC8465328 DOI: 10.1093/ofid/ofab453] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022] Open
Abstract
Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25–30 compared with >30.
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Affiliation(s)
- Vishal P Shah
- Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Wigdan H Farah
- Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - James C Hill
- Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Joseph D Yao
- Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minnesota, USA
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27
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Machado A, Salvador P, Oliveira P, Teixeira T, Figueiredo C, Nunes S, Silva L, Silva L, Costa T, Malheiro L. The Impact of SARS-CoV-2 Viral Load on the Mortality of Hospitalized Patients: A Retrospective Analysis. Cureus 2021; 13:e16540. [PMID: 34430148 PMCID: PMC8378280 DOI: 10.7759/cureus.16540] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/21/2021] [Indexed: 12/15/2022] Open
Abstract
Introduction Coronavirus disease 2019 (COVID-19) has emerged worldwide since December 2019. The standard method for diagnosis is via nucleic acid amplification testing, usually with a reverse-transcription polymerase chain reaction (RT-PCR). Hospitalized infected individuals may require ventilation and may have higher mortality rates. We aim to evaluate the clinical impact of nasopharyngeal viral load on these outcomes. Materials and methods We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 17 March 2020 to 1 June 2020 at a tertiary care hospital. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from an RT-PCR assay applied to nasopharyngeal swab samples. We compared the clinical characteristics of survivors vs. non-survivors and assessed whether the viral load was independently associated with in-hospital 30-day mortality. Results We evaluated 197 patients. Thirty-day mortality was verified in 71 (36%) subjects. In the adjusted effects model, only the E-gene Ct value [odd ratio (OR) .873; confidence interval (CI) 95% .769-.992; p .037], age, the number of days of symptoms before admission, lactate dehydrogenase (LDH), and the oxygen saturation (SatO2)-to-fraction of inspired oxygen (FiO2) ratio remained significantly associated with 30-day mortality. There was no identified association between the viral loads and disease severity, the need for ventilation, or length of stay. Discussion Our results are, in part, concordant with previous papers. One possible limitation to our study is the fact that possibly included disproportionately more patients with poorer outcomes since hospitalization was required. Therefore, further research is required. Conclusion SARS-CoV-2 viral load on admission may be an independent predictor of 30-day mortality among hospitalized patients with COVID-19. Providing this information to clinicians could potentially be used to guide risk stratification.
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Affiliation(s)
- António Machado
- Department of Medicine, Faculdade de Medicina da Universidade do Porto, Porto, PRT
| | - Pedro Salvador
- Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
| | - Pedro Oliveira
- Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
| | - Tiago Teixeira
- Infectious Diseases Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
| | - Cristóvão Figueiredo
- Infectious Diseases Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova De Gaia, PRT
| | - Sofia Nunes
- Infectious Diseases Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
| | - Luís Silva
- Pathology and Laboratory Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
| | - Leonor Silva
- Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
| | - Tiago Costa
- Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova De Gaia, PRT
| | - Luís Malheiro
- Infectious Diseases Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRT
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28
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Shenoy S. SARS-CoV-2 (COVID-19), viral load and clinical outcomes; lessons learned one year into the pandemic: A systematic review. World J Crit Care Med 2021; 10:132-150. [PMID: 34316448 PMCID: PMC8291003 DOI: 10.5492/wjccm.v10.i4.132] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/21/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is diagnosed via real time reverse transcriptase polymerase chain reaction (RT-PCR) and reported as a binary assessment of the test being positive or negative. High SARS-CoV-2 viral load is an independent predictor of disease severity and mortality. Quantitative RT-PCR may be useful in predicting the clinical course and prognosis of patients diagnosed with coronavirus disease 2019 (COVID-19). AIM To identify whether quantitative SARS-CoV-2 viral load assay correlates with clinical outcome in COVID-19 infections. METHODS A systematic literature search was undertaken for a period between December 30, 2019 to December 31, 2020 in PubMed/MEDLINE using combination of terms "COVID-19, SARS-CoV-2, Ct values, Log10 copies, quantitative viral load, viral dynamics, kinetics, association with severity, sepsis, mortality and infectiousness''. After screening 990 manuscripts, a total of 60 manuscripts which met the inclusion criteria were identified. Data on age, number of patients, sample sites, RT-PCR targets, disease severity, intensive care unit admission, mortality and conclusions of the studies was extracted, organized and is analyzed. RESULTS At present there is no Food and Drug Administration Emergency Use Authorization for quantitative viral load assay in the current pandemic. The intent of this research is to identify whether quantitative SARS-CoV-2 viral load assay correlates with severity of infection and mortality? High SARS-CoV-2 viral load was found to be an independent predictor of disease severity and mortality in majority of studies, and may be useful in COVID-19 infection in susceptible individuals such as elderly, patients with co-existing medical illness such as diabetes, heart diseases and immunosuppressed. High viral load is also associated with elevated levels of TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and C reactive protein contributing to a hyper-inflammatory state and severe infection. However there is a wide heterogeneity in fluid samples and different phases of the disease and these data should be interpreted with caution and considered only as trends. CONCLUSION Our observations support the hypothesis of reporting quantitative RT-PCR in SARS-CoV-2 infection. It may serve as a guiding principle for therapy and infection control policies for current and future pandemics.
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Affiliation(s)
- Santosh Shenoy
- Department of General and Colorectal Surgery, KCVA and University of Missouri at Kansas City, Missouri, MO 64128, United States
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29
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Smolinska A, Jessop DS, Pappan KL, De Saedeleer A, Kang A, Martin AL, Allsworth M, Tyson C, Bos MP, Clancy M, Morel M, Cooke T, Dymond T, Harris C, Galloway J, Bresser P, Dijkstra N, Jagesar V, Savelkoul PHM, Beuken EVH, Nix WHV, Louis R, Delvaux M, Calmes D, Ernst B, Pollini S, Peired A, Guiot J, Tomassetti S, Budding AE, McCaughan F, Marciniak SJ, van der Schee MP. The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs. Sci Rep 2021; 11:13476. [PMID: 34188082 PMCID: PMC8242000 DOI: 10.1038/s41598-021-92665-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 06/08/2021] [Indexed: 11/22/2022] Open
Abstract
Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3–2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation.
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Affiliation(s)
- Agnieszka Smolinska
- Owlstone Medical Ltd., Cambridge, Cambridgeshire, UK.,Department of Pharmacology and Toxicology, Maastricht University, Maastricht, The Netherlands
| | | | - Kirk L Pappan
- Owlstone Medical Ltd., Cambridge, Cambridgeshire, UK
| | | | - Amerjit Kang
- Owlstone Medical Ltd., Cambridge, Cambridgeshire, UK
| | | | - Max Allsworth
- Owlstone Medical Ltd., Cambridge, Cambridgeshire, UK
| | | | | | | | - Mike Morel
- Cambridge Clinical Laboratories Ltd., Cambridge, Cambridgeshire, UK
| | - Tony Cooke
- Cambridge Clinical Laboratories Ltd., Cambridge, Cambridgeshire, UK
| | - Tom Dymond
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
| | - Claire Harris
- Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.,University of Cambridge, Cambridge, UK
| | - Jacqui Galloway
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
| | | | | | | | - Paul H M Savelkoul
- Department of Medical Microbiology, Maastricht University Medical Center, Care and Public Health Research Institute (Caphri), Maastricht, The Netherlands
| | - Erik V H Beuken
- Department of Medical Microbiology, Maastricht University Medical Center, Care and Public Health Research Institute (Caphri), Maastricht, The Netherlands
| | - Wesley H V Nix
- Department of Medical Microbiology, Maastricht University Medical Center, Care and Public Health Research Institute (Caphri), Maastricht, The Netherlands
| | - Renaud Louis
- Repiratory Department, CHU Liège, Liège, Belgium
| | | | | | - Benoit Ernst
- Repiratory Department, CHU Liège, Liège, Belgium
| | - Simona Pollini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.,Microbiology and Virology Unit, Careggi University Hospital, Florence, Italy
| | - Anna Peired
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Julien Guiot
- Repiratory Department, CHU Liège, Liège, Belgium
| | - Sara Tomassetti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.,Interventional Pulmonology Unit, Careggi University Hospital, Florence, Italy
| | | | - Frank McCaughan
- Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.,University of Cambridge, Cambridge, UK
| | - Stefan J Marciniak
- Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.,University of Cambridge, Cambridge, UK
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30
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Salto-Alejandre S, Berastegui-Cabrera J, Camacho-Martínez P, Infante-Domínguez C, Carretero-Ledesma M, Crespo-Rivas JC, Márquez E, Lomas JM, Bueno C, Amaya R, Lepe JA, Cisneros JM, Pachón J, Cordero E, Sánchez-Céspedes J. SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome. Sci Rep 2021; 11:12931. [PMID: 34155307 PMCID: PMC8217169 DOI: 10.1038/s41598-021-92400-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 06/09/2021] [Indexed: 01/08/2023] Open
Abstract
The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient's hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.
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Affiliation(s)
- Sonsoles Salto-Alejandre
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Judith Berastegui-Cabrera
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Pedro Camacho-Martínez
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Carmen Infante-Domínguez
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Marta Carretero-Ledesma
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Juan Carlos Crespo-Rivas
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Eduardo Márquez
- Medico-Surgical Unit of Respiratory Diseases, Virgen del Rocío University Hospital, Seville, Spain
| | - José Manuel Lomas
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Claudio Bueno
- Unit of Emergencies, Virgen del Rocío University Hospital, Seville, Spain
| | - Rosario Amaya
- Intensive Care Unit, Virgen del Rocío University Hospital, Seville, Spain
| | - José Antonio Lepe
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - José Miguel Cisneros
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
| | - Jerónimo Pachón
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain. .,Department of Medicine, University of Seville, Seville, Spain.
| | - Elisa Cordero
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.,Department of Medicine, University of Seville, Seville, Spain
| | - Javier Sánchez-Céspedes
- Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain
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31
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Basile L, Guadalupe-Fernández V, Valdivia Guijarro M, Martinez Mateo A, Ciruela Navas P, Mendioroz Peña J, the Epidemiological Surveillance Network of Catalonia. Diagnostic Performance of Ag-RDTs and NAAT for SARS-CoV2 Identification in Symptomatic Patients in Catalonia. Viruses 2021; 13:v13050908. [PMID: 34068899 PMCID: PMC8156224 DOI: 10.3390/v13050908] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/10/2021] [Accepted: 05/11/2021] [Indexed: 12/17/2022] Open
Abstract
The use of rapid antigenic tests (Ag-RDTs) to diagnose a SARS-CoV-2 infection has become a common practice recently. This study aimed to evaluate performance of Abbott PanbioTM Ag-RDTs with regard to nucleic acid amplification testing (NAAT) in the early stages of the disease. A cohort of 149,026 infected symptomatic patients, reported in Catalonia from November 2020 to January 2021, was selected. The positivity rates of the two tests were compared with respect to the dates of symptom onset. Ag-RDTs presented positivity rates of 84% in the transmission phases of the disease and 31% in the pre-symptomatic period, compared to 93% and 91%, respectively, for NAAT. The detection of many false negatives with Ag-RDTs during the pre-symptomatic period demonstrates the risk of virus dissemination with this diagnostic technique if used outside the symptomatic period.
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Affiliation(s)
- Luca Basile
- Sub-Directorate General of Surveillance and Response to Public Health Emergencies, Public Health Agency of Catalonia, Generalitat of Catalonia, 08005 Barcelona, Spain; (V.G.-F.); (M.V.G.); (A.M.M.); (P.C.N.); (J.M.P.)
- Correspondence:
| | - Víctor Guadalupe-Fernández
- Sub-Directorate General of Surveillance and Response to Public Health Emergencies, Public Health Agency of Catalonia, Generalitat of Catalonia, 08005 Barcelona, Spain; (V.G.-F.); (M.V.G.); (A.M.M.); (P.C.N.); (J.M.P.)
- Unitat de Suport a la Recerca de Catalunya Central, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, 08272 Sant Fruitós de Bages, Spain
| | - Manuel Valdivia Guijarro
- Sub-Directorate General of Surveillance and Response to Public Health Emergencies, Public Health Agency of Catalonia, Generalitat of Catalonia, 08005 Barcelona, Spain; (V.G.-F.); (M.V.G.); (A.M.M.); (P.C.N.); (J.M.P.)
| | - Ana Martinez Mateo
- Sub-Directorate General of Surveillance and Response to Public Health Emergencies, Public Health Agency of Catalonia, Generalitat of Catalonia, 08005 Barcelona, Spain; (V.G.-F.); (M.V.G.); (A.M.M.); (P.C.N.); (J.M.P.)
- CIBER Epidemiologia y Salud Pública (CIBERESP), Instituto Salud Carlos III, 28029 Madrid, Spain
| | - Pilar Ciruela Navas
- Sub-Directorate General of Surveillance and Response to Public Health Emergencies, Public Health Agency of Catalonia, Generalitat of Catalonia, 08005 Barcelona, Spain; (V.G.-F.); (M.V.G.); (A.M.M.); (P.C.N.); (J.M.P.)
- CIBER Epidemiologia y Salud Pública (CIBERESP), Instituto Salud Carlos III, 28029 Madrid, Spain
| | - Jacobo Mendioroz Peña
- Sub-Directorate General of Surveillance and Response to Public Health Emergencies, Public Health Agency of Catalonia, Generalitat of Catalonia, 08005 Barcelona, Spain; (V.G.-F.); (M.V.G.); (A.M.M.); (P.C.N.); (J.M.P.)
- Unitat de Suport a la Recerca de Catalunya Central, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, 08272 Sant Fruitós de Bages, Spain
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8806 Russian patients demonstrate T cell count as better marker of COVID-19 clinical course severity than SARS-CoV-2 viral load. Sci Rep 2021; 11:9440. [PMID: 33941816 PMCID: PMC8093219 DOI: 10.1038/s41598-021-88714-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 04/13/2021] [Indexed: 12/11/2022] Open
Abstract
The article presents a comparative analysis of SARS-CoV-2 viral load (VL), T lymphocyte count and respiratory index PaO2:FiO2 ratio as prospective markers of COVID-19 course severity and prognosis. 8806 patients and asymptomatic carriers were investigated in time interval 15 March–19 December 2020. T cell count demonstrated better applicability as a marker of aggravating COVID-19 clinical course and unfavourable disease prognosis than SARS-CoV-2 VL or PaO2:FiO2 ratio taken alone. Using T cell count in clinical practice may provide an opportunity of early prediction of deteriorating a patient’s state.
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A Retrospective Analysis of the Impact of the Coronavirus Disease 2019 Pandemic on Health Care Workers in a Tertiary Hospital in Turkey. J Emerg Nurs 2021; 47:948-954. [PMID: 34294455 PMCID: PMC8006193 DOI: 10.1016/j.jen.2021.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/15/2021] [Accepted: 03/24/2021] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Several vaccines have been developed and approved for use against severe acute respiratory syndrome coronavirus-2; however, the use of personal protective equipment remains important owing to the lack of effective specific treatment and whole community immunity. Hydroxychloroquine sulfate was a treatment option in the early days of the pandemic; however, it was subsequently removed owing to a lack of evidence as an effective treatment. We aimed to evaluate the testing and infection characteristics of coronavirus disease 2019 among health care personnel and determine the effectiveness of prophylactic hydroxychloroquine sulfate use to prevent transmission. METHODS This retrospective observational study was conducted between May 1 and September 30, 2020. The health care personnel included in the study were physicians, nurses, and paraprofessional support personnel. The health records of health care personnel who had been tested for severe acute respiratory syndrome coronavirus-2 using polymerase chain reaction were retrospectively analyzed. RESULTS In total, 508 health care personnel were included in the study. A total of 152 (29.9%) health care personnel were diagnosed with coronavirus disease 2019. The positive polymerase chain reaction rate was 80.3% (n = 122). A comparison of infected and uninfected health care personnel showed a difference in age and occupation and no difference in sex, working area, and prophylactic hydroxychloroquine sulfate use. DISCUSSION Protective measures in low-risk areas of our hospital require improvements. All health care personnel should be trained on personal protective equipment use. There was no evidence to support the effectiveness of prophylactic hydroxychloroquine sulfate against severe acute respiratory syndrome coronavirus-2 transmission.
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Trunfio M, Longo BM, Alladio F, Venuti F, Cerutti F, Ghisetti V, Bonora S, Di Perri G, Calcagno A. On the SARS-CoV-2 "Variolation Hypothesis": No Association Between Viral Load of Index Cases and COVID-19 Severity of Secondary Cases. Front Microbiol 2021; 12:646679. [PMID: 33815334 PMCID: PMC8010676 DOI: 10.3389/fmicb.2021.646679] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 02/17/2021] [Indexed: 12/22/2022] Open
Abstract
Background: Emerging evidence supports the “variolation hypothesis” in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), but the derivative idea that the viral load of index cases may predict disease severity in secondary cases could be unsubstantiated. We assessed whether the prevalence of symptomatic infections, hospitalization, and deaths in household contacts of 2019 novel coronavirus disease (COVID-19) cases differed according to the SARS-CoV-2 PCR cycle threshold (Ct) from nasal-pharyngeal swab at diagnosis of linked index cases. Methods: Cross-sectional study on household contacts of COVID-19 cases randomly sampled from all the infections diagnosed in March at our Microbiology Laboratory (Amedeo di Savoia, Turin). Data were retrospectively collected by phone interviews and from the Piedmont regional platform for COVID-19 emergency. Index cases were classified as high (HVl) and low viral load (LVl) according to two exploratory cut-offs of RdRp gene Ct value. Secondary cases were defined as swab confirmed or symptom based likely when not tested but presenting compatible clinical picture. Results: One hundred thirty-two index cases of whom 87.9% symptomatic and 289 household contacts were included. The latter were male and Caucasian in 44.3 and 95.8% of cases, with a median age of 34 years (19–57). Seventy-four were swab confirmed and other 28 were symptom based likely secondary cases. Considering both, the contacts of HVl and LVl did not differ in the prevalence of symptomatic infections nor COVID-19-related hospitalization and death. No difference in median Ct of index cases between symptomatic and asymptomatic, hospitalized and not hospitalized, or deceased and survived secondary cases was found. Negative findings were confirmed after adjusting for differences in time between COVID-19 onset and swab collection of index cases (median 5 days) and after removing pediatric secondary cases. Conclusions: The amount of SARS-CoV-2 of the source at diagnosis does not predict clinical outcomes of linked secondary cases. Considering the impelling release of assays for SARS-CoV-2 RNA exact quantification, these negative findings should inform clinical and public health strategies on how to interpret and use the data.
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Affiliation(s)
- Mattia Trunfio
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
| | - Bianca Maria Longo
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
| | - Francesca Alladio
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
| | - Francesco Venuti
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
| | - Francesco Cerutti
- Microbiology and Molecular Biology Laboratory, "Amedeo di Savoia" Hospital, Turin, Italy
| | - Valeria Ghisetti
- Microbiology and Molecular Biology Laboratory, "Amedeo di Savoia" Hospital, Turin, Italy
| | - Stefano Bonora
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
| | - Andrea Calcagno
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the "Amedeo di Savoia" Hospital, Turin, Italy
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Trunfio M, Venuti F, Alladio F, Longo BM, Burdino E, Cerutti F, Ghisetti V, Bertucci R, Picco C, Bonora S, Di Perri G, Calcagno A. Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients. Viruses 2021; 13:v13020281. [PMID: 33670360 PMCID: PMC7917896 DOI: 10.3390/v13020281] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/08/2021] [Accepted: 02/09/2021] [Indexed: 12/15/2022] Open
Abstract
To date, there is no severe acute respiratory syndrome coronavirus 2-(SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤ 20.0, 20.0 < group B ≤ 28.0, and Group C > 28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C; 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p < 0.01), and presence of six-month sequelae (p < 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.
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Affiliation(s)
- Mattia Trunfio
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
- Correspondence: ; Tel.: +39-01-1439-3884
| | - Francesco Venuti
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
| | - Francesca Alladio
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
| | - Bianca Maria Longo
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
| | - Elisa Burdino
- Microbiology and Molecular Biology Laboratory, Amedeo di Savoia Hospital, ASL Città di Torino, Corso Svizzera 164, 10149 Torino, Italy; (E.B.); (F.C.); (V.G.)
| | - Francesco Cerutti
- Microbiology and Molecular Biology Laboratory, Amedeo di Savoia Hospital, ASL Città di Torino, Corso Svizzera 164, 10149 Torino, Italy; (E.B.); (F.C.); (V.G.)
| | - Valeria Ghisetti
- Microbiology and Molecular Biology Laboratory, Amedeo di Savoia Hospital, ASL Città di Torino, Corso Svizzera 164, 10149 Torino, Italy; (E.B.); (F.C.); (V.G.)
| | - Roberto Bertucci
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
| | - Carlo Picco
- Regional Department for Infectious Diseases and Emergency DIRMEI, ASL Città di Torino, Via S. Secondo 29, 10128 Torino, Italy;
| | - Stefano Bonora
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
| | - Giovanni Di Perri
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
- Regional Department for Infectious Diseases and Emergency DIRMEI, ASL Città di Torino, Via S. Secondo 29, 10128 Torino, Italy;
| | - Andrea Calcagno
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy; (F.V.); (F.A.); (B.M.L.); (R.B.); (S.B.); (G.D.P.); (A.C.)
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