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Title: Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
Authors: Young, Barnaby Edward
Ong, Sean W. X.
Ng, Lisa F. P.
Anderson, Danielle E.
Chia, Wan Ni
Chia, Po Ying
Ang, Li Wei
Mak, Tze-Minn
Kalimuddin, Shirin
Chai, Louis Yi Ann
Pada, Surinder
Tan, Seow Yen
Sun, Louisa
Parthasarathy, Purnima
Fong, Siew-Wai
Chan, Yi-Hao
Tan, Chee Wah
Lee, Bernett
Rötzschke, Olaf
Ding, Ying
Tambyah, Paul
Low, Jenny G. H.
Cui, Lin
Barkham, Timothy
Lin, Raymond Tzer Pin
Leo, Yee Sin
Renia, Laurent
Wang, Lin-Fa
Lye, David Chien
Keywords: Science::Medicine
Issue Date: 2021
Source: Young, B. E., Ong, S. W. X., Ng, L. F. P., Anderson, D. E., Chia, W. N., Chia, P. Y., Ang, L. W., Mak, T., Kalimuddin, S., Chai, L. Y. A., Pada, S., Tan, S. Y., Sun, L., Parthasarathy, P., Fong, S., Chan, Y., Tan, C. W., Lee, B., Rötzschke, O., ...Lye, D. C. (2021). Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity. Clinical Infectious Diseases, 73(9), e2932-e2942.
Project: COVID19RF-001
Journal: Clinical Infectious Diseases
Abstract: Background. Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods. We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results. Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions. We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.
ISSN: 1058-4838
DOI: 10.1093/cid/ciaa1280
Rights: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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