Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity

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 observatio...

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Main 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
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/162756
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1627562022-11-08T04:30:47Z Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity 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 Lee Kong Chian School of Medicine (LKCMedicine) National Centre for Infectious Diseases Tan Tock Seng Hospital Yong Loo Lin School of Medicine, NUS Saw Swee Hock School of Public Health, NUS Science::Medicine COVID-19 Cytokines 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. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Recruitment of study participants and sample collection was supported by the Singapore National Medical Research Council COVID-19 Research Fund (grant number COVID19RF-001). The serology work was supported by Singapore NMRC grants STPRG-FY19-001 and COVID19RF-003. The multiplex microbead-based immunoassays were supported by core funds from the Singapore Immunology Network (A*STAR). 2022-11-08T04:30:47Z 2022-11-08T04:30:47Z 2021 Journal Article 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. https://dx.doi.org/10.1093/cid/ciaa1280 1058-4838 https://hdl.handle.net/10356/162756 10.1093/cid/ciaa1280 32856707 2-s2.0-85120635253 9 73 e2932 e2942 en COVID19RF-001 STPRG-FY19-001 Clinical Infectious Diseases © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
COVID-19
Cytokines
spellingShingle Science::Medicine
COVID-19
Cytokines
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
Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
description 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
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
format Article
author 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
author_sort Young, Barnaby Edward
title Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
title_short Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
title_full Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
title_fullStr Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
title_full_unstemmed Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity
title_sort viral dynamics and immune correlates of coronavirus disease 2019 (covid-19) severity
publishDate 2022
url https://hdl.handle.net/10356/162756
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