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Title: Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity.
Authors: Young, Barnaby E
Ong, Sean WX
Ng, Lisa FP
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 GH
Cui, Lin 
Barkham, Timothy
Lin, Raymond Tzer Pin 
Leo, Yee-Sin 
Renia, Laurent 
Wang, Lin-Fa
Lye, David Chien 
Singapore 2019 Novel Coronavirus Outbreak Research Team
Keywords: COVID-19
viral culture
Antibodies, Viral
Immunoglobulin M
Middle Aged
Pneumonia, Viral
Prospective Studies
Issue Date: 2-Nov-2021
Publisher: Oxford University Press (OUP)
Citation: Young, Barnaby E, Ong, Sean WX, Ng, Lisa FP, 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 GH, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, Lye, David Chien, Singapore 2019 Novel Coronavirus Outbreak Research Team (2021-11-02). Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity.. Clinical Infectious Diseases 73 (9) : e2932-e2942. ScholarBank@NUS Repository.
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.
Source Title: Clinical Infectious Diseases
ISSN: 10584838
DOI: 10.1093/cid/ciaa1280
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