Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

• Published in: Clinical infectious diseases Vol. 73; no. 9; pp. e2932 - e2942
• Main Authors: Young, Barnaby E, 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: Journal Article
• Language: English
• Published: US Oxford University Press 02.11.2021
• Subjects: COVID-19; viral culture; cytokines; immunology; serology
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciaa1280

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. Polymerase chain reaction cycle threshold value ≤30 significantly predicts viral culture isolation, and increases with illness duration. Earlier seroconversion with higher peak immunoglobulin M/immunoglobulin G levels occurred in severe disease, as were higher levels of inflammatory markers, including interleukin-6 as a key interacting cytokine.