Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity. (28th August 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Clinical infectious diseases. Volume 73:Number 9(2021)
• Page Start: e2932
• Page End: e2942
• Publication Date: 2020-08-28
• Subjects: COVID-19 -- cytokines -- serology -- viral culture -- immunology; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1280
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : 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.