Journal
CLINICAL INFECTIOUS DISEASES
Volume 73, Issue 9, Pages E2932-E2942Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciaa1280
Keywords
COVID-19; cytokines; serology; viral culture; immunology
Categories
Funding
- Singapore National Medical Research Council COVID-19 Research Fund [COVID19RF-001]
- Singapore NMRC grants [STPRG-FY19-001, COVID19RF-003]
- Singapore Immunology Network (A*STAR)
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The study found that virus viability correlated with lower PCR Ct values in early illness, and a stronger antibody response was associated with disease severity. Overactive proinflammatory immune signatures provide potential targets for host-directed immunotherapy.
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-1a, 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.
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