tetano
Editor, Senior Moderator
Clin Infect Dis
. 2020 Aug 28;ciaa1280.
doi: 10.1093/cid/ciaa1280. Online ahead of print.
Viral dynamics and immune correlates of COVID-19 disease severity
Barnaby E Young[SUP] 1 2 3 [/SUP], Sean W X Ong[SUP] 1 2 [/SUP], Lisa F P Ng[SUP] 4 5 [/SUP], Danielle E Anderson[SUP] 6 [/SUP], Wan Ni Chia[SUP] 6 [/SUP], Po Ying Chia[SUP] 1 2 3 [/SUP], Li Wei Ang[SUP] 1 [/SUP], Tze-Minn Mak[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 6 7 [/SUP], Louis Yi Ann Chai[SUP] 8 9 [/SUP], Surinder Pada[SUP] 10 [/SUP], Seow Yen Tan[SUP] 11 [/SUP], Louisa Sun[SUP] 12 [/SUP], Purnima Parthasarathy[SUP] 13 [/SUP], Siew-Wai Fong[SUP] 4 5 14 [/SUP], Yi-Hao Chan[SUP] 4 5 [/SUP], Chee Wah Tan[SUP] 5 [/SUP], Bernett Lee[SUP] 5 [/SUP], Olaf R?tzschke[SUP] 5 [/SUP], Ying Ding[SUP] 1 [/SUP], Paul Tambyah[SUP] 8 9 [/SUP], Jenny G H Low[SUP] 6 7 [/SUP], Lin Cui[SUP] 1 [/SUP], Timothy Barkham[SUP] 2 9 [/SUP], Raymond Tzer Pin Lin[SUP] 1 [/SUP], Yee-Sin Leo[SUP] 1 2 3 9 15 [/SUP], Laurent Renia[SUP] 4 5 [/SUP], Lin-Fa Wang[SUP] 6 [/SUP], David Chien Lye[SUP] 1 2 3 9 [/SUP], Singapore 2019 Novel Coronavirus Outbreak Research team
Affiliations
Abstract
Background: Key knowledge gaps remain in the understanding of viral dynamics and immune response of 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: 57 (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen including 12 (12%) 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 of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) 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.
Conclusion: 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 offers targets for host-directed immunotherapy which should be evaluated in randomised controlled trials.
Keywords: COVID-19; cytokines; immunology; serology; viral culture.
. 2020 Aug 28;ciaa1280.
doi: 10.1093/cid/ciaa1280. Online ahead of print.
Viral dynamics and immune correlates of COVID-19 disease severity
Barnaby E Young[SUP] 1 2 3 [/SUP], Sean W X Ong[SUP] 1 2 [/SUP], Lisa F P Ng[SUP] 4 5 [/SUP], Danielle E Anderson[SUP] 6 [/SUP], Wan Ni Chia[SUP] 6 [/SUP], Po Ying Chia[SUP] 1 2 3 [/SUP], Li Wei Ang[SUP] 1 [/SUP], Tze-Minn Mak[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 6 7 [/SUP], Louis Yi Ann Chai[SUP] 8 9 [/SUP], Surinder Pada[SUP] 10 [/SUP], Seow Yen Tan[SUP] 11 [/SUP], Louisa Sun[SUP] 12 [/SUP], Purnima Parthasarathy[SUP] 13 [/SUP], Siew-Wai Fong[SUP] 4 5 14 [/SUP], Yi-Hao Chan[SUP] 4 5 [/SUP], Chee Wah Tan[SUP] 5 [/SUP], Bernett Lee[SUP] 5 [/SUP], Olaf R?tzschke[SUP] 5 [/SUP], Ying Ding[SUP] 1 [/SUP], Paul Tambyah[SUP] 8 9 [/SUP], Jenny G H Low[SUP] 6 7 [/SUP], Lin Cui[SUP] 1 [/SUP], Timothy Barkham[SUP] 2 9 [/SUP], Raymond Tzer Pin Lin[SUP] 1 [/SUP], Yee-Sin Leo[SUP] 1 2 3 9 15 [/SUP], Laurent Renia[SUP] 4 5 [/SUP], Lin-Fa Wang[SUP] 6 [/SUP], David Chien Lye[SUP] 1 2 3 9 [/SUP], Singapore 2019 Novel Coronavirus Outbreak Research team
Affiliations
- PMID: 32856707
- DOI: 10.1093/cid/ciaa1280
Abstract
Background: Key knowledge gaps remain in the understanding of viral dynamics and immune response of 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: 57 (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen including 12 (12%) 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 of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) 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.
Conclusion: 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 offers targets for host-directed immunotherapy which should be evaluated in randomised controlled trials.
Keywords: COVID-19; cytokines; immunology; serology; viral culture.