1. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity
- Author
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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, Lim, Poh Lian, Peng Ang, Brenda Sze, Lee, Cheng Chuan, U Lee, Lawrence Soon, Ling, Li Min, Ng, Oon Tek, Chan, Monica, Marimuthu, Kalisvar, Vasoo, Shawn, Wong, Chen Seong, Lee, Tau Hong, Sadarangani, Sapna, Lin, Ray Junhao, Sadasiv, Mucheli Sharavan, Ling Ng, Deborah Hee, Choy, Chiaw Yee, En Tan, Glorijoy Shi, Tan, Yu Kit, Sutjipto, Stephanie, Lee, Pei Hua, Tay, Jun Yang, Yeo, Tsin Wen, Khoo, Bo Yan, Tay, Woo Chiao, Ng, Gabrielle, Mah, Yun Yuan, Tan, Wilnard, De, Partha Pratim, Pooja, Rao, Chia, Jonathan W Z, Constance Chen, Yuan Yi, Mendis, Shehara, Toh, Boon Kiat, Choon Fong, Raymond Kok, Lin Oh, Helen May, Fong Chien, Jaime Mei, Shafi, Humaira, Cheong, Hau Yiang, Tan, Thean Yen, Tan, Thuan Tong, Tan, Ban Hock, Wijaya, Limin, Venkatachalam, Indumathi, Chua, Ying Ying, Zhi Cherng, Benjamin Pei, Zi Chan, Yvonne Fu, Wong, Hei Man, Thien, Siew Yee, Meng Goh, Kenneth Choon, Ling Tan, Shireen Yan, Ean Oon, Lynette Lin, Chan, Kian Sing, Lin, Li, Gin Chan, Douglas Su, Ooi, Say Tat, Narayana, Deepak Rama, Somani, Jyoti, Ling Oon, Jolene Ee, Yan, Gabriel Zherong, Allen, David Michael, Jureen, Roland, Yan, Benedict, Foo, Randy, Kang, Adrian, Sivalingam, Velraj, How, Wilson, Fernandez, Norman Leo, Yeo, Nicholas Kim-Wah, Chee, Rhonda Sin-Ling, Amrun, Siti Naqiah, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and Saw Swee Hock School of Public Health, NUS
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0301 basic medicine ,Microbiology (medical) ,biology ,Viral culture ,business.industry ,030106 microbiology ,COVID-19 ,medicine.disease ,03 medical and health sciences ,Pneumonia ,0302 clinical medicine ,Infectious Diseases ,Immune system ,Immunoglobulin M ,Viral pneumonia ,Immunology ,Severity of illness ,medicine ,biology.protein ,Cytokines ,Medicine [Science] ,030212 general & internal medicine ,Seroconversion ,Antibody ,business - 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.
- Published
- 2020