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

2020; Oxford University Press; Volume: 73; Issue: 9 Linguagem: Inglês

10.1093/cid/ciaa1280

1537-6591

Barnaby Edward Young, Sean Wei Xiang Ong, Lisa F. P. Ng, Danielle E. Anderson, Wan Ni Chia, Po Ying Chia, Li Wei Ang, Tze Minn Mak, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Siew‐Wai Fong, Yi‐Hao Chan, Chee Wah Tan, Bernett Lee, Olaf Rötzschke, Ying Ding, Paul Anantharajah Tambyah, Jenny G. Low, Lin Cui, Timothy Barkham, Raymond Tzer Pin Lin, Yee‐Sin Leo, Laurent Rénia, Lin‐Fa Wang, David Chien Lye, Poh Lian Lim, Brenda Ang, Cheng Chuan Lee, Lawrence S. Lee, Li Min Ling, Oon Tek Ng, Mónica Chan, Kalisvar Marimuthu, Shawn Vasoo, Chen Seong Wong, Tau Hong Lee, Sapna Sadarangani, Susan Kline, Sharavan Sadasiv Mucheli, Deborah Hee Ling Ng, Chiaw Yee Choy, Glorijoy Shi En Tan, Yu Kit Tan, Stephanie Sutjipto, Pei Hua Lee, Jun Yang Tay, Tsin Wen Yeo, Bo Yan Khoo, Woo Chiao Tay, Gabrielle Ng, Yun Yuan Mah, Wilnard Tan, Partha Pratim De, Rao Pooja, Jonathan W. Z. Chia, Yuan Yi Constance Chen, Shehara M Mendis, Boon Kiat Toh, Raymond Fong, Helen May Lin Oh, Jaime Mei Fong Chien, Humaira Shafi, Hau Yiang Cheong, Thean Yen Tan, Thuan Tong Tan, Ban Hock Tan, Limin Wijaya, Indumathi Venkatachalam, Ying Ying Chua, Benjamin Pei Zhi Cherng, Yvonne Fu Zi Chan, Hei Man Wong, Siew Yee Thien, Kenneth Choon Meng Goh, Shireen Yan Ling Tan, Lynette Lin Ean Oon, Kian Sing Chan, Li Lin, Douglas Chan, Say Tat Ooi, Deepak Rama Narayana, Jyoti Somani, Jolene Oon, Gabriel Yan, David Michael Allen, Roland Jureen, Benedict Yan, Randy Foo, Adrian Kang Eng Zheng, Velraj Sivalingam, Wilson How, Norman Leo Fernandez, Nicholas Kim‐Wah Yeo, Rhonda Sin‐Ling Chee, Siti Naqiah Amrun,

COVID-19 Clinical Research Studies

Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.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.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.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.