Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity
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 ,   Singapore 2019 Novel Coronavirus Outbreak Research Team, 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 
Published: August 2020

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 &gt;30 or &gt;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.