The number of cycles it takes for PCR to amplify SARS-CoV-2 genetic material could indicate if the patient the sample was taken from is still infectious or not.

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Reducing uncertainty about COVID-19

11 Jan 2021

A multifaceted study by the Singapore 2019 Novel Coronavirus Outbreak Research team is filling in some of the gaps left in the urgent quest to understand COVID-19 infection.

When COVID-19 first emerged, the mystery surrounding what was causing the disease and how it was being transmitted incited fear and confusion around the world. An unprecedented global research effort has since provided clarity on these matters, but important questions like how long the virus remains infectious and what causes severe disease remain.

“A clearer understanding of disease pathogenesis is necessary to support the development of risk stratification tools, improve limited medical resource allocation and develop novel or re-purpose existing therapeutics which target critical pathways in the COVID-19 inflammatory cascade,” said Lisa Ng, a Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN) and Executive Director of the A*STAR Biomedical Research Council (BMRC).

With other members of the Singapore 2019 Novel Coronavirus Outbreak Research team, an interdisciplinary group of researchers from various institutions across the country, Ng and Executive Director of A*STAR’s Infectious Diseases Laboratories Laurent Renia conducted a comprehensive study to better understand COVID-19 and improve management of the disease. “Our findings on the virus have implications on identification, patient triage and transmission control measures,” he said.

To design effective transmission control measures, it is important to know how long the virus remains infectious. While most studies have looked at the number of days the virus remains viable after infection, Ng and her team found that a proxy value called the cycle threshold, or Ct value, may also be useful.

The Ct value describes the number of cycles needed to detect the virus in a polymerase chain reaction test, the gold standard test used to detect SARS-CoV-2. Viable virus was only detected at a Ct value less than 30, or in samples collected less than 14 days after symptoms first emerged. However, Ng cautioned that additional studies are needed in more patients—including asymptomatic cases—before the Ct value can be widely used as an indicator.

The study also looked at the link between disease severity and the appearance of antibodies and inflammatory signals across time. The researchers found that patients with severe symptoms develop antibodies earlier and at higher concentrations than those with mild symptoms, knowledge that can be used to predict which patients may develop severe disease.

What’s more, severe cases had higher levels of several proinflammatory signals and growth factors. This implies that already available drugs that target and inhibit these signals could be repurposed to treat patients with severe COVID-19, Ng said.

The team is now monitoring patients throughout both disease and recovery to better understand changes in the immune response with time.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN) and A*STAR’s Infectious Diseases Laboratories (ID Labs).

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Young, B.E., Ong, S.W.X., Ng, L.F.P., Anderson, D.E., Chia W.N., et al. Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity. Clinical Infectious Diseases, ciaa1280 (2020) | article

About the Researchers

Laurent Renia

Executive Director

Infectious Diseases Horizontal Technology Center
Laurent Renia is the Executive Director of A*STAR’s Infectious Diseases Horizontal Technology Center (ID HTC), established on July 1, 2020. He earned his PhD degree in 1991 at the University Pierre et Marie Curie in Paris, France, where he studied the immune response against malaria. Before joining A*STAR, Renia was a Research Director at the French National Institute of Health and Medical Research (INSERM) and Director of the Department of Immunology at the Institut Cochin. After joining A*STAR’s Singapore Immunology Network (SIgN) in 2007, he served as its Executive Director from 2014 to 2020. He has published more than 260 articles and book chapters on research topics on infection, immunity and oncoimmunology.

Lisa F.P. Ng

Senior Principal Investigator

Singapore Immunology Network
Lisa F.P. Ng obtained her PhD in molecular virology in coronaviruses from the National University of Singapore (NUS) in 2002. After joining A*STAR’s Genome Institute of Singapore (GIS) in 2002 as a Postdoctoral Fellow, she worked on viral diseases such as hepatitis, severe acute respiratory syndrome and influenza. Ng is currently the Executive Director of A*STAR’s Biomedical Research Council (BMRC) and holds a concurrent appointment as Executive Director at A*STAR's Infectious Diseases Labs (ID Labs) where she focuses on the immune responses to arthritic arboviruses that are epidemic or highly endemic in the tropical region. Ng has won numerous accolades for her research, including the ASEAN ‘International Young Scientist and Technologist Award’ in 2008 and A*STAR’s ‘Most Inspiring Mentor Award’ in March 2013.

This article was made for A*STAR Research by Wildtype Media Group