In brief

The COVID Human Genetic Effort seeks to understand the impact of genetic variability on the severity of disease.

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The COVID-19 outliers

16 Jul 2020

An international genetics consortium seeks to unravel the mystery of why COVID-19 infection is silent in some cases and lethal in others.

When describing an ‘outlier,’ we may think of someone who is exceptionally gifted at sports, or someone with a particularly high IQ. It turns out that there are also outliers among COVID-19 patients—they exhibit massive variability in outcomes ranging from silent infection to lethal disease.

So why do some people remain seronegative despite heavy or repeated exposures to the virus, while young, previously healthy individuals end up getting admitted to intensive care for a life-threatening disease? Here, the role of human genetics in determining clinical response to the SARS-CoV-2 virus remains to be defined.

To study the immense clinical variability observed among infected individuals, the COVID Human Genetic Effort consortium was established in February 2020 by Jean-Laurent Casanova, a professor at the Rockefeller University, to recruit patients from multiple centers and countries, targeting patients below the age of 50 years with a life-threatening disease and no pre-existing medical conditions.

“This global consortium aims to study COVID-19, which is a completely new disease, and the human genetics that could define disease resistance or severity,” said Lisa F. P. Ng, a consortium member and Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN). Ng is joined on the consortium by Laurent Renia, Executive Director of A*STAR’s Infectious Diseases Horizontal Technology Centre (ID HTC).

In a commentary in the journal Cell, the authors reveal that the consortium has embarked on genome-wide association studies of COVID-19 patients based on their exome and genome data. Data analysis will take place both locally at the hubs and centrally by the consortium, followed by clinical and immunological studies.

Establishing the consortium in the early stages of the pandemic means that there remains low signal interference from confounding variables such as vaccines, previous related infections and herd immunity, the authors explained in the commentary.

Based on the data collected, the consortium researchers hope to find out whether inborn errors of inflammation, or mutation of key genes involved in the immune response, play a role in infection or immunity to COVID-19. Their effort will also determine any links between such genes and ethnicity, should they exist.

“Not only will this consortium facilitate the detection of individuals naturally resistant to SARS-CoV-2 infection, it will also open up new avenues for controlling COVID-19 in the general population by providing potential pharmacological targets for development,” Ng said.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).

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Casanova, J-L., Su, H. C., and the COVID Human Genetic Effort. A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection. Cell 181(6), 1194-1199. (2020) | article

About the Researcher

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 at A*STAR 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