Research supported by NIEHS and the National Institute of Allergy and Infectious Diseases (NIAID) may help to explain why some people with COVID-19 become severely ill while others have no symptoms at all, and why more men than women die from the disease.

The projects will increase knowledge of how genes and the environment can influence an individual’s susceptibility to COVID-19 and affect disease severity. Both initiatives examine how the immune system responds to infection.

Populations especially vulnerable to COVID-19 include minority groups, low-income individuals, pregnant women, nursing home residents, and people experiencing homelessness.

Immune function and the environment

For its part, NIEHS is funding a grant program titled “Understanding the Impact of Environmental Factors on COVID-19.” (See the Notice of Special Interest, NOT-ES-20-020.)

The goal is to bolster research into how immune function is altered by air pollution and tobacco smoke, and per- and polyfluoroalkyl substances in drinking water, for example. Such knowledge could shed light on why certain individuals are more vulnerable to COVID-19.

“From our research here at NIEHS, we know that environmental factors can affect our immune system,” said NIEHS and National Toxicology Program Director Rick Woychik, Ph.D. “We believe that pandemic research must include studies on the environment, immunity, and differential susceptibility.” Differential susceptibility suggests that some individuals may be more susceptible than others to environmental influences such as exposures and infections.

Genetic differences, disease vulnerability

NIAID and their collaborators are studying COVID-19 patients in hundreds of hospitals to find out whether genetic differences may heighten an individual’s sensitivity to the virus. NIAID co-leads, with the Rockefeller University, the COVID Human Genetic Effort — a major international project that includes more than 50 genetic sequencing hubs — to discover the molecular underpinnings of COVID-19.

In the first paper to result from the effort, published Sept. 24, the authors reported that more than 10% of people with severe COVID-19 had antibodies that attacked their own immune system instead of the virus. Another 3.5% of people who developed severe COVID-19 carried a specific kind of genetic mutation that affects immunity.

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