Sex-specific immune response in COVID-19 linked to product of cellular metabolism


Researchers studying COVID-19 patients have found a metabolic pathway that is highly correlated with immune responses only in male patients, who are known to be more likely to suffer severe cases and die of the disease, representing a potential target for therapeutic intervention.

In a study published in the journal Science Signaling, the authors report that male COVID-19 patients were more likely than female patients or healthy control subjects to have elevated levels of kynurenic acid, a product of amino acid metabolism.

High levels of kynurenic acid have been linked to several diseases, such as schizophrenia and HIV-related diseases.

Male patients with severe COVID-19 cases were also more likely to have a high ratio of kynurenic acid to kynurenine, a byproduct of the amino acid L-tryptophan, which is used to create the nutrient niacin.

The University of Strathclyde is a partner in the study, which was led at Yale University. The research has successfully identified significant differences in how the immune systems of women and men respond to the virus that causes COVID-19.

Dr Nicholas Rattray, a Chancellor’s Fellow with Strathclyde Institute of Pharmacy and Biomedical Sciences, was a partner in the research, involved in the formulation and design of the study and analysis of data.

He said: “It is so vital to understand as much of the altered biochemistry in a disease as possible. By doing so, we maximise the chances of developing an accurate disease-model and potential route to treatment.

“This research highlights the important role metabolites play in understanding COVID-19 severity and, with further investigation and validation, holds great potential for the development of further understanding of how a person’s different immune status can reflect their response to disease.”

Researchers studied blood samples drawn from 22 female and 17 male patients at Yale New Haven Hospital after confirmation of COVID-19 infection. They then compared these samples with samples from 20 uninfected health care providers.

The researchers positively identified 75 metabolites, which are molecular products of digestion and cellular processes. After adjusting for the patients’ age, body-mass index, sex, and other characteristics, the researchers determined 17 metabolites were associated with COVID-19 infection.

Further analysis revealed the strong relationship between high levels of kynurenic acid, as well as high ratios of kynurenic acid to kynurenine in the male immune response and worse patient outcomes.