Researchers have identified significant differences in how the immune systems of women and men respond to the virus that causes COVID-19, representing a potential target for drug intervention. The team led by researchers at Yale University in the US 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.
The study, published in the journal Science Signaling, shows 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, the researchers said.
Male patients with severe COVID-19 cases were also more likely to have a high ratio of kynurenic acid to kynurenine, a by-product of the amino acid L-tryptophan, which is used to create the nutrient niacin, they said. "It is so vital to understand as much of the altered biochemistry in a disease as possible. we maximise the chances of developing an accurate disease-model and potential route to treatment," said Nicholas Rattray, from the University of Strathclyde, UK.
"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," Rattray said. The 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 those 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.