Researchers studying COVID patients have uncovered a metabolic pathway linked to immune responses only in male patients, a group known to be more likely to suffer severe cases and die of the disease.
Male COVID patients were more likely than female patients or healthy control subjects to have elevated levels of kynurenic acid, a product of amino acid metabolism, according to the study. High levels of kynurenic acid have been linked to several diseases, such as schizophrenia and HIV-related diseases.
They found that male patients with severe COVID 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.
“We know that men are at higher risk than women of contracting severe cases of COVID and that sex differences in the body’s immune responses present a compelling explanation for this phenomenon,” said Caroline Johnson, an assistant professor of epidemiology at Yale School of Public Health and senior author of the study. “We also know that immune responses are regulated in part by metabolites, and so these new findings offer a key window into the mechanisms underlying how this disease affects female and male patients differently.”
The team studied blood samples drawn from 22 female and 17 male patients at Yale New Haven Hospital after confirmation of COVID infection. They then compared these samples with samples from 20 uninfected health care workers.
The researchers positively identified 75 metabolites, which are molecular products of digestion and cellular processes. After adjusting for age, body-mass index, sex, and other factors, the researchers identified 17 metabolites that were associated with COVID infection. Further analysis showed 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.
“Such sex-specific pathways provide major clues about how this disease infects and sickens individuals,” Prof Johnson said. “We can use this knowledge to create more effective treatments for this terrible disease and similar diseases.”
Source: Yale University
