Why Men Are More Often Affected by Severe COVID-19

Men are three times more likely to need intensive care compared to women during COVID-19 infection. The reason behind this isn’t fully understood, but previous research has found that complications from COVID-19 arise because of a dysregulated and hyperinflammatory immune response. Normally, the immune response produces neutrophil extracellular traps (NETs) that entangle and restrict invading pathogens. These NETs allow immune cells called neutrophils to kill the pathogen without damaging host cells. However, in a hyperinflammatory state, such as that seen during severe COVID-19, NETs are linked to immunothrombosis and increased mortality. 

A recent study examined plasma from study participants with confirmed SARS-CoV-2 infection. In this study, researchers treated neutrophils with the plasma samples from the patients and observed what happened to the neutrophils. They saw that neutrophils treated with plasma from COVID-19 patients triggered more NET release and that the response depended on disease severity: plasma from individuals with more severe disease triggered more NET release.

The researchers also looked at cytokine levels, finding that samples from patients with severe COVID-19 had higher levels of some proinflammatory cytokines that activate neutrophils. One cytokine known to be involved in NET formation was higher in men than in women.

This research paves the way for other studies and potential treatments that target neutrophil activation and NET production.

Citation

Backman, E., et al. (2025). Elevated Plasma Levels of NET Components in Men with Severe COVID-19 Correlates to Increased Amounts of IL-18. European Journal of Immunology, 55(5), e202451546. https://doi.org/10.1002/eji.202451546