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Autoantibody Responses in Males versus Females Following COVID-19

A study published in the Journal of Translational Medicine in late December 2021 explored how COVID-19 infection can trigger immune reactions that differ between men and women. Researchers at Cedars-Sinai Medical Center analyzed blood samples from 177 healthcare workers who had recovered from COVID-19, 65% women and 35% men. Their results were compared to samples from healthy pre-pandemic controls and from patients with systemic lupus erythematosus (SLE).

The researchers looked for autoantibodies, which are immune proteins that mistakenly target the body’s own cells. Normally, antibodies help fight infections, but when they persist or attack healthy tissue, they can contribute to autoimmune disease or post-viral complications.

All participants who had been infected with SARS-CoV-2 showed increased autoantibody activity, but the pattern varied by sex and symptom severity.

  • Asymptomatic infections: Women showed broader autoantibody activity, reacting to about 72% of the tested proteins, compared to 28% in men.
  • Mild infections: Men showed stronger activity, reacting to 64% of the proteins, compared to 36% in women.
  • Moderate infections: The difference widened further, with 80% of autoantibodies elevated in men and 18% in women.

This was the first study to show that even mild or symptom-free COVID-19 can set off lasting autoimmune activity, and that the pattern is reversed between men and women.

While autoimmune diseases are generally more common in women, men were more likely to experience strong immune activation after symptomatic infection. In contrast, women tended to develop autoimmune responses quietly, even when no symptoms were present.

The immune changes persisted for up to six months after infection. According to the researchers, these findings may help explain why men often have more severe cases of COVID-19, while women may be more prone to lingering, immune-related effects such as Long COVID.

Citation

Liu, Y., Ebinger, J.E., Mostafa, R. et al. Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection. J Transl Med 19, 524 (2021). https://doi.org/10.1186/s12967-021-03184-8