Autoantibody Responses in Males versus Females Following COVID-19 Infection

January 31, 2022

Researchers at Cedars-Sinai recruited 177 healthcare workers with confirmed SARS-CoV-2 infection to study autoantibody levels depending on the severity of COVID-19 between males and females. 65% of the patients included in the study were female; 35% were male. Autoantibody reactivity was compared to a cohort of SLE patients, as well as 91 antigens which span typical autoimmune diseases.

Most symptoms related to COVID-19 infection were experienced by both males and females. All patients with confirmed COVID-19 infection had elevated levels of autoantibodies. “Among the [healthcare worker] cases, males demonstrated an overall broader and more diverse elevation in [autoantibody] levels than females, particularly in relation to greater symptom burden.”

While females are more often afflicted with autoimmune disease, males have been observed to experience severe COVID-19 more often than females. “Among asymptomatic individuals, the breadth and magnitude of [autoantibody] reactivity was much more pronounced in females compared to males.” In this cohort of asymptomatic COVID-19 patients, [autoantibody] reactivity to 28% antigens was detected in males; 72% was detected in females. Among individuals with mild symptoms, autoantibodies to 64% of antigens showed positive reactivity in men, versus 36% in women. Among participants with moderate symptoms, autoantibodies to 80% of antigens showed positive reactivity in males versus 18% in females.

This is the first time a study has demonstrated autoimmune activation in females following an asymptomatic infection compared to males. Researchers speculate that autoantibody positivity in females following asymptomatic infection “represents initiation or proliferation and then persistence of self-reactive immunity with implications for post-acute chronic immune driven disease states.” These findings may shed light on long Covid following SARS-CoV-2 infection, and the clinical differences in its manifestation in males and females.

Researchers also observed sex-specifc autoantibody associations “up to 6 months following symptomatology, indicating that SARS-CoV-2 triggers a complement of [autoantibody] responses that persists over time – in a sex-specifc manner and irrespective of illness severity.”