Autoantibody Response to Prior SARS-CoV-2 Infection Differs by Sex

Researchers assessed the difference in autoantibody response between men and women with previous SARS-CoV-2 infection.

Prior SARS-CoV-2 infection, even in the absence of severe COVID-19, is associated with an autoantibody (AAB) response that varies between men and women, according to study results published in the Journal of Translational Medicine. However, AAB reactivity patterns were found to be present in both sexes for up to 6 months after COVID-19 symptoms.

Recent studies have reported a possible association between SARS-CoV-2 infection and autoimmune activation after infection. Despite women being predominantly affected by many autoimmune conditions, emerging evidence shows a paradoxical shift to predominant autoimmune activation in men than women following severe COVID-19. The prevalence of such paradoxical sex-differences in autoimmune response across the broader clinical spectrum of SARS-CoV-2 infection is unclear.

In the current study, researchers sought to investigate the sex-specific autoimmune activation after SARS-CoV-2 exposure in the absence of severe disease.

Using an array to detect AABs to 91 antigens previously linked to a range of classic autoimmune diseases, the researchers comprehensively examined the diversity of AAB responses in health care workers (HCWs) who were exposed to SARS-CoV-2 infection

A total of 177 participants were included in the primary cohort, with a mean age of 35 years; 65% were women; and 68% non-White, with 28% of Hispanic/Latinx ethnicity. Participants had a prior SARS-CoV-2 infection confirmed by a positive anti-N IgG index and self-reported the presence or absence of distinct symptoms associated with COVID-19 via an electronic survey. The symptoms burden score was constructed based on the total number of reported symptoms (21 symptoms) experienced within 6 months prior to the blood draw.

The participants were categorized into 3 groups: asymptomatic with no symptoms reported (n=23), mildly symptomatic with 1 to 7 symptoms reported (n=64), and more than mildly symptomatic with more than 7 symptoms reported (n=90).

The secondary comparator cohort included 53 healthy control participants (51% men) and 6 patients with systemic lupus erythematosus (SLE).

Results of the study reported no significant difference in the rates of sex-specific positivity for the AABs between the HCW group and the control group. Among the HCWs, an overall broader and diverse increase in AAB levels was observed in men compared with women. Among asymptomatic individuals, men had 28% AAB reactivity (25 of 91 antigens), whereas women had 72% AAB reactivity (66 antigens). In contrast, among individuals with mild and more than mild symptoms, men had an AAB reactivity of 64% (58 antigens) and 82% (75 antigens) and women had an AAB reactivity of 36% (33 antigens) and 18% (16 antigens), respectively.

Researchers also reported a sex-specific AAB response to symptom clusters, with men vs women showing predominant associations that varied by symptom burden. The sex-specific AAB associations were observed for up to 6 months following symptom-onset, irrespective of disease severity.

Limitations of the study included limited generalizability of the findings, the small sample size of men, and potential bias due to self-reported symptom burden.

Researchers concluded, “Our results reveal that prior SARS-CoV-2 infection, even in the absence of severe clinical disease, can lead to a broad AAB response that exhibits sex-specific patterns of prevalence and antigen selectivity. Further understanding of the nature of triggered AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.”


Liu Y, Ebinger JE, Mostafa R, et al. Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection. J Transl Med. 2021;19(1):524. doi:10.1186/s12967-021-03184-8

This article originally appeared on Rheumatology Advisor