Sex- and Gender-specific Risk Factors of Post-COVID-19 Syndrome: A Population-based Cohort Study in Switzerland

Gebhard, C. E.; Suetsch, C.; Bengs, S.; Deforth, M.; Buehler, K. P.; Nadia Hamouda, N.; Meisel, A.; Schuepbach, R. A.; Zinkernagel, A. S.; Brugger, S. D.; Acevedo, C.; Patriki, D.; Wiggli, B.; Beer, J. H.; Friedl, A.; Twerenbold, R.; Kuster, G. M.; Pargger, H.; Tschudin-Sutter, S.; Schefold, J. C.; Spinetti, T.; Dussault-Cloutier, A.; Henze, C.; Pasqualini, M.; Sager, D. F.; Mayrhofer, L.; Grieder, M. C.; Tontsch, J.; Franzeck, F.; Wendel Garcia, P. D.; Hofmaenner, D. A.; Scheier, T.; Bartussek, J. D.; Chrobok, L.; Staehli, D.; Lott, N.; Graemer, M.; Mikail, N.; Rossi, A.; Zellweger, N.; Opic,

Background: Evidence to date indicates that mortality of acute coronavirus disease (COVID-19) is higher in men than in women. Conversely, women seem more likely to suffer from long-term consequences of the disease and pronounced negative social and economic impacts. Sex- and gender-specific risk factors of COVID-19-related long-term effects are unknown. Methods: We conducted a multicentre prospective observational cohort study of 5838 (44.6% women) individuals in Switzerland who were tested positive for SARS-CoV-2 RNA between February and December 2020. Of all surviving individuals who met the inclusion criteria, 2799 (1285 [45.9%] women) completed a follow-up questionnaire. Findings: After a mean follow-up time of 197{+/-}77 days, women more often reported at least one persistent symptom (43.0% vs 31.5%, p<0.001) with reduced exercise tolerance and reduced resilience being the most frequently reported symptom in both sexes. Critical illness (intermediate or intensive care unit admission) during acute SARS-CoV-2 infection (odds ratio[95%CI]: 4.00[2.66-6.02], p<0.0001 was a risk factor of post-COVID-19 syndrome in both women and men. Women with pre-existing mental illness (1.81[1.00-3.26], p=0.049), cardiovascular risk factors (1.39[1.03-1.89], p=0.033), higher self-reported domestic stress levels (1.15[1.08-1.22], p<0.0001), and feminine gender identity (1.12[1.02-1.24], p=0.02) increased the odds of experiencing post-COVID syndrome. Conversely, obesity (1.44[1.03-2.02], p=0.034) increased the odds of post-COVID-19 syndrome in men, but not in women. Being responsible for household work (men, OR 0.82[0.69-0.97], p=0.021), taking care of children/relatives (women, 0.90[0.84-0.96], p=0.002) or being pregnant at the time of acute COVID-19 illness (OR 0.48[0.23-1.01], p=0.054) was associated with lower odds of post-COVID syndrome. Interpretation: Predictors of post-COVID syndrome differ between men and women. Our data reinforce the importance to include sex and gender to identify patients at risk for post-COVID syndrome so that access to care and early intervention can be tailored to their different needs.