Sex differences of post-Covid patients undergoing outpatient pulmonary rehabilitation

Abstract

Following years of pandemic severe acute respiratory syndrome coronavirus 2 infections labelled Covid-19, long lasting impairment summarized as post-Covid syndrome (PCS) challenges worldwide healthcare. Patients benefit from rehabilitation programs, but sex specific aspects of improvement remain little understood. The aim of the study was to assess whether women and men differ in response to outpatient pulmonary rehabilitation for PCS. 263 (54.4% female) patients partaking in outpatient pulmonary rehabilitation (OPR) due to PCS between March 2020 and July 2022 were included in a prospective observational cohort study. Outcomes were assessed at baseline and before discharge from OPR and included six-minute walking distance (6MWD), 1-second forced expiratory volume (FEV1), diffusion capacity for carbon monoxide, maximal inspiratory pressure (MIP), dyspnea (medical research council scale), and post-Covid functional status scale (PCFS). Sexspecific changes in outcomes following OPR were assessed by linear mixed model and presented as mean differences (MD) with 95% confidence intervals. Linear regression was applied to test whether 6MWD correlates with PCFS and the minimal clinically important difference (MCID) in 6MWD regarding an improvement of at least one point in PCFS was computed with logistic regression. Significant improvement throughout OPR was observed for all outcomes (all p < 0.0001). Despite less severe Covid-19 infections, PCFS scores remained higher in females after OPR (p = 0.004) and only 19.4% of women compared to 38.5% of men achieved remission of functional impairment. At baseline as well as after OPR, females showed higher symptom load compared to men in dyspnea (p = 0.0027) and scored lower in FEV1 (p = 0.009) and MIP (p = 0.0006) assessment. Performance in 6MWD was comparable between men and women. An increase of 35 m in 6MWD was computed as minimal clinically important difference to improve functional impairment. Both subjective symptoms such as fatigue and dyspnea and objective impairment in performance in pulmonary function were more frequently observed among women. Despite improvement throughout OPR in both women and men, the sex-gap in symptom load could not be closed as women less often achieved remission from functional impairment due to PCS. Intensified treatment of these symptoms should be considered in women undergoing rehabilitation for PCS. While female sex is protective during the acute infection of Covid-19, women are at increased risk of developing post-Covid syndrome (PCS) even after only mild Covid-19 infections. Severity and frequency of symptoms such as fatigue and shortness of breath are known to be higher in women compared to men. Many different rehabilitation protocols are used for PCS, but a knowledge gap regarding sex related differences in rehabilitation success remains. Both female and male patients with PCS undergoing outpatient pulmonary rehabilitation improved in the maximum walking distance achieved within 6 min and selfrated impairment in everyday living. Although women less frequently required inpatient treatment for acute Covid-19 infection, female patients with PCS showed higher impairment in everyday living, lower capacity of physical exercise and more frequent shortness of breath, fatigue and breathing muscle weakness. Only 19.4% of women compared to 38.5% of men achieved complete remission of impairment in everyday living. Our results show that women treated for PCS retain greater symptom burden and are at risk of unsuccessful rehabilitation, calling for more targeted treatment in female patients after Covid-19 infection. Six weeks of outpatient pulmonary rehabilitation successfully improved 6-minute walking distance, pulmonary function and Covid-19 related functional limitations in daily living. Women achieved remission of functional limitations less often than men (19.4% vs. 38.5%). Women reported more severe dyspnea and showed greater impairment of maximal inspiratory pressure and forced expiratory volume compared to men.