Sex-specific patterns of symptom burden, psychological distress, and work productivity impairment in post-acute sequelae of COVID-19: a 10-month dynamic cohort study.
A considerable proportion of patients experience post-acute sequelae of COVID-19 (PASC). Increasing evidence suggests sex-related differences, yet systematic longitudinal analyses remain limited. This study aimed to examine sex-specific differences in symptoms, psychological burden, work productivity and physical activity over ten months following acute COVID-19.
In this prospective, dynamically enrolled cohort study, patients with ongoing symptoms after confirmed SARS-CoV-2 infection were followed over a 10-month observation period. Patients conducted at the post-COVID outpatient clinic of the department of respiratory medicine and infectious diseases at Hannover Medical School, Germany. The assessment included patient-reported outcome measures, pulmonary function tests, six-minute walk tests, and capillary blood gas analysis. All outcome comparisons between sexes were adjusted for age, BMI, COVID-19 severity, and comorbidities using generalised linear mixed-effects models, with sex-by-time interaction terms tested to assess whether differences changed over follow-up, and p-values corrected for multiple testing across all outcome comparisons using the Holm method. A sensitivity analysis was performed in the subgroup of patients with complete follow-up at all four visits.
Five hundred ninety patients attended to our clinic and a total of 433 patients were eligible and consecutively enrolled. Males were older (56 years vs. 52 years, p = 0.002), had more cardiovascular comorbidities (16% vs. 5%, p < 0.001), and experienced more severe COVID-19 (28% vs. 8%, p < 0.001). After adjustment for age, BMI, COVID-19 severity, and comorbidities, and Holm correction for multiple testing across all 27 outcome comparisons, females showed higher fatigue (Fatigue Assessment Scale, adjusted β = 3.3, Holm-adjusted p = 0.006), higher anxiety (GAD-2, β = 0.5, p = 0.021), lower quality of life (EQ-5D-3L, β = -0.6, p = 0.004), and greater work productivity impairment, both as a continuous score (WPAI-VAS, β = 1.3, p = 0.031) and as a binary indicator of clinically relevant impairment (OR = 3.0, p = 0.020). Females also had higher percent-predicted (pp) total lung capacity (p < 0.0001) and lower pCO2 (p < 0.0001), whereas males had higher pp diffusion capacity (p = 0.001). Headache (p < 0.001) and chest tightness (p = 0.011) were reported more frequently by females. None of these differences varied significantly over the 10-month follow-up (all sex-by-time interaction p ≥ 0.41), indicating no evidence that these differences changed over time. No significant sex differences remained after adjustment for depression (PHQ-2), lung function parameters, sex/height-adjusted exercise capacity, post-exercise dyspnoea or oxygen saturation, or most acute-COVID-19 symptoms other than headache and chest tightness. Regression models separately for each sex revealed fever (OR = 2.48, 95% CI: 1.11-5.57, p = 0.027) and diarrhoea (OR 2.33, 95%CI: 1.05-5.16, p = 0.038) during acute COVID-19 were associated with higher odds of work productivity impairment (WPAI-VAS ≥ 2) in males. In females, higher BMI (OR = 2.06, 95% CI: 1.13-3.76, p = 0.018) and dyspnoea during acute COVID-19 (OR = 4.38, 95% CI: 1.55-12.40, p = 0.005) were associated with increased odds. Formal interaction analyses showed a significant interaction only for dyspnoea after Holm correction.
After accounting for baseline imbalance in age, BMI, COVID-19 severity, and comorbidities, and after correcting for multiple testing, sex-specific differences persisted for fatigue, anxiety, quality of life, and work productivity impairment, as well as selected lung function parameters. These differences did not change significantly across the 10-month observation period and did not show a significant sex-by-time interaction. The findings support the need for individualised, sex-specific follow-up focused on fatigue, psychological burden, and work productivity in patients with PASC.
In this prospective, dynamically enrolled cohort study, patients with ongoing symptoms after confirmed SARS-CoV-2 infection were followed over a 10-month observation period. Patients conducted at the post-COVID outpatient clinic of the department of respiratory medicine and infectious diseases at Hannover Medical School, Germany. The assessment included patient-reported outcome measures, pulmonary function tests, six-minute walk tests, and capillary blood gas analysis. All outcome comparisons between sexes were adjusted for age, BMI, COVID-19 severity, and comorbidities using generalised linear mixed-effects models, with sex-by-time interaction terms tested to assess whether differences changed over follow-up, and p-values corrected for multiple testing across all outcome comparisons using the Holm method. A sensitivity analysis was performed in the subgroup of patients with complete follow-up at all four visits.
Five hundred ninety patients attended to our clinic and a total of 433 patients were eligible and consecutively enrolled. Males were older (56 years vs. 52 years, p = 0.002), had more cardiovascular comorbidities (16% vs. 5%, p < 0.001), and experienced more severe COVID-19 (28% vs. 8%, p < 0.001). After adjustment for age, BMI, COVID-19 severity, and comorbidities, and Holm correction for multiple testing across all 27 outcome comparisons, females showed higher fatigue (Fatigue Assessment Scale, adjusted β = 3.3, Holm-adjusted p = 0.006), higher anxiety (GAD-2, β = 0.5, p = 0.021), lower quality of life (EQ-5D-3L, β = -0.6, p = 0.004), and greater work productivity impairment, both as a continuous score (WPAI-VAS, β = 1.3, p = 0.031) and as a binary indicator of clinically relevant impairment (OR = 3.0, p = 0.020). Females also had higher percent-predicted (pp) total lung capacity (p < 0.0001) and lower pCO2 (p < 0.0001), whereas males had higher pp diffusion capacity (p = 0.001). Headache (p < 0.001) and chest tightness (p = 0.011) were reported more frequently by females. None of these differences varied significantly over the 10-month follow-up (all sex-by-time interaction p ≥ 0.41), indicating no evidence that these differences changed over time. No significant sex differences remained after adjustment for depression (PHQ-2), lung function parameters, sex/height-adjusted exercise capacity, post-exercise dyspnoea or oxygen saturation, or most acute-COVID-19 symptoms other than headache and chest tightness. Regression models separately for each sex revealed fever (OR = 2.48, 95% CI: 1.11-5.57, p = 0.027) and diarrhoea (OR 2.33, 95%CI: 1.05-5.16, p = 0.038) during acute COVID-19 were associated with higher odds of work productivity impairment (WPAI-VAS ≥ 2) in males. In females, higher BMI (OR = 2.06, 95% CI: 1.13-3.76, p = 0.018) and dyspnoea during acute COVID-19 (OR = 4.38, 95% CI: 1.55-12.40, p = 0.005) were associated with increased odds. Formal interaction analyses showed a significant interaction only for dyspnoea after Holm correction.
After accounting for baseline imbalance in age, BMI, COVID-19 severity, and comorbidities, and after correcting for multiple testing, sex-specific differences persisted for fatigue, anxiety, quality of life, and work productivity impairment, as well as selected lung function parameters. These differences did not change significantly across the 10-month observation period and did not show a significant sex-by-time interaction. The findings support the need for individualised, sex-specific follow-up focused on fatigue, psychological burden, and work productivity in patients with PASC.
Authors
Sauer Sauer, Boblitz Boblitz, Drick Drick, Wiestler Wiestler, Scharbau Scharbau, Pries Pries, Bollmann Bollmann, Hoeper Hoeper, Pink Pink
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