Sex-Based Differences in Pulmonary Function and Cardiopulmonary Response 30 Months Post-COVID-19: A Brazilian Multicentric Study

Abstract

Aim: (I) to verify if there are sex differences in respiratory function, respiratory muscle strength, and effort limitation in individuals recovered from severe acute COVID-19 30 months after the initial infection, and (II) to evaluate the influence of length of stay on cardiorespiratory capacity among men and women. Methods: Cross-sectional observational multicentric study with participants from five Brazilian states (São Paulo, Amazonas, Minas Gerais, Bahia, and Brasília). We assessed lung function and respiratory muscle strength by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and cardiorespiratory fitness by cardiopulmonary exercise test (CPET). Results: 86 individuals were stratified by sex (48 women and 38 men). Females had significantly longer hospitalization for acute COVID-19 (p < 0.05) and showed a marked reduction in MIP (cmH₂O and % predicted). Regarding the CPET, women presented lower V˙O₂% predicted, O₂ pulse, and oxygen uptake efficiency slope (OUES, % predicted) (p < 0.05). In addition, women also had greater abnormal combinations between RER < 1.10, OUES < 80% predicted, VE/VVM < 15% [3 (6.2%)] and V˙O₂% predicted < 80%, V˙E/V˙CO₂ slope and V˙O₂/workload < 8.4 mL/min/W [8 (17%)]. The regression analysis showed a significant influence of age, length of hospitalization (< and >10 days), and FEV₁/FVC (%) on the V˙O₂ peak (mL·kg^-1·min^-1). Secondarily, we found that women hospitalized for more than 10 days had worse O₂ pulse (p = 0.03), OUES % predicted (p < 0.001), and worse V˙O₂% predicted (p < 0.009). Conclusion: Women exhibited more pronounced impairments in several key indicators of cardiopulmonary function 30 months post-infection.

Keywords: COVID-19; cardiopulmonary health; cardiorespiratory fitness; exercise test; long-COVID.

Figure 1

Stratification of patients by sex (men and women) and days of hospitalization (more and less than 10 days) in the acute phase of COVID-19 to evaluate differences in (A) age, (B) OUES (% predicted), (C) O₂ pulse and (D) $\dot{\mathrm{V}}$O₂ (% predicted). Notes: oxygen uptake efficiency slope (OUES); ANOVA two-way.

Figure 2

Venn diagram depicting the overall differences between females (C,D) and males (A,B) with an abnormal RER < 1.10, OUES < 80% predicted, VE/VVM < 15%, $\dot{\mathrm{V}}$O₂% predicted < 80%, $\dot{\mathrm{V}}$E/$\dot{\mathrm{V}}$CO₂ slope, and $\dot{\mathrm{V}}$O₂/workload < 8.4 mL/min/W. The figure illustrates the N^o of patients (%) within each area. Chi-square: RER < 1.10 p = 0.34; OUES < 80% predicted p = 0.05; VE/VVM < 15% p = 0.87; $\dot{\mathrm{V}}$O₂% predicted < 80% NA; $\dot{\mathrm{V}}$E/$\dot{\mathrm{V}}$CO₂ slope p = 0.06; $\dot{\mathrm{V}}$O₂/worload < 8.4 p = 0.10.