Predictors of Functional Outcome After COVID-19 Illness: A Prospective Study in Mexico

Rationale: Clinical outcomes after coronavirus-2019 disease (COVID-19) have been well described, including persistent symptoms and abnormalities on pulmonary function tests and imaging. However, the presence and underlying mechanism of functional impairments after COVID-19 remain unclear. Methods: Patients with SARS-CoV-2 confirmed by real-time polymerase chain reaction were recruited from a hospital in Yucatan, Mexico. Patients who were able to complete surveys, pulmonary function tests, and 6-minute walk tests within 30-90 days after symptom onset were included. COVID-19 severity based on the location of treatment and need for supplemental oxygen was categorized as follows: mild (ambulatory, no hypoxemia), moderate (ambulatory, supplemental oxygen (O2) ≤ 5 l/min), or severe (hospitalised, O2 > 5 l/min without invasive mechanical ventilation). The association between COVID-19 severity and 6-minute walk distance (6MWD) was determined using multivariable linear regression, and underlying mechanisms for reduced 6MWD were then explored. Unadjusted and adjusted linear regression models were used to determine the association between potential predictor variables (Borg dyspnea, Borg fatigue, and end-exercise SpO2) and 6MWD. A final model with Borg dyspnea and end-exercise SpO2 as co-primary endpoints was performed to explore the independent relationship of these two predictors with 6MWD. All models were adjusted for age, sex, smoking, and body mass index (BMI). Results: There were 148 eligible patients with a mean age of 47±14 years and BMI of 32±7kg/m2, with 66% males and 19% current or past-smokers. There were 26% patients with mild, 10% with moderate, and 64% with severe COVID-19 illness. The mean follow-up time was 59 days. The mean 6MWD was 450±104m (83±19% predicted). Patients with severe COVID-19 had a lower 6MWD compared to patients with mild COVID-19 (- 52m [95%CI -88,-15], p=0.006). There was no difference in 6MWD between mild and moderate COVID-19. For every unit increase, Borg dyspnea (coefficient -21m [95%CI -31,-10]) and end-exercise SpO2 (coefficient 13m [95%CI 8,18]) were associated with 6MWD (both p<0.001);however, Borg fatigue was not. When Borg dyspnea and end-exercise SpO2 were included as co-primary predictors, both variables remained independently associated with reduced 6MWD with coefficients of -13m (95%CI -23,-2) and 10m (95%CI 5,16), respectively, after adjusting for covariates (Table 1). Conclusions: Patients with severe COVID-19 had significantly lower 6MWD compared to those with mild disease. Exertional dyspnea and hypoxemia were independent predictors of lower 6MWD, suggesting that dyspnea related to hypoxemia is not the sole driver of reduced functional capacity in COVID- 19 survivors.