Factors affecting exercise performance at the 6-min walk test in long-COVID: a multicenter study from Italy

The cofactors potentially affecting exercise performance after COVID-19 are still incompletely investigated. The contribution of several clinical and demographic variables to the exercise capacity measured with the 6-min walk test was assessed in multivariable analyses that used the absolute distance walked in 6 min (6MWD) and an impaired performance (6MWD < 60% of the predicted value) as study outcomes. The variables considered were age, sex, preexisting comorbidities, COVID-19 severity, pandemic phase, treatments administered in acute phase, SARS-CoV-2 vaccination, reinfection, time from acute infection, and presence of 30 persisting symptoms. The mean 6MWD recorded among 686 patients at a mean interval of 184 days from COVID-19 was 474 m, with 8.3% of them presenting values below 60% of the predicted value. 6MWD was affected by sex, comorbidities, COVID-19 severity, and some persisting symptoms. The estimated effect sizes were -29.9 m for severe/critical acute disease, between -26 and -87 m for six comorbidities (atrial fibrillation, renal failure, chronic liver disease, chronic pulmonary disease, ischemic heart disease, diabetes) and between -21 and -99 m for four persisting symptoms (nausea/vomiting, paresthesia, depressed mood, dyspnea). The 6MWD increased by 2.6 m per month elapsed from acute infection. A 6MWD < 60% was associated with female sex, more intensive respiratory support, four comorbidities (atrial fibrillation, renal failure, chronic pulmonary disease and ischemic heart disease), and two persisting symptoms (nausea/vomiting and palpitations/tachycardia). Exercise performance after COVID-19 is affected by multiple factors, with estimated effect sizes that are clinically relevant. The results also suggest some spontaneous improvement over time.