key: cord-0874528-psc93kn5 authors: Wong, Alyson W.; López-Romero, Stephanie; Figueroa-Hurtado, Esperanza; Vazquez-Lopez, Saul; Milne, Kathryn M.; Ryerson, Christopher J.; Guenette, Jordan A.; Cortés-Telles, Arturo title: Predictors of reduced 6-minute walk distance after COVID-19: a cohort study in Mexico date: 2021-03-26 journal: Pulmonology DOI: 10.1016/j.pulmoe.2021.03.004 sha: b27e759b4dade3ea430bf21745277a4c7a282eda doc_id: 874528 cord_uid: psc93kn5 nan Clinical sequelae after COVID-19 have been well described, including abnormalities in pulmonary function tests, chest imaging, and patient-reported outcome measures. 1, 2 However, functional outcomes after COVID-19 are not well understood. We sought to identify the presence and underlying mechanisms of functional impairments after COVID-19. We hypothesized that patients with more severe COVID-19 would have a lower 6-minute walk distance (6MWD) at follow-up and that exertional dyspnea, fatigue, and hypoxemia would independently predict a lower 6MWD. This was a consecutively-enrolled prospective cohort study. Patients who were seen in a hospital in Yucatan, Mexico with SARS-CoV-2 confirmed by real-time polymerase chain reaction were referred to a COVID-19 clinic for follow-up. Patients who were able to complete surveys, pulmonary function tests (PFTs), and 6-minute walk tests (6MWT) were included. There were no exclusion criteria. PFTs and 6MWT were conducted according to international guidelines. [3] [4] [5] Patients did not receive formal physical rehabilitation during their recovery. This study received institutional ethics approval. COVID-19 severity was categorized as mild (no hypoxemia), moderate (hypoxemia without mechanical ventilation), or severe (hypoxemia with mechanical ventilation). The association between COVID-19 severity and 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, first in separate models and then in a final model with both Borg dyspnea and end-exercise SpO2 as co-primary endpoints to explore the independent relationship of these two predictors with 6MWD. All models were adjusted for age, sex, smoking, body mass index (BMI), and time from symptom onset. Statistical analyses were performed using R version 3.6.3 (R Foundation). A total of 295 patients were referred to the COVID-19 clinic between May and August 2020, of whom 225 were enrolled (65 patients declined and 5 were lost to follow-up). The overall cohort had 62% males and 19% ever-smokers, with a mean age of 47±13 years and BMI of 32±7kg/m 2 ( predictors in a single model, both variables remained independently associated with 6MWD with coefficients of -13m (95%CI -22,-3) and 7m (95%CI 3,10), after adjusting for covariates ( Table 2) . A lower 6MWD was independently associated with exertional dyspnea and hypoxemia, suggesting that dyspnea and hypoxemia may have distinct mechanisms through which they impact functional capacity. Of the patients who had exertional hypoxemia (i.e., SpO2 decline ≥4%), 45% had a walk distance less than the lower limits of normal (LLN) and 100% had a DLCO < LLN, which suggests that desaturation during exercise is associated with parenchymal and/or pulmonary vascular phenomena. Although dyspnea is typically accompanied by hypoxemia during acute COVID-19 illness, 6 our study found that exertional dyspnea predicted reduced J o u r n a l P r e -p r o o f functional capacity, regardless of whether end-exercise hypoxemia was present or not. The underlying mechanisms of persistent dyspnea after COVID-19 remain unclear; however, it is likely that physiologic sequelae contribute to this lingering symptom. In a previous study using the same cohort, we demonstrated that patients with persistent dyspnea had lower FVC, forced expiratory volume in 1 second, and higher proportion of restrictive ventilatory pattern compared to patients without persistent dyspnea. Furthermore, patients with abnormal DLCO at follow-up are more likely to have an elevated d-dimer on admission, suggesting that microangiopathies could contribute to dyspnea. 7 This study had several limitations. First, our data did not include validated tools such as the Charlson Comorbidity Index to assess how comorbidities impact 6MWD. Second, this study was from a single Mexican center. However, this unique population adds to the understanding of COVID-19 recovery in diverse patient backgrounds. Third, we did not have information on treatment during the acute illness which could impact outcomes. We demonstrate the impact that persistent dyspnea and hypoxemia have on functional capacity in patients after COVID-19. Further research to understand the underlying mechanisms of persistent symptoms, particularly dyspnea that is disproportionate to physiologic and radiologic findings, is needed in order to help patients recovering from COVID-19. A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations Patient-reported outcome measures after COVID-19: a prospective cohort study ERS/ATS standards for single-breath carbon monoxide uptake in the lung Standardization of Spirometry ATS statement: guidelines for the sixminute walk test Pulmonary function and functional capacity in COVID-19 survivors with persistent dyspnea Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery The authors received no funding for this work. The authors declare that there is no conflict of interest.