ABSTRACT
Rationale: Dyspnea is one of the most common symptoms associated with coronavirus disease 2019 (COVID-19). Over 40% of COVID-19 survivors experience persistent dyspnea approximately 60 days following hospital discharge (Carfi et al., JAMA, 2020). Understanding differences in pulmonary function and functional capacity between those that do and do not experience persistent dyspnea may provide insight into the underlying mechanisms of this symptom in survivors of COVID-19. Accordingly, the purpose of this study was to compare spirometry, diffusing capacity of the lungs for carbon monoxide (DLCO), and 6-minute walk test (6MWT) outcomes in COVID-19 patients with and without persistent dyspnea. We hypothesized that COVID-19 patients with persistent dyspnea would have lower forced vital capacity (FVC), DLCO, and 6-minute walk distance (6MWD) compared to patients without persistent dyspnea. Methods: Non-critical patients (n=186) with varying degrees of COVID-19 severity reported all persistent symptoms using a standardized questionnaire and underwent pulmonary function testing and a 6MWT between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n=70) and those without (n=116) persistent dyspnea. Independent t-tests and Fisher's Exact test were used where appropriate to compare anthropometric, pulmonary function, symptoms, and 6MWT variables. Results: There was no difference in the time of experimental testing relative to the onset of acute COVID-19 symptoms between those with vs. those without dyspnea (59±13 vs. 60±14 days, respectively). Groups had similar age, height, mass, body mass index, sex, and frequency of comorbidities. Patients with persistent dyspnea had significantly lower FVC (p=0.03), forced expiratory volume in 1 second (p=0.04), and DLCO (p=0.01) compared to non-dyspnea patients. 47% of patients with persistent dyspnea had a restrictive pattern on spirometry compared to 33% in the non-dyspnea group. Patients with persistent dyspnea also had lower 6MWD (% predicted, p=0.03) and nadir oxygen saturation (p<0.001), and higher Borg 0-10 ratings of dyspnea and fatigue (both p<0.001) during the 6MWT compared to patients without persistent dyspnea. Conclusions: We have shown that dyspnea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnea had a number of abnormalities compared to well-matched patients without persistent dyspnea, including greater restriction on spirometry, lower DLCO, reduced functional capacity, and increased desaturation and exertional symptoms during a 6MWT. This suggests that there is a true physiological mechanism that may explain persistent dyspnea after COVID-19.
ABSTRACT
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.