Factors associated with phenotypes of dyspnea in post-COVID-19 condition: a cross-sectional study

Post-COVID-19 condition (PCC) is defined as the persistence of symptoms, like fatigue and dyspnea, at least 3 months post-COVID infection. As dyspnea is a common symptom, we attempted to further clinically phenotype those with PCC-associated dyspnea. 1642 adults (average age of 49.6y with 63% female-predominance and BMI of 31.2 kg/m²) with physician confirmed diagnosis of PCC from June 2020-April 2023 in Alberta, Canada were included. Those with dyspnea were more likely to be female (56.5%, p = 0.005) and have higher BMI (31.3 kg/m² vs. 29.5 kg/m²; p = 0.0008), history of asthma (21.1% vs. 12.3%; p < 0.001), more persistent PCC symptoms (p = 0.0001), more functional limitations, as well as lower quality of life (p < 0.0001). Multivariable-adjusted logistic regression analysis demonstrated dyspnea was independently associated with fatigue (OR = 4.20; CI = 2.71,6.59) and inversely associated with hospitalization for COVID-19 (OR = 0.53; CI = 0.32,0.91), age (OR = 0.98 per one year of age; CI = 0.96,0.99) and 6-min-walk-distance per 10 m difference (OR = 0.98, CI = 0.96,1.0). Fatigue was a predictor of dyspnea, and was associated with milder infection, higher BMI, and reduced 6-min-walk-distance despite normal pulmonary function. Reduced TLC or DLCO was associated with more severe infection and reduced 6-min-walk-distance. Thus, we speculate there are at least two dyspnea-associated phenotypes: phenotype with pronounced fatigue (normal PFT) and phenotype with pronounced pulmonary abnormalities (abnormal PFT). Improved understanding of the dyspnea-associated phenotypes may allow for better targeted rehabilitation.