Diagnostic Usefulness of Spiroergometry and Risk Factors of Long COVID in Patients with Normal Left Ventricular Ejection Fraction

Abstract

The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic has brought forth various clinical manifestations and long-term complications, including a condition known as long COVID. Long COVID refers to a persistent set of symptoms that continue beyond the acute phase of the disease. This study investigated the risk factors and the utility of spiroergometry parameters for diagnosing patients with long COVID symptoms. The 146 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with normal left ventricular ejection fraction and without respiratory diseases were included and divided into two groups: the group demonstrating long COVID symptoms [n = 44] and the group without long COVID symptoms [n = 102]. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. ClinicalTrials.gov Identifier: NCT04828629. Patients with long COVID symptoms had significantly higher age [58 (vs.) 44 years; p < 0.0001], metabolic age [53 vs. 45 years; p = 0.02)], left atrial diameter (LA) [37 vs. 35 mm; p = 0.04], left ventricular mass index (LVMI) [83 vs. 74 g/m2, p = 0.04], left diastolic filling velocity (A) [69 vs. 64 cm/s, p = 0.01], the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E’) [7.35 vs. 6.05; p = 0.01], and a lower ratio of early to late diastolic transmitral flow velocity (E/A) [1.05 vs. 1.31; p = 0.01] compared to the control group. In cardiopulmonary exercise testing (CPET), long COVID patients presented lower forced vital capacity (FVC) [3.6 vs. 4.3 L; p < 0.0001], maximal oxygen consumption measured during incremental exercise indexed per kilogram (VO2max) [21 vs. 23 mL/min/kg; p = 0.04], respiratory exchange ratio (RER) [1.0 vs. 1.1; p = 0.04], forced expiratory volume in one second (FEV1) [2.90 vs. 3.25 L; p = 0.04], and a higher ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) [106 vs. 100%; p = 0.0002]. The laboratory results pointed out that patients with long COVID symptoms also had a lower rate of red blood cells (RBC) [4.4 vs. 4.6 × 106/uL; p = 0.01]; a higher level of glucose [92 vs. 90 mg/dL; p = 0.03]; a lower glomerular filtration rate (GFR) estimate by Modification of Diet in Renal Disease (MDRD) [88 vs. 95; p = 0.03]; and a higher level of hypersensitive cardiac Troponin T (hs-cTnT) [6.1 vs. 3.9 pg/mL; p = 0.04]. On the multivariate model, only FEV1/FVC% (OR 6.27, 95% CI: 2.64–14.86; p < 0.001) independently predicted the long COVID symptoms. Using the ROC analysis, the FEV1/FVC% ≥ 103 was the most powerful predictor of spiroergometry parameters (0.67 sensitive, 0.71 specific, AUC of 0.73; p < 0.001) in predicting the symptoms of long COVID. Spiroergometry parameters are useful in diagnosing long COVID and differentiating it from cardiovascular disease.