3.1 Study desing
From October 2020 to February 2021, pediatric patients recovered from coronavirus infection were evaluated according to the protocols in force: the first 17 control patients were evaluated according the PA protocol; the next 28 patients were evaluated according to the revised protocols applied to all athletes (A), not just professionals.
Inclusion criteria: age less than 18 years; previous SARS-CoV-2 infection documented by polymerase chain reaction on a nasopharyngeal swab; negativity for at least 30 days; patients practicing competitive sports.
Exclusion criteria: non-cooperating patients for functional tests due to age and/or psycho-physical limitations; patients with a negative swab for less than 30 days; symptomatic patients (cough, cold, fever); patients with a history of congenital heart disease even if corrected and cured; patients with a positive history of hyper or hypokinetic arrhythmias; patients with bronchial asthma.
It was also decided to exclude one patient with Multi-System Inflammatory Syndrome in Children (MIS-C) as this case was included in a different study protocol.
For all patients we described demographic data, duration of infection, severity of symptoms according to NIH classification [10].
All patients were subjected to a serological test to rule out any false positives.
Blood chemistry tests, including markers of myocardial damage, were performed only in PA group.
All patients underwent an echocardiographic evaluation with determination of the ejection fraction.
Patients in PA protocol underwent a symptom-limited cardiopulmonary exercise test (CPET) using a treadmill, following the modified Bruce protocol with continuous 12-lead electrocardiographic monitoring system.
Data collected during cardiopulmonary test included: respiratory quotient (RQ), the peak of VO2 consumption during the test (Peak VO2, defined as the average value in the last 20 seconds of the effort in relative –ml/kg/min-values) and the ratio between ventilation and exhaled carbon dioxide (VE/VCO2).
We considered the test as maximal when subjects reached at least RQ > 1 and we used for VO2max and VE/VCO2 ratio the cut-off suggested by Takken et al. [11]: a VO2max > 50 mL/kg/min has been considered as normal, 40–50 mL/kg/min good, 20–40 reduced; 35 was considered the cut-off for VE/VCO2 ratio.
A standard 24 h Holter ECG monitoring was performed in this group.
Patients in A protocol underwent a maximal exercise test using a treadmill, following the modified Bruce protocol with continuous 12-lead electrocardiographic monitoring system.
We considered the test as maximal when the heart rate reached at least 85% of the theoretical value for age.
Desaturation during effort was considered as losing 4 or more point of blood oxygen saturation.
Systolic blood pressure was also obtained at baseline (BP), during and at the end of exercise (BP max).
Lung function was measured by conventional spirometry; Forced Vital Capacity (FVC) and Forced Expiratory Volume at the 1st second (FEV1) were expressed as percentage of predicted values [12].
In the PA group, although not required by the protocols, lung diffusion capacity for carbon monoxide (DLCO) was also assessed, measured by means of the single-breath test. The hemoglobin value was taken for correcting the DLCO. Measurements were expressed as percentages of predicted normal values. Diffusion deficit was considered as DLCO < 80% of predicted value.
All pulmonary function test was performed according to the protocols for the prevention of coronavirus disease [13].
3.2 Data analysis
Continuous variables were described using mean with standard deviation (SD) and compared with unpaired Student’s t-test, if normally distributed, or with Mann-Whitney U test, if not normally distributed. Categorical variables were reported as frequencies and compared with Chi-square test.
A p value of < 0.05 was considered statistically significant. All statistical analyses were performed using MedCalc Statistical Software version 15.8 (MedCalc Software bvba, Ostend, Belgium; https://www.medcalc.org; 2015).