Cardiopulmonary exercise testing in COVID-19 patients at 3 months follow-up
Authors: De Marzo V , Clavario P , Lotti R , Barbara C , Porcile A , Guglielmi G , Russo C , Autala A J , Griffo R , Parati G , Corra' U , Porto I 
Published: October 2021

Abstract

Background
Long-term effects of Coronavirus Disease of 2019 (COVID-19) and their sustainability are of the utmost relevance. For the chronic phase, the main concerns are the development of pulmonary interstitial disease and/or lingering cardiovascular involvement. How to intercept, assess, and treat these patients with long-term consequences of COVID-19 remains uncertain.

Purpose
We aimed to determine: 1) functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2) those characteristics associated with CPET performance; 3) safety and tolerability of CPET.

Methods
We prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 discharged alive at a single hospital in northern Italy. At 3-month from hospital discharge, complete clinical evaluation, trans-thoracic echocardiography, cardiopulmonary exercise testing (CPET), pulmonary function test (PFT), and dominant leg extension (DLE) maximal strength evaluation were performed.

Results
From 225 patients discharged from March to November 2020 we excluded 12 incomplete/missing cases, and 13 unable to perform CPET leading to a final population of 200 patients. At PFT all median parameters were within normality range.
Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3–103.1). Ninety-nine (49.5%) patients had %pVO2 below, whereas 101 (50.5%) above the 85% predicted value (indicating normality).
Sixteen (16.2%) patients had respiratory, 28 (28.9%) cardiac, 21 (21.2%) mixed-cardiopulmonary, and 34 (34.3%) non-cardiopulmonary limitation of exercise. One-hundred sixty (80.0%) patients complain at least one symptom, without relationship with peakVO2.
Multivariate linear regression analysis showed percent-predicted forced expiratory volume in one-second (β=5.29, p=0.023), percent-predicted diffusing capacity of lungs for carbon monoxide (β=6.31, p=0.001), and DLE maximal strength (β=14.09, p=0.008) independently associated with peakVO2.
At sensitivity analysis, the results of previous multivariate linear regression analysis were also similar among sub-groups of patients with no previous significant disease in anamnesis (cardiovascular disease except for arterial hypertension, respiratory disease, kidney disease, or cancer) and of those with a length of hospital stay ≤7 days.
None major event was reported during/after CPET, whereas only two cases (1.0%) had a mild symptomatic hypotension post exercise. None of the involved health professionals developed COVID-19.

Conclusions
CPET after COVID-19 is safe and about 1/3rd of COVID-19 survivors show functional capacity limitation mainly explained by muscular impairment, calling for future research to identify patients at higher risk of long-term effects that may benefit from careful surveillance and targeted rehabilitation.

Funding Acknowledgement
Type of funding sources: None. Types of mainly CPET limitationPeak VO2 per leg extension strength