In a recent issue of JACC: Heart Failure, Mancini et al1 report on cardiopulmonary exercise testing (CPET) in 41 patients with persistent dyspnea more than 3 months after recovery from a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. The main findings were disordered breathing and decreased peripheral oxygen extraction (EO2), much like reported in the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Is this enough for a CPET phenotyping of post-acute sequelae of SARS-CoV2 infection, or long coronavirus disease-2019 (COVID-19)?
The results of Mancini et al1 actually confirm those reported in 581 long COVID-19 patients from 11 studies, which we reviewed in June 2021.2 Our meta-analysis uncovered a hazy CPET profile with mild decrease in maximum O2 uptake (VO2), decreased anaerobic threshold, normal ventilation to carbon dioxide (VE/VCO2) slope on average but somewhat skewed to increased values, preserved ventilatory reserve and decreased EO2, all suggestive of deconditioning on the recovery of an acute inflammatory process, prolonged bed rest and post-traumatic syndrome (PST).
Mancini et al1 go into detailed analysis of individual responses. This is prone to false-positive signals as CPET measurements are numerous and exposed to variability, particularly in middle-aged patients with comorbidities (which were noted in 31 of the reported patients). Comparing with matched controls rather than predicted values would have been preferable. Yet the patients showed erratic increases in respiratory rate, with early CPET tachypnea as typically seen in PTS. There also was a tendency to decreased peripheral EO2. This was wrongly calculated as arteriovenous O2 content differences (DavO2) divided by hemoglobin rather than by arterial O2 content, but characteristic anyway of deconditioning. Preload failure diagnosed in a subgroup of 7 patients disclosed vagotonic deconditioning as occurs in sedentary overweight subjects. Only 1 patient had upper limit of normal (at 1.97 WU) of pulmonary vascular resistance at exercise, not convincingly diagnostic of exercise-induced pulmonary hypertension.
Long COVID-19 and ME/CFS are patient advocacy–derived entities. Generously funded research to uncover their physiologic or biologic determinants (since 1987 for ME/CFS) has failed until now. Admirable efforts such as those reported by Mancini et al1 should not distract from adequate attention to their dominant psychological components.
Footnotes
The authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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