Singh I; Joseph P; Heerdt PM; Cullinan M; Lutchmansingh DD; Gulati M;
Possick JD; Systrom DM; Waxman AB

Chest. 161(1):54-63, 2022 01.VI 1

BACKGROUND: Some patients with COVID-19 who have recovered from the acute
infection after experiencing only mild symptoms continue to exhibit
persistent exertional limitation that often is unexplained by conventional
investigative studies.
RESEARCH QUESTION: What is the pathophysiologic mechanism of exercise
intolerance that underlies the post-COVID-19 long-haul syndrome in
patients without cardiopulmonary disease?
STUDY DESIGN AND METHODS: This study examined the systemic and pulmonary
hemodynamics, ventilation, and gas exchange in 10 patients who recovered
from COVID-19 and were without cardiopulmonary disease during invasive
cardiopulmonary exercise testing (iCPET) and compared the results with
those from 10 age- and sex-matched control participants. These data then
were used to define potential reasons for exertional limitation in the
cohort of patients who had recovered from COVID-19.
RESULTS: The patients who had recovered from COVID-19 exhibited markedly
reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared
with control participants (70 +/- 11% predicted vs 131 +/- 45% predicted;
P < .0001). This reduction in peak VO2 was associated with impaired
systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen
content difference to arterial oxygen content ratio) compared with control
participants (0.49 +/- 0.1 vs 0.78 +/- 0.1; P < .0001), despite a
preserved peak cardiac index (7.8 +/- 3.1 L/min vs 8.4+/-2.3 L/min; P >
.05). Additionally, patients who had recovered from COVID-19 demonstrated
greater ventilatory inefficiency (ie, abnormal ventilatory efficiency
[VE/VCO2] slope: 35 +/- 5 vs 27 +/- 5; P = .01) compared with control
participants without an increase in dead space ventilation.
INTERPRETATION: Patients who have recovered from COVID-19 without
cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a
peripheral rather than a central cardiac limit, along with an exaggerated
hyperventilatory response during exercise.