Cardiorespiratory Abnormalities in Patients Recovering from Coronavirus Disease 2019

Abstract

Background Large number of patients around the world are recovering from COVID-19; many of them report persistence of symptoms. Objectives We sought to test pulmonary, cardiovascular and peripheral responses to exercise in patients recovering from COVID-19. Methods We prospectively evaluated patients who recovered from COVID-19 using a combined anatomic/functional assessment. All patients underwent clinical examination, laboratory tests, and a combined stress echocardiography and cardiopulmonary exercise test. We measured left ventricular volumes, ejection fraction, stroke volume, heart rate, E/e' ratio, right ventricular function, VO 2 , lung volumes, Ventilatory efficiency, O 2 saturation and muscle O 2 extraction in all effort stages and compared them to historical controls. Results A total of 71 patients were assessed 90.6±26 days after onset of COVID-19 symptoms. Only 23 (33%) were asymptomatic. The most common symptoms were fatigue (34%), muscle weakness/pain (27%) and dyspnea (22%). VO 2 was lower among post-COVID-19 patients compared to controls (p=0.03, group by time interaction p=0.007). Reduction in peak VO 2 was due to a combination of chronotropic incompetence (75% of post-COVID-19 patients vs. 8% of controls, p<0.0001) and insufficient increase in stroke volume during exercise (p=0.0007, group by time interaction p=0.03). Stroke volume limitation was mostly explained by diminished increase in left ventricular end-diastolic volume (p=0.1, group by time interaction p=0.03) and insufficient increase in ejection fraction (p=0.01, group by time interaction p=0.01). Post-COVID-19 patients had higher peripheral O 2 extraction (p=0.004) and did not have significantly different respiratory and gas exchange parameters compared to controls. Conclusions Patients recovering from COVID-19 have symptoms associated with objective reduction in peak VO 2 . The mechanism of this reduction is complex and mainly involves a combination of attenuated heart rate and stroke volume reserve.

Chronotropic Incompetence in Non-Hospitalized Patients with Post-COVID-19 Syndrome

“…The results showed the presence of chronotropic incompetence in 12.5% of ambulatory patients as a possible central cause for these symptoms and not only due to skeletal muscle dysfunction as other have suggested [28]. To our knowledge, this is one of few studies [11,28,29] exploring functional cardiorespiratory abnormalities in post-COVID-19 conditions and the first to describe the long-term chronotropic incompetence persistence in a non-hospitalized post-COVID-19 syndrome cohort.…”

“…Chronotropic incompetence is defined as a limitation to increase HR in response to the metabolic demands proposed by exercise and may be responsible for the appearance of fatigue and exercise intolerance in patients with post-COVID-19 condition [11]. During exercise, the increase in HR is mainly due to the cessation of parasympathetic activity induced by movement and, secondarily, by adrenergic sympathetic stimulation.…”

Evidence for impaired chronotropic responses to and recovery from 6‐minute walk test in women with post‐acute COVID‐19 syndrome

“…Therefore, the relationship between %Pred 6MWT and lung volumes would be expected. Yet, our observations cannot eliminate the possibility that the capacity to perform higher‐intensity exercise would be impaired in women recovering from mild‐to‐moderate illness, especially given that peak aerobic capacity appears to be reduced during recovery from mild‐to‐critical COVID‐19 in comparison to matched control subjects (Singh et al., 2021 ; Szekely et al., 2021 ). Additional work is needed to clarify whether relationships exist between reduced lung volumes and exercise tolerance at higher relative work intensities among individuals recovering from COVID‐19.…”

“…Other accounts have provided evidence supporting impaired chronotropic responses to maximal exercise in individuals recovering from COVID‐19 (Dorelli et al., 2021 ; Szekely et al., 2021 ). Chronotropic incompetence (defined as failure to achieve ≥ 80% HR reserve) during a maximal cardiopulmonary exercise test was observed in 75% of individuals ∼3 months into recovery from mild‐to‐critical SARS‐CoV‐2 illness compared with 8% of control subjects (Szekely et al., 2021 ). These changes were accompanied by higher right atrial pressures at rest along with reduced left ventricular end‐diastolic volume and left ventricular ejection fraction during exercise (Szekely et al., 2021 ).…”

“…Chronotropic incompetence (defined as failure to achieve ≥ 80% HR reserve) during a maximal cardiopulmonary exercise test was observed in 75% of individuals ∼3 months into recovery from mild‐to‐critical SARS‐CoV‐2 illness compared with 8% of control subjects (Szekely et al., 2021 ). These changes were accompanied by higher right atrial pressures at rest along with reduced left ventricular end‐diastolic volume and left ventricular ejection fraction during exercise (Szekely et al., 2021 ). Additionally, a delayed HRR during the initial minute after maximal graded exercise has been documented in previously hospitalized SARS‐CoV‐2 patients exhibiting exercise ventilatory inefficiency (minute ventilation/carbon dioxide production slope above upper limits of normal) in comparison to those with normal ventilatory efficiency slopes (Dorelli et al., 2021 ).…”