Hyperventilation: A Possible Explanation for Long-Lasting Exercise Intolerance in Mild COVID-19 Survivors?

Abstract

Since the outbreak of the coronavirus (COVID-19) pandemic, most attention has focused on containing transmission and addressing the surge of critically ill patients in acute care settings. As we enter the second phase of the pandemic, emphasis must evolve to post-acute care of COVID-19 survivors. Persisting cardiorespiratory symptoms have been reported at several months after the onset of the infection. Information is lacking on the pathophysiology of exercise intolerance after COVID-19. Previous outbreaks of coronaviruses have been associated with persistent dyspnea, muscle weakness, fatigue and reduced quality of life. The extent of Covid-19 sequelae remains to be evaluated, but persisting cardiorespiratory symptoms in COVID-19 survivors can be described as two distinct entities. The first type of post-Covid symptoms are directly related to organ injury in the acute phase, or the complications of treatment. The second type of persisting symptoms can affect patients even with mild initial disease presentation without evidence of organ damage. The mechanisms are still poorly qualified to date. There is a lack of correlation between initial symptom severity and residual symptoms at exertion. We report exercise hyperventilation as a major limiting factor in COVID-19 survivors. The origin of this hyperventilation may be related to an abnormality of ventilatory control, by either hyperactivity of activator systems (automatic and cortical ventilatory control, peripheral afferents, and sensory cortex) or failure of inhibitory systems (endorphins) in the aftermath of pulmonary infection. Hyperventilation-induced hypocapnia can cause a multitude of extremely disabling symptoms such as dyspnea, tachycardia, chest pain, fatigue, dizziness and syncope at exertion.

Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation

“…It thus appears that circulatory impairment might be the missing link that could explain some of the residual symptoms in post-COVID-19 syndrome, but we should keep in mind that the mechanism remains obscure. The ventilatory inefficiency observed in our symptomatic cohort is also observed in the hyperventilation syndrome [36], which has been recently suggested as a potential mechanism of the post-COVID-19 syndrome [37]. In fact, this syndrome has been described in broad lung conditions, such as acute pulmonary embolism, pneumonia, chronic interstitial lung diseases, and after viral infections [36].…”

“…Finally, another potential mechanism could be the autonomic dysfunction. Maladaptive function of the autonomic nervous system in COVID-19 survivors may contribute to the persistence of fatigue, shortness of breath, and palpitations [37]. Consistent with this hypothesis, Dorelli et al observed a slower heart rate recovery suggestive of dysautonomia among post-COVID-19 patients with ventilatory inefficiency [39].…”

“…Motiejunaite et al reviewed eight patients with residual symptoms after COVID-19 infection and reported similar findings to us. All of them showed a decreased exercise capacity, and five patients showed an elevated VE/V CO2 ratio suggestive of hyperventilation syndrome [37]. In this respect, hyperventilation may induce hypocapnia and it is believed to be caused by an abnormal ventilatory control by either stimulation of activator systems or suppression of inhibitory systems.…”

“…Both groups presented similar RER (1.08 (1.05-1.16) vs. 1.13 (1.05-1.28); p = 0.172) and % of predicted O 2 pulse (98 (73-110) vs. 106 (96-110); p = 0.054). Regarding the ventilatory efficiency, a higher VE/V CO2 slope (32 (28-37.4) vs. 29.4 (26.9-31.4); p = 0.022) and lower PET CO2 at AT (34.5 (32)(33)(34)(35)(36)(37)(38)(39) vs. 38 (36)(37)(38)(39)(40); p = 0.025) in patients with persistent dyspnea were detected. Neither desaturation on exercise nor differences in breathing reserve were detected.…”

More complaints than findings - Long-term pulmonary function in children and adolescents after COVID-19

“…Further studies with a larger, more representative cohort (including patients with critical respiratory involvement) and over a longer period are needed for better understanding of the respiratory longterm impairment after SARS-CoV-2 infection in children and adolescents. The discrepancy between subjective persistent respiratory complaints and normal pulmonary function might be caused by functional respiratory disorders, for example hyperventilation, as already described in adults [26,27].…”