Post COVID Individuals Can Continue To Suffer From Exercise Ventilatory Inefficiency 34 Months After Hospital Discharge!

COVID-19 News: The repercussions of SARS-CoV-2 infection extend beyond the acute phase, raising concerns about lingering health effects in post-COVID individuals. Among these concerns, exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequelae with potential implications for respiratory and cardiovascular health. This COVID-19 News report delves into the extended aftermath of COVID-19, examining the persistence of EVin 34 months after hospital discharge and its intricate association with cardiorespiratory responses during exercise in post-COVID patients.


Post COVID Individuals Can Continue To Suffer From Exercise
Ventilatory Inefficiency 34 Months After Hospital Discharge

Understanding Post-COVID Condition and Exercise Ventilatory Efficiency
Post-COVID condition encompasses a spectrum of symptoms and clinical findings that persist beyond the acute phase of SARS-CoV-2 infection. The cardiopulmonary exercise test (CPET) has been instrumental in revealing a reduction in maximal exercise capacity and oxygen uptake (VO2peak) in these patients, shedding light on the underlying pathophysiological mechanisms contributing to exercise intolerance and unexplained dyspnea.
 
Exercise ventilatory efficiency is a key parameter evaluated through the examination of how minute ventilation (VE) correlates with the amount of carbon dioxide produced (VCO2). Metrics such as the slope of VE against VCO2 (VE/VCO2slope), the lowest observed value (nadir), and the carbon dioxide ventilatory equivalent at the first ventilatory threshold (VE/VCO2 at θL) are used to quantify this relationship. Elevated values of VE/VCO2 commonly indicate EVin, a condition associated with breathing dysfunction due to excessive ventilation.
 
Ventilatory inefficiency serves as a global indicator of cardiorespiratory response to exercise and a prognostic marker in chronic patients, ranking second only to VO2peak. EVin is recognized as a hallmark of pulmonary vascular diseases, including pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, where it serves as an excellent prognostic marker.

The origins of EVin in the context of COVID-19 involve a subset of asymptomatic survivors exhibiting this condition. Prevalence rates have been reported at 29% and 17% at 6 and 12 months post-discharge, respectively. Post-COVID patients with EVin exhibit lower values of end-tidal pressure of CO2 (PETCO2) throughout exercise, indicating hyperventilation and correlating with impairments in diffusing capacity (DLCO). Evidence at 12 months following severe COVID-19 infections suggests that despite achieving normal VO2peak levels, patients may display signs of EVin linked to pulmonary microvascular disease and increased dead space ventilation.
 
Assessing Long-Term Persistence of EVin
To explore the persistence of EVin in post-COVID patients, a longitudinal study was conducted on 32 selected individuals. Two CPETs were performed at 6 months (T0) and 34 months (T1) after hospital discharge. The study aimed to investigate the long-term presence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Various cardiorespiratory parameters, including VO2peak, PETCO2 levels, oxygen uptake efficiency slope (OUES), and others, were measured, with statistical significance set at p<0.05. The presence of EVin at both T0 and T1 defines persisting EVin (pEVin).
 
Analyzing the Results: Persistent EVin and Cardiovascular Responses
Out of the cohort, 16% exhibited pEVin at 34 months post-discharge. Subjects with pEVin demonstrated lower PETCO2 levels throughout exercise, indicating hyperventilation compared to those with ventilatory efficiency (EVef). EVef subjects showed selective improvements in DLCO and oxygen pulse, suggesting a potential recovery in cardiorespiratory function over time. However, those with pEVin did not exhibit these improvements.
 
Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse, and OUES. These correlations underscore the potential prognostic value of OUES and EVin in post-COVID follow-ups. The study highlights the clinical importance of long-term follow-up for post-COVID patients, as those with persistent EVin demonstrated altered and potentially unfavorable cardiovascular responses to exercise.
 
Unraveling the Mechanisms: Hyperventilation and Cardiovascular Dysfunction
Hyperventilation emerges as a common manifestation in subjects recovering from COVID-19, frequently associated with ventilatory inefficiency. The exact cause of this hyperventilation remains unknown but is believed to be related to an imbalance in ventilatory control resulting from heightened activation of activator systems or suppression of inhibitory systems. In post-COVID survivors, there is a close relationship between hypocapnia resulting from resting hyperventilation and residual DLCO, the most common functional abnormality in the early convalescence phase.
 
Despite maintaining normal lung functionality, maximal exercise capacity, and VO2peak, some asymptomatic post-COVID patients exhibit EVin. Higher VE/VCO2slope than the normal range is an indicator of EVin, potentially influenced by anthropometric variables. EVin in post-COVID patients may be caused by altered arterial partial carbon dioxide pressure (PaCO2) set-point and chemosensitivity, or an abnormally high dead space fraction during exercise involving ventilation or pulmonary perfusion.
 
Cardiovascular Implications of EVin in Post-COVID Patients
Post-COVID patients, even those who recover from severe infections, may face long-term cardiovascular complications. EVin is recognized as a hallmark of pulmonary vascular disease and increased dead-space ventilation. Studies indicate that EVin prevalence correlates with D-Dimer plasma concentrations during hospital stays, indicating potential microvascular damage. Normotensive post-COVID patients may exhibit significantly higher blood pressure responses in post-exercise recovery during CPET, emphasizing the intricate interplay between EVin and cardiovascular responses.
 
Oxygen pulse (O2 pulse), reflecting the amount of oxygen extracted by tissues per heartbeat, and oxygen uptake efficiency slope (OUES) are key parameters to assess cardiovascular risk. Low O2 pulse values during exercise may be related to increased cardiovascular and all-cause mortality in certain populations.
 
Longitudinal studies on post-COVID patients suggest a reduced aerobic capacity and O2 pulse independent of VO2peak levels, hinting at potential subclinical signs of altered cardiovascular response due to the infection.
 
Conclusion: Emphasizing the Need for Prolonged Follow-Up
In conclusion, the longitudinal analysis conducted at 34 months post-discharge confirms the persistence of EVin in 16% of post-COVID individuals. These subjects exhibit a hyperventilation status that closely correlates with an altered and unfavorable cardiovascular response to exercise. The study emphasizes the importance of prolonged follow-up studies in individuals recovering from COVID-19 to unravel the underlying mechanisms and long-term implications of EVin on respiratory and cardiovascular health.
 
These findings underscore the need for continued monitoring and tailored interventions to optimize patient outcomes and improve the quality of life for post-COVID individuals. The complex interplay between EVin, hyperventilation, and cardiovascular responses warrants further research to guide comprehensive management strategies and enhance our understanding of the long-term consequences of COVID-19. Given the persistent nature of EVin and its correlation with unfavorable cardiovascular responses, ongoing investigations are crucial for delineating effective management approaches and interventions tailored to post-COVID patients.
 
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.researchsquare.com/article/rs-3928238/v1
 
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