Long-term Effects of COVID-19 on the Cardiopulmonary System in Adults & Children: Current Status & Questions to be Resolved … RECOVER, 2024, Rischard+

Long-term Effects of COVID-19 on the Cardiopulmonary System in Adults and Children: Current Status and Questions to be Resolved by the NIH RECOVER Initiative
Franz Rischard; Natasha Altman; Jacqueline Szmuszkovicz; Frank Sciurba; Erika Berman-Rosenzweig; Simon Lee; Sankaran Krishnan; Ngan Truong; John Wood; Aloke V. Finn

Topic Importance
Long COVID may occur in at least 10% of subjects recovering from severe acute respiratory syndrome coronavirus-2 (SARS-Co-V-2) infection and is often associated with debilitating symptoms. Among the organ systems that might be involved in its pathogenesis, the respiratory and cardiovascular systems may be central to common complaints seen in survivors of COVID including fatigue, dyspnea, chest pain, cough, and exercise intolerance. Understand the exact symptomatology, causes, and effects of Long COVID on the heart and lungs may help to discover new therapies. To that end, the National Institutes of Health (NIH) is sponsoring a national study population of diverse volunteers to support large-scale studies on the long-term effects of COVID-19.

Review Findings
The NIH (REsearching COVID to Enhance Recovery) RECOVER Initiative is currently recruiting participants in the United States to answer critical questions about Long COVID. The study consists of adult and pediatric cohorts as well as an electronic health records (EHR) cohort. Based upon symptoms, individuals undergo prespecified medical testing to understand whether abnormalities can be detected and followed longitudinally. Here we outline current understanding of the clinical symptoms and pathophysiology of Long COVID with respect to the cardiopulmonary system in adults and children and then determine how the clinical, EHR, and autopsy cohorts of RECOVER will attempt the answer the most pressing questions surrounding the long-term effects of COVID-19.

Conclusions
Data generated from RECOVER will provide guidance about missing gaps in our knowledge about Long COVID and how they might be filled by data gathered through RECOVER.


Link | Paywall (CHEST)

 

Summarising the "Research questions to be answered by the RECOVER Study" —

Arrhythmias

• What is the incidence of palpitations in patients with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) compared to a non-COVID infected cohort? • How are palpitations and electrocardiographic abnormalities related to abnormalities (inflammation or scarring) found on cardiac magnetic reasonance imaging (MRI)?

Microangiopathic and thrombotic coronary and cerebrovascular disease

• Are there long-term changes to cardiac structure and function attributable to COVID-19, as measured by echocardiography and cardiac MRI?
• Are symptoms such as chest pain and worsening dyspnea related to changes in cardiac structure, function and possible inflammation or fibrosis?

Myopericarditis

• Can viral persistence in cardiac specimens, as measured in the RECOVER autopsy cohort, be considered an explanation for cardiac dysfunction post COVID?
• What is the true prevalence of myopericarditis, as diagnosed via biomarkers, echocardiogram, and cardiac MRI, in patients recovering from COVID-19 infection?

Inappropriate Sinus Tachycardia and Postural Orthostatic Tachycardia Syndrome (POTS)

• What is the incidence of inappropriate sinus tachycardia and POTS in patients suffering from Long-COVID symptoms?
• Can autonomic reflex testing and invasive cardiac hemodynamics better explain the pathophysiology of POTS development following COVID infection?

Abnormalities in pulmonary function and chest imaging: From acute SARS CoV-2 to Long COVID

• What is the incidence of PFT and CT chest imaging abnormalities in a well-matched control group versus potential Long COVID?
• How do persistent abnormalities on PFT and CT chest relate to patient symptom complexes or clusters in Long COVID?
• What combination of CT and PFT abnormalities after acute COVID place a patient at risk for progression of interstitial lung disease (ILD)?

Diffuse Lung Disease and Interstitial Lung Disease

• What factors during acute COVID predispose subjects to PC-ILD when compared to infected asymptomatic subjects?
• Does persistent viral infection, autoimmunity or both underlie the pathophysiology of PC-ILD?
• What are the CT patterns of PC-ILD versus infected asymptomatic individuals and uninfected matched controls and what is the clinical trajectory (i.e., progression, stability, or regression).

Pulmonary Macro and Micro Thrombotic Disease

• What is the incidence and prevalence of pulmonary embolism among subjects >3 months from acute COVID-19 relative to uninfected matched control subjects?
• What is the incidence and prevalence of micro-vascular change on CT and dual-energy CT among subjects > 3 months from acute COVID relative to matched uninfected controls?
• What is the relationship between macro and micro vascular CT findings after acute COVID and patient symptomatology?
• Is there a mechanistic association between macro and micro vascular CT changes and coagulopathy (i.e., d-dimer, fibrinogen, etc.) and/or the inflammasome activation?
• Of the patients with dyspnea and exertional intolerance after acute COVID, what is the incidence and prevalence of post-COVID cardiovascular disease, post COVID cardiovascular syndrome, and PC-ILD?
• What are the CPET associated abnormalities of the PASC-cardiovascular syndrome and to what degree do dysfunctional breathing and abnormalities in peripheral oxygen extraction/utilization account for these abnormalities?
• Do CPET abnormalities correspond to specific symptom clusters or phenotypes based on multi-dimensional clustering such as echocardiography, cardiac MRI, PFT, CT chest?

Cardiovascular Impact of Pediatric Long COVID

• What is the prevalence of cardiac symptoms and abnormalities on cardiac imaging and electrophysiologic testing in a well-matched control group versus children with Long COVID?
• How do persistent abnormalities on cardiac imaging and electrophysiologic testing relate to symptom complexes in children with Long COVID?

Pulmonary Impact of Pediatric Long COVID

• What is the prevalence of respiratory symptoms in children with Long COVID versus a well-matched control group?
• What is the prevalence of abnormalities in pulmonary function testing and cardiopulmonary exercise testing in children with Long COVID versus a well-matched control group?
• How do persistent abnormalities on PFT relate to patient symptom complexes in children with Long COVID?

Multisystem Inflammatory Syndrome in Children (MIS-C)

• What is the range of symptoms that children with PASC are experiencing?
• What is the prevalence of cardiac symptoms and abnormalities on cardiac imaging and electrophysiologic testing in a well-matched control group versus children with PASC?
• How do persistent abnormalities on cardiac imaging and electrophysiologic testing relate to patient symptom complexes or clusters in children with PASC?
• What is the prevalence of respiratory symptoms, pulmonary function testing and cardiopulmonary testing in a well-matched control group versus children with PASC?