Reduced exercise capacity, chronotropic incompetence, early systematic inflammation in cardiopulmonary phenotype Long COVID, 2023, Durstenfeld et al

Preprint.
Inflammation during early post-acute COVID-19 is associated with reduced exercise capacity and Long COVID symptoms after 1 year, 2022, Durstenfeld

Abstract

BACKGROUND Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.

METHODS We performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; NCT04362150) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms (dyspnea, chest pain, palpitations, and fatigue) adjusted for confounders and linear regression to estimate differences between those with and without symptoms adjusted for confounders.

RESULTS Out of 120 participants in the cohort, 46 participants (unselected for symptom status) had at least one advanced cardiac test performed at median 17 months following initial SARS-CoV-2 infection. Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), higher extracellular volume was associated with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/23 (57%) with cardiopulmonary symptoms or fatigue had reduced exercise capacity (peak VO2<85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). The adjusted difference in peak VO2 was 5.9 ml/kg/min lower (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006) among those with symptoms. Chronotropic incompetence was the primary abnormality among 9/15 (60%) with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-α) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO2 more than 1 year later.

CONCLUSIONS Cardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with objectively reduced exercise capacity measured on cardiopulmonary exercise testing more than 1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC.

https://www.medrxiv.org/content/10.1101/2022.05.17.22275235v2

Now published: see later post for abstract

 

This again. I can't say I understand much of it. But here it is again.

 

Now published as Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID (2023, J Infectious Diseases) and tagged as a major article.

 

Open access, some liberal summary quotes on findings and hypotheses —

 

They are, but I think for this paper they were looking at mechanisms for baseline exertion intolerance, rather than mechanisms that might contribute to PEM. From their prior paper Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis (2022) —

 

How many times are they planning to repeat these same old CPET/ICPET studies that always return the same results? Isn't research supposed to be incremental?

 

See also Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS (2023)
and Orthostatic Intolerance and Chronotropic Incompetence in Patients With Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (2023)

ETA

and Chronotropic incompetence an overlooked determinant of symptoms and activity limitation in ME/CFS (2019, Frontiers in Pediatrics)
and Chronotropic Incompetence (2011, Circulation) as noted in that 2019 thread by @Snow Leopard.

 

Free fulltext:
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad131/7159960

JOURNAL ARTICLE ACCEPTED MANUSCRIPT

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Matthew S Durstenfeld, Michael J Peluso, Punita Kaveti, Christopher Hill, Danny Li, Erica Sander, Shreya Swaminathan, Victor M Arechiga, Scott Lu, Sarah A Goldberg,
Rebecca Hoh, Ahmed Chenna, Brandon C Yee, John W Winslow, Christos J Petropoulos, J Daniel Kelly, David V Glidden, Timothy J Henrich, Jeffrey N Martin, Yoo Jin Lee, Mandar A Aras, Carlin S Long, Donald J Grandis, Steven G Deeks, Priscilla Y Hsue



The Journal of Infectious Diseases, jiad131, https://doi.org/10.1093/infdis/jiad131

Published:

11 May 2023




Abstract
BACKGROUND
Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.

METHODS
We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in a post-COVID cohort, compared those with or without symptoms, and correlated findings with previously measured biomarkers.

RESULTS
Sixty participants (median age 53, 42% female, 87% non-hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted) compared to 3/19 (16%) without symptoms (p = 0.02). Adjusted peak VO2 was 5.2 ml/kg/min lower (95%CI 2.1-8.3; p = 0.001) or 16.9% lower percent predicted (95%CI 4.3-29.6; p = 0.02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias were absent.

CONCLUSIONS
Cardiopulmonary symptoms >1 year following COVID-19 were associated with reduced exercise capacity, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary Long COVID.