Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing post-COVID-19

Abstract

Background The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Methods Fifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. Findings At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET. By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4.3 mls/m2, P=0.005) decreased and RV ejection fraction (+3.2%, P=0.0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2 secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. Interpretation In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. Funding NIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.

Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection

“…We report prevalence of cardiac impairment (19% and 15% at 6 and 12 months) consistent with previous studies, providing standardisation of metrics and definition, which can be used at scale in research and practice to document and monitor cardiac impairment(8,9,14, 21, 24). We confirm that abnormalities in T1 (in line with previous research(8,9,14,15,25), T2 and LGE, as well as functional abnormalities (8,13,26,28) are most common in Long COVID patients. Acute Covid can present with myocardial inflammation; ongoing COVID-19 patients can also have myocarditis, but it is harder to diagnose, and often missed with echocardiography.…”

“…Blood biomarkers and symptoms did not differentiate hospitalised and non-hospitalized groups. On MRI assessment, cardiac T1 abnormalities(12,29) and multi-organ involvement (particularly renal)(8,9,13) were more prevalent in those with cardiac impairment and acute COVID-19 hospitalisation, as in other published studies.…”

“…On MRI assessment, cardiac T1 abnormalities(12,29) and multi-organ involvement (particularly renal)(8,9,13) were more prevalent in those with cardiac impairment and acute COVID-19 hospitalisation, as in other published studies. improvement on CMR nor lung parenchymal recovery(13). There are implications for roles of blood investigations and imaging in diagnosis and follow up of cardiac and multi-organ impairment in detailed biochemical and imaging characterisation of multi-organ function starting in April 2020.…”

“…Our results indicate that, despite women being more affected by Long COVID, men have higher risk of cardiac impairment(19). Potential contributory factors include: influence of biological sex on expression and regulation of angiotensin-converting enzyme 2, sex-differences in genetic and hormonal regulation of immune responses(20), sex-dependent patterns of coagulation, smoking or drinking(11–13)(22).…”

“…Dyspnoea, palpitations and chest pain are common, even 1 year after infection (11), but associations with cardiac impairment are unclear, and the subtypes more likely to recover have not been identified. In a large UK, post-COVID assessment service, almost half of individuals where cardiac magnetic resonance (CMR) scans were performed, had evidence of mild myocarditis (12) and symptom improvement at 6 months was neither correlated with improvement on CMR imaging nor lung parenchymal recovery (13).…”