Ongoing myocardial inflammation and cardiac involvement in recovered COVID-19 patients
Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)
Introduction and methods
Case reports have suggested that COVID-19 affects the CV system in hospitalized patients [1-5]. However, much remains unknown about CV sequelae in unselected patients who recovered from COVID-19, including those who recovered at home, with no preexisting conditions, or had only mild or no symptoms. This prospective observational cohort study investigated the prevalence, extend, and type of CV sequelae in unselected patients who recently recovered from COVID-19 using serological markers of cardiac injury and cardiovascular magnetic resonance (CMR) imaging.
Participants were identified from the University Hospital Frankfurt COVID-19 Registry, which covers the area of the State of Hesse in Germany. Eligible participants were diagnosed with SARS-CoV-2 by RT-PCR on a swab test, had no respiratory symptoms after a minimum of 2 weeks from the original diagnosis, and had a negative result on a swab test at the end of the isolation period. A total of 100 patients who recently recovered from COVID-19 were included in this study, 53 were male and the median age was 49 (IQR 45-53) years. High sensitivity troponin T (hsTnT) and N-terminal pro-b-type natriuretic peptide were determined from blood samples and participants underwent CMR examination. Median time interval between COVID-19 diagnosis and CMR was 71 (IQR 64-92) days.
Comparisons were made with age-matched and sex-matched healthy controls (normotensive adults who were not taking cardiac medications, had normal cardiac volumes and function and had no evidence of scar; n=50). Comparisons were also made with risk factor-matched patients (matched for age, sex, hypertension, diabetes, smoking, known coronary artery disease, or comorbidities; n=57).
- In this unselected cohort of 100 patients who recently recovered from COVID-19, most patients recovered at home (n=67), of which 18 were asymptomatic and 49 patients had minor to moderate symptoms. A total of 33 patients required hospitalization, of which 28 required oxygen supplementation. 2 Patients underwent mechanical ventilation and 17 patients underwent non-invasive ventilation with positive airway pressure.
- Direct questioning about symptoms on the day of CMR examination revealed palpitations (n=20) and atypical chest pain (n=17). 36 Participants reported ongoing shortness of breath and general exhaustion compared with pre-COVID-19 status. No patients reported typical angina symptoms or recent syncope.
- hsTnT values were detectable (≥ 3pg/mL) in 71 participants and significantly elevated (>13.9 pg/mL) in 5 participants.
- Patients who recently recovered from COVID-19 had lower LVEF and RVEF, higher left ventricular volume and mass and raised native T1 and T2 measures, compared with healthy controls and risk factor-matched controls.
- A total of 78 participants had abnormal CMR findings, including raised myocardial native T1 (n=73), raised myocardial native T2 (n=60), myocardial late gadolinium enhancement (LGE; n=32), and pericardial enhancement (n=22). 12 Participants had an ischemic-type pattern of myocardial LGE. An endomyocardial biopsy was taken in 3 participants with severe abnormalities (significantly higher hsTnT, native T1, native T2 measures in upper tertile, LGE, and LVEF<50%). This revealed active lymphocytic inflammation without evidence of any viral genome.
- A small but significant difference for native T1 measures was found between patients who recovered at home vs. those who recovered in the hospital (median native T1 measures: 1122 [IQR 1113-1132] ms vs. 1143 [IQR 1131-1156] ms, P=0.02). No significant differences between patients who recovered at home vs. in the hospital were found for native T2, hsTnT or N-terminal pro-b-type natriuretic peptide.
- No significant correlation with duration between the positive test for COVID-19 and the myocardial measures (native T1, native T2 and hsTnT) was observed.
- hsTnT was significantly correlated with native T1 (r=0.35, P<0.001), native T2 (r=0.22, P=0.03), and left ventricle mass (r=0.32, P<0.001). A cross-correlation between native T1 and T2 was also observed (r=0.43, P<0.001).
- Native T1 and T2 measures had the best discriminatory ability to detect COVID-19-related myocardial pathology, with respective cutoff values for confirmation and exclusion of cardiac involvement.
This prospective observational study evaluated the presence of myocardial injury in an unselected cohort of 100 patients who recently recovered from COVID-19 infection. CMR revealed cardiac involvement in 78% of patients and ongoing myocardial inflammation (defined as abnormal native T1 and T2 measures) in 60% of patients. Cardiac involvement and myocardial inflammation were independent of preexisting conditions, severity and overall course of the COVID-19 disease in the acute stage, and time from the original diagnosis. These findings highlight the need for further studies towards long-term CV consequences of COVID-19.