By Denise Baez
In today’s DG Alert, we cover the incidence of myocardial injury in patients with coronavirus disease 2019 (COVID-19), and the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and symptom severity and outcomes.
According to a study published in Circulation, myocardial injury is common in hospitalised patients with COVID-19 and not exclusive to patients with acute coronary syndrome or pulmonary emboli.
Daniel S. Knight, MD, Royal Free London NHS Foundation Trust, London, United Kingdom, and colleagues offered cardiovascular magnetic resonance (CMR) to all patients with COVID-19 who had been discharged from the Royal Free London NHS Foundation Trust (until April 30, 2020) with myocardial injury — defined as having high-sensitivity troponin T (hsTnT) levels >14 ng/L.
Of 828 patients, 586 (71%) had elevated hsTnT, which was associated with higher in-patient mortality (41% vs 8%; P< .001). Of the patients with elevated hsTnT, 51 were referred for CMR, 22 of whom had ≥1 identifiable causes for troponin elevation and/or known cardiac pathology and were excluded from the final analysis. The remaining 29 patients had unexplained myocardial injury and no cause for prior myocardial scarring, 19 of whom underwent additional adenosine stress perfusion.
Of the 29 patients, 83% were male, 97% tested positive for SARS-CoV-2 on reverse transcriptase-polymerase chain reaction, and 34% required ventilator support. On admission, hsTnT levels were 23.0 ng/L (range, 19.0-32.8 ng/L).
Mean biventricular systolic function for the overall cohort was normal. There was 1 patient with mild left ventricular (LV) dysfunction and 1 patient with severe biventricular dysfunction.
Using the LGE technique and stress perfusion imaging where possible, 20 patients (69%) had an identifiable mechanism of myocardial injury, classified as non-ischaemic heart disease related (38%), ischaemic heart disease-related (17%) or dual ischaemic and non-ischaemic pathology (14%).
A non-ischaemic etiology of elevated hsTnT was conferred by the presence of non-infarct pattern LGE (not corresponding to a coronary territory and sparing the endocardium). The LGE patterns were myocarditis-like in 13 (45%) patients, with 2 other patients having non-specific mid-wall LGE only. These patients all had normal LV function with no regional wall motion abnormalities. The median extent of the myocarditis-pattern LGE was 2 (range, 1-2.5) segments with no significant residual myocardial oedema in the overall cohort. Peak C-reactive protein and hsTnT levels were not significantly elevated compared with patients without myocarditis.
Nine of the 29 patients were considered to have an ischaemic etiology of their elevated hsTnT. Of these, 7 had inducible ischaemia, 1 had a prior unknown myocardial infarction by LGE, and 1 had both inducible ischaemia and a prior infarction by LGE. When present, inducible ischaemia was multi-territorial in half of these cases. Four patients had dual ischaemic and non-ischaemic pathology: 2 had myocarditis-pattern LGE and inducible ischaemia, and 2 had non-specific mid-wall LGE along with either inducible ischaemia or a MI.
“Myocardial injury was associated with cardiac abnormalities detected by CMR where troponin elevation was unexplained even when cardiac function is normal,” the authors wrote.
“The main limitation of this study is its cross-sectional design which prompts caution regarding causality of myocardial injury and its relationship to previous COVID-19 infection,” the authors noted. “Nevertheless, CMR frequently revealed occult coronary artery disease, high rates of myocarditis-like LGE and sometimes dual pathology. The lack of oedema in these patients suggests the myocarditis-like scar may be permanent. Further serial study would clarify this and assess the long-term clinical consequences of these findings.”
Another study published in The American Journal of Pathology showed that non-hospitalised patients with COVID-19, with less severe symptoms, have a higher SARS-CoV-2 viral load (VL) than hospitalised patients with more severe symptoms.
In a cohort of 205 patients treated at a tertiary care centre in New York City who were tested using both qualitative RT-PCR and quantitative RT-PCR to obtain diagnostic SARS-CoV-2 VL at initial presentation, Kimon V. Argyropoulos, New York University Langone Health, New York, New York, and colleagues found that diagnostic viral load (VL) was significantly lower in hospitalised patients than in patients not hospitalised (log10 VL = 3.3 vs 4.0; P = .018) after adjusting for age, sex, race, body mass index, and comorbidities.
Higher VL was associated with shorter duration of symptoms in all patients (P< .001). Among hospitalised patients only, higher VL was also associated with shorter duration of symptoms (P = .002) and with shorter hospital stay (P = .013).
No significant association was noted between VL, admission to intensive care unit, length of oxygen support, and overall survival.
Non-hospitalised patients were overall younger (median age, 45 vs 60 years; P< .001). The median duration of symptoms from symptom onset to nasopharyngeal swab collection in the hospitalised group was 5 days compared with 3 days in the non-hospitalised group (P = .017) .
“These findings are interesting when interpreted within our current knowledge of the natural history of COVID-19,” the authors wrote. “While many COVID-19 patients recover from their initial symptoms over the course of 14 to 21 days, a sizeable proportion of patients show clinical deterioration to severe disease which usually occurs a week after symptom onset. In our cohort, viral loads detected from nasopharyngeal sampling in patients requiring hospitalisation — most of which had severe or critical symptoms — were obtained at a later time point in the disease course. This fact is on par with prior studies demonstrating that longer disease duration is not necessarily associated with a higher viral load but rather a lower viral load.”
“Patients with mild COVID-19 symptoms may represent the most important ‘overlooked’ source of shedding given the higher viral load,” the authors added. “We believe containment strategies can utilise quantitative viral loads to identify patients with high viral titres. In the hospital triage setting, the information from the viral load can be utilised to determine which patient would receive a negative pressure room. In the outpatient setting, clinicians can utilise viral load as a quantitative metric to reinforce the importance of self-isolation and face coverings to reduce the risk spreading the infection.”