The Role of Adaptive Immunity in COVID-19 Associated Myocardial Injury
The Role of Adaptive Immunity in COVID-19 Associated Myocardial Injury
COVID-19 is associated with complications including ARDS and myocardial injury, which informs prognosis and patient outcome. The laboratory plans to perform immunophenotyping of peripheral T-cells in patients with COVID-19 and complications (ARDS, ITU admission, myocardial injury) and map this against clinical patient outcomes. The aim is to determine if there is a specific T-cell immunophenotype associated with COVID-19 and/or complications, which can be used to inform prognosis and potential therapies.
Infection with the novel coronavirus COVID-19 is designated a pandemic by the World Health Organisation (WHO).COVID-19 infection can result in severe lung inflammation which, when present, dominates the clinical course for most patients. However, other organs may also be involved and the cardiovascular (CV) system appears to have complex interactions with COVID-19. Published reports suggest evidence of heart muscle damage in 20-40% of hospitalised cases presenting as cardiac chest pain, heart failure, abnormal heart rhythms and cardiac death.
Many affected were previously well, but approximately half of those admitted to hospital COVID-19 have other medical problems, increasing in those requiring ITU admission or those that died. Patients with pre-existing CV conditions have some of the worst outcomes. Although pre-existing disorders reduce an individual's capacity to withstand severe illness, it is also likely that CV diseases may increase the risk of developing complicated COVID-19 disease. Our hypothesis is that immunological abnormalities acquired as a consequence of pre-existing disorders is responsible for this.
A question central to potential therapeutic options is the extent to which COVID-19 related myocardial injury results from viral replication (cytopathic), is immune mediated or is due to other mechanisms. Given that rapid onset cardiac injury can occur at 7-14 days after onset of COVID symptoms we propose to evaluate the contribution of adaptive T-cell mediated immunity in patients with and without myocardial injury. If successful, we may be able to identify treatments that suppress discrete components of the immune system to prevent myocardial damage without depressing protective immune function.
Group 1: COVID-19 positive without evidence of myocardial injury (n=120). Inclusion criteria: All adult (age≥18 but <100 years of age) inpatients with confirmed COVID-19 infection. Exclusion criteria: No biochemical evidence of acute myocardial injury (serum troponin>99th centile within previous 48-hour period)
Group 2: COVID-19 positive with myocarditis (n=20). Inclusion criteria: All adult (age≥18 but <100 years of age) inpatients with confirmed COVID-19 infection and clinically suspected or confirmed myocarditis including evidence of acute myocardial injury (troponin >99th centile within the previous 48-hour period) at the time of recruitment.
Exclusion criteria: significant chronic kidney disease (eGFR ≤30 or dialysis-dependent) or septic shock at the time of initial assessment. We will also exclude patients with a diagnosis of chronic heart muscle disease and those with known significant chronic or acute obstructive coronary disease.
Group 3: Group 1 and 2 study participants with a complicated course (estimated 14-35 patients).
Inclusion criteria: Participants form Groups 1 and 2 in whom a prespecified complication ocurs will be included in a derived Group3.