We report worse prognosis among older adults presenting with MIN, even without myocardial necrosis, during the acute episode of SARS-CoV-2 infection. MIN led to a worse prognosis with more severe clinical presentation, prolonged time to recovery, and higher mortality rates among older adults, as had been reported in other series (11, 12). We found age, male gender and pre-existing cardiovascular disease to be key factors associated with higher prevalence of MIN. These are also well established risk factors for adverse events in general in outbreaks of respiratory virus infections (13)(14). Nonetheless, when controlling for these possible confounders, MIN was still associated with worse clinical prognosis. Recently, has been shown that high sensitivity troponin I improves mortality and cardiovascular risk stratification in older adults beyond traditional risk factors (15). In our study we found similar results in the SARS-CoV-2 infection with hs-TnT.
Based on the accepted definition of MIN and myocardial infarction (5), we considered as acute MIN cases where there was a significant increase in hs-TnT with an absence of electric signs of ischemia or myocarditis. Remarkably, we found this to be as frequent as 50% of our overall cohort, and up to 70% when looking into older adults. In other studies, acute MIN has been reported as less frequent, in up to 12% of patients with COVID-19 (16–18). The difference between our study and other prior reports may be explained because we are only considering cases that required hospitalization, which presumably means they have more severe forms of the disease, meanwhile prior studies included mixed series with in-hospital and out-patients (16). Another additional reason is that the median age of our cohort was higher compared to previous studies (12).
It would be interesting to see if this myocardial injury also results significantly in myocardial dysfunction. What we have seen in our series is that individuals presenting with myocardial injury at admission had heart failure more frequently, both by clinical and biochemical signs measured by NT-proBNP. Unfortunately, we were not able to measure ejection fraction during the episode, due to unbelievable pressure on healthcare in the acute moment of the pandemic. All the same, with our data we are inclined to assess that there is an impairment of function as well.
Older adults showed significantly higher mortality than those younger counterparts, showing probably that the differences are not only because of MIN but with all the other comorbidities together added to age. However, there is evidence that show that patients with MIN are also more prone to die. There are many hypotheses trying to discern the causes of troponin elevation during SARS-CoV-2 infection, and also the role it plays in the evolution of the disease (6). An interesting hypothesis is that cardiac injury may reflect an ongoing pathological insult due to inflammation or secondary to hypoxemia (19). In our series, we found no differences between older adults with or without MIN in terms of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaFi) at admission, moving us away from the theory that it is related to hypoxemia. On the other hand, we did find a positive correlation between all inflammatory markers that we studied and troponin levels, and have found consistently that individuals with MIN showed significantly higher inflammatory markers that those individuals without MIN. It also goes in consonance with the fact that older adults would be a more vulnerable population due to increased underlying inflammation secondary to the ageing of the immune system (3). Moreover, an increased immune response due to SARS-CoV-2 infection is one of the hallmarks of COVID-19. Acute myocardial events could be associated with inflammation triggered by SARS-CoV-2, as it has been suspected in other scenarios such as cytokine release syndrome, which seems to increase troponin after antigen receptor T-cell therapy and cytokine storm (6).
Ageing is associated with an immune alteration that has being characterized. Briefly it consists in the reduction in the number of peripheral blood naïve cells, with a relative increase in the frequency of memory cells. This leads to a dysregulation of immune control and an age increased inflammation called inflamm-aging, altogether are considered the hallmarks of immunosenescence (20). An older immune system is defined by these cells presenting a specific phenotype and responding abnormally to some external agents (19, 20). It has been reported that the acute infection of SARS-CoV-2 leads to an expansion of precisely immunosenescent cells (21). Altogether leads us to entertain the hypothesis that may be an additive effect between the SARS-CoV-2 infection and age, where a more senescent immune system leads to increased tissue damage, including myocardium.
Our study has some limitations since it was conducted in a single center in the first wave of the COVID-19 outbreak. It has a mid-size sample and we were not able to conduct cardiac ultrasound or MRI, as a consequence, we were only able to define acute myocardial injury by troponin elevation without detailing myocardial tissue characteristics and haemodynamic function. Moreover, during this first wave many older adults with SARS-CoV-2 infection remained in long term care facilities. In that case we can say that our hospital was the reference center for many long term care facilities of the area and a fluid drainage of these long term care facilities even in the moments with highest incidence. Moreover, we find that a key strength of our study is how representative it is of an older adult population, belonging to a large city that has had high incidence of SARS-CoV-2 infection, which makes the results directly relevant to the clinical setting.
We can conclude that MIN was very common in individuals with SARS-CoV-2 infection, especially in older adults and in patients with pre-existing comorbidities and with higher inflammatory levels. We can also conclude that it impacted the clinical outcomes of individuals that experienced it, being associated with greater time to clinical recovery, more severe presentation of the disease and higher odds of in-hospital mortality. The consistent association that we found between inflammation and MIN makes the hypothesis of an inflammatory insult as responsible to heart damage plausible. This is more relevant in a group with higher inflammatory levels due to immune dysregulation linked to ageing and maybe deserves further attention. Ultimately, due to its widespread presence, and its likely role in prognosis, it is advisable that we direct attention to this matter.