In December 2019, the coronavirus (COVID-19) was first identified in Wuhan, China in some patients characterized by mild flu-like symptoms to acute pneumonia leading to deadly respiratory distress syndrome with mortality rate of more than 1%.
In 2020 the virus was isolated and later identified as a new strain of COVID-19 and named Severe Acute Respiratory Syndrome Coronavirus 2 also known as SARS-COV-2. Due to multiorgan dysfunction, the mortality rate has been quite high in case of COVID-19.
The first case of myocarditis was recognized in COVID-19 patients as a major cause of death but before that, Covid myocarditis was given much medical attention.
Initial mechanism of SARS-COV-2
The coronavirus is surrounded by a fatty membrane known as envelope. It gains entry into a host cell using glycoproteins to fuse their own membrane to that of the cells. One of these functional units binds to a protein on the surface of the host cells called Angiotensin-converting enzyme 2 (ACE2).
ACE2 is a peptide hormone responsible for vasoconstriction and hypertension. This eventually moves towards membrane fusion. The spike protein is responsible for assembly and a stable structure. The serine protease acts as a nucleophilic primer to hydrolyse the proteins. It’s Ser residue at the active site is critical for the catalysis of the virus uptake. The Angiotensin-converting enzyme 2 is present in all the tissues but especially it is found in heart, vessels, kidney, lungs, gut and brain.
Thus, the complications of these organs in COVID-19 patients is explained by this mechanism. This is the reason why these organs are under a potential threat of Covid infection. Further, this explains several health complications like bowel movement and shortness of breath forth more.
Hence, all the tissues representing ACE2 like cardiovascular and general body cells are at a risk to get infected by SARS COVID-19 including lung cells, which seems to be at a greater risk for health professionals. The Covid Cardiovascular health conditions can be linked with pericarditis, myocarditis and pericardial effusion.
Reported cases of Covid Myocarditis
- Total incidents: 8% – 22% of cardiovascular complication have been reported out of which 22% in ICU while 59% died.
- Around 16% – 49% patients reported in ICU due to pulmonary thrombosis, arterial and venous thromboembolism.
- 52% of patients admitted due to heart failure and only 12% got recovered.
- 4% cases reported of acute coronary syndrome with ST segment elevation. Around 50% went through coronary angiography with obstructive disease detection.
- 9% of arrhythmia cases reported overall with 8.9% suffering from mild illness while 44.4% cases are critical.
- Myocarditis case reports demonstrate infection of SARS COV-2 but in myocardial cells not in macrophages.
- Pericardial cases were reported demonstrating symptoms of pericardial effusion.
Myocardial and pericardial injury with COVID-19 accounts for 7% to 28% of cases and is associated with a higher rate of morbidity and mortality. A proinflammatory surge, the so-called cytokine storm is thought to be pivotal to the pathogenesis of the acute lung injury acute respiratory distress syndrome that amplifies the immune response of the alveolar tissue. This phenomenon is thought to be a contributing factor to myocardial injury observed in other forms of viral infections such as H1N1. Patients who required intensive care showed higher concentrations of cytokines and chemokine.
The lungs, heart, vessels, kidney, brain, and gut are potential target organs for COVID-19.
Elevated troponin and other biomarker levels are commonly seen in patients hospitalized with COVID-19. High troponin levels are a potent predictor of 30day in-hospital mortality. A simple risk score can stratify patients at risk for COVID-19 associated mortality. A simple risk score can stratify patients at risk for COVID-19 associated mortality i.e. a pooled prevalence of 20.8% in patients with COVID-19 on hospital admission.
Hence, troponin levels may be used as an additional tool for risk stratification and decision guide in hospitalized patients. However it is uncertain if myocarditis is the actual cause of troponin increase in previous case series.
It has been observed that in the case of myocardial infarction, inflammation and viral invasion cause plaque instability (type I MI). Moreover, hypoxia and infection cause oxygen supply/demand imbalance (type I MII). But no histological diagnosis of myocarditis in COVID-19 patients reported so far.
An increase in troponin levels in the case of COVID-19 can explain different causes:
Myocardial infarction is widespread among COVID-19 patients hospitalized, which increases the chances of death due to the high levels of troponin in the patient’s blood.
There are two possible causes in the settings of pericardial disease which can be considered:
- The patient got infected with SARS Covid-2 after getting treated from pericarditis
- The COVID-19 patient diagnosed with pericardial effusion or pericarditis
In either conditions, health professionals are doubtful about the safety of using non-steroidal anti-inflammatory drugs (NSAIDS), colchicine, corticosteroids and other biological agents like anti IL1 agents which are widely used for treating refractory cases.
Currently, most of the data gathered demonstrates myocardial involvement with elevated troponin levels in COVID-19 cases, but very limited data is available on COVID-19 patients who developed pericardial effusion or pericarditis.
However, for Covid-19 patients NSAIDS can be used but it requires further investigation as most of the pericarditis treatments including colchicine, corticosteroids and ankara do not apparently contradict in the case of COVID-19 disease.
Ongoing treatments for pericarditis and COVID-19 infection
- Use of NSAIDs for 1 – 2 weeks until symptoms resolve and CRP gets normal. The drug is graded A in loss of exclusivity, though the harmful effects on COVID-19 patients is still unknown.
- Use of colchicine for at least 3 months for acute while 6 months for recurring cases. It is also graded A in loss of exclusivity. Potential therapy is needed for COVID-19 patients.
- Use of Corticosteroid for up to 1 month. Dose of prednisone 0.2 – 0.5mg/kg per day and therapy is required for advanced Covid cases.
- Use of Azathioprine for 6 months duration but the effects on Covid patients is unknown.
- Use of NHIG for 5 days with 400 – 500 mg/kg per day but can be repeated after a month.
- Use Anakinra for 3- 6 months then taper. Dose intake 2mg/kg up to 100mh/kg per day.
In patients, pericarditis treatment must not be discontinued and if they have been dosed on corticosteroids and anakinra, then there are higher chances of getting infected by superimposed bacteria. In fact, these agents are being rigorously tested for success in COVID-19 patients and if go well, will become a part of the treatment.
The World Health Organization has declared COVID-19 as a pandemic now, a clinical syndrome caused by Sars-Cov-2. Respiratory complication is the hallmark of COVID-19, which ranges from mild upper respiratory syndrome to acute respiratory distress (ARDS). Though, there have been several series of cases indicating multi-organ dysfunctioning in the patients among which cardiac complication was involved among the COVID-19 patients hospitalized.
Moreover, 51% was the mortality rate among the patients due to cardiac injury. COVID-19 has extensive cardiovascular complications including, acute coronary syndrome, acute on-set heart failure, cardiac arrest and myocarditis. Amongst them, myocarditis is the deadliest one observed till date.
Heart and organs are the prospects of COVID-19 infection however, there is no evidence to prove direct replication of Sars-Cov-2 virus in heart cells. Hence, more findings and studies on pathology and autopsy would be helpful to clarify the possibilities of Sars-Cov-2 to attack myocardium and cause myocarditis.