Scientific statement from the American Heart Association on COVID-19 and cardiovascular complications in children and adolescents

A recent scientific statement published in Circulation reviewed the current knowledge on coronavirus disease 2019 (COVID-19).

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the coronavirus that causes COVID-19, which generally causes fever, cough, chills, hypoxia, and dyspnea. Besides, COVID-19 is implicated as a complex multi-organ disease affecting various extra-pulmonary organs. Pre-existing cardiovascular disorders increase the risk of COVID-19-related morbidity and mortality.

In the present statement, researchers elucidated the epidemiology, pathophysiology, clinical presentations, treatment, and outcomes of COVID-19. They also reviewed the health consequences in young adults and children with congenital or acquired heart disease.

Epidemiology, pathophysiology, and clinical presentation of COVID-19

SARS-CoV-2 infections have been recorded globally across all age groups, races, and ethnicities. Early in the pandemic, children and young adults were less frequently or severely affected by COVID-19 than older adults. Nevertheless, some young adults and children are at a higher risk of severe illness. Underlying medical conditions in children increase the odds of hospitalization, intensive care, and mortality.

SARS-CoV-2 attaches to the host angiotensin-converting enzyme-2 (ACE2) through its spike (S) protein, where the transmembrane protease, serine 2 (TMPRSS2) of the host cells cleaves and activates the S protein, facilitating entry cells. As with the cardiovascular involvement in COVID-19, several mechanisms have been proposed, including 1) direct SARS-CoV-2 invasion of cardiomyocytes that highly express ACE2 causing cellular damage, 2) injury of cardiomyocytes due to the overwhelming inflammatory response, and 3) ischemic myocardial injury due to hypoxia.

As ACE2 receptors increase on the cell surface with age, the lower levels of ACE2 might explain why children experience less severe disease. Clinically, COVID-19 results in the acute or hyperinflammatory phase. Around 8% – 19% of children and adolescents develop asymptomatic COVID-19, and symptomatic cases present cough and fever. Moreover, ageusia and anosmia are less frequently reported in children than adults. Cardiovascular manifestations are uncommon during acute COVID-19 in children. Although comorbid children are at a higher risk for symptomatic COVID-19 than healthy children, cardiovascular complications, severe illness, and mortality are uncommon.

Multisystem inflammatory syndrome in children (MIS-C)

Children with COVID-19 rarely develop MIS-C, a severe complication of the disease. A systematic review of more than 900 children revealed that MIS-C symptoms were fever, diarrhea, vomiting, abdominal pain, oral mucosal changes, non-purulent conjunctivitis, and rash. Nearly half the MIS-C cases have myocardial involvement, including myocarditis (in up to 19% of cases), coronary artery dilation (12% – 21%), decreased left ventricular function (28% – 55%), and pericardial effusion (23%). Fortunately, MIS-C resolves within one to four weeks of diagnosis with a mortality rate of 1.4% – 1.9%.

COVID-19 treatment and management

A health care professional may evaluate COVID-19 patients complaining of dyspnea, while those with severe disease or comorbidities may be managed in hospitals. Antivirals and immune modulators may be indicated for severe illness. Although no COVID-19-specific antiviral therapy exists, existing drugs such as antivirals, antimalarial, and antibacterial drugs have been repurposed.

Remdesivir is the only drug approved by the food and drug administration (FDA) for hospitalized patients aged 12 years or above. Using dexamethasone during severe disease has reduced the adult mortality rate. At the same time, it is indicated for children who need high-flow oxygen, invasive or non-invasive ventilation, or extracorporeal membrane oxygenation (ECMO). Dexamethasone is not recommended for children with mild or moderate disease. Treatment of patients with MIS-C mainly modulates the inflammatory state and supportive care.

Congenital heart disease, pulmonary hypertension, and organ transplantations

Reports regarding the severity of COVID-19 in children and adolescents with congenital heart disease are conflicting, with some suggesting a high risk of severe illness and others reporting variable risk. Low infection and mortality rates have been observed for children with congenital heart disease. However, an underlying syndrome such as trisomy 21 increases the risk of severe COVID-19.

One study found a similar mortality rate among children and adults with congenital heart disease. Pulmonary arterial hypertension (PAH) is associated with a high risk of severe COVID-19. However, some studies suggested a similar infection rate between pediatric patients with idiopathic PAH and general pediatric patients.

Studies on children with solid-organ transplants found no evidence of high risk. However, more research is needed to explicitly understand the risk of SARS-CoV-2 on the graft. Interestingly, tacrolimus indicated in immunosuppressive therapy demonstrated in vitro activity against the viral replication, suggesting that the continued use of the drug might be reasonable.

Conclusions

COVID-19 remains a relatively new disease, and the associated knowledge on disease prognosis, prevention, and treatment is still evolving. It is crucial to understand the mechanisms of MIS-C better and find an optimal and effective treatment. Furthermore, antiviral therapies should be evaluated in clinical trials, including in children. More research is required to delineate the associated risks of congenital heart disease. The impact of COVID-19 on the heart and the consequences of the post-COVID-19 syndrome or long COVID need to be elucidated in children and adolescents.