Coronavirus disease-2019 (COVID-19), a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had an unprecedented global impact. Presentations of infection vary widely, ranging from asymptomatic to multiorgan failure and death. Among patients diagnosed with COVID-19, many cardiovascular complications and abnormalities in cardiac testing have been reported.

• COVID-19 infection can have highly varied clinical presentations, ranging from asymptomatic to critical illness with severe multiorgan dysfunction.
• Per CDC case surveillance of over 1 million people in the U.S with confirmed COVID-19 infection, the most common symptoms include cough (50%), subjective or objective fever of >100.4° F/38° C (43%), myalgia (36%), headache (34%), dyspnea (29%), sore throat (20%), diarrhea (19%), nausea or vomiting (12%), anosmia or dysgeusia (<10%), abdominal pain (<10%), and rhinorrhea (<10%).⁴
• Multiple cardiovascular complications of COVID-19 infection have been reported and can be categorized into the following (Table E1):
  1. Myocardial Injury
     1. Myocardial injury, as defined by elevations in cardiac biomarkers, has been commonly described in COVID-19 and, per early studies in China, reported in nearly one fourth of patients hospitalized with the infection.⁵
     2. There appears to be a direct correlation between higher troponin levels and more severe disease.⁵
     3. In a recent multicenter prospective cohort study (ECHOVID-19) of hospitalized patients with confirmed COVID-19, among 129 patients, 79.1% had evidence of myocardial injury as defined by decreased systolic function by echocardiography and/or elevated cardiac biomarkers; 20 patients (15%) with evidence of myocardial injury developed acute respiratory distress syndrome (ARDS), whereas only 2 patients (1.5%) without any evidence of myocardial injury developed ARDS.⁶
     4. In a prospective observational cohort study of 100 patients recently recovered from COVID-19 illness in Germany, 78 patients (78%) had abnormal cardiac MRI markers, with 60 patients (60%) showing cardiac MRI signs of active myocardial inflammation, independent of coexisting medical conditions.⁷
  2. Acute Coronary Syndrome
     1. As evidenced by prior viruses, including SARS and influenza, viral infection can lead to increased incidence of acute coronary syndrome.²
     2. Patients with acute ST elevation myocardial infarction (STEMI) in the setting of COVID-19 infection presented with more atypical symptoms (including symptoms more typical of COVID-19 infection such as fever, cough, and dyspnea) rather than with chest pain.²
     3. Multiple case series have shown that the majority of patients who present with concomitant STEMI and COVID-19 required revascularization with percutaneous coronary intervention.³
     4. Reports have also suggested increased risk of coronary stent thrombosis in patients with COVID-19 and coronary artery disease.³
     5. Increased rates of venous and arterial thromboembolic events have been described in patients diagnosed with COVID-19 infection, including reports of spontaneous thrombosis involving the aorta, peripheral arteries, cerebrovascular arteries, and renal arteries.⁵
     6. STEMI mimickers, including stress cardiomyopathy and myopericarditis, have also been described in patients with COVID-19.^2,9
  3. Heart Failure
     1. Among early cases in China, heart failure (HF) was recognized as a common manifestation of COVID-19, seen in approximately 20% of all patients and 49% of those who died of COVID-19.³
     2. The spectrum of heart failure in COVID-19 can range from mild cardiogenic pulmonary edema to cardiogenic shock.⁴
     3. Numerous case reports have documented typical features of myocarditis, ranging from mild to fulminant, in patients with COVID-19. Stress (Takotsubo) cardiomyopathy has also been reported.⁴
     4. Right-sided myocardial strain has also been frequently reported and secondary to submassive or massive pulmonary embolism, pulmonary hypertension secondary to ARDS, sepsis-associated myocardial dysfunction, or HF.⁴
     5. Brain natriuretic peptide (BNP) has been used as a biomarker and prognostic indicator of HF in patients with COVID-19, although patients with COVID-19 infection have been shown to have elevated levels of BNP even in the absence of ventricular dysfunction.¹
  4. Arrhythmia
     1. Multiple observational reports have found increased tachycardia in patients hospitalized with COVID-19 infection, even in the absence of hypotension or fever. This tachycardia persisted in up to 40% of patients on discharge.⁸
     2. Both tachyarrhythmias and bradyarrhythmias have been reported in patients with COVID-19 disease, including atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, sinus node dysfunction, and atrioventricular node dysfunction, leading to high-grade atrioventricular blocks including complete heart block.⁸
     3. A Brugada-like ECG pattern has been reported with confirmed COVID-19 illness, which may be related to the fever that can induce a Brugada pattern in patients. This may be a presentation of underlying Brugada Syndrome in some patients.
     4. Early studies from Wuhan, China, analyzing in-hospital cardiac arrests in patients hospitalized with COVID-19 showed that cardiac arrests were mainly secondary to asystole (89.7%), followed by shockable rhythm (5.9%) and pulseless electrical activity (4.4%).⁸
     5. Cardiac arrhythmias and cardiac arrests are likely due to overall systemic illness rather than purely caused by COVID-19 infection.⁸

• Myocardial injury in COVID-19 illness can be secondary to both direct and indirect mechanisms. Direct mechanisms include acute plaque rupture leading to acute coronary syndrome or direct infiltration of the myocardium by the virus. Indirect mechanisms are due to the increased inflammatory response consequent to cytokine storm, microvascular thrombosis, and myocardial oxygen supply/demand mismatch.³
• New left ventricular dysfunction associated with COVID-19 has been proposed to be related to direct viral infiltration leading to myocarditis, endothelial dysfunction, stress cardiomyopathy, and myocardial inflammation.⁵
• Arrhythmias associated with COVID-19 may be caused by myocardial strain and myocarditis, myocardial ischemia, hypoxia, electrolyte derangements, fluid shifts and volume imbalances, and side effects of medications.⁸

• Other infectious etiologies, including other coronaviruses, influenza, acute HIV
• Myocarditis
• Ischemic cardiomyopathy
• Stress (Takotsubo) cardiomyopathy
• Tachycardia-induced cardiomyopathy
• Pulmonary hypertension/cor pulmonale
• Acute coronary syndrome
• Valvular disease
• Pulmonary embolism
• ARDS

• Exposure history
• ECG
• Serum troponin and BNP levels
• SARS-CoV-2 polymerase chain reaction
• Transthoracic echocardiogram
• Coronary angiography to evaluate for coronary artery disease and acute coronary syndrome
• Cardiac MRI

• Laboratory markers, including CBC with differential, serum electrolytes, renal function, hepatic function, lactate dehydrogenase, prothrombin time, partial prothrombin time, fibrinogen, ferritin, D-dimer, C-reactive protein, erythrocyte sedimentation rate, troponin, BNP, and inflammatory markers, are useful in the evaluation of suspected COVID-19 infection.²
• Common abnormalities found on laboratory testing include lymphopenia, thrombocytopenia, elevated troponin and BNP, elevated aminotransferase and lactate dehydrogenase levels, and elevated inflammatory markers, including D-dimer levels.²

• Baseline ECG will help evaluate for presence of arrhythmias, signs of myocardial injury or acute coronary syndrome, and baseline QT interval.²
• Chest x-ray examinations or chest computed tomography (CT) may show evidence of consolidations, ground-glass opacities, air bronchograms, pleural effusions, or pericardial effusions.⁵
• Transthoracic echocardiography can be used if the results will change the prognosis or significantly affect management. Transthoracic echocardiographic findings in COVID-19 infection may show ventricular dysfunction (both left and right) with and without regional variation, valvular dysfunction, and pericardial effusion.⁵
• Cardiac MRI or possible endomyocardial biopsy can be used to diagnose myocarditis and differentiate this from other cardiomyopathies.⁷

• In patients with severe COVID-19 illness with mixed shock and respiratory failure with unclear extent of cardiac involvement, placement of a pulmonary artery catheter may help guide management.⁵
• Patients with multiorgan dysfunction and mixed or refractory cardiogenic shock may benefit from extracorporeal membrane oxygenation (ECMO) support. A multidisciplinary approach should be taken to determine which patients should be initiated on ECMO. Other temporary mechanical circulatory support devices such as percutaneous left ventricular assist device and intraaortic balloon pump can also be considered.⁵
• Patients with signs and symptoms of acute coronary syndrome and confirmed COVID-19 infection should be managed on a case-by-case basis, although coronary angiography and primary percutaneous coronary intervention are preferred in most cases. A fibrinolytic strategy may be more appropriate for some patients. During intervention, protective measures should be taken to ensure safety of all staff and other patients.

• Dexamethasone may be beneficial in patients hospitalized with severe illness on supplemental oxygen or mechanical ventilation.³
• Monoclonal antibodies were utilized during the pandemic, and bamlanivimab received FDA Emergency Use Authorization (EUA) for outpatient treatment of recently diagnosed mild to moderate COVID-19 in patients who are older than 12 yr of age, weigh at least 40 kg, and are at high risk for progressing to severe disease and/or hospitalization.⁵ Due to emerging data showing a rise in SARS-CoV-2 variants resistant to bamlanivimab, the FDA revoked this EUA in April 2021.
• The antivirals nirmatrelvir, which inhibits a SARS-CoV-2 protein from replicating, and ritonavir, which slows down nirmatrelvir’s breakdown, are available in oral formulation (Paxlovid) administered twice daily for 5 days. Paxlovid was authorized under EUA by the FDA in December 2021 for treatment of mild to moderate COVID-19 infection in patients who are older than 12 yr of age, weigh at least 40 kg, and are at high risk for progressing to severe disease and/or hospitalization. There have been reports of individuals who experienced rebound symptoms after taking Paxlovid, and a current randomized control trial is underway to assess whether a second course of Paxlovid may be beneficial in those who experienced rebound symptoms after the first course of treatment.¹
• Remdesivir is an antiviral therapy that prevents RNA replication. It was issued EUA by the FDA in 2020 for patients with severe COVID-19 illness with signs of hypoxia requiring supplemental oxygen, mechanical ventilation, or mechanical circulatory support requirements.² The recommended dosage is 200 mg intravenous on day 1, infused over 30 to 120 min, followed by 100 mg once daily. The recommended treatment duration is 10 days for patients who need mechanical ventilation and/or ECMO and 5 days for those who do not. It should be avoided in patients with an eGFR <30 ml/min. Clinical trials have produced mixed results. The drug has been shown to shorten the time to recovery in hospitalized adults. It appears to be most beneficial when given earlier in the illness.
• Convalescent plasma obtained from patients who recovered from COVID-19 infection may be useful for patients with severe COVID-19 illness.⁵ Observational data suggest favorable clinical effects and reduction of mortality. The FDA has approved emergency authorization use in patients with severe COVID-19 illness.
• Inotropic support should be considered in patients with cardiogenic shock or mixed shock with a cardiac component.³
• In patients with arrhythmias, secondary causes should be addressed, including correction of electrolyte derangements, treatment of hypoxia, treatment of myocardial injury or ischemia, and withdrawal of any offending medications. Patients with unstable tachyarrhythmias and bradyarrhythmias, including malignant ventricular arrhythmias, should be treated according to standard resuscitation protocols. In patients with Brugada-pattern ECG in the setting of febrile COVID-19 illness, aggressive measures should be taken to reduce fever.⁸

• There was initial apprehension for using ACE inhibitors or angiotensin receptor blockers (ARBs) since SARS-CoV-2 uses the ACE-2 cell receptors for entry. Initially, there was theoretical concern that renin-angiotensin-aldosterone system inhibition may upregulate ACE-2 receptors and thereby render a host more susceptible to infection. However, clinical data do not support this theory, and COVID-19-infected patients on ACE-inhibitor and ARB therapy were found to have lower all-cause mortality compared to those not on ACE inhibitors or ARBs. Therefore, patients receiving ACE inhibitors or ARBs should continue treatment with these agents without discontinuation in the setting of COVID-19 infection (unless there are other reasons for discontinuation such as hypotension).⁵
• Telehealth visits should be used to closely follow up with patients diagnosed with COVID-19.⁹

Disposition varies based on signs and symptoms, but in general, those with severe dyspnea, hypoxia, altered mental status, signs or symptoms of acute coronary syndrome including chest pain, and hypotension will likely require emergency department evaluation and possible hospitalization.

Close follow-up with a cardiologist

• Cardiovascular manifestations and complications occur commonly in patients with COVID-19 infection and can lead to a worsened prognosis. These manifestations can be categorized as myocardial injury, acute coronary syndrome, heart failure, and arrhythmia.
• Treatment of cardiac effects of COVID-19 illness remains largely supportive. Treatments targeting SARS-CoV-2 and COVID-19 are becoming increasingly available.
• Some patients experience long-term symptoms and cardiovascular sequelae, known as postacute sequelae of SARS-CoV-2 infection (PASC).

• Vaccinations: Four vaccines are approved or authorized to prevent COVID-19: BioNTech/Fosun Pharma/Pfizer, Moderna, Johnson & Johnson’s Janssen, and Novavax.¹⁰
• Myocarditis and pericarditis have been reported as rare complications of vaccinations as noted by the CDC.¹¹ This effect was not observed in clinical trials of vaccinations, and the mechanism resulting in myocarditis/pericarditis remains unclear.¹² All reported cases quickly resolved their symptoms and were discharged in stable condition.¹³ The CDC is actively monitoring further reports of myocarditis and pericarditis after vaccination.
• Given the known risks of COVID-19 infection, which far outweigh the potential risk of a rare adverse vaccination reaction, the CDC strongly recommends all adults and children ages 12 yr or older get vaccinated.¹¹

• Preventive measures are of utmost importance to combat the COVID-19 pandemic and reduce the spread of disease. Widespread vaccination of the general population and following basic safety protocols, such as maintaining social distancing (at least 6 ft), practicing proper hand hygiene, quarantining if symptomatic, and wearing masks in public, are strongly recommended during the course of the pandemic.

• PASC is defined by symptoms (without evidence of cardiovascular disease) or cardiovascular sequelae that are new, persistent, or recurrent beyond the acute phase of COVID-19 infection (at least 4 wk after initial infection), and it may affect up to 10% to 30% of individuals with COVID-19 infection.¹⁴
• Cardiopulmonary symptoms of PASC include dyspnea, cough, fatigue, palpitations, chest pain, and dizziness.¹⁵
• Cardiovascular complications seen in PASC include myocarditis, heart failure (both right- and left-sided), arrhythmia (majority with atrial arrhythmias but some with ventricular arrhythmias), abnormal ECG (ST segment or T wave abnormalities, bundle branch blocks), dysautonomia, thromboembolism, abnormal cardiac MRI findings (late gadolinium enhancement, pericardial enhancement), and minimally elevated troponin.^14,15
• Some abnormalities in cardiac testing, including abnormal cardiac MRI, have not been associated with any symptoms, and these findings are of unclear clinical significance.¹⁶
• Treatment for PASC is currently focused on management of cardiopulmonary symptoms. If no contraindications, cardiopulmonary rehabilitation, and graduated exercise, including initial use of semirecumbent exercise for patients with postural orthostatic symptoms, is recommended.¹⁴
• Cardiology consultation is recommended for patients with PASC who have abnormal cardiac testing, known cardiovascular disease with new or worsening symptoms, evidence of cardiovascular complications during acute COVID-19 infection, and those who have persistent cardiopulmonary symptoms that are otherwise unexplained.¹⁴
• For competitive athletes with PASC and ongoing cardiopulmonary symptoms, the American College of Cardiology recommends “triad testing” with ECG, high-sensitivity troponin, and echocardiography prior to returning to play.¹⁴

COVID-19 Disease (Related Key Topic)

Pediatric COVID-19 Disease (Related Key Topic)