Cardiovascular Disease, Influenza, and COVID-19
Seasonal influenza (A and B) and COVID-19 have both been linked to cardiovascular complications in otherwise healthy people without preexisting conditions; they pose even greater risks for complications and mortality in people with preexisting cardiovascular disease.1 Although vaccination can mitigate further cardiovascular risk from influenza,2 the same remains to be shown for COVID-19.
This article will discuss associations of cardiovascular disease risk and outcomes with seasonal influenza, as well as emerging information on associations with COVID-19. Laboratory testing is important for recognizing potential cardiovascular effects of these illnesses.
Influenza and COVID-19
Human influenza can be due to influenza virus types A and B, which target the upper respiratory tract and cause inflammation.3 The interferon response and immune reaction to the viral infection are responsible for the viral syndrome.3
COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a single-stranded enveloped RNA virus.4,5 SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor and uses it to enter into the host cell.4,5 ACE2 is highly expressed in the lungs (alveolar cells), heart, intestinal epithelium, vascular endothelium, and kidneys.4,5
A comparison of the 2 infections is presented in the Sidebar. Although data are accumulating, not much is known about COVID-19 and influenza coinfection.10 The primary method of diagnosis for both infections is testing for the presence of viral RNA (ie, nucleic acid amplification test/polymerase chain reaction [NAAT/PCR]).3,7
Respiratory Tract Infections and Cardiovascular Disease
Influenza and other viral respiratory illnesses have been linked to increased risk of cardiovascular events, including acute myocardial infarction and stroke (reviewed in Berhrouzi et al11). People with influenza and preexisting cardiovascular disease are at increased risk of serious complications, such as viral pneumonia, secondary bacterial pneumonia, hemorrhagic bronchitis, and death.3 These complications can develop as soon as 2 days after symptoms appear.3
Preexisting cardiovascular and other conditions can also markedly increase the risks for hospitalization and death in patients with COVID-19 (see Sidebar). Of patients with COVID-19 who died early in the pandemic, 40% had hypertension, 20% had diabetes, and 22% had preexisting cardiovascular disease.10 Cardiovascular disease was associated with the highest case fatality rate: 10.5%, compared with 6.0% for hypertension and 7.3% for diabetes.11
Any person who becomes infected with COVID-19, regardless of medical history, is at increased risk for arrhythmia, myocarditis, acute coronary syndrome, venous thromboembolism, cardiogenic shock, and heart failure.7 Children with current or recent COVID-19 may be at risk of Multisystem Inflammatory Syndrome in Children (MIS-C), which includes fever, gastrointestinal and cutaneous manifestations, and, in severe cases, hypotension and shock. Children with MIS-C may also have laboratory evidence of heart damage (eg, troponin; B-type natriuretic peptide [BNP] or proBNP), myocarditis, cardiac dysfunction, and acute kidney injury.14
Influenza- and COVID-19-Related Coagulopathy
In severe influenza infections, an expansive immune response can result in dysfunction of the coagulation system manifesting as vascular leakage, disseminated intravascular coagulation (DIC), and microemboli in the lungs.15 Coagulopathy is believed to be related to the overproduction of proinflammatory cytokines and overactivation of immune cells during the infection.15
In COVID-19, the high prevalence of blood clots, stroke, cardiac damage, and organ failure may be caused by viral infection of blood vessels.16 Microvascular thrombosis may be involved in hypoxemic respiratory failure in some patients with COVID-19, and DIC is not uncommon in patients with severe infections.17
For patients with influenza or COVID-19 and suspected coagulopathy, laboratory testing, including measuring D-dimer levels and fibrin degradation, may be appropriate.18
For seasonal influenza, vaccination has been shown to reduce adverse cardiovascular and respiratory outcomes. In a 2013 meta-analysis, the risk of composite cardiovascular events was much lower for people who had been vaccinated (2.9% risk) than for those who had not (4.7% risk).19 A 2020 literature review and analysis showed similar results: the relative risks for persons who were vaccinated for influenza, compared to those who were not, were 0.74 for cardiovascular diseases, 0.82 for respiratory diseases, and 0.57 for all-cause mortality.2 Because COVID-19 vaccines have only recently become available, their effects on cardiovascular outcomes are not yet known.