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.
Comparison of Influenza Infection and COVID-19

Similarities include
  • Symptoms: Both may present with fever, cough, shortness of breath, fatigue, sore throat, runny or stuffy nose, muscle pain and aches, headaches, and sometimes nausea and diarrhea.6
  • Mode of transmission: Both are spread by respiratory droplets that are expelled from the mouth during coughing, sneezing, and talking3,7—both infections can be transmitted by asymptomatic carriers.3,7
  • Radiologic features: Both share similar chest computed tomography (CT) findings, including ground-glass opacities.8
  • Disease course: Both cause self-limited illnesses in most persons, but have the potential to develop into serious disease, especially in persons who are older and have underlying co-morbidities.5,9

Differences include
  • Symptoms: COVID-19 differs from influenza in that many people develop a change in or loss of taste and smell; it can take up to 14 days to develop symptoms (influenza symptoms typically develop 1-4 days after infection); and more people with COVID-19 can develop a serious illness.6
  • Degree of transmission: COVID-19 is more infectious.3,7
  • Radiologic features: CT findings differ in the distribution of lesions.8
Persons at Risk for Severe COVID-19 Disease and Complications

People with comorbidities are at increased risk for more serious disease and death, but it is important to know that young people with no comorbidities can also develop critical illness, including multi-organ failure and death.5
Preexisting Conditions Increase the Risk of Hospitalization in Persons With COVID-19 

Preexisting conditions that increase the risk of hospitalization include9
  • Hypertension, obesity (BMI > 30), or diabetes: 3-fold increase
  • Asthma: 1.5-fold increase
  • Chronic kidney disease: 4-fold increase
  • Two of the above conditions: 4.5-fold increase
  • Three or more conditions: 5-fold increase

These preexisting conditions have been associated with an average of a 2.6-fold increase in risk of mortality due to COVID-19.12 Importantly, persons with diabetes who become infected with COVID-19 with poor glucose control have worse outcomes (mortality) than those with good glucose control.13
How the Laboratory Can Help

Delay or avoidance of routine medical care is a major health issue that may have grave consequences in terms of excess deaths attributed directly, or indirectly, to the COVID-19 pandemic.20 In response, Quest Diagnostics is committed to assisting healthcare providers and patients during the COVID-19 pandemic by providing
  • Routine testing to establish an understanding of a patient’s baseline cardiometabolic health, as well as possible prior undiagnosed SARS-CoV-2 exposure
  • Testing in symptomatic individuals to differentiate between suspected active respiratory infections, including COVID-19 and influenza
  • Postinfection testing to detect acute and chronic changes in cardiometabolic biomarkers

Please complete the form below to recieve the latest updates.


  1. Ganatra S, Dani SS, Shah S, et al. Management of cardiovascular disease during coronavirus disease (COVID-19) pandemic. Trends Cardiovasc Med. 2020;30(6):315-325. doi:10.1016/j.tcm.2020.05.004
  2. Cheng Y, Cao X, Cao Z, et al. Effects of influenza vaccination on the risk of cardiovascular and respiratory diseases and all-cause mortality. Ageing Res Rev. 2020;62:101124. doi:10.1016/j.arr.2020.101124
  3. Boktor SW, Hafner JW. Influenza. In: StatPearls [Internet]. StatPearls Publishing; 2020. Updated November 21, 2020. Accessed December 9, 2020.
  4. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). Centers for Disease Control and Prevention. Updated December 8, 2020. Accessed December 9, 2020.
  5. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Infectious Diseases Society of America. Updated December 2, 2020. Accessed December 9, 2020.
  6. Similarities and differences between flu and COVID-19. Centers for Disease Control and Prevention. Reviewed October 6, 2020. Accessed December 9, 2020.
  7. Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-2371. doi:10.1016/j.jacc.2020.03.031
  8. Onigbinde SO, Ojo AS, Fleary L, et al. Chest computed tomography findings in COVID-19 and influenza: a narrative review. Biomed Res Int. 2020;2020:6928368. doi:10.1155/2020/6928368
  9. People with certain medical conditions. Centers for Disease Control and Prevention. Updated December 1, 2020. Accessed December 9, 2020.
  10. Lang JP, Wang X, Moura FA, et al. A current review of COVID-19 for the cardiovascular specialist. Am Heart J. 2020;226:29-44. doi:10.1016/j.ahj.2020.04.025
  11. Behrouzi B, Araujo Campoverde MV, Liang K, et al. Influenza vaccination to reduce cardiovascular morbidity and mortality in patients with COVID-19: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;76(15):1777-1794. doi:10.1016/j.jacc.2020.08.028
  12. Weekly updates by select demographic and geographic characteristics: provisional death counts for coronavirus disease 2019 (COVID-19). Centers for Disease Control and Prevention. Updated December 9, 2020. Accessed December 9, 2020.
  13. Mazucanti CH, Egan JM. SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Immun Ageing. 2020;17:21. doi:10.1186/s12979-020-00192-y
  14. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). Centers for Disease Control and Prevention. Reviewed August 28, 2020. Accessed December 23, 2020.
  15. Yang Y, Tang H. Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia. Cell Mol Immunol. 2016;13(4):432-442. doi: 10.1038/cmi.2016.1
  16. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5
  17. COVID-19 and VTE/anticoagulation: frequently asked questions. American Society of Hematology. Reviewed November 30, 2020. Accessed December 9, 2020.
  18. Guzik TJ, Mohiddin SA, Dimarco A, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020;116(10):1666-1687. doi:10.1093/cvr/cvaa106
  19. Udell JA, Zawi R, Bhatt DL, et al. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA. 2013;310(16):1711-1120. doi:10.1001/jama.2013.279206
  20. Czeisler MÉ, Marynak K, Clarke KEN, et al. Delay or avoidance of medical care because of COVID-19–related concerns—United States, June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(36):1250-1257. doi:10.15585/mmwr.mm6936a4

Content reviewed 1/2021