Cardiovascular Disease, Diabetes, and COVID-19

The COVID-19 global pandemic has changed our way of life as we know it, and the long-term impact on our health and the economy is not known. While most people with COVID-19 infection have only mild symptoms and recover uneventfully, certain groups are at increased risk for serious disease, complications, and death.1-3 To understand and improve this situation, researchers studying the pandemic are identifying these at-risk groups and the associations between COVID-19 infection, comorbidities, and outcomes.

This article will discuss COVID-19 and the comorbidities of cardiovascular disease (CVD) and diabetes. People with these conditions are more likely to contract a severe COVID-19 infection and are among those identified as being at higher risk for poorer outcomes (see Sidebar).

The information in this article is current at the time of writing. However, readers are encouraged to review the latest public health information from the Centers for Disease Control and Prevention (CDC) at Coronavirus.gov and the most recent research from the National Institutes of Health (NIH) at NIH.gov/coronavirus.
COVID-19 Infections: Mechanism and Severity
COVID-19 is the name given to an infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an enveloped, single-stranded RNA virus.1,4 SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor, and uses it to enter into the host cell.1,4 ACE2 is highly expressed in alveolar cells in the lungs.1,4 Importantly, ACE2 is also highly expressed in the heart as well as the intestinal epithelium, vascular endothelium, and kidneys.1,4

An unknown number of people have asymptomatic infections. For those with symptoms of COVID-19 infection1,4
  • Most people (around 80%) have a mild to moderate illness.
  • About 15% of people have a serious illness requiring hospitalization.
  • About 5% have a critical illness that requires invasive ventilation for acute respiratory. distress syndrome (ARDS) with multi-organ failure that can lead to death.
Laboratory Findings in Patients With COVID-19
Lymphopenia is the most common laboratory abnormality in patients with COVID-19.1 It is found in up to 83% of hospitalized COVID-19 patients and may be a marker of greater disease severity.1 Other laboratory findings that may be associated with illness severity include neutrophilia and elevated levels of serum alanine aminotransferase and aspartate aminotransferase, lactate dehydrogenase, C-reactive protein (CRP), ferritin, and D-dimer.1 Mortality is associated with elevated D-dimer levels and lymphopenia.1 Procalcitonin levels are typically normal on admission but may increase among patients admitted to the intensive care unit (ICU).1

Patients with critical illness may have elevated levels of inflammatory markers and proinflammatory cytokines such as interleukin (IL)-1 and IL-6, which suggests that the virus can cause immune dysregulation and a “cytokine storm”.1,6
CVD and COVID-19
Patients with preexisting CVD are at increased risk for severe COVID-19 infection and death.7,8 The mortality rate for patients with CVD is around 11% compared with a 2% overall mortality rate.8 The reasons are unclear but may be related to a generally poorer health status, changes in ACE2 receptors as a result of medical treatment, or underlying immune dysfunction as a result of the CVD.7,9,10 Patients with preexisting CVD are also at risk for developing a critical illness.7,9,10 In addition, patients with comorbidities such as diabetes, chronic kidney disease, and chronic obstructive pulmonary disease (COPD) are at increased risk of cardiac involvement during a COVID-19 infection.7,9,10

Acute myocardial injury and arrhythmias (bradycardia and tachycardia) are the most common manifestations of COVID-19 cardiac involvement.10 Acute cardiac injury has been reported in 8% to 12% of patients, defined as elevated high-sensitivity cardiac troponin I (hs-cTnI).7 Higher hs-cTnI levels, and progressively increasing levels, are associated with mortality.7

Potential pathogenic mechanisms of acute cardiac injury include direct effects of the virus on heart muscle via ACE2, systemic inflammation, increased myocardial demand, plaque rupture and coronary artery thrombosis, electrolyte imbalance, and the effect of therapies for COVID-19 infection.7

Overall, myocardial injury is significantly associated with fatal outcomes of COVID-19 infections; however, patients with underlying CVD but without myocardial injury have a relatively favorable prognosis.9

In addition, microvascular effects such as microvascular thrombosis may be involved in hypoxemic respiratory failure in some patients with COVID-19.11 While its prevalence in COVID-19 is unknown, a study has reported thromboembolism resulting in the need for amputation.12 The American Society of Hematology recommends all hospitalized patients with COVID-19 receive pharmacologic thromboprophylaxis with LMWH or fondaparinux and that healthcare providers consider continuing anticoagulation treatment after patients are discharged.11

Reports are indicating that children and infants may rarely develop a multi-system inflammatory syndrome, related or similar to Kawasaki disease.13,14 The condition includes cardiac inflammation and elevated levels of hs-cTnI and brain natriuretic peptide (BNP).13,14
Diabetes and COVID-19
Similar to patients with preexisting CVD, patients with diabetes are at increased risk of a severe COVID-19 infection and critical illness for similar reasons.3,7,9,10 Data suggest that 14% to 32% of patients with diabetes who become infected with COVID-19 will develop serious or critical disease, with an overall mortality rate of about 7%.1,3

Disease severity and complications may be due, at least in part, to the expression of ACE2 in the kidneys and pancreas, as well as the lungs, heart, and other locations.3 Patients without preexisting diabetes have become hyperglycemic during a COVID-19 infection.3 Individuals infected with SARS-CoV-1 during the past epidemic showed persistent hyperglycemia for 3 years after recovery. Thus, persistent hyperglycemia after recovery from COVID-19 is possible. Accordingly, monitoring glucose levels after COVID-19 infection is important.3
Persons at Risk for Severe Disease and Complications

People with comorbidities are at increased risk for more serious disease, but it is important to know that young people with no comorbidities can also develop critical illness, including multi-organ failure and death.4

Current evidence indicates that individuals who are at high risk for developing a severe or critical COVID-19 infection include4,5

  • People 65 years and older
  • People who live in a nursing home or long-term care facility
  • People of any age with an underlying medical condition, particularly if the condition is not well controlled
  • Serious heart conditions or underlying CVD
  • Diabetes
  • Chronic lung disease or moderate to severe asthma
  • Severe obesity (body mass index [BMI] ≥40 kg/m2)
  • Chronic kidney disease undergoing dialysis
  • Liver disease
  • Cancer

People who are immunocompromised are also at risk of more serious illness. Conditions associated with an immunocompromised state include cancer treatment, smoking, bone marrow or organ transplantation, immune deficiencies, poorly controlled HIV or AIDS, and prolonged use of corticosteroids and other medications that can suppress the immune system.4,5
How the Laboratory Can Help

Quest Diagnostics is committed to assisting healthcare providers during the current COVID-19 pandemic. Healthcare providers can view the latest information about COVID-19 testing at QuestDiagnostics.com/home/Covid-19/HCP/. Information for patients is available at QuestDiagnostics.com/home/Covid-19/Patients/.

We also provide a wide range of tests to assist in the diagnosis and care of patients with COVID-19 who develop serious or critical disease:

  • Tests to evaluate inflammation and general disease severity include
  • C-Reactive Protein (CRP) (test code 4420)
  • Cytokine Panel
  • Ferritin (test code 457)
  • Glucose (test code 483)
  • Interleukin-1 Beta (test code 1757)
  • Interleukin-6 (IL-6), Serum (34473)
  • Procalcitonin (test code 16265)
  • Tests to determine myocardial damage include
  • CK-MB (CK-2) (test code 17581)
  • High-sensitivity (hs)-CRP (test code 10124)
  • NT-proBNP (test code 11188)
  • Troponin I (test code 34693)
  • Other tests that can be useful in the care of patients with serious or critical disease include
  • D-Dimer, Quantitative (test code 8659)
  • Fibrinogen Comprehensive Panel without Consultation (test code 14458)

Additional information about cardiovascular testing is available from QuestDiagnositics.com/home/physicians/testing-services/condition/cardiovascular/ and the Cleveland Heart Lab at ClevelandHeartLab.com. Additional information about diabetes testing is available from QuestDiagnositics.com/home/physicians/testing-services/condition/diabetes/.

Please complete the form below to recieve the latest updates.

References

  1. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). Centers for Disease Control and Prevention. Reviewed April 6, 2020. Accessed April 15, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
  2. ACC’s COVID-19 Hub. American College of Cardiology. Accessed April 15, 2020. https://www.acc.org/latest-in-cardiology/features/accs-coronavirus-disease-2019-covid-19-hub#sort=%40fcommonsortdate90022%20descending
  3. Singh AK, Gupta R, Ghosh A, et al. Diabetes in COVID-19: prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020;14:303-310. doi:10.1016/j.dsx.2020.04.004
  4. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Infectious Diseases Society of America. Accessed April 15, 2020. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
  5. People who are at higher risk for severe illness. Centers for Disease Control and Prevention. Reviewed April 15, 2020. Accessed April 15, 2020. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-higher-risk.html
  6. Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVID-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34:1. doi:10.23812/CONTI-E
  7. Clerkin KJ, Fried JA, Raikhelkar J, et al. Coronavirus disease 2019 (COVID-19) and cardiovascular disease. Circulation. 2020;141:1648-1655. doi:10.1161/CIRCULATIONAHA.120.046941
  8. COVID-19 clinical guidance for the cardiovascular care team. American College of Cardiology. Reviewed March 6, 2020. Accessed April 8, 2020. https://www.acc.org/latest-in-cardiology/features/~/media/Non-Clinical/Files-PDFs-Excel-MS-Word-etc/2020/02/S20028-ACC-Clinical-Bulletin-Coronavirus.pdf
  9. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;e201017. doi:10.1001/jamacardio.2020.1017
  10. Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020;14:247-250. doi:10.1016/j.dsx.2020.03.013
  11. COVID-19 and VTE/anticoagulation: frequently asked questions. American Society of Hematology. Updated April 17, 2020. Accessed May 7, 2020. https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation
  12. Bellosta R, Luzzani L, Natalini G, et al. Acute limb ischemia in patients with COVID-19 pneumonia. J Vascular Surg. 2020;S0741-5214(20)31080-6. doi:10.1016/j.jvs.2020.04.483.
  13. 2020 Health Alert #13: Pediatric multi-system inflammatory syndrome potentially associated with COVID-19. NYC Health. May 4, 2020. Accessed May 7, 2020. https://www1.nyc.gov/assets/doh/downloads/pdf/han/alert/2020/covid-19-pediatric-multi-system-inflammatory-syndrome.pdf
  14. PICS statement. Increased number of reported cases of novel presentation of multi-system inflammatory disease. Pediatric Intensive Care Society. April 27, 2020. Accessed May 7, 2020. https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020.pdf

Content reviewed 7/2020