The Intersection Between COVID-19, Hypertension, and Diabetes May Be with the ACE-2 Receptor

Of the early COVID patients in the Hubei province, diabetes and HTN were frequent comorbidities

With Laurence Gerlis MD

In more than 80% of infected individuals, COVID-19 manifests itself in a temperature and cough 1,2. Less common are labored breath (dyspnea) and muscle fatigue1-3 . Most patients also have low white blood cell count (lymphocytopenia) and nearly all have pneumonia 2,3. Lung CT scans of infected individuals have revealed lesions in multiple lobes with a “ground-glass” opacity2,4. Approximately 1% of people with a positive COVID-19 test result are asymptomatic5.

Hypertension and diabetes: Comorbidities at greater risk

Besides age, diabetes and hypertension (HTN) may also be substantial risk factors for COVID-19 infection with poorer outcomes. According to Robert A. Gabbay, MD, Chief Medical Officer and Senior Vice President at Joslin Diabetes Center, and Associate Professor at Harvard Medical School, diabetes patients are “more likely to have severe illness,” pointing to the influenza cases as an example. Dr. Gabbay says he suspects that it may be the same for diabetics with Coronavirus.

Of the early COVID-19 patients in the Hubei province, diabetes and HTN were frequent comorbidities1-3,6. Furthermore, these patients tended to have a poor prognosis6,7. On February 28, 2020, the World Health Organization (WHO) in conjunction with Chinese health officials published crude fatality ratios for patient populations8. These data were confirmed in a recent JAMA article5.

Case Fatality Rates (as of February 2020)

  • Overall (2.3%)
  • No comorbidities (1.4%)
  • >80 years old (14.8-21.9%)
  • Diabetes (7.3-8.4%)
  • Hypertension (6.0-8.0%)
  • Cardiovascular disease (9.2-10.5%)
  • Chronic respiratory disease (6.3-8.0%)
  • Cancer (5.6-7.6%)

As more data are published, these results are likely to shift and stabilize. As it is though, patients with one or more of these comorbidities should be watched carefully.

To emphasize the risk of diabetes further, the journal Diabetes Research and Clinical Practice offered a pre-proof article directed at endocrine professionals and the care of diabetic patients7. According to Wang et al.7 COVID-19 could trigger a stress condition in diabetic patients, leading to the secretion of hyperglycemic hormones, abnormal glucose variability, and diabetic complications. Based on their experience with patients in China, frontline healthcare professionals were not necessarily monitoring blood glucose levels in diabetic COVID-19 patients.

According to Dr. Laurence Gerlis, infections increase blood sugar levels, which is something that all healthcare professionals treating COVID-19 patients with diabetes need to keep in mind. Patients should be aware as well, he says, even if they are not eating because they are unwell. In this case, patients need to maintain their insulin levels based on regular blood glucose assessment.

The diabetics as well as others with comorbid conditions often experienced rapid progression to ARDS and septic shock compared to other COVID-19 patients. The authors, then, urge the importance of close glucose monitoring for all diabetic patients at this time regardless of infection, taking advantage of remote medical consulting options7.

Angiotensin-converting enzyme 2 (ACE-2): A link to comorbidities

The virus that causes COVID-19 is similar to the virus which caused the SARS outbreak between 2002 and 20039,10. Both are classified as coronaviruses. The similarity between these two viruses may shed light on the current COVID-19 outbreak, especially in those with HTN and diabetes.

Early studies using the SARS virus (SARS-CoV-1) revealed that the virus used the angiotensin-converting enzyme 2 (ACE-2) to gain access to cells11,12. ACE-2 is a membrane bound enzyme which converts angiotensin I and II into their active forms. Preliminary studies suggest that the SARS-CoV-2 virus infects cells in the same way 9,10.

Using published single-celled RNA sequencing (scRNA-seq) data sets for ACE-2, several investigative teams compiled a list of organs at risk of SARS-CoV-2 infection. Based on these data sets the following organs and cells are at risk of becoming reservoirs for COVID-19 viral infection: (% cells with ACE-2 expression)13,14

  • Lungs- Type 2 alveolar epithelial cells (83%)
  • Ileum- epithelial cells (30%)
  • Heart- myocardial cells (7.5%)
  • Kidney- proximal tubule cells (4%)
  • Bladder- urothelial cells (2.4%)
  • Esophagus- epithelial cells (1%)

In some organs the percentages seem low. However in the unlisted organs (i.e. stomach), less than 1% of cells expressed ACE-2. The pattern of ACE-2 expression corresponds to the most common causes of death in COVID-19 patients. In the early reported deaths from China, most patients died from pneumonia, pulmonary edema, acute respiratory distress syndrome (ARDS), and multiple organ failure 1,13,15.

A commentary by David S. Fedson (Chemin Du Lavoir, France), Steven M. Opal (Department of Medicine, Warren Alpert School of Medicine, Brown University, RI, USA), and Ole Martin Rordam (Trondheim, Norway) have suggested that COVID-19 infection might be treated using statins and/or angiotensin receptor blockers (ARBs)16. These drugs work by upregulating the activity of ACE-2. They offer this hypothesis:

“They (statins and ARBs) act largely (although not exclusively) on endothelial dysfunction, which is a common feature of many virus infections…Combination treatment with these two drugs appears to accelerate a return to homeostasis, allowing patients to recover on their own.”

The idea comes from unorthodox data out of Sierra Leone and the Netherlands, where patients with ARDS were treated with a combination of the two drugs, reducing the severity of ARDS16. At this time however, there is no data to suggest that COVID-19 patients taking statins or ARBs for pre-existing conditions experience less severe disease. This will be a “watch and wait” scenario as more data accumulates. 

Maintaining a clean environment in healthcare facilities

In a study published earlier this month in The New England Journal of Medicine, researchers tested the viability of the SARS-CoV-2 virus in aerosol form. The duration of their study lasted 3 hours, at which point viable virus was still found. Viral viability on surfaces were also tested with the following results: (viral titer half-life)17

  • Aerosol: ~3 hours (~1.2 hours)
  • Copper: 4-8 hours (~1.2 hours)
  • Cardboard: 24-48 hours (~3 hours)
  • Stainless Steel: 48-72 hours (~6 hours)
  • Plastic: 72-96 hours (~7 hours)

In many cases, the SARS-CoV-2 virus displayed a viability profile similar to the SARS-CoV-1 virus17.

Considering the length of time active virus can stay on a surface, routine disinfecting of surfaces is important, especially frequent touch surfaces in healthcare settings. The following agents have shown to be effective against other coronaviruses such as SARS-CoV-1 and MERS in suspension tests6,18:

  • >70% ethanol
  • 75% isopropyl alcohol
  • 0.5% hydrogen peroxide
  • > 0.1% sodium-hypochlorite (bleach)
  • > 1% providine iodine

Less effective were benzalkonian chloride and chlorhexidine digluconate6,18. Stainless steel surfaces can be disinfected with at least 70% ethanol or 0.1% sodium-hypochlorite solution18.

The takeaway

It is important to remember that the facts concerning COVID-19 are still emerging, and our understanding of the disease in at-risk populations may change in the days or weeks ahead. Continuing good hygiene practices is essential, but being especially mindful of patients with HTN or diabetes is an additional but important task for endocrine specialists. 

According to Sarah Sato, NP, CDE, of The Alpine Center for Diabetes, Endocrinology, and Metabolism, patients should be advised to make sure they have medication for at least 2 weeks’ worth of time in the event of a quarantine. For diabetics, “self-care should mimic what they have already been taught for sick-day management, like increasing rest and hydration, monitoring for higher and less predictable blood sugars, and keeping away from sugary remedies if possible,” Sato says.

Remote monitoring should be one method of staying connected to patients during this time. Additionally, patients should also have a predetermined emergency contact who is a friend or family member designated to help them, according to Dr. Laurence Gerlis. “This is especially important for people who are living alone who may need to self-isolate.”

The authors report no competing conflicts concerning their involvement in conducting or discussing this study.

 

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