By Dr. Chris Magryta
Salisbury Pediatric Associates

As occurred last March, times change rapidly in the world of COVID-19. Latest numbers show that on balance COVID-19 incidence and death is rising rapidly nationally with some of the bigger states getting hit hard with more than 5,000 new cases a day. This is not a surprise as the realities of COVID are always a guessing game and close human interaction is skyrocketing. I reiterate that this is likely to be an infectious disease that keeps us frustrated for another year or more until and if a vaccine is found. As with the first newsletter on this topic, keep solace with the fact that there is a 99+% chance of survival for all of us.

 1. Why are individuals with diabetes mellitus at higher risk for SARS2 infection and COVID disease risk?

In the section from a paper by Dr. Muniyappa below, the author refers to ACE2 as the receptor. Thus, the data shows us that individuals with diabetes have increased volumes of ACE2 receptors providing increased attachment locations for the virus to gain access to the lungs and other tissues. The second part of the discussion notes that people with diabetes have elevated levels of a circulating furin protease enzyme that cleaves part of the SARS2 spike protein allowing for improved cellular entry.

The nightmare of this diabetic associated situation is that viral entry is enhanced by increased ACE2 receptor and furin protease activity allowing the virus the ability to replicate rapidly and thus overwhelm the innate immune response that should keep it at bay. Couple this with the knowledge that people with diabetes generally have significant systemic inflammation at baseline and you have the perfect storm for ARDS and death from COVID-19.

Hard data: “Augmented ACE2 expression in alveolar AT2 cells, myocardium, kidney, and pancreas may favor increased cellular binding of SARS-CoV-2. Increased expression of ACE2 has been demonstrated in the lung, kidney, heart, and pancreas in rodent models of DM. Insulin administration attenuates ACE2 expression, while hypoglycemic agents such as glucagon-like peptide-1 (GLP-1) agonists (liraglutide) and thiazolidinediones (TZDs; pioglitazone), antihypertensives such as ACE inhibitors, and statins upregulate ACE2. Until recently, whether DM was causally linked to ACE2 expression levels in the lung in humans was unknown. Using a phenome-wide Mendelian randomization study, Rao et al. explored diseases or traits that may be causally linked to increased ACE2 expression in the lung. Interestingly, they found that DM was causally associated with increased lung ACE2 expression. Circulating levels of furin, a cellular protease involved in facilitating viral entry by cleaving the S1 and S2 domain of the spike protein, are elevated in patients with DM (13). These studies support the hypothesis that patients with DM are susceptible to SARS-CoV-2 infection. Indeed, a recent study reported that clearance of SARS-CoV-2 was delayed in patients with DM, a finding that needs to be confirmed in larger studies.” (Muniyappa et. al. 2020)

See the Scientific American link below for an awesome pictorial experience of COVID.

Thus, it makes prudent sense to revolt against the antecedent triggers of diabetes:

a. excessive sedentary behavior
b. any diabetes-promoting chemical exposures
c. excessive consumption of processed refined carbohydrates
d. excessive consumption of refined oils of the saturated and omega-6 polyunsaturated class

2. Follow up to my story of the perceived COVID-19 infection. Early data from China and other studies are showing that many individuals have waning immune antibody levels by 4-12 weeks post infection making it appear as if the person was either not infected or not immune anymore. Forty percent of asymptomatic and 13% of symptomatic COVID patients tested negative to IgG antibody presence by eight weeks. This is drama at its best. You can get sick, develop an antibody response and then appear to have no circulating antibodies by eight weeks. (Long et. al. 2020) Do you still have any immune memory to prevent the infection again? The common cold could be our historical precedence. Thirty percent of common colds are of coronaviral origin and we get reinfected all the time. The truth is still murky whether SARS2 will act similarly, but it is hypothesized that the T-cell response is still present and providing targeted immunity in the absence of antibody production and memory. (Grifoni et. al. 2020) Stay tuned.

3. Italy has had some follow-up data of close contacts of COVID patients. In a study: 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy, were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. More than 73% of all infected individuals aged less than 60 years did not develop symptoms. The risk of symptoms increased with age. More than 6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk. (Poletti et. al. 2020)

4. Anyone interested in the Swedish experiment can look at the Bloomberg article for a follow up to their different approach. (Rolander, N 2020). I believe that we have not seen the final answer on the Swedish experiment. In two years when the final IFR data is released, then and only then can we assess the impact of this social experiment. It may be that Sweden just hastened the disease onset and death while not actually changing the end infection fatality rate.

5. Asymptomatic individuals still have clinical findings. “Lab values and imaging were not entirely normal for the asymptomatic group. Eleven had increased C-reactive protein levels and six had elevated levels of alanine aminotransferase. Chest CT found “focal ground-glass opacities” in 11 and “stripe shadows and/or diffuse consolidation” in another 10 of the group; in two-thirds of these 21 patients, the abnormalities were in only one lung. The remaining 16 showed entirely normal imaging.” (Long et. al. 2020)

This virus is impressive to say the least. A 120-nanometer organism can do so much!

Knowledge is power.

Dr. Chris Magryta is a physician at Salisbury Pediatric Associates. Email him at newsletter@salisburypediatrics.com.