11:25 AM

455 - Recurrent COVID Risk, T2D and Kidney Health, An “Awe-Full” Life

Take 3 – Practical Practice Pointers©

From the Pre-Review Literature

1)  Risks Associated With Recurrent COVID Infection


It is known that first infection with SARS-CoV-2 is associated with increased risk of acute and post-acute death and sequelae in multiple organ systems.  However, whether reinfection adds to the risk incurred after the first infection is not clear and has important implications for reinfection prevention. 

The authors of this study, which was released pre-review, used the national health care databases of the US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855) to estimate risks and 6-month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes.

In the reinfection group, 12.29% had two infections, 0.76% had three, and 0.08% had four or more infections.  Using a variety of statistical analyses including hazard ratios and the adjusted excess burden of each adverse clinical outcome, the authors found that compared with people with first infection, reinfection with SARS-CoV-2 contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extrapulmonary organ systems, including cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders.   The risk and burden increased in a graded fashion according to the number of infections and were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection.  Additionally, the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection.

The authors conclude that reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

Mark’s Comments:

I’m highlighting this study with some trepidation.  The disclaimer at Research Square, which has posted this study, indicates they publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.  Additionally, there are some significant concerns with the study design that could impact the results and conclusions. 

Having said that, the authors of this study are prolific researchers, and have already had numerous studies published in Nature Medicine regarding COVID break through infections and persistent or emergent COVID sequalae after acute infection (“long COVID”).   What caught my attention about these findings is that I’m finding many patients (and a not insignificant number of colleagues) appear to be treating COVID infection as a once-and-done phenomenon, with the expectation that if any subsequent infection occurs, it will be milder than the first. 

But what if the opposite is true, and we should actually be counselling our patients who have had past infection to be more cautious in preventing future infection?  While not wanting to cause undue emotional distress, it would seem reasonable for these people to continue to practice physical distancing and masking in social circumstances, and to not place themselves at increased risk.  This might be particularly true for those who already have greater risk for complications.  

Obviously, there is much yet to learn about the impact of this virus and its many offspring.  One thing we do owe to those we care for is to not become complacent due to our own COVID fatigue. 


Al-Aly, Z; Bowe, B; Xie, Y.  Outcomes of SARS-CoV-2 Reinfection.  Nature Portfolio. Prereview version 1 posted on Research Square 17 June 2022.  Link


From the American Diabetes Association (ADA)

2)  Why Yearly Albumin/creatinine Measures for All with Diabetes? 


Last year, the National Committee on Quality Assurance (NCQA, the folks that make the population health metrics) changed the “microalbuminuria measure” for diabetic patients to a “kidney health” metric. This new kidney health metric requires BOTH a urine albumin-creatinine ratio (uACR…don’t use the term “microalbumin” anymore) and an estimated glomerular filtration rate (eGFR) on ALL patients with diabetes every year.

Many have asked: “Why? We used to just order a microalbumin so that we could start angiotensin converting enzyme (ACE) inhibitors. If they were already on an ACE, there was no reason to check.”

True, but the evidence has now changed…

First, there is no high-quality evidence that measuring these labs annually leads to better patient-oriented outcomes – just to get that out of the way. Instead, it appears that the American Diabetes Association guidelines (and the National Kidney Foundation) recommend doing this testing so that we can apply the important new treatment evidence discussed below. The same thing happened when the guideline organizations made statin recommendations to reduce cardiovascular disease risk, assuming that we’ll get the lipid panel routinely in order to calculate the risk.

Once you get the yearly eGFR and uACR testing, here are the interventions to consider (from the ADA guideline):

A recommendations (evidence from at least one large, good-quality randomized controlled trial):

·         Optimize blood pressure and blood glucose control.

·         For patient with CKD 3 or higher – advise reducing protein intake to 0.8 g/kg of body weight.

·         For patients with an uACR >= 300 or eGFR < 60 and hypertension prescribe an ACE/ARB to reduce progression of CKD.

·         For patients with diabetes, an eGFR >= 25 and uACR>=300 prescribe a SGLT2 to reduce cardiovascular events.

·         For patients with CKD at risk for CVD or CKD progression, and if unable to use SGLT2, consider a nonsteroidal mineralocorticoid receptor antagonist (finerenone) to reduce CVD risk and CKD progression.

·         For patients with a mild increase in their serum creatinine (<=30%) in the absence of volume depletion, do not discontinue ACE/ARB.

·         For patients with an eGFR < 30, refer to nephrology.

B recommendations (supportive evidence from cohort studies):

·         For patients with DM and HTN and uACR of 30-299, prescribe an ACE/ARB to reduce progression of CKD.

·         For patients with CKD and uACR ≥300 mg/g, try to reduce ACR by 30% or greater (with the interventions above) to slow chronic kidney disease progression.

John’s Comments: These guidelines use a mix of patient- and disease-oriented evidence as well as high and medium validity evidence to create their recommendations. There is a lot of attention paid to “kidney health” these days and some of it seems overstated to me. However, there is enough evidence here – especially about modifying cardiovascular risk with SGLT2s – that I can accept the recommendation to check the eGFR and uACR yearly.


·         ADA Professional Practice Committee.  Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes—2022.  Diabetes Care. Diabetes Care 2022;45(Supplement 1):S175–S184.  Accessed July 12, 2022. Link

From PeerRxMed ( www.PeerRxMed.org )

3)  Creating an “Awe-Full” Life


“Take the time to pause and open your mind to those things which you do not fully understand. You will be the better for it.”  Dacher Keltner, PhD, Psychologist and Awe Researcher

He was absolutely giddy as he described the pictures.  “Oh!  This is just stupefying detail!”  There was Neil deGrasse Tyson, PhD, the world’s most renown astrophysicist and science communicator extraordinaire, explaining the nuances of the first pictures to be shared this week from the James Webb Space Telescope.  “This is the color you would see if your eyes could see infrared light …. and just look at that quintet of galaxies, GALAXIES!....

And they were stunning, the pictures taken from a telescope which is almost 1 million miles from earth, allowing viewers to peer deeper into our universe than anyone in the earth’s history has ever done, showing innumerable galaxies each containing an estimated 100 billion stars, and revealing light which has been traveling in some cases for an estimated 13.5 billion years. 

Wait … What!?!  How to grasp 13.5 billion light years?  Some scientists estimate that if we could peer back 13.8 billion light years, we would be getting a glimpse into the origins of our universe.  In other words, it’s A LOT – so much so that we really can’t grasp it, try as we may.  We can, however, be filled with awe.

Awe, the feeling of being in the presence of something that transcends, challenges, or deepens our understanding and/or appreciation of the world – a sense that we are part of something bigger than ourselves.  It might be found in nature, art, a mind-stretching idea, or an impressive feat.  The experience can be grand, such as peering at a picture containing 13.5-billion-year-old light and numerous galaxies, but is often much more subtle, such as appreciating the intricacies of a flower, being moved by a piece of music, watching a butterfly in flight, taking in a sunrise or sunset, or looking into the eyes of a child.  And though “giddy” may be one response, more often it will be one of silent, wide-eyed reverence.

While majestic images from space are certainly awe-inspiring, what if you could peer more deeply into the “universe” of your daily life and in doing so, to regularly fill your day with moments of wonderment and awe? 

Well, I have good news for you.  You can.  All that is required is for you to refocus your “awe lens.”  How?  Start by taking this brief quiz ( The Power of Awe Quiz ).  When you're finished, you'll receive tips for expanding your daily experiences of awe.   And as this happens, remember to share your “wow!” moments with others.  Afterall, it would be a shame to keep such “awe-full” moments to yourself.   


Mark and John

Carilion Clinic Department of Family and Community Medicine

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Email: mhgreenawald@carilionclinic.org