Immunosenescence, Exhausted Immune System and COVID-19: research review

by Mike Mutzel


Key Takeaways:

-Markers of immune exhaustion are linked increased COVID-19 disease severity.

-Low lymphocyte percentage has been used as a proxy to predict disease severity. If you’re lymphocytes naturally hoover on the low normal side, there’s good reason to exercise extra caution.

– Increased disease severity is linked with higher expression of immune inhibitor receptors on natural killer and other T helper cells. This so called NKG2A receptor is a target in cancer cells, as rapidly growing cancers and raise it’s levels, which suppresses the immune system and allows the cancer to grow with less inhibition.  

What's Known VS Unknown:

Age-related thymic involution (atrophy of the thymus gland, the organ that makes many key immune cells) is a concept we addressed in the context of epigenetic age in recent months.

HIV positive individuals have been shown to have an ‘aged thymus gland’ (thymic involution) as well as elevated levels of the same immune cell inhibitory-immune molecule (NKG2) found to be elevated in severe COVID-19 patients.

Time will tell if thymic involution (a proxy of immunosenescence) plays into susceptibility and disease pathology of those with severe COVID-19 disease.

Immune Exhaustion is Linked with More Severe COVID-19 Disease

Data is emerging from multiple COVID-19 case reports that immunosenescence (aged immune system) plays a role in disease severity.

Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study
Dynamic changes of LYM% in the death cases (n = 15), severe-cured cases (n = 15), and moderate-cured cases (n = 40). Data are shown as means ± Two cutoff time points of these three curves were set as 1st time point (day 10–12) and 2nd time point (day 17–19). (1)

Immunology can be complex, so I made a brief video & audio podcast to help explain the implications of this emerging finding.

Here’s the gist of it…

Roughly 15% of those infected have poor outcomes and increased COVID-19 disease severity.

Absolute number of T cells, CD8+ T cells, and NK cells in the peripheral blood of healthy controls (n = 25) and patients with mild (n = 55) and severe (n = 13) infection with SARS-CoV-2 (2).

Although mainstream media isn’t talking about this (yet) there’s multiple papers discussing this finding of an ‘exhausted immune system’ as part of the reason why some get hit hard and others don’t.

Why talk about this now when you’re hunkered down at home?

Understanding the characteristics of those with severe vs non-severe disease states can lead to better decision making now and down the road.

Related Video: Purging Your Body’s Cache: senescence and senolytic therapies explained

For example, as discussed in the video, those with a history of low white blood cell counts and other chronic infections (Epstein Barr, for example) probably shouldn’t be the ones doing grocery shopping and may need to exercise greater overall caution. (3)

Also, we it's been known that diabetics have lower numbers of the same T helper cell found to be altered in COVID-19, which may increase the risk of disease severity. (4)

The exciting part is there’s things we can all do now to potentially influence our immune system’s functional capacity down the road.

Cytotoxic T Lymphocytes and NK get exhausted via affecting the immune system checkpoint inhibitor NKG2A on key immune cells.

Interestingly, in cancers, this same immune system checkpoint is inhibited which allows the cancer to grow in a defenseless immune system.

Functional exhaustion of antiviral lymphocytes in COVID-19 patients
Absolute number of T cells, CD8+ T cells, and NK cells in the peripheral blood of healthy controls (n = 25) and patients with mild (n = 55) and severe (n = 13) infection with SARS-CoV-2. (2)
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It’s normal to be stressed and emotionally eat foods you normally wouldn’t during these uncertain times. But just remember that better blood sugar control is linked with various immune parameters, including better outcomes in critically ill patients and reduced surgical infections and more. So when/if you go off the rails a bit, do some push ups, air squats or take a brisk walk/sprint outside. Neutrophils have been shown to be important in the initial innate response to this novel Coronavirus and as this image illustrates, hyperglycemia (elevated blood sugar) alters various aspects of neutrophil function. For the record, I’m not saying Keto cures Coronavirus! But, based on the known immunological data, guzzling Mountain Due and Krispy Kreams is not going to help anyone right now (especially health professionals!). I’ve been taking 1-2 caps of @myoxcience Berberine HCl + ALA at night as my step count is way down. Feel that it helps. P.S. Just uploaded a new video all about the ‘exhausted immune system’ theory and COVID-19 on my YouTube channel/iTunes. If you like this immunology stuff, you may find that helpful, interesting! P.P.S This is a great time to test your glucose! Check out @nutrisenseio ‘s Continuous Glucose Monitor to see how the foods you eat impact your blood sugar. REF: 1. Jafar N, Edriss H, Nugent K. The Effect of Short-Term Hyperglycemia on the Innate Immune System. The American Journal of the Medical Sciences. 2016;351(2):201-211. doi:10.1016/j.amjms.2015.11.011. #immune #coronamemes #codvid19 #coronavirus #housearrest #selfquarantine #socialdistancing #functionalmedicine.

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1. Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduction and Targeted Therapy. March 2020:1-3. doi:10.1038/s41392-020-0148-4.

2. Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cellular & Molecular Immunology. March 2020:1-3. doi:10.1038/s41423-020-0402-2.

3. Jaiswal SR, Bhakuni P, Bhagwati G, Aiyar HM, Chakrabarti A, Chakrabarti S. Alterations in NKG2A and NKG2C Subsets of Natural Killer Cells Following Epstein–Barr Virus Reactivation in CTLA4Ig-based Haploidentical Transplantation Is Associated With Increased Chronic Graft-Versus-Host Disease. Transplantation. 2020;104(1):e23-e30. doi:10.1097/TP.0000000000002941.

4. Bailin SS, McGinnis KA, of WMTJ, 2020. T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus. academicoupcom

5. Gui J, Mustachio LM, Su D-M, Craig RW. Thymus Size and Age-related Thymic Involution: Early Programming, Sexual Dimorphism, Progenitors and Stroma. Aging and disease. 2012;3(3):280-290.

6. Decreased Counts of T Lymphocyte Subsets Predict Prognosis in SARS-CoV-2- Infected Pneumonia in Wuhan, China: a Retrospective Study. The Lancet Respiratory Medicine. February 2020:1-29.

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