Opinion Human Leukocyte Antigen (HLA) at the Root of Persistent Antigens and Long COVID, 2025, Georgopoulos et al

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Human Leukocyte Antigen (HLA) at the Root of Persistent Antigens and Long COVID

Apostolos P. Georgopoulos, Lisa M. James, Phillip K. Peterson

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Abstract
Here we offer a perspective on recent findings of persistent SARS-CoV-2 antigens in Long COVID through the lens of immunogenetic risk and protection, namely in the context of the fundamental role of Human Leukocyte Antigen (HLA) in eliminating viral infections. Specifically, we attribute the persistence of viral antigens to the lack or weak protection conferred by HLA against SARS-CoV-2 in individuals carrying HLA alleles with low binding affinities to the virus.

We suggest that determining the HLA Class I and II makeup of Long COVID patients will provide valuable new information in elucidating the cause for antigen persistence underlying the development of Long COVID and pave the way for successful interventions.

Link | PDF (Journal of Immunological Sciences) [Open Access]
 
It should be noted that the present case of persistent SARS-CoV-2 antigens is actually a subset of a larger family of persistent harmful antigens involved in chronic disease, including the peptidoglycan in the case of chronic Lyme arthritis [9], the anthrax vaccine antigen in Chronic Multisymptom Illness (formerly Gulf War Illness) [10], and potentially other persistent antigens in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) [11].

9. Jutras BL, Lochhead RB, Kloos ZA, et al. Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A. 2019;116(27):13498–507. Available from: https://doi.org/10.1073/pnas.1904170116.

10. James LM, Carpenter AF, Engdahl BE, et al. Anthrax vaccination, Gulf War Illness, and Human Leukocyte Antigen (HLA). Vaccines (Basel). 2024;12(6):613. Available from: https://doi.org/10.3390/vaccines12060613.

11. James LM, Georgopoulos AP. At the root of 3 "Long" Diseases: Persistent antigens inflicting chronic damage on the brain and other organs in Gulf War Illness, Long-COVID-19, and chronic fatigue syndrome. Neurosci Insights. 2022;17:26331055221114817. Available from: https://doi.org/10.1177/26331055221114817.
 
With respect to SARS-CoV-2 and other viral insults, the immediate defense lies with the Human Leukocyte Antigen (HLA) Class I (HLA-I) system which typically eliminates the virus during the first ~10 days of infection2, after which the viral infection, if it persists, tends to become chronic.

Is it proven that >10 day infections become chronic in general, for Covid-19 or for any of the other mentioned infections?

They use both PACS and Long COVID (LC), and I don’t understand what they mean with either.

The phone won’t let me copy any more text, but figure 1 seems to define LC as persistent antigens.
 
I generally look at these gene explanations as a form of victim blaming.

Regardless, there is no need for HLA to explain persistence, at least as far as Lyme is concerned. But who knows? Well, perhaps the relentless group of mainstream spirochete sleuths that have viewed HLA as the holy grail of explanations for close to three decades. And have yet to prove it.
 
I generally look at these gene explanations as a form of victim blaming.

I don’t agree with that interpretation in general, but I can understand why someone with ME/CFS would be very wary of victim blaming.

I have a close friend that’s genetically predisposed to cancer, I can’t think or any situation where she would be blamed for getting cancer.
 
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