Genetic association between LONG COVID and TMPRSS2 polymorphisms (rs12329760 and rs2070788) in Brazilian healthcare professionals, 2026, Telles et al

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Genetic association between LONG COVID and TMPRSS2 polymorphisms (rs12329760 and rs2070788) in Brazilian healthcare professionals

Telles, Alysson Fellipe Costa; Menezes Junior, Bearli Souza; Santos, Cliomar Alves dos; Sena, Ludmila Oliveira Carvalho; Alves, Maria Rosa Melo; Moraes, Maria Luiza Aguiar Martins; Cipolotti, Rosana

Abstract
Long COVID syndrome has a multifactorial cause that is not fully understood and may be influenced by both external and intrinsic factors. In this context, a Genome-Wide Association Study (GWAS) was proposed to evaluate the association between Single Nucleotide Polymorphisms (SNPs) in TMPRSS2 (rs12329760 and rs2070788) and the occurrence of Long COVID in 363 Brazilian healthcare professionals, recruited using a non-probabilistic method.

The study employed a self-report questionnaire to collect sociodemographic and clinical data from both the acute and chronic phases and also collected oral mucosa cells for genotypic analysis by qPCR using Taqman probes. The categorized information was analyzed using the PSPP software using Pearson’s chi-square test in three genetic statistical models: additive, dominant, and recessive.

Assessing long COVID in general, only clinical variables such as increased susceptibility, presence of symptoms, and severity influenced the occurrence of the syndrome.

When specifying the main reported symptom, brain fog, females and young adults (18 to 29 years old) are the most vulnerable, and rs2070788 in the recessive model proved to be relevant. This association is more evident when evaluating only the symptomatic group in the post-COVID period, as the additive model also influences the groups. rs12329760 showed no relevant influence on the groups.

Therefore, this study provides unprecedented evidence of the association between brain fog and rs2070788, requiring case-control studies to better clarify how this association occurs.

Web | DOI | PDF | Frontiers in Cellular and Infection Microbiology | Open Access
 
From -

The association between TMPRSS2 gene rs2070788 and rs12329760 variants and COVID-19 susceptibility and severity: A study from Jordan​



Transmembrane serine protease 2 enzyme (TMPRSS2) belongs to the transmembrane serine protease type 2 family,8 and it is an enzyme widely expressed in the prostate, lung tissues, cardiac muscles, and renal/gastrointestinal systems.9 Under normal physiological conditions, TMPRSS2 plays a role in digestion, coagulation, inflammation, and cell death10; however, in the context of viral pathogenesis, its function can be described as a virus trafficker, and many viruses, including influenza viruses and human coronaviruses, use it to invade host cells.

Has this been looked at in ME/CFS?
 
hotblack said:
Second paper for LC it’s popped up in (see the tag or here for the other) but nothing of significance showed up in DecodeME (here’s the locuszoom for the region with the genecards info on regulatory elements all in that area)
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This one tested it, but did not find an association with post-COVID symptoms, according to the abstract:

Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors (2022, Genes)

Based on what the introduction of that paper says, it seems like this is a gene that may be involved in acute COVID severity, and if there's an association with long COVID, I would guess it's probably related to increased severity during the acute infection.
Examples include rs12329760 and rs2070788 of the TMPRSS2 (Transmembrane Serine Protease 2) gene, an enzyme involved in the infectious process of viral entry into the host cell, and whose polymorphisms are associated with susceptibility and severity of the acute phase of the infection (Choudhary et al., 2021; Schönfelder et al., 2021; de Andrade et al., 2022).
Click to expand...

I haven't read the thread paper, but I'd want to check if they took that into consideration, for example by matching based on severity.
 
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