Einfluss der HLA-G 3'-UTR-Haplotypen 3 und 7 auf das Outcome nach SARS-CoV-2-Infektion und Long-COVID
Hana Rohn (Essen / DE), Fynn Elisher (Essen / DE), Louisa Larbig (Essen / DE), Sarah Jansen (Essen / DE), Sabine Schramm (Essen / DE), Mona Otte (Essen / DE), Margarethe Konik (Essen / DE), Krystallenia Paniskaki (Essen / DE), Peter Weber (Essen / DE), Johanna Reinold (Essen / DE), Anja Gäckler (Essen / DE), Adalbert Krawczyk (Essen / DE), Benjamin Wilde (Essen / DE), Mirko Trilling (Essen / DE), Rafael T. Michita (Houston, TX / US), Birte Möhlendick (Essen / DE), Winfried Siffert (Essen / DE), Thorsten Brenner (Essen / DE), Hannah Dinse (Essen / DE), Eva M. Skoda (Essen / DE), Peter A. Horn (Essen / DE), Oliver Witzke (Essen / DE), Vera Rebmann (Essen / DE)
HLA-G has been suggested as one of the key players in regulating the immune response to SARS-CoV-2 virus. Single-nucleotide polymorphisms (SNP) in the HLA-G 3' untranslated region (UTR), which form haplotypes, are crucial for the regulation of HLA-G expression and thus may contribute as host factors on SARS-CoV-2 infection. The COVID-19 pandemic, continues to pose significant challenges both in terms of acute COVID-19 as well as the enigmatic Long COVID condition. Thus, comprehending the molecular mechanisms and pathogenesis remains critically important.
HLA-G 3´UTR gene polymorphisms were investigated in this monocentric prospective study through sequencing. Unvaccinated patients from the first and second COVID-19 waves in Germany were recruited. The first cohort comprised 505 hospitalized patients with acute SARS-CoV-2 infection and the second sub-cohort included 253 patients presenting at least one month post-recovery. Detailed baseline demographic and clinical characteristics, symptom assessment, and patient-reported outcome measure questionnaires were collected.
Overall, there were no statistically significant differences between patients and controls in HLA-G 3´UTR haplotype frequencies or distribution. The recruited cohort was representative in terms of COVID-19 associated risk factors. Our findings reveal that the HLA-G 3´UTR-3 haplotype is an independent prognostic risk factor for fatal COVID-19 besides the known risk factors age and obesity. The HLA-G 3´UTR-7 haplotype emerged as an independent prognostic factor, besides sex and diabetes, for persistence of at least one Long COVID manifestation following SARS-CoV-2 infection.
Our study highlights that regulatory genetic elements of the immunomodulatory HLA-G molecule contribute to either fatal outcomes after SARS-CoV-2 infection or the persistence of Long COVID. These findings suggest that specific HLA-G gene polymorphisms play a significant role in influencing COVID-19 prognosis and have long-term effects on health conditions. By spotlighting HLA-G, the importance of the genetic background of Immune Checkpoints and their pivotal role in modulating immune responses during and after COVID-19 are emphasized.
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