ABSTRACT
Background The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. In addition to polymorphic T-cell receptor alpha/beta constructs, less variable T-cell receptor gamma/delta cells may respond to a specific peptide presented by MHC molecules of antigen presenting cells as well as other target tissues. Methods: High-resolution HLA typing was performed in 536 non-hospitalized patients infected with SARS-CoV2. For HLA-Class I we obtained results from 519 patients, and for HLA-Class-II from 531. Patients who became ill between March 2020 and August 2021 were tested for the 22 most common HLA class I (HLA-A, -B, -C) or HLA class II (HLA –DRB1/3/4, -DQA1, -DQB1) haplotypes in this collective. The identified HLA haplotypes were associated to disease severity. We also analyzed the influence of CCR5 and the ABO blood groups on the disease duration.Results: The influence of the HLA haplotypes on disease severity was stronger than the influence of age, sex, AB0 blood group, or wave of infection with different mutants of the virus. The presence of mutated CCR5 resulted in a longer recovery period.Conclusion: The existence of certain HLA haplotypes is associated with more severe disease..
Subject(s)
COVID-19ABSTRACT
COVID-19, the pandemic infection caused by SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients’ adaptive immune responses without progression to severe disease with patients’ Human Leukocyte Antigen (HLA) genetics, the presence or absence of near-loss-of-function delta 32 deletion mutant of C-C chemokine receptor type 5 (CCR5) and AB0 blood group antigens. We further analyzed the association of these immunogenetic background characteristics with patients’ humoral antiviral immune response patterns, assessed longitudinally. The study enrolled 157 convalescent adult patients followed up for up to 250 days. Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01) associated with reduced durations of disease and decreased (rather than increased) total anti-S IgG levels providing virus neutralizing capacity comparable to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:2 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A seeming association of a heterozygous CCR5 delta 32 mutation with prolonged disease duration suggested by univariate analyses was not confirmed by hierarchical multivariate testing.In conclusion, the current study shows that the presence of certain "protective" HLA alleles is of even stronger association with reduced duration of mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations assessing the impact of HLA genetics on the capacity of mounting protective vaccination responses may be warranted.
Subject(s)
Infections , COVID-19ABSTRACT
The coronavirus disease 2019 (COVID‐19) is associated with a wide clinical spectrum of skin manifestations, including chilblain‐like, urticarial, vesicular and vasculitic lesions. Recently, delayed skin reactions following mRNA vaccination against SARS-CoV-2 have been reported. The exact pathomechanisms underlying these skin lesions remain unknown. Here, we describe eleven cases of delayed skin reactions after SARS-CoV-2 vaccination with the mRNA-1273 vaccine, discuss their transient and benign clinical courses and consider their potential pathomechanisms based on histopathological analyses. We conclude that further investigations to characterize the precise molecular and cellular mechanisms underlying this rare phenomenon are warranted.