Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection (preprint)

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..

Acute cardiac side effects after COVID-19 mRNA vaccination, a case series (preprint)

Background: Since development and approval of the world´s first mRNA vaccines, created under pressure of the global pandemic caused by SARS-CoV-2, potential side effects have naturally been a much-debated topic. Vaccination may be one, if not the only way out of the pandemic claiming more than 4 million deaths worldwide to date. Potential side effects from vaccination have long been controversial, and case reports of fatal side effects have been published. Therefore, data are needed to identify persons being at high risk for potential side effects. Until September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© in young adults were registered by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©).Patients and Methods: Eight patients between 13-56 years of age, vaccinated with mRNA vaccine either BNT162b2 or mRNA-1273 between January and August 2021 developed cardiac side effects shortly after either their first or second vaccination. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after onset of symptoms and investigated further in severe cases. Symptoms were defined as dyspnea, chest pain, cardiac arrhythmia as determined by electrocardiography.Results: Eight patients (five males and three females) developed cardiac symptoms compatible with myocarditis according to CDC criteria shortly after SARS-CoV-2 mRNA vaccination. Three patients (two males, one female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within seven days after symptom onsetConclusion: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Association of HLA and Mutated CCR5 With the Clinical Course of the Disease in Subjects With mild / moderate disease following COVID-19 infection (preprint)

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.

Delayed Skin Reaction After mRNA-1273 Vaccine Against SARS-CoV-2 (preprint)

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.