ABSTRACT
In a study of two Hospitals in Saxony (Chemnitz and Leipzig), we analyzed the antibody development towards SARS-CoV-2 and against a variety of endemic coronaviruses. Here we analyzed 760 sera from a Saxonian cohort for antibody reactivity against: Common cold coronaviruses, HCoV-229E, HCoV-HKU 1, HCoV-NL63 and HCoV-OC43, MERS-CoV and SARS-CoV. For the SARS CoV-2 immune response we tested the following antigens: Spike, S1, S2, RBD and nucleocapsid. These 11 antigen determinants were tested in a commercial multiplex Luminex based assay. We tested sera from 544 individuals (347 females and 197 males;498 SARS-CoV-2 PCR positive and 262 SARS-CoV-2 PCR negative) between May 2020 and March 2022. We observed up to 10% reactivity against the MERS virus in both the PCR positive and negative group. Against the common cold corona viruses 80%-90 % of the individuals in both groups show detectable antibodies. Regarding the antibody response against SARS-CoV a significant difference was observe. Only 19% of COVID-19 infected individuals show antibodies against the virus, while 81% of the PCR-positive individuals produced antibodies. The presence of antibodies against the SARS-CoV-2 is positively correlated with those against SARS-CoV (p = 0.001). No changes in endemic antibody responses were see in the two groups. The antibody status after first immunization event (infection/ vaccination) shows differences in nucleocapsiddirected antibody production, found in the natural infection group (about 60%). In the vaccination group, more individuals (up to 95%) show an immune response against Spike, S1 and RBD compare with natural infection. In summary, the examined cohort shows a general immunization up to 90% against most endemic corona viruses. Correlation analyses show cross-reactivity between SARS-CoV-2 and SARS-CoV. Longitudinal antibody analyses are under way, as also correlations of humoral response with immunogenetic factors.
ABSTRACT
Since the beginning of the SARS-Cov-2 pandemic, in 2020, numerous data with respect to the influence of immunogenetics to the predisposition and infection severity have been reported worldwide. It is well accepted that immunogenetics plays a pivotal role in infection and vaccination, as well as vaccination failures and/or breakthrough. Factors of the major histocompatibility complex and the common ABO blood group system have been so far discussed. Here, we describe the association of HLA-A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1, -DPB1, and HLA-E, -F, -G, -H on the results of molecular detection of COVID-19 or in some cases on antibody detection upon first testing. Furthermore, we defined molecularly 22 blood group systems comprising 26 genes and 5 platelet antigen genes. We observed 37% COVID-19 PCR negative individuals and 63% positive. Within the negative subjects HLA-B*57:01, HLA-B*55:01, DRB1*13:01, DRB1*01:01, were enriched, and in the positive group homozygosity for DQA1/DQB1, DRB1*09:01 and DRB1*15:01. For HLA-DQA1 we observe an enrichment for DQA1*01:01, DQA1*02:01 and DQA1*01:03. For HLADQB1 we found HLA-DQB1*06:02 was enriched in the positive group while HLA-DQB1*05:01 and HLA-DQB1*06:03 in the negative group. We observed a significant enrichment of homozygosity for DQA1/DQB1 in the positive group. The homozygous platelet antigen HPA-1a was significantly enriched in the negative group, contrasting the result of HPA-1ab that was enriched in the COVID-19 infected group. Despite limitations of our study, the data presented here show clearly that COVID-19 infection and all the consequences of that are multifactorial and multigenetic. The virus is in a continuous mutation/selection process leading to escape possibilities. Therefore, associations are a momentum in science.
ABSTRACT
Breakthrough infections with SARS-CoV-2 after a full series of vaccination are increasingly reported. Waning of vaccine immune response (VE) and immune evasion of emerging virus variants are main causes of vaccination failure. Reasons for early breakthrough infections (BInf) in immunocompetent persons are less clearly defined. Host factors which ameliorate the immune response to vaccination are yet to be identified. We looked for potential risk factors in a case series of health care workers with early breakthrough infection after a full primary vaccination series against SARS-CoV-2. During the two first waves, ten previously healthy health care workers (HCW) which experienced BInf within 3 months after completion of a full primary vaccine series with mRNA vaccines (two vaccines) were analyzed for humoral (One Lambda) and T-cell ELISPOT (Oxford Immunotec Ltd.) response to SAS-CoV-2 viral antigens. ABO Blood group genotyping by real-time PCR (BAG, One Lambda), HLA genotyping by NGS (One Lambda, CareDx) and analysis for cytokine promoter gene polymorphisms (One Lambda) were done as well. In addition, the second cohort of eight patients with a full vaccine series (three vaccines) experienced Blnf during the eruption of the omicron variant and analyzed as mentioned above. All individuals of the two first waves had antibodies against SARS-CoV-2 spike S1 epitope but only 2/10 had nucleocapsid (N) antibodies detectable. Specific T cell response against spike protein, N protein and matrix protein each was intermediate or low compared to positive control in 7/8 indicating a diminished cellular immune response. Similar results were obtained with the probands of the omicron wave. None of the individuals had the IFN gamma high-expression cytokine polymorphism. In contrast, six had the lowlevel IFN gamma expression genotype, pointing towards a more Th2-directed response, 4/5 had also low T cell responses to vaccine antigens. In contrast, TGF-beta gene expression pattern were high in 7/10 and intermediate in 3/10. Host factors for decreased vaccine responsiveness to SARS-CoV-2 are still a matter of discussion. In our small case series, we found weak T cell responses combines with predominant hypo-inflammatory cytokine genotype and distinct MHC II and non-classical MHC I genes. Larger controlled case series are needed to explain the significance of those findings.