Apart from older age, overweight has been described as an additional risk factor for severe COVID-19 progression usually linked with functional impairment of immune cells and decreased immunity as a result of chronic inflammation and hypercytokinemia [30, 31]. anti-S2 was the least prevalent IgG reactivity (valuevalueAppetite loss??Anti-S/N IgG0.3670.1141.4431.155C1.8020.0012Bronchial secretions??Blood type A?+?1.7490.7375.7501.356C24.3890.0177Cough??Blood type A?+?2.7651.14415.8821.687C149.4900.0156??ORF3a S177I???3.0411.1080.0480.054C0.4190.0061Night sweat??Anti-S/N IgG0.4040.1531.4981.109C2.0230.0084??Anti-S/N IgM0.3000.1481.3501.011C1.8040.0419Oxygen need??Anti-S/N IgM0.4130.1881.5111.045C2.1850.0282??Cardiovascular disease3.0751.43221.6471.306C358.7380.0318Pneumonia??Anti-S/N IgM0.3100.1441.3631.027C1.8080.0317Hospitalization??Anti-S/N IgM0.4410.2011.5541.992C2.3060.0284??Cardiovascular disease3.7081.54040.7731.992C834.5490.0161Taste and smell disorders??NSP12 Q444H1.6950.8365.4441.058C28.0110.0426??(B) Multiple regressionCoefficientStd. errorvalueHospitalization duration??Anti-S/N IgM0.3050.1090.0075??Tumour disease5.9801.300?0.0001??Chronical lung disease2.2243.3340.0017Symptom duration??Chronical lung disease19.2507.4560.0053??N E253A12.5714.2610.0137 Open in a separate window Along with the presence of tumour and chronic lung diseases, a higher anti-S/N IgM level was significantly associated with longer Eact hospitalization (multiple regression analysis, P?0.05, respectively). Chronic lung disease and the SNV N E253A were significantly associated with symptom duration (multiple regression analysis, P?0.05, respectively). Discussion More than a year after its identification, SARS-CoV-2 has shown a high degree of genome alteration [14]. To investigate virus-host interactions, we examined PCR-positive patients of a south-western German region who were referred to a local reference laboratory Eact and answered a questionnaire on personal and COVID-19 characteristics. Thus, WGS of the viral genome of 55 enrolled COVID-19 patient samples revealed genetic alterations Eact mainly as SNVs, with about half of these resulting in changes of the amino acid sequence. When looking at the absolute variant count per gene and patient, most variants were located within ORF1ab representing the largest SARS-CoV-2 ORF. Nevertheless, ORF1ab showed a significantly lower variation rate normalized on the gene length compared to the other genes, while the N gene was the only gene with a significantly higher normalized variation rate. Overall, RNA viruses are known to accumulate variants rapidly during their replication cycle because RNA copying enzymes are prone to error [15, 16]. A high variation rate of the N gene was reported elsewhere [17, 18]. ORF10 was the only gene without variants in our study which was also demonstrated elsewhere [18]. Furthermore, our study corroborated published data on the S gene stability [19]. We observed four variants present in all samples (ORF1ab F924F, ORF1ab P4715L, S D614G and 5?UTR 241C?>?T), representing signature variants of the most dominant SARS-CoV-2 type VI strain [20]. In particular, the D614G exchange in the S protein has been extensively studied and is postulated to provide a selection advantage through increased viral infectivity [21C23]. All samples were assigned to the root lineage B based on Rambauts nomenclature [24]. The highest level lineage was B.1, encompassing the major Italian outbreak in early 2020 and then spreading across Europe [24]. The other identified lineages were sub-lineages of B.1, which match the geographical origin of the samples. Remarkably, the earliest description dates of the lineages in the Pango strain database coincided with our sample collection date (2020C04-07 to 2020C05-07). At the time of writing this manuscript, the lineages B.1.322, B.1.353 and B.1.5 have already been reassigned as more and more SARS-CoV-2 whole genomes have been sequenced over time and lineage formation and extinction continue to progress [24]. Given the high genetic variability of SARS-CoV-2, we sought to investigate the Mouse monoclonal to WIF1 emergence of the humoral immune response by determining specific IgM and IgG against the most immunogenic S and N proteins in average 83?days after PCR testing [25, 26]. As expected, all patients revealed detectable anti-S/N and anti-N IgG while only one patient out of the examined 49 did not show anti-S1 IgG. The higher anti-S/N IgG prevalence in contrast to IgM probably Eact indicates the effect of an immunological memory likely induced by previous infections with endemic coronaviruses, as primary immune responses would induce stronger anti-SARS-CoV-2 IgM responses. For all antibodies tested, there was no correlation between time from SARS-CoV-2 PCR testing and antibody levels within the examined period of 83?days on average after SARS-CoV-2 PCR testing. However, it cannot be ruled out that anti-S/N IgM levels, in particular, may have decreased to negative values in the period leading up to blood collection for antibody determination. Rank correlation and multiple regression analyses using genetic SARS-CoV-2 variants and patient characteristics as independent variables for the prediction of anti-SARS-CoV-2 antibody levels revealed an association of older age (>?65?years) and overweight (BMI?>?25) with higher anti-S/N and anti-S1 IgG levels. In contrast, higher anti-N IgG levels were only associated with older age. The average age of enrolled patients was Eact 52.2?years which is in agreement with the reported age of around 50?years for COVID-19 patients [1, 27]..
Apart from older age, overweight has been described as an additional risk factor for severe COVID-19 progression usually linked with functional impairment of immune cells and decreased immunity as a result of chronic inflammation and hypercytokinemia [30, 31]