Comparison of mRNA Vaccinations with BNT162b2 or mRNA-1273 in Anti-CD20-Treated Multiple Sclerosis Patients.

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann-Whitney test and Fisher's exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4-49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19.

Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response.

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild-moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild–moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild–moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild–moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

The COVID-19 vaccination acceptance/hesitancy rate and its determinants among healthcare workers of 91 Countries: A multicenter cross-sectional study.

The aim of this study was to investigate the COVID-19 vaccination acceptance rate and its determinants among healthcare workers in a multicenter study. This was a cross-sectional multi-center survey conducted from February 5 to April 29, 2021. The questionnaire consisted of 26 items in 6 subscales. The English version of the questionnaire was translated into seven languages and distributed through Google Forms using snowball sampling; a colleague in each country was responsible for the forward and backward translation, and also the distribution of the questionnaire. A forward stepwise logistic regression was utilized to explore the variables and questionnaire factors tied to the intention to COVID-19 vaccination. 4630 participants from 91 countries completed the questionnaire. According to the United Nations Development Program 2020, 43.6 % of participants were from low Human Development Index (HDI) regions, 48.3 % high and very high, and 8.1 % from medium. The overall vaccination hesitancy rate was 37 %. Three out of six factors of the questionnaire were significantly related to intention to the vaccination. While 'Perceived benefits of the COVID-19 vaccination' (OR: 3.82, p-value<0.001) and 'Prosocial norms' (OR: 5.18, p-value<0.001) were associated with vaccination acceptance, 'The vaccine safety/cost concerns' with OR: 3.52, p-value<0.001 was tied to vaccination hesitancy. Medical doctors and pharmacists were more willing to take the vaccine in comparison to others. Importantly, HDI with OR: 12.28, 95 % CI: 6.10-24.72 was a strong positive determinant of COVID-19 vaccination acceptance. This study highlighted the vaccination hesitancy rate of 37 % in our sample among HCWs. Increasing awareness regarding vaccination benefits, confronting the misinformation, and strengthening the prosocial norms would be the primary domains for maximizing the vaccination coverage. The study also showed that the HDI is strongly associated with the vaccination acceptance/hesitancy, in a way that those living in low HDI contexts are more hesitant to receive the vaccine.

External Quality Assessment of SARS-CoV-2 Sequencing: an ESGMD-SSM Pilot Trial across 15 European Laboratories.

This first pilot trial on external quality assessment (EQA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing, initiated by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Genomic and Molecular Diagnostics (ESGMD) and the Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing. Ten samples with various viral loads were sent out to 15 clinical laboratories that had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centers were compared were the identification of (i) single nucleotide polymorphisms (SNPs) and indels, (ii) Pango lineages, and (iii) clusters between samples. The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to various depths (up to a 100-fold difference across centers). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignments. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data. The pilot EQA was overall a success. It was able to show the high quality of participating laboratories and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.

Re-emergence of invasive pneumococcal disease (IPD) and increase of serotype 23B after easing of COVID-19 measures, Switzerland, 2021.

Incidence of invasive pneumococcal disease (IPD) has been low during the peak of the COVID-19 pandemic. In this study, we found that the IPD numbers again increased in Switzerland during the first six months of 2021 and that this coincides with the loosening of COVID-19 measures. Vaccine pneumococcal serotypes have continued to decrease and non-vaccine type serotype 23B has emerged (8% of the isolates in 2021). Worryingly, serotype 23B is associated with reduced susceptibility to penicillin.

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.

Accuracy of serological testing for SARS-CoV-2 antibodies: First results of a large mixed-method evaluation study.

BACKGROUND: Serological immunoassays that can identify protective immunity against SARS-CoV-2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed-design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS-CoV-2 proteins and assessed the neutralizing activity of antibodies in patient sera. METHODS: Consecutive patients admitted with confirmed SARS-CoV-2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in-house enzyme-linked immunosorbent assay utilizing recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was developed and compared to three commercially available enzyme-linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1), and a lateral flow immunoassay (LFI) based on full-length spike protein. Neutralization assays with live SARS-CoV-2 were performed. RESULTS: One thousand four hundred and seventy-seven individuals were included comprising 112 SARS-CoV-2 positives (defined as a positive real-time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS-CoV-2 positive individuals, 96.3% showed full neutralization of live SARS-CoV-2 at serum dilutions ≥ 1:16, while none of the 6 SARS-CoV-2-negative sera revealed neutralizing activity. CONCLUSIONS: ELISAs targeting RBD and S1 protein of SARS-CoV-2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS-CoV-2.