SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data.

We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.

Oral Biofilm Composition, Dissemination to Keratinocytes, and Inflammatory Attenuation Depend on Probiotic and Synbiotic Strain Specificity.

Several inflammatory diseases are characterized by a disruption in the equilibrium between the host and its microbiome. Due to the increase in resistance, the use of antibiotics for the widespread, nonspecific killing of microorganisms is at risk. Pro-microbial approaches focused on stimulating or introducing beneficial species antagonistic toward pathobionts may be a viable alternative for restoring the host-microbiome equilibrium. Unfortunately, not all potential probiotic or synbiotic species and even subspecies (to strain level) are equally effective for the designated pathology, leading to conflicting accounts of their efficacy. To assess the extent of these species- and strain-specific effects, 13 probiotic candidates were evaluated for their probiotic and synbiotic potential with glycerol on in vitro oral biofilms, dissemination from biofilms to keratinocytes, and anti-inflammatory activity. Species- and strain-specific effects and efficacies were observed in how they functioned as probiotics or synbiotics by influencing oral pathobionts and commensals within biofilms and affected the dissemination of pathobionts to keratinocytes, ranging from ineffective strains to strains that reduced pathobionts by 3 + log. In addition, a minority of the candidates exhibited the ability to mitigate the inflammatory response of LPS-stimulated monocytes. For a comprehensive assessment of probiotic therapy for oral health, a judicious selection of fully characterized probiotic strains that are specifically tailored to the designated pathology is required. This approach aims to challenge the prevailing perception of probiotics, shifting the focus away from "form over function." Rather than using unproven, hypothetical probiotic strains from known genera or species, one should choose strains that are actually functional in resolving the desired pathology before labelling them probiotics.

Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks.

Coronavirus Disease 2019 (COVID-19) vaccination has resulted in excellent protection against fatal disease, including in older adults. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20-35% fatal cases among residents) by combining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosol monitoring, whole-genome phylogenetic analysis and immunovirological profiling of nasal mucosa by digital nCounter transcriptomics. Phylogenetic investigations indicated that each outbreak stemmed from a single introduction event, although with different variants (Delta, Gamma and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 d after the initial infection. Combining demographic, immune and viral parameters, the best predictive models for mortality comprised IFNB1 or age, viral ORF7a and ACE2 receptor transcripts. Comparison with published pre-vaccine fatal COVID-19 transcriptomic and genomic signatures uncovered a unique IRF3 low/IRF7 high immune signature in post-vaccine fatal COVID-19 outbreaks. A multi-layered strategy, including environmental sampling, immunomonitoring and early antiviral therapy, should be considered to prevent post-vaccination COVID-19 mortality in nursing homes.

Genomic evidence of co-identification with Omicron and Delta SARS-CoV-2 variants: a report of two cases.

On November 24, 2021, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant assigned to the lineage B.1.1.529 (Omicron) was first reported to the World Health Organization from South Africa. Despite the co-circulation of several SARS-CoV-2 variants, co-infection by different variants is not commonly identified. Here, we report two cases of SARS-CoV-2 co-identifications with the Omicron and Delta variants.

IgG Anti-Spike Antibodies and Surrogate Neutralizing Antibody Levels Decline Faster 3 to 10 Months After BNT162b2 Vaccination Than After SARS-CoV-2 Infection in Healthcare Workers.

Background: IgG anti-spike (S) antibodies arise after SARS-CoV-2 infection as well as vaccination. Levels of IgG anti-S are linked to neutralizing antibody titers and protection against (re)infection. Methods: We measured IgG anti-S and surrogate neutralizing antibody kinetics against Wild Type (WT) and 4 Variants of Concern (VOC) in health care workers (HCW) 3 and 10 months after natural infection ("infection", n=83) or vaccination (2 doses of BNT162b2) with ("hybrid immunity", n=17) or without prior SARS-CoV-2 infection ("vaccination", n=97). Results: The humoral immune response in the "vaccination" cohort was higher at 3 months, but lower at 10 months, compared to the "infection" cohort due to a faster decline. The "hybrid immunity" cohort had the highest antibody levels at 3 and 10 months with a slower decline compared to the "vaccination" cohort. Surrogate neutralizing antibody levels (expressed as %inhibition of ACE-2 binding) showed a linear relation with log10 of IgG anti-S against WT and four VOC. IgG anti-S corresponding to 90% inhibition ranged from 489 BAU/mL for WT to 1756 BAU/mL for Beta variant. Broad pseudoneutralization predicted live virus neutralization of Omicron BA.1 in 20 randomly selected high titer samples. Conclusions: Hybrid immunity resulted in the strongest humoral immune response. Antibodies induced by natural infection decreased more slowly than after vaccination, resulting in higher antibody levels at 10 months compared to vaccinated HCW without prior infection. There was a linear relationship between surrogate neutralizing activity and log10 IgG anti-S for WT and 4 VOC, although some VOC showed reduced sensitivity to pseudoneutralization.

Corrigendum: IgG anti-spike antibodies and surrogate neutralizing antibody levels decline faster 3 to 10 months after BNT162b2 vaccination than after SARS-CoV-2 infection in healthcare workers.

[This corrects the article DOI: 10.3389/fimmu.2022.909910.].