Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study (preprint)

It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged [≥]16 years 35{+/-}8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.

Follow-up study in the ski-resort Ischgl: Antibody and T cell responses to SARS-CoV-2 persisted for up to 8 months after infection and transmission of virus was low even during the second infection wave in Austria (preprint)

Background: In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a cross-sectional study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April. To answer the question of how long immunity persists and what effect this high-level immunity had on virus transmission, we performed a follow-up study in early November, 2020. Methods: Of the 1259 adults that participated in the baseline study, 801 could be included in the follow-up. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 infections in Ischgl was compared to the incidence in similar municipalities in Tyrol throughout 2020. Findings: For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9 - 54.9) to 45.4% (95% CI 42.0 - 49.0). Median antibody concentrations dropped considerably but antibody avidity increased. T cell responses were analysed in 93 cases, including all 4 formerly seropositive cases that had lost antibodies in all assays, three of which still had detectable T cell memory. In addition, the incidence in the second COVID-19 wave that hit Austria in November 2020, was significantly lower in Ischgl than in comparable municipalities in Tyrol or the rest of Austria. Interpretation: This study has important implications as it shows that although antibodies to SARS-CoV-2 declined, T and B cell memory can be detected for up to 8 months. Complemented by infection prevention measures a level of around 40-45% immunity in Ischgl significantly reduced local virus transmission during the second wave in Austria in November 2020. Funding: Funding was provided by the government of Tyrol and the FWF Austrian Science Fund.

N-chlorotaurine, a novel inhaled virucidal antiseptic is highly active against respiratory viruses including SARS-CoV-2 (COVID-19) (preprint)

N-chlorotaurine (NCT) is a long-lived oxidant generated in activated cells of the innate immune system, namely neutrophilic and eosinophilic granulocytes and monocytes. NCT acts as an antiseptic agent that can be synthesized chemically and applied topically on different infected body sites. Even treatment of the lower respiratory tract via inhalation, which has been in development in the last years, was well tolerated in a recent phase I clinical trial. In this study, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, in fact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus. NCT revealed broad virucidal activity against all viruses tested. In the presence of organic proteinaceous material simulating body fluids, this activity was enhanced by transchlorination mechanisms so that significant inactivation of viruses could be achieved within 1 – 10 minutes. Inhalation of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.