Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study.

BACKGROUND: Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer-BioNTech) vaccination against COVID-19. METHODS: In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARS-CoV-2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure IgG and neutralising antibody concentrations above each value observed in the study data. FINDINGS: From 16 675 detected index cases in the study region, 5718 household members agreed to participate, 1461 of whom were eligible to be included in our study. 333 (22·8%) of 1461 household members who were not infected with SARS-CoV-2 at baseline were infected within 21 days of follow-up. The baseline (pre-exposure) IgG and neutralising antibodies were higher in participants who remained uninfected than in those who became infected (geometric mean IgG antibody concentration 168·2 binding antibody units [BAU] per mL [95% CI 158·3-178·7] vs 130·5 BAU/mL [118·3-143·8] and geometric mean neutralising antibody titre 197·5 [181·9-214·4] vs 136 ·7 [120·3-155·4]). Increasing IgG and neutralising antibody concentrations were also significantly associated with a reduced probability of increasing disease severity. Odds of infection were significantly reduced each time baseline IgG antibody concentration increased by a factor of ten (odds ratio [OR] 0·43 [95% CI 0·26-0·70]) and each time baseline neutralising antibody titre increased by a factor of two (0·82 [0·74-0·92]). In our cohort, the probability of infection if IgG antibody concentrations were higher than 500 BAU/mL was 11% and the probability of moderate disease severity was 1%; the probability of infection if neutralising antibody titres were above or equal to 1024 was 8% and the probability of moderate disease severity was 2%. T-cell activation rates were not significantly associated with reduced probability of infection (OR 1·04, 95% CI 0·83-1·30). INTERPRETATION: Both IgG and neutralising antibodies are correlates of protection against SARS-CoV-2 infection. Our data suggest that IgG concentrations higher than 500 BAU/mL and neutralising antibody titres of 1024 or more are thresholds for immunological protection from SARS-CoV-2 delta variant infection. Potentially, updated protective thresholds against emerging variants of concern could be calculated, which could support decision makers on administration of new vaccination strategies and on the optimal period between vaccine doses. FUNDING: Israeli Ministry of Health.

The Use of Rapid COVID-19 Antigen Test in the Emergency Department as a Decision-Support Tool.

The emergency department (ED) is the initial point of contact between hospital staff and patients potentially infected with SARS-CoV-2, thus, prevention of inadvertent exposure to other patients is a top priority. We aimed to assess whether the introduction of antigen-detecting rapid diagnostic tests (Ag-RDTs) to the ED affected the likelihood of unwanted SARS-CoV-2 exposures. In this retrospective single-center study, we compared the rate of unwarranted exposure of uninfected adult ED patients to SARS-CoV-2 during two separate research periods; one before Ag-RDTs were introduced, and one with Ag-RDT used as a decision-support tool. The introduction of Ag-RDTs to the ED significantly decreased the relative risk of SARS-CoV-2-negative patients being incorrectly assigned to the COVID-19 designated site ("red ED"), by 97%. There was no increase in the risk of SARS-CoV-2-positive patients incorrectly assigned to the COVID-19-free site ("green ED"). In addition, duration of ED admission was reduced in both the red and the green ED. Therefore, implementing the Ag-RDT-based triage protocol proved beneficial in preventing potential COVID-19 nosocomial transmission.

Rapid Antigen Tests For Safe School Opening in the COVID-19 Pandemic Era.

BACKGROUND: Since the beginning of the Sever Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, school closure as a mitigating measure was at the center of a public and professional debate. While the negative effects of school closure cannot be ignored, accumulating data suggested that it is necessary for reducing community transmission. Our study presents an optional strategy for safe school opening during a pandemic, implemented in selected Israeli high schools by a special task force constructed by the Sheba Medical Center (SMC). METHODS: The study took place between November 2020 and April 2021. Three schools from different areas of Israel were enrolled. The participants were asked to undergo bi-weekly SARS-CoV-2 rapid diagnostic antigen tests (Ag-RDT). Those who tested positive were requested to self-isolate, whereas their school contacts were tested daily by Ag-RDT. Participants with a previously documented SARS-CoV-2 infection or who were found to be SARS-CoV-2 seropositive upon enrollment were exempted from screening. RESULTS: Of a total of 361 participants who enrolled in the study, 12.3% were found to be seropositive. Fourteen SARS-CoV-2 cases were detected (3.5%), 12 of them in one single school located in an endemic area for SARS-CoV-2. The 14 cases resulted in 84 days of COVID-19-related absence from school, comparing with 1775 potential days of COVID-19-related absence under a strategy implementing self-isolation instead of testing. CONCLUSIONS: Safe continuation of academic routine during the pandemic is possible when using rapid Ag-RDT as a screening tool, while allowing swab collection by trained students and teachers.

Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose.

As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1-66.7) to 96.3% (95% CI, 94.2-98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.

Impact of BNT162b2 Vaccination and Isolation on SARS-CoV-2 Transmission in Israeli Households: An Observational Study.

Several studies have characterized the effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, estimates of their impact on transmissibility remain limited. Here, we evaluated the impact of isolation and vaccination (7 days after the second dose) on SARS-CoV-2 transmission within Israeli households. From December 2020 to April 2021, confirmed cases were identified among health-care workers of the Sheba Medical Centre and their family members. Recruited households were followed up with repeated PCR for at least 10 days after case confirmation. Data were analyzed using a data augmentation Bayesian framework. A total of 210 households with 215 index cases were enrolled; 269 out of 667 (40%) susceptible household contacts developed a SARS-CoV-2 infection. Of those, 170 (63%) developed symptoms. Compared with unvaccinated and unisolated adult/teenager (aged >12 years) contacts, vaccination reduced the risk of infection among unisolated adult/teenager contacts (relative risk (RR) = 0.21, 95% credible interval (CrI): 0.08, 0.44), and isolation reduced the risk of infection among unvaccinated adult/teenager (RR = 0.12, 95% CrI: 0.06, 0.21) and child contacts (RR = 0.17, 95% CrI: 0.08, 0.32). Infectivity was reduced in vaccinated cases (RR = 0.25, 95% CrI: 0.06, 0.77). Within households, vaccination reduces both the risk of infection and of transmission if infected. When contacts were unvaccinated, isolation also led to important reductions in the risk of transmission.