Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25−82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

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.

Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection.

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2-4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission.

Existence of immunological memory response in true sero-negative individuals post COVID-19 molecular diagnosis.

Approximately 1-8% of individuals do not develop antibodies following SARS-CoV-2 infection (sero-negatives). One BNT162b2 dose resulted in potent humoral response in 14 sero-negatives and 15 sero-positives, significantly higher than the response of 15 naïve-individuals, to two doses suggesting that COVID-19 provoked a memory response in individuals without detectable antibodies.

Early Immunogenicity and Safety of the Third Dose of BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Among Adults Older Than 60 Years: Real-World Experience.

BACKGROUND: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. METHODS: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys. RESULTS: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. CONCLUSIONS: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

Immunoglobulin (Ig)A seropositivity against SARS-CoV-2 in healthcare workers in Israel, 4 April to 13 July 2020: an observational study.

IntroductionThe COVID-19 pandemic has put healthcare workers (HCW) at significant risk. Presence of antibodies can confirm prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.AimThis study investigates the prevalence of IgA and IgG antibodies against SARS-CoV-2 in HCW.MethodsPerformance of IgA and IgG antibody ELISA assays were initially evaluated in positive and negative SARS-CoV-2 serum samples. IgA and IgG antibodies against SARS-CoV-2 were measured in 428 asymptomatic HCW. We assessed the risk of two groups: HCW with high exposure risk outside work (HROW) residing in areas where COVID-19 was endemic (n = 162) and HCW with high exposure risk at work (HRAW) in a COVID-19 intensive care unit (ICU) (n = 97).ResultsSensitivities of 80% and 81.2% and specificities of 97.2% and 98% were observed for IgA and IgG antibodies, respectively. Of the 428 HCW, three were positive for IgG and 27 for IgA. Only 3/27 (11%) IgA-positive HCW had IgG antibodies compared with 50/62 (81%) in a group of previous SARS-CoV-2-PCR-positive individuals. Consecutive samples from IgA-positive HCW demonstrated IgA persistence 18-83 days in 12/20 samples and IgG seroconversion in 1/20 samples. IgA antibodies were present in 8.6% of HROW and 2% of HRAW.ConclusionsSARS-CoV-2 exposure may lead to asymptomatic transient IgA response without IgG seroconversion. The significance of these findings needs further study. Out of work exposure is a possible risk of SARS-CoV-2 infection in HCW and infection in HCW can be controlled if adequate protective equipment is implemented.

BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers.

BACKGROUND: Concurrent with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. METHODS: We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1-2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4-5 (ie, 1-2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. FINDINGS: Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19-0·31) and immunosuppressed individuals (0·21, 0·14-0·31) compared with individuals aged 18·00-45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80-0·89), older age (ie, ≥66 years; 0·64, 0·58-0·71), immunosuppression (0·44, 0·33-0·58), and other specific comorbidities: diabetes (0·88, 0·79-0·98), hypertension (0·90, 0·82-0·98), heart disease (0·86, 0·75-1·00), and autoimmune diseases (0·82, 0·73-0·92). INTERPRETATION: BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. FUNDING: Sheba Medical Center, Israel Ministry of Health.

Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy.

BACKGROUND: The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines' efficacy in this population. OBJECTIVE: To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients. STUDY DESIGN: This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels. RESULTS: The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0-39.7) and 20.2 (interquartile range, 12.7-29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2-12.8) and 4.9 (interquartile range, 3.8-6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001). CONCLUSION: Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

BNT162b2 mRNA COVID-19 vaccination in immunocompromised patients: A prospective cohort study.

BACKGROUND: Trials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs. METHODS: A prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs). Antibodies were measured two-four weeks after vaccination by SARS-CoV-2 anti-receptor binding domain IgG antibodies (RBD IgG) and pseudo-virus neutralization assays. Multivariable logistic regression analyses were used to identify factors associated with vaccine-induced antibody response. Adverse events (AEs) were monitored. FINDINGS: RBD-IgG antibodies were detected in 154/156 (98.7%) of patients with HIV, 75/90 (83.3%) with solid malignancies, 149/187 (79.7%) with myeloma, 83/111 (74.8%) following hematopoietic stem cell transplants, 25/36 (69.4%) following liver transplantation, 26/43 (60.5%) with myelodysplastic syndrome, 96/188 (51.0%) with chronic lymphocytic leukemia/non-Hodgkin's lymphoma, 50/110 (45.5%) following kidney transplantation, 15/80 (18.8%) following heart transplantation, and 269/272 (98.9%) in controls. There was a significant correlation r = 0.74 (95%CI 0.69,0.78) between RBD-binding IgG and neutralizing antibodies in all groups. Multivariate logistic regression analysis showed that age > 65 years (OR 0.41,95%CI 0.30,0.57) and underlying immunosuppression (OR 0.02,95%CI 0.01,0.07) were significantly associated with a non-reactive response of IgG antibodies. HIV patients showed a similar immunological response as healthy adults. The vaccine was safe without any episodes of rejection, graft-versus-host disease (GVHD) or allergy. Immunocompetent HCWs experienced significantly more AEs than ICPs. INTERPRETATION: Antibody response to the Pfizer-BioNTech vaccine was highly variable among different ICPs; thus, individual recommendations should be provided for the different immunosuppression states.

Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months.

BACKGROUND: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. METHODS: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. RESULTS: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). CONCLUSIONS: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living with HIV-1.

OBJECTIVES: The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with human immunodeficiency virus type 1 (PLWH) are unknown. We aimed to assess the immunogenicity and safety of this vaccine in PLWH. METHODS: In this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health-care workers (HCWs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored. RESULTS: At a median of 18 days (interquartile range 14-21 days) after the second dose, anti-RBD-IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD-IgG at a median of 26 days (interquartile range 24-27 days) after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCWs, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue and headache. AIDS-related adverse events were not reported. Human immunodeficiency virus load increased in 3/143 (2%) patients from <40 copies/mL to ≤100 copies/mL. CD4+ T-cell count decreased from a geometric mean of 700 cells/µL (95% CI 648-757 cells/µL) to 633.8 cells/µL (95% CI 588-683 cells/µL) (p < 0.01). CONCLUSIONS: BNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on antiretroviral therapy with unsuppressed CD4 count and suppressed viral load.

Decreased infectivity following BNT162b2 vaccination: A prospective cohort study in Israel.

BACKGROUND: BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine's effect on infectivity is thus a critical priority. METHODS: Among all 9650 HCW of a large tertiary medical center in Israel, we calculated the prevalence of positive SARS-CoV-2 qRT-PCR cases with asymptomatic presentation, tested following known or presumed exposure and the infectious subset (N-gene-Ct-value<30) of these. Additionally, infection incidence rates were calculated for symptomatic cases and infectious (Ct<30) cases. Vaccine effectiveness within three months of vaccine rollout was measured as one minus the relative risk or rate ratio, respectively. To further assess infectiousness, we compared the mean Ct-value and the proportion of infections with a positive SARS-CoV-2 antigen test of vaccinated vs. unvaccinated. The correlation between IgG levels within the week before detection and Ct level was assessed. FINDINGS: Reduced prevalence among fully vaccinated HCW was observed for (i) infections detected due to exposure, with asymptomatic presentation (VE(i)=65.1%, 95%CI 45-79%), (ii) the presumed infectious (Ct<30) subset of these (VE(ii)=69.6%, 95%CI 43-84%) (iii) never-symptomatic infections (VE(iii)=72.3%, 95%CI 48-86%), and (iv) the presumed infectious (Ct<30) subset (VE(iv)=83.0%, 95%CI 51-94%).Incidence of (v) symptomatic and (vi) symptomatic-infectious cases was significantly lower among fully vaccinated vs. unvaccinated individuals (VE(v)= 89.7%, 95%CI 84-94%, VE(vi)=88.1%, 95%CI 80-95%).The mean Ct-value was significantly higher in vaccinated vs. unvaccinated (27.3±1.2 vs. 22.2±1.0, p<0.001) and the proportion of positive SARS-CoV-2 antigen tests was also significantly lower among vaccinated vs. unvaccinated PCR-positive HCW (80% vs. 31%, p<0.001). Lower infectivity was correlated with higher IgG concentrations (R=0.36, p=0.01). INTERPRETATION: These results suggest that BNT162b2 is moderately to highly effective in reducing infectivity, via preventing infection and through reducing viral shedding. FUNDING: Sheba Medical Center, Israel.

SARS-CoV-2 outbreak in a synagogue community: longevity and strength of anti-SARS-CoV-2 IgG responses.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.

Fetal and Perinatal Outcome Following First and Second Trimester COVID-19 Infection: Evidence from a Prospective Cohort Study.

A novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus causing coronavirus disease 2019 (COVID-19) disease, which emerged as a global pandemic. Data regarding the implications of COVID-19 disease at early gestation on fetal and obstetric outcomes is scarce. Thus, our aim was to investigate the effect of first and second trimester maternal COVID-19 disease on fetal and perinatal outcomes. This was a prospective cohort study of pregnant women with a laboratory-proven SARS-COV-2 infection contracted prior to 26 weeks gestation. Women were followed at a single tertiary medical center by serial sonographic examinations every 4-6 weeks to assess fetal well-being, growth, placental function, anatomic evaluation and signs of fetal infection. Amniocentesis was offered to assess amniotic fluid SARS-COV-2-PCR (polymerase chain reaction) and fetal brain magnetic resonance imaging (MRI) was offered at 30-32 weeks gestation. Demographic, obstetric and neonatal data were collected from history intake, medical charts or by telephone survey. Perinatal outcomes were compared between women infected at first vs. second trimester. 55 women with documented COVID-19 disease at early gestation were included and followed at our center. The mean maternal age was 29.6 ± 6.2 years and the mean gestational age at viral infection was 14.2 ± 6.7 weeks with 28 (51%) women infected at the first trimester and 27 (49%) at the second trimester. All patients but one experienced asymptomatic to mild symptoms. Of 22 patients who underwent amniocentesis, none had evidence of vertical transmission. None of the fetuses exhibited signs of central nervous system (CNS) disease, growth restriction and placental dysfunction on serial ultrasound examinations and fetal MRI. Pregnancies resulted in perinatal survival of 100% to date with mean gestational age at delivery of 38.6 ± 3.0 weeks and preterm birth <37 weeks rate of 3.4%. The mean birthweight was 3260 ± 411 g with no cases of small for gestational age infants. The obstetric and neonatal outcomes were similar among first vs. second trimester infection groups. We conclude SARS-CoV-2 infection at early gestation was not associated with vertical transmission and resulted in favorable obstetric and neonatal outcomes.

The Sheba Medical Center healthcare workers' children's school: can we open schools safely?

OBJECTIVE: The role of school closure in mitigating coronavirus disease 2019 (COVID-19) transmission has been questioned. In our medical centre, during a 9-week national lockdown, an alternative school was opened for health-care workers' (HCW) children with a small number of children per class and strict symptom surveillance. After lockdown was lifted we screened children and their parents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology. METHODS: We conducted a cross-sectional study of HCW parents and their children after one teacher contracted COVID-19 following exposure at home and 53 children were exposed, isolated and tested by RT-PCR. We compared families with children attending the alternative school with families whose children who remained at home during the 9-week lockdown. Epidemiological and medical data were collected using a short questionnaire; nasopharyngeal and oropharyngeal swabs were obtained and tested for SARS-CoV-2 by RT-PCR, and blood was collected for SARS-CoV-2 IgA and IgG titres. RESULTS: A total of 435 children attended the Sheba alternative school. Among the 53 children exposed to the infected teacher, none tested positive by RT-PCR. Of these, 18 children-parent pairs were tested for serology and all were negative. A total of 106/435 (24%) children and their 78 parents were recruited for the cross-sectional study; 70 attended the Sheba school and 36 did not. Approximately 16% of children in either group reported symptoms (11/70 in the school group and 6/36 in the 'stay home' group), but SARS-CoV-2 was not detected by PCR in any, and previous exposure, as determined by serological tests, was low and not significantly different between the groups. CONCLUSION: In an alternative school for children of HCWs, active during COVID-19 national outbreak, we found no evidence of increased infection compared with children that stayed home.