key: cord-0318391-mi6bdisx authors: Amir, O.; Goldberg, Y.; Mandel, M.; Bar-On, Y. M.; Bodenheimer, O.; Freedman, L.; Alroy-Preis, S.; Ash, N.; Huppert, A.; Milo, R. title: Protection against omicron severe disease 0-7 months after BNT162b2 booster date: 2022-05-05 journal: nan DOI: 10.1101/2022.05.04.22274647 sha: ec1be4471f76b271f4dba5ca7727802a3140b8c2 doc_id: 318391 cord_uid: mi6bdisx Following a rise in cases due to the delta variant and evidence of waning immunity after 2 doses of the BNT162b2 vaccine, Israel began administering a third BNT162b2 dose (booster) in July 2021. Recent studies showed that the 3rd dose provides a much lower protection against infection with the omicron variant compared to the delta variant and that this protection wanes quickly. In this study, we used data from Israel to estimate the protection of the 3rd dose against severe disease up to 7 months from receiving the booster dose. The analysis shows that protection conferred by the 3rd dose against omicron did not wane over a 7-month period and that a 4th dose further increased protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts. Following a rise in cases due to the delta variant and evidence of waning immunity after 2 doses of the BNT162b2 vaccine, 1 Israel began administering a third BNT162b2 dose (booster) in July 2021. The 3rd dose was very effective against both confirmed infections and severe disease caused by the Delta variant. 2 However, recent studies showed that the 3rd dose provides a much lower protection against infection with the omicron variant and that this protection wanes quickly. 3 A "fresh" 3rd dose was shown to be effective against severe disease caused by the omicron variant. 4 However, it is not yet known how long this protection lasts. A study from the UK estimated 85% vaccine effectiveness for individuals 65 years of age or older 15 weeks after receiving the 3rd dose. 5 Here, we report on the protection against severe disease with the omicron variant in individuals aged 60 or older up to 7 months after receiving a 3rd BNT162b2 dose. The Ministry of Health (MOH) in Israel collects all COVID-19 related variables in a central database. These include data on all PCR and antigen tests and results, vaccination dates and type (almost all received the Pfizer-BioNTech vaccine), daily clinical status of all COVID-19 hospitalized patients, and COVID-19 related deaths. Specifically, the data used for conducting this study included vaccination dates, PCR and state-regulated rapid antigen tests (dates and results), hospital admission dates (if relevant), clinical severity status (severe illness or death), and demographic variables such as age, sex, and demographic group (General Jewish, Arab, ultra-Orthodox Jewish). The data for the study was retrieved on March 26, 2022. Severe illness due to Covid-19 during 14 days following a confirmed infection (defined using the NIH definition 6 as a resting respiratory rate of more than 30 breaths per minute, an oxygen saturation of less than 94% while breathing ambient air, or a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 300). Thus, the study period was set from January 16, 2022, to March 12, 2022, to allow for 14 days of follow-up from infection to severe disease. Those who died from COVID-19 during the first 14 days after confirmed infection were also counted as severe disease cases in our analysis. Surveillance of COVID-19-associated hospitalizations is continuously performed by the MOH. Data from all hospitals are updated daily, and often twice a day. In accordance with national guidelines, healthcare providers report all hospitalizations and deaths among individuals with laboratory-confirmed SARS-CoV-2 infection. Quality assurance of data was performed extensively over the course of the pandemic. The data are monitored daily by the MOH, and are continuously used for public health decision-making. We conducted an observational study during Israel's fifth wave, which was omicron-dominant, 7 with both BA.1 and BA.2 sublineage present (initially BA.1 dominated, later BA.2 dominated). The study included persons who were 60 years of age or older, who received their 2nd dose at least four months before the end of the study, who were not infected by SARS-CoV-2 before the study period, had available data regarding sex and demographic sector, had not stayed abroad . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 5, 2022. ; during the whole study period, and had not been vaccinated with a vaccine different from BNT162b2 before the study period (see Figure 1 ). We estimated the adjusted rates of severe disease in nine cohorts: people who received only 2 doses of the vaccine and for whom at least 4 months had passed since receiving the second dose, people who received a 3rd vaccine dose (divided into 7 cohorts based on the number of months that passed since the administration of that dose), and people who recently received a 4th vaccine dose. Figure 2 shows the vaccination dynamics during the study period, and Table 1 reports basic descriptive statistics for the different cohorts. A Poisson regression model was used to estimate the adjusted rate of severe disease per 100,000 risk days. The model included covariates adjusting for age category (60-69, 70-79, 80+), gender, sector (Arab, General Jewish, Ultra-Orthodox), and epidemiological week. We further conducted two sensitivity analyses. First, we allowed for severe illness up to 21 days following a confirmed infection. Second, we examined the adjusted rates of severe disease by age category (60-69, 70-79, and 80+). The results of the Poisson regression are summarized in Table 2 and in Figure 3 . The protection conferred by the 3rd dose against omicron did not show signs of waning over a 7-month period, with rates of severe disease at approximately 4 per 100,000 risk days in all 3-dose cohorts. This rate was approximately 3-fold lower than in the 2-dose cohort. The 4th dose further increased protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts. Both sensitivity analyses yielded estimates of the rate ratios between the groups that were similar to those obtained in the main analysis. Recent studies have shown that the protection of a 3rd BNT162b2 dose against confirmed omicron infections is substantially lower than against the Delta variant, and wanes quickly. Our results show that the effectiveness of the 3rd dose in preventing severe disease does not appear to wane over a 7-month period, and that a 4th dose provides additional protection. The study was approved by the Institutional Review Board of the Sheba Medical Center. Figure 1 . Study population. The participants in the study included persons who were 60 years of age or older, who received 2nd dose at least four months before the end of the study, who were not infected by SARS-CoV-2 before the study period, had available data regarding sex and demographic sector, had not stayed abroad during the whole study period, and had not been vaccinated with a vaccine different from BNT162b2 before the study period. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 5, 2022. ; https://doi.org/10.1101/2022.05.04.22274647 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 5, 2022. ; Figure 3 . Adjusted rates of severe illness per 100,000 risk days obtained from Poisson regression analysis for the study period January 16, 2022, to March 12, 2022, adjusted for age category (60-69, 70-79, 80+) , gender, sector, and exposure (based on the epidemiological week). . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 5, 2022. ; . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 5, 2022. ; https://doi.org/10.1101/2022.05.04.22274647 doi: medRxiv preprint Waning Immunity after the BNT162b2 Vaccine in Israel Protection of BNT162b2 vaccine booster against Covid-19 in Israel Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa Effectiveness of COVID-19 Vaccines against Omicron and Delta Hospitalisation: Test Negative Case-Control Study. Epidemiology COVID-19 Treatment Guidelines SARS-CoV-2 variants in analyzed sequences. Our World in Data All authors declare no competing interests.