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Natural immunity in Israel Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1 Early vaccinees were demonstrated to be significantly more at risk than late vaccinees Maccabi Healthcare Services N = 2.5 million 26% of the population Provides a representative sample of the Israeli population Study comparing three groups SARS-CoV-2-naïve individuals with 2 doses of Pfizer (n = 673,676) Previously infected, not been vaccinated (n = 62,883) Previously infected with one dose of Pfizer (n = 42,099) We evaluated four outcomes June 1st to August 14th 2021 (Delta times) SARS-CoV-2 infection Symptomatic disease COVID-19-related hospitalization Deaths Results SARS-CoV-2-naïve individuals with 2 doses of Pfizer (no infection, doubly vaccinated) (Only with vaccine protection) If first exposure every (infection or vaccination) was in Jan or Feb 2021 13.06-fold increased risk for breakthrough infection compared to those previously infected Comparing infections in vacationed with previously infected 238 infections in the vaccinated group 19 infections in the previously infected (not vaccinated) group Increased risk of symptomatic disease fever, cough, breathing difficulties, diarrhea, loss of taste or smell, myalgia, weakness, headache and sore throat 191 cases in the vaccinated group 8 in the previously infected group Significant (P less than 0.001) Increased risk of hospital admission 8 admissions in the vaccinated group 1 in the previously infected group Deaths No deaths in either group March 2020 to February 2021 Evidence of waning natural immunity was demonstrated But SARS-CoV-2 naïve vaccinees (i.e. vaccinated but no natural infection) 5.96-fold increased risk for breakthrough infection 7.13-fold increased risk for symptomatic disease Previously infected vs. vaccinated and previously infected individuals Previously infected individuals to those who were both previously infected and received a single dose of the vaccine 20 infections in the infected plus one vaccine dose 37 infections in the infected but no vaccine group No deaths in either group Conclusions This study demonstrated that natural immunity confers longer lasting and stronger protection, against infection, symptomatic disease and hospitalization caused by the Delta, compared to the BNT162b2 two-dose vaccine-induced immunity Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant Question 2: Are the data on natural immunity also valid for the Omicron variant? Answer: Yes, (Letter to NEJM) Protection against the Omicron Variant from Previous SARS-CoV-2 Infection Qatar https://www.nejm.org/doi/full/10.1056/NEJMc2200133 In addition, we performed sensitivity analyses that included adjustment for vaccination status and that excluded vaccinated persons from the analysis. Protection against reinfections is moderately lower for the Omicron variant The effectiveness of previous infection in preventing reinfection was estimated to be 90.2% against the alpha variant 85.7% against the beta variant, 92.0% against the delta variant, and 56.0%magainst the omicron variant Protection against severe, critical or fatal COVID-19 is similar as for other variants The effectiveness with respect to severe, critical, or fatal Covid-19 69.4% against the alpha variant, 88.0% against the beta variant 95% to 100% against the delta variant 87.8% against the omicron variant The median interval between previous infection and PCR testing 254 days to 376 days

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