Beyond their substantial protection of individual vaccinees, coronavirus disease 2019 (COVID-19) vaccines might reduce viral load in breakthrough infection and thereby further suppress onward transmission. In this analysis of a real-world dataset of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results after inoculation with the BNT162b2 messenger RNA vaccine, we found that the viral load was substantially reduced for infections occurring 12-37 d after the first dose of vaccine. These reduced viral loads hint at a potentially lower infectiousness, further contributing to vaccine effect on virus spread.The recently authorized BNT162b2 Coronavirus Disease 2019 (COVID-19) messenger RNA (mRNA) vaccine is approximately 95% efficient in preventing polymerase chain reaction (PCR)-confirmed symptomatic disease from 7 d after the second dose and also provides some early protection starting 12 d after the first dose 1,2 . As countries race to vaccinate a substantial portion of their populations in the coming months, it is hoped that the basic reproduction number of the virus will decrease. This effect can be achieved by reducing the number of susceptible people, as well as by reducing viral load and, thereby, viral shedding of post-vaccination infections, which might render them less infectious [3][4][5][6][7] . However, the effect of vaccination on viral load in COVID-19 post-vaccination infections is currently unknown 8 .As of February 11, 2021, Maccabi Healthcare Services (MHS) in Israel has vaccinated more than 1 million of its members as part of a national rapid rollout of the vaccine. MHS member SARS-CoV-2 tests are often carried out in the MHS central laboratory, which offers the opportunity to track post-vaccination infections. In this study, we retrospectively collected and analyzed the quantitative reverse transcription PCR (RT-qPCR) test measurements of three SARS-CoV-2 genes-E, N and RdRp (Allplex 2019-nCoV assay, Seegene)-from positive post-vaccination tests performed at the MHS central laboratory between December 21, 2020, and February 11, 2021 (n = 4,938 patients, study population; Table 1). The study period was characterized by high and steady rates of positive COVID-19 tests (Extended Data Fig. 1), indicating an ongoing epidemic wave.In an analysis of the infection cycle threshold (Ct) over time, we found that the mean viral load substantially decreased 12 d after vaccination with the first vaccine dose, coinciding with the known early onset of vaccine-mediated protection 1 . When we calculated the mean Ct for post-vaccination infections identified on each day

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection between June 1 and July 27, the date of analysis. After controlling for potential confounders as age and comorbidities, we found a significant 1.51 fold (95% CI, 1.38–1.66) increased risk for infection for early vaccinees compared to those vaccinated later that was similar across all ages groups. The increased risk reached 2.26- fold (95% CI, 1.80–3.01) when comparing those who were vaccinated in January to those vaccinated in April. This preliminary finding of vaccine waning as a factor of time from vaccince should prompt further investigations into long-term protection against different strains.

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Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, 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.