How effective is the BNT162b2 mRNA vaccine against SARS-CoV-2 transmission and infection? A national programme analysis in Monaco, July 2021 to September 2022

We quantified SARS-CoV-2 dynamics in different community settings and the direct and indirect effect of the BNT162b2 mRNA vaccine in Monaco for different variants of concern (VOC). Between July 2021 and September 2022, we prospectively investigated 20,443 contacts from 6320 index cases using data from the Monaco COVID-19 Public Health Programme. We calculated secondary attack rates (SARs) in households (n = 13,877), schools (n = 2508) and occupational (n = 6499) settings. We used binomial regression with a complementary log-log link function to measure adjusted hazard ratios (aHR) and vaccine effectiveness (aVE) for index cases to infect contacts and contacts to be infected in households. In households, the SAR was 55% (95% CI 54-57) and 50% (48-51) among unvaccinated and vaccinated contacts, respectively. The SAR was 32% (28-36) and 12% (10-13) in workplaces, and 7% (6-9) and 6% (3-10) in schools, among unvaccinated and vaccinated contacts respectively. In household, the aHR was lower in contacts than in index cases (aHR 0.68 [0.55-0.83] and 0.93 [0.74-1.1] for delta; aHR 0.73 [0.66-0.81] and 0.89 [0.80-0.99] for omicron BA.1&2, respectively). Vaccination had no significant effect on either direct or indirect aVE for omicron BA.4&5. The direct aVE in contacts was 32% (17, 45) and 27% (19, 34), and for index cases the indirect aVE was 7% (- 17, 26) and 11% (1, 20) for delta and omicron BA.1&2, respectively. The greatest aVE was in contacts with a previous SARS-CoV-2 infection and a single vaccine dose during the omicron BA.1&2 period (45% [27, 59]), while the lowest were found in contacts with either three vaccine doses (aVE - 24% [- 63, 6]) or one single dose and a previous SARS-CoV-2 infection (aVE - 36% [- 198, 38]) during the omicron BA.4&5 period. Protection conferred by the BNT162b2 mRNA vaccine against transmission and infection was low for delta and omicron BA.1&2, regardless of the number of vaccine doses and previous SARS-CoV-2 infection. There was no significant vaccine effect for omicron BA.4&5. Health authorities carrying out vaccination campaigns should bear in mind that the current generation of COVID-19 vaccines may not represent an effective tool in protecting individuals from either transmitting or acquiring SARS-CoV-2 infection.