The added effect of non-pharmaceutical interventions and lifestyle behaviors on vaccine effectiveness against severe COVID-19 in Chile: A matched case-double control study

•This study includes novel community geospatial matched controls in addition to hospitalized controls and therefore provides a robust design.•Collecting detailed lifestyle behaviors first-hand data and the inclusion of medical and laboratory records provided high data quality for a better comprehension of COVID-19 vaccine effectiveness in a real-world setting.•Vaccine' effectiveness in preventing ICU admission and severe disease,including death reached 98% two weeks after a two-dose vaccination, mostly with the inactivated vaccine Sinovac in Chile, during the Gamma wave.•Lifestyle behavioral factors and adherence to non-pharmaceutical interventions significantly influenced vaccine effectiveness in this real-world setting. World Health Organization approved vaccines have demonstrated relatively high protection against moderate to severe COVID-19. Prospective vaccine effectiveness (VE) designs with first-hand data and population-based controls are nevertheless rare. Neighborhood compared to hospitalized controls, may differ in compliance to non-pharmacuetical interventions (NPI) compliance, which may influence VE results in real-world settings. We aimed to determine VE against COVID-19 intensive-care-unit (ICU) admission using hospital and community-matched controls in a prospective design. We conducted a multicenter, observational study of matched cases and controls (1:3) in adults ≧18 years of age from May to July 2021. For each case, a hospital control and two community controls were matched by age, gender, and hospital admission date or neighborhood of residence. Conditional logistic regression models were built, including interaction terms between NPIs, lifestyle behaviors, and vaccination status; the model’s β coefficients represent the added effect these terms had on COVID-19 VE. Cases and controls differed in several factors including education level, obesity prevalence, and behaviors such as compliance with routine vaccinations, use of facemasks, and routine handwashing. VE was 98·2% for full primary vaccination and 85·6% for partial vaccination when compared to community controls, and somewhat lower, albeit not significantly, compared to hospital controls. A significant added effect to vaccination in reducing COVID-19 ICU admission was regular facemask use and VE was higher among individuals non-compliant with the national vaccine program, and/or tonroutine medical visits during the prior year. VE against COVID-19 ICU admission in this stringent pr