Efficacy and Safety of an Inactivated Whole-Virion SARS-CoV-2 Vaccine (CoronaVac) in Brazilian Healthcare Professionals: The PROFISCOV Trial

BackgroundCoronaVac, an inactivated COVID-19 vaccine, underwent evaluation for its efficacy and safety during the PROFISCOV study conducted in Brazil. MethodsBetween July 21, 2020, and July 29, 2021, 13,166 participants provided informed consent, with 12,688 randomized for the trial. Participants were allocated between vaccine and placebo arms (1:1) and monitored for symptomatic COVID-19 cases, severity of disease, and adverse reactions after two doses given 14 days apart. FindingsThe primary efficacy analysis revealed a vaccine efficacy of 50{square}39% (95% confidence interval [CI], 35{middle dot}26% to 61{middle dot}98%; p=0{middle dot}0049) in preventing symptomatic COVID-19, leading to the issuance of Emergency Use Authorization for CoronaVac in January 2021. Upon completion of follow-up, vaccine efficacy was 44{square}58% [95% CI, 34{middle dot}89% to 52{middle dot}83%; p= 0{middle dot}0023] in preventing COVID-19 and 82{square}14% (95% CI, 64{middle dot}93% to 90{middle dot}90%; p<0{middle dot}0001) in preventing severe COVID-19. Safety data indicated that adverse reactions were more frequent in the vaccine arm, primarily mild to moderate, with pain at the injection site and headache being the most common. InterpretationCoronaVac demonstrated moderate efficacy in preventing symptomatic COVID-19 and high efficacy against severe disease. While reactions were slightly more common in the vaccine group, they were generally mild and manageable. FundingFundacao Butantan, Instituto Butantan, and Sao Paulo Research Foundation (FAPESP; Grants 2020/10127-1 and 2020/06409-1). Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSAt the time of the studys design in 2020, the world was grappling with the COVID- 19 pandemic, with no licensed vaccine available. A global race to develop a safe and effective vaccine was underway, leading to the exploration of several vaccine candidates based on various technologies and mechanisms of action. Among these candidates was CoronaVac, an inactivated vaccine developed by Sinovac Life Sciences. PubMed was searched for pre-clinical and clinical trials using terms "COVID-19", "SARS-CoV-2", "Vaccine", "Vaccine Efficacy", without language or data restrictions. Additionally, information on clinical trials was sought from the ClinicialTrials.gov database and regulatory agencies. The focus was on late-stage clinical trials evaluating the safety, immunogenicity, and efficacy of CoronaVac. Positive safety and immunogenicity results from phase I/II clinical trials in younger and older adults, coupled with expanding pandemic, motivated the design and implementation of this phase III trial in healthcare professionals directly caring for or likely to be in close contact with COVID-19 patients in Brazil. No previous phase III study focusing on the efficacy and safety of CoronaVac in this high-risk population was identified. Added value of this studyBetween July 21, 2020, and July 29, 2021, 12,688 participants were randomized to receive either CoronaVac or placebo. We evaluated symptomatic COVID-19 cases, disease severity, and adverse reactions after two doses given 14 days apart. We found that CoronaVac met the predefined efficacy criteria, providing a moderate efficacy against symptomatic COVID-19 of 50{square}39% (95% CI: 35{middle dot}26-61{middle dot}98) in the primary analysis. Notably, CoronaVac demonstrated high effective against severe disease, with a vaccine efficacy of 82{square}14% (64{middle dot}93-90{middle dot}90) in the final analysis. Regarding safety, CoronaVac was shown to be safe, with most reactions being mild and manageable, albeit more commonly reported in the CoronaVac group. The inclusion of a high-risk study population comprising healthcare workers directly involved in the care of COVID-19 patients in Brazil is a key differentiator of our trial, as other studies of CoronaVac in China, Indonesia, Chile and Turkey at that time were not restricted to healthcare workers. Implications of all the available evidence.The primary efficacy analysis data from this study supported the Emergency Use Authorization issued for CoronaVac in Brazil in January 2021. Subsequently, a national vaccination campaign was initiated, with CoronaVac being the first vaccine to be incorporated in the COVID-19 vaccination program in Brazil. Since then, more than 100 million doses of CoronaVac have been administered in Brazil through the National Health System. The efficacy and safety of two doses of CoronaVac were demonstrated in the final analysis of the study. CoronaVacs ability to prevent severe disease is a crucial attribute that has had a positive impact on pandemic control and public health. It represents a promising option for COVID-19 vaccination, especially in low- or middle-income countries, given its moderate efficacy against symptomatic disease and favorable safety profile, in addition to its lower cost and ease of manufacturing compared to other vaccines available early in the pandemic. The impact on the immunogenicity and safety profile of XBB-updated versions of the vaccine used as a booster vaccination needs to be investigated in future studies.