On the safety and effectiveness of COVID-19 vaccines, certainties and uncertainties / Sobre a segurança e efetividade das vacinas para COVID-19, certezas e incertezas

ABSTRACT

Introduction: The COVID-19 vaccines in use (inactivaded virus, encapsulated m-RNA, non-replicating adenovirus-vectored DNA) were clinically tested in randomized placebo- controlled phase-3 studies. Objective: To address certainties and uncertainties about safety and effectiveness of COVID-19 vaccines that were approved for use in various countries.Method: The evidence provided by clinical studies on the efficacy and safety of COVID-19 vaccines was critically appraised. Results: COVID-19 vaccines proved to be efficacious and safe in clinical trials. Adverse events were mostly those of minor severity commonly noted with other vaccines such as injection site pain, mild flu-like symptoms, headache and asthenia. Although being very rare, anaphylaxis-like reactions were noted with mRNA vaccines. Uncertainties regarding vaccine effectiveness refer mainly to the (long-term) duration of immunity provided by vaccination, the degree of protection conferred to elderly people, and how effective vaccines are against emerging SARS-CoV-2 variants. There are few uncertainties about vaccine safety including the absence of clinical trial data in pregnant women (and the impact on the unborn child), children and adolescents. Conclusions: Notwithstanding the knowledge gaps about effectiveness and safety of COVID-19 vaccines (to be further addressed by observational studies), there is overwhelming evidence that public health benefits of vaccination by far outweigh any foreseeable risk.

RESUMO

Introdução: As vacinas contra COVID-19 (vírus inativado, m-RNA encapsulado, vetor adenovírus não replicante) foram testadas em ensaios clínicos randomizados (fase-3) controlados com placebo. Objetivo: Abordar as certezas e incertezas sobre segurança e efetividade das vacinas para COVID-19 já aprovadas para uso em vários países. Método: A evidência clínica de eficácia e segurança das vacinas contra COVID-19 foram examinadas criticamente. Resultados: As vacinas (COVID-19) mostraram ser eficazes e seguras nos ensaios clínicos. Os eventos adversos foram predominantemente os de menor gravidade comumente observados com outras vacinas, tais como dor no local da injeção, sintomas gripais leves, cefaleia e fraqueza. Embora sejam raras, reações do tipo anafilático foram registradas com vacinas mRNA. As incertezas sobre efetividade referem-se à duração da imunidade conferida pela vacina, o grau de proteção de idosos, e a efetividade das vacinas contra as novas variantes do SARS-CoV-2. As incertezas sobre segurança são poucas e incluem a ausência de estudos clínicos em grávidas (e sobre o bebê no útero), em crianças e adolescentes. Conclusões: Não obstante as poucas lacunas acerca da efetividade e segurança das vacinas contra COVID-19 (a serem abordadas por estudos observacionais), os previsíveis benefícios da vacinação para a saúde pública excedem de longe quaisquer riscos antecipáveis.