Phase 4 clinical trials in the era of the Coronavirus Disease (COVID-19) pandemic and their importance to optimize the COVID-19 vaccination

Since the appearance of SARS-CoV-2, the scientific community has worked relentlessly to gather enough information about the illness caused by this virus infection. Such great effort has resulted in increased scientific publication, including phase 4 clinical trials addressing the applicability of COVID-19 vaccines. In those trials that investigated the properties of the vaccine among participants with morbidities, mainly immunocompromised individuals, the safety was recommended, but in the presence of immunogenicity, such protection was considered of short and medium terms. It was also observed that a physically active lifestyle might increase the immunogenicity of the COVID-19 vaccination in patients with autoimmune rheumatic diseases and in immunocompromised patients. The coadministration of different types of vaccine such as the combination of the recombinant adenovirus type 5 (AD5)-vectored Convidecia as heterologous reinforcement vs. CoronaVac with homologous reinforcement in adults previously vaccinated with CoronaVac, as well as the coadministration of inactivated COVID-19 vaccine followed by the administration of the tetravalent influenza vaccine (Fragmented, Inactivated) and the pneumococcal vaccine 23 presented satisfactory immunogenicity. However, the heterologous reinforcement had better immunogenicity when compared to the homologous reinforcement. Simultaneous COVID-19 vaccination and vaccines against seasonal influenza did not raise safety issues, producing acceptable levels of adverse reactions and preserving the antibody responses against SARS-CoV-2. In the lot-to-lot consistency evaluation, CoronaVac was seen to induce an immune response considered relatively high, and the lots presented a similar profile of stability and immunogenicity, thus enabling their large-scale distribution. In brief, this article addressed, mainly, the importance of evaluating the immunological response in the COVID-19 vaccination in patients with specific health conditions (e.g., immunocompromised individuals) aiming at enabling adjustments to the vaccine calendar in national vaccination programs.