Implementing a multi-centric cohort study during the SARS-CoV-2 pandemic in a resource-constrained setting: challenges, adaptive solutions, and lessons from Brazil

Conducting multicenter, longitudinal epidemiological studies on emerging pathogens in real time during health emergencies presents significant challenges, especially in low- and middle-income countries, where substantial logistical and resource constraints hinder the rapid design and implementation of research protocols. This is particularly difficult when the disease spreads rapidly and its nature changes due to the onset of vaccination. During the COVID-19 pandemic, a cohort study (AVISA) was conducted in eleven research sites to assess seroprevalence. The objective of this study is to identify the challenges to the successful execution of the AVISA study through a retrospective analysis of quantitative and qualitative indicators. The rapid spread of SARS-CoV-2 infections, particularly in large urban areas in Brazil, and the initiation of COVID-19 vaccination in January 2021 posed significant challenges for recruiting individuals who met the eligibility criteria. Participant enrollment was slower than initially planned, and fewer participants from the youngest and oldest cohorts were recruited. The implementation of the study protocol encountered significant logistical and operational challenges due to the evolving COVID-19 context, including the effects of vaccination, the loosening of social distancing measures, and difficulties conducting household visits and collecting samples in high-risk areas. To ensure participant retention and protocol adherence, the study employed flexible strategies, including rescheduling visits, enhancing communication, and mobilizing experienced staff, which were crucial for maintaining data collection and study continuity over time. Despite concurrent demands of the COVID-19 response, Instituto Butantan and its partners successfully mobilized resources, staff, and infrastructure to conduct the AVISA study across 11 sites, leveraging existing collaborations from prior clinical trials. The study conducted over 16,000 household visits, collected nearly 7,000 blood samples, and gathered detailed clinical and sociodemographic data from participants. Despite the complexities of conducting real-time research during a public health emergency, the AVISA study demonstrated that large-scale, multi-site longitudinal studies can be implemented in resource-constrained settings through adaptive strategies, institutional partnerships, and flexible field operations. The lessons learned offer essential insights for strengthening the design and execution of epidemiological studies in future health emergencies, particularly in low- and middle-income contexts.