The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups

Abstract

Background: Despite continuing efforts to improve the inclusion of underserved groups in clinical research, gaps in diversity remain. Participation of special populations is especially important when facing problems of unprecedented complexity such as the COVID-19 pandemic. A better understanding of factors associated with the immune response in diverse populations would advance future preventive and curative approaches.

Objective: The objective of this study was to investigate the factors potentially responsible for adverse events following COVID-19 immunization. The study population included adults from rural areas, transitional countries, and those with medically understudied conditions, across a broad age range.

Methods: The study evolved from peer support networks developed during the COVID-19 pandemic. Participants were recruited digitally through online neighborhood and health communities. Some of the participants volunteered as study investigators assisting with offline recruitment and safety monitoring. Individuals who consented to participate were asked to share their vaccination experiences either using constantly evolving web-based surveys or via one-on-one communication. Inferential statistical analysis to estimate differences between study groups was performed using parametric and nonparametric tests.

Results: Of 1430 participants who shared their vaccination experiences, 648 had outcome measures at their 1.5-year follow-up. Significant differences were found between age groups, types of vaccine adverse events (VAEs), incidences of breakthrough infections, and health conditions linked to the microbiome. Pairwise comparisons showed that VAEs interfering with daily activities were significantly higher in both younger (18-59 years) and older age groups (80-100 years, P<.001) than in the 60-79-year age group. Short-term VAEs were associated with lower incidence of breakthrough COVID-19 infections relative to those who reported either minimal or long-term adverse events (P<.001). A genetic origin was suggested for some adverse reactions.

Conclusions: The findings of this study demonstrate that vaccine adverse reactions in older individuals are being overlooked, and the incidence of VAEs impairing immunity may be higher than previously perceived. Better preventive measures are needed for all those at risk for life-threatening and long-term adverse events due to vaccination. Supportive community-based studies focusing on these populations could add important data to the current body of knowledge. Further and more comprehensive studies should follow.

Trial registration: ClinicalTrials.gov NCT04832932; https://ichgcp.net/clinical-trials-registry/NCT04832932.

International registered report identifier (irrid): RR2-10.1101/2021.06.28.21256779.

Keywords: COVID-19; COVID-19 vaccines; aging; breakthrough infections; decentralized participatory study; elderly; elderly population; genetic disparity; impaired immunity; medically underserved populations; microbiome disparity; older individuals; vaccination; vaccine adverse events.

Conflict of interest statement

Conflicts of Interest: None declared.

©Irene S Gabashvili. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.11.2022.

Figures

Figure 1

CONSORT (Consolidated Standards of Reporting Trials) flow diagram. Participant flow through the study. Asterisks denote data for the centenarians with publicly available profiles, followed up from early 2021. The population pyramid chart (blue: males; pink: females; transparent shades: no follow-up) shows age and sex distribution of vaccinated individuals (n=1430) and those who were recently followed up (n=648). VAE: vaccine adverse event.

Figure 2

Distribution of participants by adverse event. A white background indicates no or minimal VAEs, while an orange background depicts participants who reported VAEs that prevented them from performing daily activities, diagonal stripes denote breakthrough COVID-19 infection, and solid black represents fatal outcomes. VAE: vaccine adverse event.

Figure 3

Area charts of CIs for relative risk of vaccine adverse events (VAEs; light blue) vs breakthrough infections (orange) shown for the 648 individuals with recently updated information. Relative risk is shown as a solid line (dark blue: VAEs; orange: COVID-19).