Cohort Profile: Immune Responses to SARS-COV-2 Vaccination and Infection in a Longitudinal Sampling Amidst the COVID-19 Pandemic (LONGTONG-SARS2) in Malaysia
Authors: Che-Kamaruddin Naim , Johari Jefree , Yahaya Hasmawati , Nguyen Huy C. , Letizia Andrew G. , Hontz Robert D. , AbuBakar Sazaly 
Published: March 2024

ABSTRACTPurposeThis prospective, longitudinal study aims to evaluate the durability and functionality of SARS-CoV-2 Ancestral strain (Wuhan-Hu-1)-specific immune responses induced by COVID-19 vaccination and natural infection over a 12-month period. This article reviews the study protocol, design, methodology, ongoing data collection, analysis procedures, and demographic characteristics of the cohort enrolled.ParticipantsBetween March 2021 and May 2022, 400 participants were enrolled with a 12-month follow-up, concluding in May 2023. Two main groups of participants: (1) serologically SARS-CoV-2-naïve individuals receiving the BNT162b2 primary series vaccination (referred to as VAC) and (2) those who recently recovered from COVID-19 infection within 30 days, regardless of vaccination history (referred to as COV). Additionally, a subset of 45 participants with selected COVID-19 exposure histories provided peripheral blood mononuclear cells (PBMCs) for cross-sectional analysis six months after enrollment.Findings to dateOut of 400 participants, 66.8% (n=267) completed the follow-up. Among them, 52.8% (n=141) were in VAC, and 47.2% (n=126) were in COV. As the study progressed, we acknowledged cross-over between initial groups, leading to restructuring into five revised groups based on sequential exposure events. Sociodemographic factors revealed statistically significant age distribution differences (p=0.001) in both initial and revised groups, with no significant differences observed for sex.Future plansLONGTONG-SARS2 assesses the host-pathogen interactions central to the development of COVID-19 immunity. With enrollment spanning two years of the pandemic, most participants exhibited mixed SARS-CoV-2 exposures—via vaccination and infection—resulting in diverse subgroups of interest. Notably, the inclusion of SARS-CoV-2-naïve, pre-exposure serum samples allowed for robust comparator and reduced potential biases. Ongoing analyses will include serology kinetics, memory cells ELISpots, B cells repertoire analysis, cytokine/chemokine profiling, and proteomic pathway to comprehensively examine the immune response against the SARS-CoV-2, thus informing and potentially predicting dynamic longitudinal responses against new more transmissible, immune-evasive SARS-CoV-2 variants.STRENGTH AND LIMITATIONS OF THIS STUDY- LONGTONG-SARS2 is a prospective longitudinal study that comprehensively evaluates the SARS-CoV-2 immune response among a diverse group of individuals, stratified based on the sequential order of SARS-CoV-2 exposure events, whether from COVID-19 vaccination or infection.- Pre-vaccination serum samples were collected from serologically SARS-CoV-2 naive individuals scheduled to receive the BNT162b2 primary series vaccination during the initial mass COVID-19 vaccination phase in Malaysia in early 2021.- The longitudinal serum sample collection spanned two years of the COVID-19 pandemic, from March 2021 to May 2023. This extended duration allows for robust monitoring of the immune response against SARS-CoV-2 variants in comparison to the ancestral strain.- There is a risk of misclassification of some individuals’ SARS-CoV-2 exposure status through serology, as certain sampling timepoints had intervals of three months. Additionally, our study relies on self-reported data through theMySejahteraapplication (Malaysia’s electronic medical record by the Ministry of Health) for second confirmation, potentially leading to underdiagnosed and underreported cases of asymptomatic infection.