Cohort Profile: Immune Responses to SARS-COV-2 Vaccination and Infection in a Longitudinal Sampling Amidst the COVID-19 Pandemic (LONGTONG-SARS2) in Malaysia

Purpose This 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. Participants Between 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 date Out 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 plans LONGTONG-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 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by funds from the U.S. Joint Program Executive Office under the 2020-2021 Coronavirus Aid, Relief, and Economic Security (CARES) Act. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from Universiti Malaya Medical Centre (MREC-UMMC SID: 2021226-9886) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors