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Understanding Immunity to SARS-CoV-2 in Malaysia

A study on immune responses to COVID-19 vaccination and infection in Malaysia.

― 7 min read


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Table of Contents

COVID-19, caused by a virus called SARS-CoV-2, is a respiratory illness that started spreading globally in 2019. SARS-CoV-2 is a type of virus known as a coronavirus, and it is closely related to other coronaviruses that have caused severe respiratory illnesses in the past, such as SARS-CoV-1 and MERS-CoV. Since its emergence, there have been over 773 million reported cases and more than 7 million deaths worldwide. However, the true number of deaths may be higher due to difficulties in tracking and reporting in many regions.

Most people infected with SARS-CoV-2 experience mild or moderate symptoms and recover without needing hospitalization. A smaller number of individuals can develop more severe symptoms, leading to critical conditions.

The Importance of Vaccines

Vaccines developed for SARS-CoV-2 have demonstrated effectiveness in helping to prevent COVID-19. However, researchers have observed that the levels of Antibodies produced can decrease after a few months following vaccination or infection. This decline in antibodies highlights the need for booster shots to maintain protection against the virus and any new variants it might produce.

Previous research has indicated that the risk of getting reinfected may be linked to the decrease in neutralizing antibodies. Not all individuals who recover from COVID-19 will have detectable antibodies in their system, leading to concerns about immune response variability. Booster doses have been shown to improve antibody levels and response to newer variants of the virus.

Immune Response to SARS-CoV-2

When a person is exposed to SARS-CoV-2 through vaccination or natural infection, their body develops an immune response. This includes two main components: humoral immunity, which involves the production of antibodies, and cellular immunity, which involves immune cells like B and T cells. These immune cells create a memory of the virus, enabling the body to respond quickly if it encounters the virus again.

Memory B and T cells can provide lasting protection, even when antibody levels drop. However, there are complexities in how these immune cells respond to variants of the virus. The immune system must adapt to changing variants, making it vital to study how different exposure histories to SARS-CoV-2 shape these Immune Responses in various populations.

Study Objectives

The study aims to observe and analyze the immune response of individuals who have been vaccinated and/or infected with SARS-CoV-2 in Malaysia. The focus is on understanding how long immunity lasts and how effective the immune system is at fighting back against future exposures to the virus.

Specific Objectives

  1. Measure the levels of antibodies against SARS-CoV-2 over 12 months using blood tests.
  2. Examine how well memory B and T cells are working after exposure to the virus.
  3. Investigate the role of signaling molecules called Cytokines in the immune response.
  4. Analyze changes in proteins in the blood before and after vaccination or infection.
  5. Look at how different factors like age and health conditions affect the immune response to the virus.

Who is in the Study?

Participants in the study included healthy individuals aged seven and older who were either vaccinated or had recovered from COVID-19. People with certain health conditions, such as cancer or HIV, were excluded to ensure a clearer understanding of the immune response in healthy individuals.

Data collected from participants includes basic information such as age, gender, and health history, as well as their vaccination and infection records. This helps researchers track how different variables might influence immune response.

Study Design

The study enrolled two groups:

  1. Individuals who were naïve to SARS-CoV-2 (unexposed) and were receiving the COVID-19 vaccine for the first time.
  2. Individuals who had previously been infected with COVID-19, regardless of whether they had been vaccinated.

Participants were informed about the study's purpose and procedures and were asked to give their consent to take part. The study has a rigorous design that allows researchers to gather data over time, with blood samples taken at various intervals to track changes in the immune response.

Methods of Data Collection

The study involved taking blood samples at several time points over a 12-month period. Individuals who received the vaccine had their blood sampled at nine different stages, while those who had been previously infected had seven sampling points.

Blood samples were used to test for antibodies and to analyze cellular responses to understand how effective the immune system is at recognizing and fighting off the virus.

Laboratory Investigations

The laboratory part of the study consists of several different tests focused on different aspects of the immune response:

  1. Antibody Monitoring: This involves measuring specific antibodies in the blood related to SARS-CoV-2. Different tests are used to quantify antibodies produced, which helps researchers understand how well the immune system is responding over time.

  2. Memory Cell Functionality: Researchers will assess how well memory B and T cells react to the virus when exposed again. This indicates the immune memory built from prior exposure.

  3. Cytokine Profiling: This examines signaling molecules in the immune system that communicate how immune cells should act. Understanding these signals can help clarify the immune response's effectiveness.

  4. Proteomic Profiling: This focuses on the various proteins present in the blood and how they change in relation to SARS-CoV-2 exposure. This gives insights into how the immune system operates at a protein level.

Participant Engagement

Throughout the study, maintaining participant involvement was important. Participants were informed of their serology test results to engage them in their health care. Moreover, mobile follow-up services were implemented to collect samples and keep participants engaged, especially during times when movement was restricted due to public health measures.

Findings to Date

Since the start of the study, around 400 participants have been enrolled, with a retention rate of 70% throughout various sampling points. Participants were informed of their serology test results, which contributed to their continued engagement.

Challenges arose due to changes in health policies and vaccination distribution, leading to fewer naïve participants enrolled over time. However, individuals with prior infections were more readily available to participate as the study progressed.

Cross-Exposure of Vaccination and Infection

As the study unfolded, it became clear that many participants experienced both vaccination and infection. This overlap complicated the initial groupings but also provided valuable insights into how hybrid immunity may emerge. The data show that a significant number of participants experienced breakthrough infections post-vaccination, indicating the need to study how these exposures affect immune responses.

Future Directions of the Study

The study will continue to explore how exposure to SARS-CoV-2 affects immunity over time. It will specifically look at factors that influence the durability and efficacy of the immune response. Additionally, researchers will investigate how different vaccination regimens and previous infections shape immunity.

The cohort created through this study will provide insights into the diversity of immune responses that emerge from various types of exposure to SARS-CoV-2.

Ethics and Collaboration

Ethical standards are paramount in the study. Approvals were obtained to ensure that all participant rights are respected, and all data collected is handled confidentially. The study has collaboration with various organizations to support its goals and spread findings to a broader audience.

The research team is committed to sharing outcomes not just within scientific circles but also with participants to foster transparency and trust within the community.

Conclusion

This study represents a comprehensive effort to understand the immune response to SARS-CoV-2 in Malaysia, with a specific focus on both vaccination and natural infection. The findings will contribute to our knowledge of COVID-19 and may help shape future public health strategies, especially as new variants continue to emerge. Through ongoing research and participant engagement, the study aims to provide critical insights into how we can better protect individuals and populations against COVID-19.

Original Source

Title: COHORT PROFILE: IMMUNE RESPONSES TO SARS-COV-2 VACCINATION AND INFECTION IN A LONGITUDINAL SAMPLING AMIDST THE COVID-19 PANDEMIC (LONGTONG-SARS2) IN MALAYSIA

Abstract: PurposeThis 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-naive 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-naive, 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 the MySejahtera application (Malaysias electronic medical record by the Ministry of Health) for second confirmation, potentially leading to underdiagnosed and underreported cases of asymptomatic infection.

Authors: Sazaly AbuBakar, N. Che-Kamaruddin, J. Johari, H. Yahaya, H. C. Nguyen, A. G. Letizia, R. D. Hontz

Last Update: 2024-03-28 00:00:00

Language: English

Source URL: https://www.medrxiv.org/content/10.1101/2024.03.26.24304850

Source PDF: https://www.medrxiv.org/content/10.1101/2024.03.26.24304850.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to medrxiv for use of its open access interoperability.

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