Study: Two-years antibody responses following SARS-CoV-2 infection in humans: A study protocol. Image Credit: Cryptographer /

Human antibody responses to SARS-CoV-2 infection after two years

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Coronavirus disease 2019 (COVID-19), which is caused by infection with the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been diagnosed in nearly 600 million people worldwide and It has caused nearly 6.5 million deaths. Although the role of the humoral immune response against SARS-CoV-2 infection is well understood, the duration of post-infection protection remains to be determined.

To study: Antibody responses two years after SARS-CoV-2 infection in humans: a study protocol. Image Credit: Cryptographer /


Several studies have indicated that there is a significant improvement in the levels of anti-SARS-CoV-2 antibodies between the 16the and 35the day after the onset of symptoms. These antibody levels remain high for the first few months after recovery from COVID-19, after which they decline and remain stable for the next few months.

This finding indicates the possibility of immune protection for a longer period. In fact, SARS-CoV-2-specific immunoglobulin G (IgG) levels have been reported to persist for six to eight months, after which they decline.

A detailed immunological evaluation of COVID-19 patients has shown that, in most cases, anti-SARS-CoV-2 receptor-binding domain (RBD) and spike (S) IgG levels increase between 15 and 28 days after symptom onset. Thereafter, there is a gradual decline in antibody levels for up to six months and thereafter remaining stable for the next fifteen months. This study also detected SARS-CoV-2-specific IgM on day 7, which peaked on day 28.the day.

Another factor that influences antibody levels is the severity of the disease. Like other coronaviruses, such as Middle East respiratory syndrome (MERS-CoV) and SARS-CoV, seroconversion rates and antibody levels increase with disease severity.

There remains a need to develop an appropriate disease prevention model for the general population. This would require a proper surveillance system that can accommodate data from hundreds of respondents.

In a recent plus one journal study, scientists describe a protocol to assess antibody response dynamics up to two years after SARS-CoV-2 infection. In this paper, the authors also assess the risk and protective factors related to COVID-19 that were prevalent in the community.

The study protocol

An ongoing three-year research project began enrolling patients in January 2021. The first two years will focus on participant enrollment, screening and laboratory analysis, while findings will be disseminated in the third year.

The current study includes a prospective cohort study and a case-control study. To determine the kinetics of anti-SARS-CoV-2 antibodies over two years, with respect to disease severity, the scientists adapted a prospective observation method.

In contrast, the case-control study determined the risk and protective factors associated with COVID-19. More specifically, this study compared patients with confirmed SARS-CoV-2 infection (case group) with people in their respective neighborhoods (control group).

Scientists focused on developing a cohort system to manage the COVID-19 pandemic. This included hospital and population-based longitudinal data that were collected in Sleman District, Indonesia.

Study Findings

Participants for the case study were recruited from Universitas Gadjah Mada Academic Hospital (UGM) in Yogyakarta. For each confirmed case of COVID-19, three uninfected control candidates living within a one kilometer (km) radius of the infected person’s residence were recruited, for a total of 165 COVID-19 patients and 495 healthy control individuals.

Travel patterns, social structure, and individual behaviors, such as adherence to health protocols and sleep patterns, were hypothesized to be important determinants of COVID-19 incidence. To test this hypothesis, detailed demographic data on community variables, including contact history and environmental density, as well as behaviors, comorbidities, pregnancy, anthropometric parameters, and COVID-19 vaccination status, were collected. 19, from medical records and direct interviews.

Anti-SARS-CoV-2 IgM/IgG levels were hypothesized to be associated with disease severity. To test this hypothesis, quantification of peripheral blood IgM/IgG anti-S RBD titers was measured using chemiluminescent microparticle immunoassay (CMIA).


It is important to investigate the levels of anti-SARS-CoV-2 antibodies in a given population, as this metric could provide information on past and present infections. Additionally, these data will help examine the protective antibody-mediated immunity and immunopathology of COVID-19.

The current study design may help determine the unknown rates of seroconversion and seroreversion in hospitalized patients. Evaluation of the time required for seroconversion could help predict the severity of the disease.

One of the limitations of the present study is related to its longitudinal form, which makes it necessary to maintain the entire cohort throughout the entire research period. Therefore, there is a risk that candidates will be less willing to continue participating in the study over time.

To overcome this challenge, scientists offer incentives, such as free basic medical checkups after each follow-up visit. Because of affordability issues, the researchers adopted an inexpensive screening method for controls, which included breathprint analysis of patients instead of nucleic acid amplification testing (NAAT).

The results of the study will provide better insights into populations at risk for COVID-19, as well as the duration of immune protection.

Magazine Reference:

  • Arguni, E., Dewi, FST, Fachiroh, J., et al. (2022). Antibody responses two years after SARS-CoV-2 infection in humans: a study protocol. plus one 17(8): e0272690. doi:10.1371/journal.pone.0272690.

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