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

The 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 almost 600 million people worldwide and caused almost 6.5 million deaths. Although the role of the humoral immune response against SARS-CoV-2 infection is well understood, the duration of protection post-infection has yet to be determined. 

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

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


Several studies have indicated that a significant enhancement in anti-SARS-CoV-2 antibody levels occurs between the 16th and 35th day after the onset of symptoms. These antibody levels remain high for the first few months following recovery from COVID-19, after which they decline and remain stable for the next several 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 wane off.

A detailed immunological screening 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 the onset of symptoms. Thereafter, a gradual decline of antibody levels occurs for up to six months and subsequently remains stable for the next fifteen months. This study also detected SARS-CoV-2-specific IgM on the seventh day, which peaked on the 28th day.

Another factor that influences antibody levels is disease severity. Similar to other coronaviruses, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, seroconversion rates and antibody levels increase depending on the disease severity. 

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

In a recent PLoS ONE journal study, scientists describe a protocol to evaluate antibody response dynamics up to two years following SARS-CoV-2 infection. Herein, the authors also assess the protective and risk factors related to COVID-19 that prevailed in the community. 

The study protocol

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

The current study includes one prospective cohort study and a case-control study. To determine the anti-SARS-CoV-2 antibody kinetics for two years, with respect to disease severity, the scientists adapted a prospective observational method.

Conversely, 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) to individuals in their respective neighborhoods (control group).

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

Study findings

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

It was hypothesized that traveling patterns, societal structure, and individual behaviors, such as adherence to health protocols and sleep patterns, were important determining factors for the incidence of COVID-19. To assess 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 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 were measured using the chemiluminescent microparticle immunoassay (CMIA). 


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

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

One of the limitations of the current study is related to its longitudinal form, which requires maintaining the entire cohort for the complete research period. Thus, there is a risk of reduced willingness of the candidates to continue participating in the study over time.

To overcome this challenge, the scientists offer incentives, such as free basic medical check-ups after every follow-up visit. Owing to affordability issues, the researchers adopted an inexpensive screening method for the controls, which included patients’ breath-print analyses rather than the nucleic acid amplification test (NAAT). 

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

Journal reference:
  • Arguni, E., Dewi, F. S. T., Fachiroh, J., et al. (2022) Two-years antibody responses following SARS-CoV-2 infection in humans: A study protocol. PLoS ONE 17(8): e0272690. doi:10.1371/journal.pone.0272690.
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.


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  1. Scott Wheat Scott Wheat United States says:

    I'm unable to give credit to the mRNA vaccine (two does Pfizer) or the prophylaxis I take daily (quercetin 500mg, zinc 50mg, vitamin C 2000mg, magnesium 250mg, selenium 100mcg, vitamin D 125 mcg w/K2 100mcg, B complex, NAC, etc. Regardless of what prevents it, I'm just glad I've been spare the misery of this dread disease, the same one the killed my mother. Bless everyone with health Lord Jesus.

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