Antibody response 18 months after SARS-CoV-2 infection in vaccinated and unvaccinated individuals

Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged since the 2019 coronavirus disease (COVID-19) pandemic. These variants can be combated by thoroughly evaluating the long-term effectiveness of the immune response in both vaccinated and recovered individuals. The World Health Organization (WHO) campaign for vaccine equity is a global challenge to ensure equal distribution of vaccines in all countries. Several recent studies have reported that immunity after infection is long-lasting, durable, and protective.

Study: Long-term persistence of IgG antibodies in recovered COVID-19 individuals at 18 months and the effects of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on antibody response. Credit: Kateryna Kon/Shutterstock

Individuals who have recovered from COVID-19 infection are advised to undergo full vaccination, similar to naïve individuals with no history of infection. However, whether two doses of the vaccine are required for recovered people, or whether one dose would be sufficient, is still a question.

Real-time data has shown that a single dose of the vaccine can adequately improve immunity in recovered individuals with protective immunity compared to a double dose. However, ideal vaccine dosing schedules or recall responses have not been studied in recovered individuals.

Studies suggest that vaccination may elicit a more specific and potent response, centered on the spike receptor binding domain (S-RBD) rather than the nucleocapsid (NCP), compared to natural infection.

A new study published on the preprint server medRxiv* assessed the dynamics of IgG titers over 18 months in patients recovering from COVID-19 infection in March 2020. The study also looked at the effect of two doses of BNT162b2 vaccine (Pfizer-BioNTech) on antibody titers in these patients compared to patients who received no dose of the vaccine.

About the study

The study enrolled patients from the Umbria region of Italy who had tested positive for SARS-CoV-2 by real-time polymerase chain reaction reverse transcription (RT-qPCR). Patients were required to complete a questionnaire to provide information about their COVID-19-related clinical history, symptoms, and treatment received. Blood samples were also taken from the patients who entered the study.

Patient antibody titers were analyzed from May 2020 to January 2021. The first blood sample taken in May 2020 after infection in March 2020 was defined as T0. Thereafter, the samples were analyzed three months (T1), five months (T2), seven months (T3), eight months (T4) and ten months (T5) after infection.

Study participants were divided into two groups, Group A consisted of recovered patients who were vaccinated with two doses of BNT162b2 vaccine and Group B consisted of unvaccinated recovered patients. The presence of anti-S-RBD antibodies was analyzed in both groups from February 2021 to September 2021. In addition, for group B, anti-NCP antibody detection was performed to determine the persistence of infection-induced immunity not elicited by vaccination.

study results

The results show that double-dose vaccination had a major impact on antibody titers in recovered individuals. Antibody titers were found to rise rapidly after vaccination, but the increase was short-lived, explaining the importance of booster vaccinations. It was reported that IgG titers increased 161-fold while IgM titers increased by an amount of 0.773.

However, it was found that unvaccinated recovered individuals tested positive for anti-S-RBD antibodies 18 months after infection. No cases of reinfection were reported in these individuals, although several mutant strains emerged, causing multiple waves of infection. Most recovered individuals also tested positive for anti-NCP antibodies 18 months after infection.

Therefore, the current study shows that the immunity conferred by SARS-CoV-2 infection lasts longer compared to vaccination. Although the antibodies are significantly increased after vaccination, this reaction is short-lived. Testing for anti-NCP antibodies can also help analyze the type of immunity a person has. Further research is needed to determine the dosing regimen and timing of vaccination to ensure an adequate immune response in an individual.


The study had certain limitations. First, the sample size of the study was small. Second, a simultaneous determination of the antibody titer for both NCP and S-RBD would have provided better results for the comparative analysis. However, the S-RBD assay received emergency use authorization in late 2020.

*Important NOTE

medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be relied upon as conclusive, guide clinical practice/health behavior or be treated as established information.

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