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The impact of prior SARS-CoV-2 infection and vaccination on Omicron infection

In a recent study posted to the medRxiv* preprint server, researchers explored the effects of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on SARS-CoV-2 Omicron infection.

Study: The effect of previous SARS-CoV-2 infection and COVID-19 vaccination on SARS-CoV-2 Omicron infection and relation with serological response – a prospective cohort study. Image Credit: CROCOTHERY/Shutterstock


Prior coronavirus disease 2019 (COVID-19) infection with vaccination results in hybrid immunity, reducing the risk of SARS-CoV-2 Omicron infection compared to immunization alone. The increased usage of self-administered antigen testing, as well as untested illnesses, may affect the results of these case-control studies. The relationship between the sequence and quantity of immunizing events with respect to hybrid immunity in response to Omicron infection and circulating antibody concentrations is still unclear.

About the study

In the present study, researchers determined the protective impact of past infections and vaccines against infection with SARS-CoV-2 Omicron.

From May 2021 to December 2021, random mailings and campaigns on social media were used to recruit The Vaccine Study COVID‐19 (VASCO) participants. Adults residing in the community between 18 and 85 years were included, and those aged 60 to 85 years were oversampled. At baseline, participants answered a questionnaire on demographics, COVID-19 vaccination, past SARS-CoV-2 infections, and comorbidities.

Monthly follow-up surveys included questions regarding COVID-19 immunization, COVID-19-like symptoms, and testing practices. After the first year of participation, follow-up surveys were gathered quarterly instead of monthly. Participants are also required to report each COVID-19 vaccination as well as every positive SARS-CoV-2 test using an online application to allow the real-time collection of data.

Participants were requested to self-collect a fingerprick sample for serum analysis at baseline as well as every six months throughout follow-up. If applicable, participants were also invited to provide a fingerprick sample one month following the primary SARS-CoV-2 vaccination schedule. Self-administered antigen testing was supplied to participants who had COVID-19-like symptoms or had close contact with an individual infected with SARS-CoV-2.

The study outcome involved SARS-CoV2 infection throughout the study period. COVID-19 infection was determined by any self-reported SARS-CoV-2-positive test and either the detection or four-times increase in SARS-CoV-2 nucleoprotein (N)-antibodies.


Between January 10, 2022, and September 1, 2022, a total of 43,257 individuals provided 8,291,966 person-days and 20,418 SARS-CoV-2 infection cases. Almost 11% of these infections were diagnosed exclusively by N-antibodies, and the rest were reported as per a SARS-CoV-2-positive (self) test. Also, 12.9% of the 9,727 infections that occurred prior to the research period were discovered by N-antibodies alone, while the remaining were diagnosed via a positive (self) test.

Hybrid immunity robustly conferred greater protection against SARS-CoV-2 Omicron infection than vaccine-elicited immunity for up to 30 weeks since the last immunizing event in all three cohorts, including individuals with two, three, or four prior immunizing events. A 71% to 85 % reduction in the hazard rate in the four to 10 weeks following the last immunizing event was observed compared to the vaccine-elicited immunity.

The comparison with infection-elicited immunity could be conducted for persons with two prior immunizing experiences. It was extremely rare during the research period for subjects to have had over two prior infections and no vaccination. In the stratum of two prior immunizing events, infection-induced immunity provided more protection than hybrid immunity; however, this difference did not show statistical significance.

Compared to vaccine-elicited immunity, protection against SARS-CoV-2 infection diminished significantly more rapidly with time since the previous incident for hybrid immunity. In the strata with three past immunizing episodes, for instance, hybrid and vaccine-induced immunity against SARS-CoV-2 infection was almost 80% and 33% lower 30 to 40 weeks after in comparison to four to 10 weeks since the last event.

Hybrid immunity continually provided greater protection against infection until it approached the level of immunity induced by vaccination in the 30 to 40-week period. Additionally, geometric mean concentrations (GMC) associated with hybrid immunity were lower than those for vaccine-induced immunity following 20 to 30 weeks.

Comparable rates of SARS-CoV-2 spike (S)-antibody loss were observed for vaccine-only and hybrid immunity. Notably, in the strata with three prior immunizing episodes, the drop in S-antibody concentration between weeks 30 and 40 and weeks four and 10 for hybrid and vaccine-induced immunity was 64%. Furthermore, GMC values were significantly lower for infection-induced immunity than hybrid or vaccine-induced immunity, even though infection-induced immunity was highly efficient. However, these estimations are based on small sample sizes and are thus uncertain.

Regardless of the number or type of immunizing episodes, S-antibody level was correlated with the risk of developing an infection in the three weeks following receipt of the serological sample in a dose-response trend. This was noted as a 71% lower occurrence of infection was observed among those with the highest S-antibody concentration compared to those with the lowest concentrations.


The study findings concluded that hybrid immunity provided superior protection against SARS-CoV-2 Omicron infection compared to vaccine-induced immunity. This impact appears independent of the order or quantity of immunizing events. Having many infections and immunizations when a person is not particularly sensitive may, however, give protection against catastrophic consequences during times of greater vulnerability or the introduction of new variants.

*Important notice

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

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