What is the immune protection produced by SARS-CoV-2 Delta, Omicron BA.1 and BA.2 against Omicron BA.4 and BA.5?

In a recent study published in medRxiv*Server preprint Researchers evaluated the immune protection conferred by previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Delta and Omicron BA.1/BA.2 sub-infections and updated SARS-CoV-2 vaccines v. Omicron BA.4/5 Infections and Associated Hospital Admissions.

Study: Protection conferred by delta and BA.1/BA.2 infection against BA.4/BA.5 infection and hospitalization: a retrospective study.  Image credit: Lightspring/Shutterstock
Stady: Protection conferred by delta and BA.1/BA.2 infection against BA.4/BA.5 infection and hospitalization: a retrospective study. Image credit: Lightspring/Shutterstock


The continued emergence of SARS-CoV-2 variants with mutations that confer greater transmissibility and immuno-evasiveness threatens effectiveness Coronavirus disease 2019 (COVID-19) treatments such as vaccines and monoclonal antibodies. Previous SARS-CoV-2 infection stimulates antibody formation, and it is critical to assess immunity generated by previous infection against the Omicron BA.4/5 immunoglobulin to inform policy-making and guide personalized vaccine development.

about studying

In the current retrospective cohort study, the investigators assessed levels of immunity against Omicron BA.4/5 infection and hospitalization resulting from previous Delta and BA.1/BA.2 infection.

The study included Cleveland Clinic Health Care System patients with a previous history of polymerase chain reaction (PCR)-confirmation of a delta variant or Omicron BA.1/BA.2 subinfection between July 1, 2021, and August 18, 2022 and who were retested during BA.4/ 5 Sovereignty (between June 25, 2022, and August 18, 2022). All patients were ≥18 years old.

PF values ​​(preventable fraction) were obtained by dividing the infection/hospitalization rate of previously SARS-CoV-2-infected individuals by previously SARS-CoV-2-negative individuals by the age of the patient. Logistic regression modeling was used to analyze data adjustments for sex, age, comorbidities, and COVID-19 vaccines using logistic regression.

Individuals tested for SARS-CoV-2 between July 1, 2021, and December 25, 2021 made up the variant delta group, and those tested between December 26, 2021, and June 24, 2021 made up the Omicron BA.1/BA group. 2. The team excluded individuals with a positive report of SARS-CoV-2 before July 1, 2021 or during delta and Omicron BA.1/BA.2 waves and those with a positive report of SARS-CoV-2 in 90 days from Omicron BA.4/5. the test.

The team confirmed the case for SARS-CoV-2 vaccines during the dominance of Omicron BA.4/5 by reviewing the individuals’ electronic medical records (EMR). Data were obtained for participants’ gender, age, body mass index (BMI), International Classification of Diseases, and the ninth revision (ICD-9) codes for diabetes, hypertension, heart failure, stroke, chronic kidney disease, history, and type of disease. COVID-19 vaccines, history and indications for PCR testing, hospital admission, ventilator requirements, and admission to the intensive care unit (ICU).

Participants were classified as up-to-date/up-to-date if they had received two vaccines from Pfizer or Moderna or a Janssen or Astra Zeneca vaccine from Johnson & Johnson, followed by another vaccination in the 6 months prior to June 25, 2022.

Results and discussion

In all, 20,987 COVID-19 patients met the eligibility criteria, of whom the average age was 59, and 57% were women. In times of delta predominance, 15,658 individuals underwent PCR testing, of whom 15.0% were infected with SARS-CoV-2. During the Omicron BA.1/BA.2 dominance, 10,545 individuals underwent PCR testing, of which 18% tested positive for SARS-CoV-2.

In all, 17% of previously infected individuals had SARS-CoV-2 infection during Omicron BA.4/5 predominance. Prior delta infection did not protect against Omicron BA.4/5 infection (PF 12%) and conferred minimal immune protection against Hospital admission (PF 11%). Conversely, prior BA.1/BA.2 infection conferred 46% immune protection against BA.4/5 infection and 19% protection against hospitalization.

The updated vaccines conferred modest levels of protection against BA.4/5 infection and associated hospitalization. Adults younger than 65 years with previous infection with Omicron BA.1/BA.2 derive greater immune protection against SARS-CoV-2 re-infection with Omicron BA.4/5 compared with young adults.

Unexpected age-related outcomes can be explained based on differences in social behaviour. Older adults infected with SARS-CoV-2 may take greater precautions to avoid reinfection, while younger adults may not, putting them at elevated risk of re-exposure to SARS-CoV-2 and re-infection. However, there were no significant differences by age with previous delta infection, indicating that the results were not entirely based on social behavior.

A possible explanation is that SARS-CoV-2 infection may be dose-dependent. The behavior of the elderly may have reduced the volume of the vaccine. Because the individuals were infected with BA.1/BA.2 and had some immunogenic and immune protection, they avoided reinfection. In contrast, elderly people previously infected with delta were susceptible to even minor exposure to SARS-CoV-2. Alternatively, the effects of infection on behavior may be short-lived.

The results showed that previous infections with BA.1/BA.2 and the updated vaccines conferred modest immune protection against BA.4/5 infection and hospitalization. In contrast, previous delta infection conferred minimal immune protection against hospitalization and no protection against reinfection with the BA.4/5 variant.

*Important note

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, directing clinical practice/health-related behaviour, or treated as hard information.

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