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

In a recent study posted to the medRxiv* preprint server, researchers evaluated immune protection conferred by previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant and Omicron BA.1/BA.2 subvariant infections and updated SARS-CoV-2 vaccines against Omicron BA.4/5 infections and associated hospitalizations.

Background

The continual emergence of SARS-CoV-2 variants with mutations conferring greater transmissibility and immune evasiveness has threatened the efficacy of coronavirus disease 2019 (COVID-19) therapeutics such as vaccines and monoclonal antibodies. Previous SARS-CoV-2 infections induce antibody generation, and it is critical to assess immunity generated by previous infections against the immune-evasive Omicron BA.4/5 to inform policy-making and guide tailored vaccine development.

About the study

In the present retrospective cohort study, researchers assessed immunity levels against Omicron BA.4/5 infections and hospitalizations generated by previous Delta and BA.1/BA.2 infections.

The study comprised Cleveland clinic healthcare system patients with prior history of polymerase chain reaction (PCR)-confirmed Delta variant or Omicron BA.1/BA.2 subvariant infections between 1 July 2021 and 18 August 2022 who were retested during BA.4/5 predominance (between 25 June 2022 and 18 August 2022). All patients were aged ≥18 years.

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

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

The team confirmed the status of SARS-CoV-2 vaccinations during Omicron BA.4/5 dominance by reviewing the individuals’ electronic medical records (EMR). Data were obtained for participant sex, age, body mass index (BMI), International classification of diseases, ninth revision (ICD-9) codes for diabetes mellitus, hypertension, heart failure, stroke, and chronic renal illness, date, and type of COVID-19 vaccinations, date, and indications for PCR testing, hospital admissions, mechanical ventilator requirements, and intensive care unit (ICU) admissions.

The participants were categorized as updated/up-to-date if they had received two Pfizer or Moderna vaccinations or one Johnson & Johnson’s Janssen or Astra Zeneca vaccination followed by another vaccination in 6.0 months before 25 June 2022.

Results and discussion

In total, 20,987 COVID-19 patients met the eligibility criteria, among whom the mean age was 59 years, and 57% were women. In times of Delta predominance, 15,658 individuals underwent PCR testing, among whom 15.0% were SARS-CoV-2-positive. During the predominance of Omicron BA.1/BA.2, 10,545 individuals underwent PCR testing, among whom 18% tested SARS-CoV-2-positive.

On the whole, 17% of previously infected individuals were SARS-CoV-2-positive during Omicron BA.4/5 predominance. Prior Delta infections did not protect against Omicron BA.4/5 infections (PF 12%) and conferred minimal immune protection against hospital admissions (PF 11%). On the contrary, previous BA.1/BA.2 infections conferred 46% immune protection against BA.4/5 infections and 19% protection against hospital admissions.

Updated vaccines conferred modest levels of protection against BA.4/5 infections and associated hospital admissions. Adults aged ≥65 years with prior Omicron BA.1/BA.2 infections derived greater immune protection against SARS-CoV-2 reinfections with Omicron BA.4/5 compared to young adults.

The unexpected age-related finding could be explained based on differences in social conduct. SARS-CoV-2-infected elders may take greater precautions to avoid reinfections, whereas young individuals may not do so, placing them at an elevated risk of SARS-CoV-2 re-exposure and reinfection. However, there were no age-stratified significant differences with previous Delta infections, indicating that the findings were not entirely based on social behavior.

A possible explanation is that SARS-CoV-2 infections may be dose-dependent. The behavior of elder individuals might have decreased the inoculum size. Since the individuals have been infected with BA.1/BA.2 and had some immune protection and immunity, they avoided reinfection. In contrast, elders previously infected with Delta were vulnerable to even minor SARS-CoV-2 exposures. Alternatively, the effects of infection on conduct might have been short-term.

The findings showed that previous BA.1/BA.2 infections and updated vaccines conferred modest immune protection against BA.4/5 infections and hospital admissions. In contrast, previous Delta infections conferred minimal immune protection against hospital admissions and no protection against reinfections with the BA.4/5 variant.

*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.