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.

Study: Protection conferred by Delta and BA.1/BA.2 infection against BA.4/BA.5 infection and hospitalization: A Retrospective Cohort Study. Image Credit: Lightspring/Shutterstock
Study: Protection conferred by Delta and BA.1/BA.2 infection against BA.4/BA.5 infection and hospitalization: A Retrospective Cohort Study. Image Credit: Lightspring/Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

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.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • May 16 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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