In a recent study published in medRxiv preprint server*, researchers in the United States investigated the efficacy of an XBB1.5 (Pfizer/BioNTech 2023-2024) variant-modified vaccine with severe acute respiratory syndrome BNT162b2 to provide additional immune protection against the coronavirus Inpatient and ambulatory visits in individuals across the United States (US) related to disease 2019 (COVID-19). They also investigated whether previous versions of vaccines continued to protect people compared to unvaccinated individuals.
Study: BNT162b2 XBB1.5 Adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults. Image credit: Corona Borealis Studio / Shutterstock
*Important note: medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered definitive, guide clinical practice/health-related behavior or be treated as established information.
The SARS-CoV-2 XBB lineage and its subtypes are circulating in the US from January 2023 onwards. Improved SARS-CoV-2 monovalent messenger ribonucleic acid (mRNA) vaccines targeting the XBB1.5 strain have been approved by the US Food and Drug Administration (FDA) or subjects aged ≥6.0 months. Following CDC preparedness guidelines, these vaccinations became widely available in the US on September 15, 2023. However, the relationship between lineage-adapted XBB1.5 vaccinations and therapeutically relevant outcomes of SARS-CoV infection -2 warrants further investigation.
About the study
The present study investigators evaluated the relationship between receipt of the 2003–2004 XBB1.5 lineage-adapted BNT162b2 vaccine and outcomes of SARS-CoV-2 infection in US adults.
The researchers examined the odds of receiving a modified BNT162b2 SARS-CoV-2 XBB1.5 vaccination among patients with COVID-19 and SARS-CoV-2-negative controls enrolled in the Kaiser Permanente Southern California (KPSC) healthcare system between October 11 and December 10, 2023. The primary endpoint of the study was a BNT162b2 SARS-CoV-2 XBB1.5-modified vaccine versus an unmodified XBB1.5 vaccine, regardless of prior COVID-19 vaccinations and history of SARS-CoV-2 infections. The researchers also compared previous versions of the COVID-19 vaccine (not modified with SARS-CoV-2 XBB1.5) to the absence of SARS-CoV-2 vaccination to determine the residual protection provided by earlier versions of the vaccine.
Cases were persons who tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) during hospitalization, urgent care (UC), emergency department (ED), and outpatient contacts. The team limited the PCR tests to those provided two weeks before the initial acute respiratory infection (ARI) exposure and three days after the interaction in patients and controls.
The trial began two weeks after vaccinations adapted to the XBB1.5 lineage became available to KPSC members and circulated mainly XBB substrains. After mid-November, JN.1, a subvariant of SARS-CoV-2 BA2.86, began to co-circulate with a rapid increase in frequency. Participants had one year of participation in a health program to assess medical history and comorbidities. Patients with other medical problems were not allowed to participate in the trial. The team obtained data from the California Immunization Registry, which requires healthcare professionals to submit COVID-19 vaccines within 24 hours. They performed multivariate logistic regression modeling to determine adjusted odds ratios (ORs).
Results
SARS-CoV-2 PCR testing found that 24,007 individuals from 26,187 ARI encounters met the survey selection criteria. Eighteen percent tested positive for SARS-CoV-2, with 6.6% receiving the series-matched BNT162b2 XBB1.5 vaccine. Vaccination was administered to 17% and 7.4% of subjects in the case (n=4,232) and control (n=19,775) groups, respectively. Among participants, 93% had never received the XBB1.5-modified COVID-19 vaccination and 11% had no prior history of vaccination against COVID-19. The median time since receiving the most recent prior dose of COVID-19 vaccination among recipients of the BNT162b2 SARS-CoV-2 XBB1.5-modified vaccine was 363 days, and the median time since receiving the XBB1.5-modified vaccine it was 30.0 days.
Adjusted ORs for testing positive for SARS-CoV-2 among subjects who received BNT162b2 SARS-CoV-2 XBB1.5-modified vaccine (versus those who did not receive any XBB1.5-modified vaccine) were 0.4, 0 ,4 , and 0.4 for hospitalizations related to SARS-CoV-2 infection, UC/ED visits, and outpatient visits, respectively. BNT162b2 SARS-CoV-2 XBB1.5-adapted vaccination conferred significant additional protection against various outcomes of SARS-CoV-2 infection during the dominance of XBB subtypes, with JN.1 circulating. Regardless of dose number and type, older versions of the COVID-19 vaccine provided negligible protection compared to no vaccination, including hospitalization for COVID-19. Previous recipients of the COVID-19 vaccine did not have a significantly lower risk of SARS-CoV-2 infection-related outcomes, including hospitalization, than the unvaccinated.
The risk of SARS-CoV-2 seropositivity was similar in all groups, including recipients of BA.4 and BA.5-modified bivalent vaccines, no SARS-CoV-2 XBB1.5-modified vaccines, or three or two doses of ancient SARS – CoV-2 strain vaccines without boosters adapted for SARS-CoV-2 variants. Results were broadly comparable across ages, with trends toward a higher risk reduction for outpatient contacts for those over 65 years of age. Labor, delivery, medical emergency, surgery/neurosurgery, sepsis, and other medical disorders were the most common causes of hospitalization in eliminated cases.
The study findings showed that the COVID-19 vaccines developed for XBB1.5 provided additional immunological protection against the effects of SARS-CoV-2 infection. After 30 days, recipients of BNT162b2-modified SARS-CoV-2 XBB1.5 vaccine had 63%, 58%, and 58% lower risks of hospitalization, ED/UC contacts, and outpatient visits, respectively. Most cases were almost certainly XBB sublines. Previous vaccinations against COVID-19 provided minimal protection due to waning immunity and the ongoing evolution of SARS-CoV-2. Regular updates on COVID-19 vaccinations are vital to maintaining protection against the virus as it spreads.
*Important note: medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered definitive, guide clinical practice/health-related behavior or be treated as established information.
