#17,255
Last summer, - with existing vaccine efficiency flagging and BA.5/BA.4 surging in the United States - the FDA Authorized Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose incorporating a spike protein from these variants.
Uptake of the vaccine, however, has been disappointing (see below), as the public's perception of COVID being an `emergency' has waned and vaccine fatigue (and anti-vax information) has soared.
Complicating matters, testing and reporting of home test results have dropped dramatically over the past 6 months, we've seen our first strong flu/ILI season since the pandemic began, and we've seen two new variants (BQ.1.x followed by XBB.1.5) rise while BA.4 & BA.5 plummeted.
While early studies on the bivalent vaccine's effectiveness have been mixed , this week we saw a preprint (see Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants) that reported `a nearly complete escape of these variants from neutralizing antibodies stimulated by three doses of mRNA vaccine', but suggested that neutralization can be improved (2~8-fold higher nAb titers) by receipt of the bivalent booster.
They warned, however, that two new variants (CH.1.1 and CA.3.1), which have have not yet made a significant dent in the United States, appear to be `highly resistant to both monovalent and bivalent mRNA vaccinations'.
While useful, these laboratory studies can't tell us what we really want to know; how much `real-world' protection does this (or any) vaccine provide. Antibody neutralization studies can only tell us so much, as the human immune system is multi-layered and complex.
Yesterday, the CDC's MMWR published the first early estimates of the protection provided by the bivalent booster shot against the newer Omicron XBB/XBB.1.5 variants. (Full Disclosure: I got the booster in October).
Early Estimates of Bivalent mRNA Booster Dose Vaccine Effectiveness in Preventing Symptomatic SARS-CoV-2 Infection Attributable to Omicron BA.5– and XBB/XBB.1.5–Related Sublineages Among Immunocompetent Adults — Increasing Community Access to Testing Program, United States, December 2022–January 2023
Early Release / January 25, 2023 / 72
Ruth Link-Gelles, PhD1; Allison Avrich Ciesla, PhD1,2; Lauren E. Roper, MPH1; Heather M. Scobie, PhD1; Akilah R. Ali, MPH1; Joseph D. Miller, PhD3; Ryan E. Wiegand, PhD1; Emma K. Accorsi, PhD1,4; Jennifer R. Verani, MD1; Nong Shang, PhD1; Gordana Derado, PhD1; Amadea Britton, MD1; Zachary R. Smith, MA3; Katherine E. Fleming-Dutra, MD1 (VIEW AUTHOR AFFILIATIONS)View suggested citation
Summary
What is already known about this topic?
The SARS-CoV-2 Omicron BA.2-related sublineage XBB.1.5 is gaining predominance nationwide. Vaccine effectiveness against XBB and XBB.1.5 is unknown.
What is added by this report?
Using spike (S)-gene target presence as a proxy for BA.2 sublineages, including XBB and XBB.1.5, during December 2022–January 2023, the results showed that a bivalent mRNA booster dose provided additional protection against symptomatic XBB/XBB.1.5 infection for at least the first 3 months after vaccination in persons who had previously received 2–4 monovalent vaccine doses.
What are the implications for public health practice?
As new SARS-CoV-2 variants emerge, continued vaccine effectiveness monitoring is important. All persons should stay up to date with recommend COVID-19 vaccines, including receiving a bivalent booster dose when eligible.
The SARS-CoV-2 Omicron sublineage XBB was first detected in the United States in August 2022.* XBB together with a sublineage, XBB.1.5, accounted for >50% of sequenced lineages in the Northeast by December 31, 2022, and 52% of sequenced lineages nationwide as of January 21, 2023. COVID-19 vaccine effectiveness (VE) can vary by SARS-CoV-2 variant; reduced VE has been observed against some variants, although this is dependent on the health outcome of interest. The goal of the U.S. COVID-19 vaccination program is to prevent severe disease, including hospitalization and death (1); however, VE against symptomatic infection can provide useful insight into vaccine protection against emerging variants in advance of VE estimates against more severe disease.
Data from the Increasing Community Access to Testing (ICATT) national pharmacy program for SARS-CoV-2 testing were analyzed to estimate VE of updated (bivalent) mRNA COVID-19 vaccines against symptomatic infection caused by BA.5-related and XBB/XBB.1.5-related sublineages among immunocompetent adults during December 1, 2022–January 13, 2023. Reduction or failure of spike gene (S-gene) amplification (SGTF) in real-time reverse transcription–polymerase chain reaction (RT-PCR) was used as a proxy indicator of infection with likely BA.5-related sublineages and S-gene target presence (SGTP) of infection with likely XBB/XBB.1.5-related sublineages (2).
Among 29,175 nucleic acid amplification tests (NAATs) with SGTF or SGTP results available from adults who had previously received 2–4 monovalent COVID-19 vaccine doses, the relative VE of a bivalent booster dose given 2–3 months earlier compared with no bivalent booster in persons aged 18–49 years was 52% against symptomatic BA.5 infection and 48% against symptomatic XBB/XBB.1.5 infection.
As new SARS-CoV-2 variants emerge, continued vaccine effectiveness monitoring is important. Bivalent vaccines appear to provide additional protection against symptomatic BA.5-related sublineage and XBB/XBB.1.5-related sublineage infections in persons who had previously received 2, 3, or 4 monovalent vaccine doses. All persons should stay up to date with recommended COVID-19 vaccines, including receiving a bivalent booster dose when they are eligible.
(Continue . . . )
While not a resounding result, these numbers suggest that receipt of the bivalent vaccine provides additional protection, at least in the short term. The authors do discuss 4 limitations to their study (see below), of which I believe #3 may be significant.
- First, vaccination status, previous infection history, and underlying medical conditions were self-reported and might be subject to recall bias. Self-reported frequency of previous infections differed by vaccination status, test result positivity, and SGTF status, but statistical power was not adequate to stratify by presence of previous infection >90 days earlier. Further, previous infection is likely underreported (9). Previous infection provides some protection against repeat infection (10); therefore, VE estimates in this study might be biased toward no effect.
- Second, bivalent booster dose coverage to date has been low (6%–39% among persons aged ≥18 years among different age groups as of January 14, 2023),¶¶¶ which could bias results if persons getting vaccinated earlier are systematically different from those vaccinated later.
- Third, data on SARS-CoV-2 exposure risk and mask use were not collected; biases might also arise because of differences in testing behaviors between vaccinated and unvaccinated persons, which might result in residual confounding.
- Finally, this analysis did not control for time since last monovalent dose; however, because monovalent VE against symptomatic infection with Omicron sublineages wanes quickly (4), this likely had a minimal effect on results.
In my fairly limited circle of friends and family I know of roughly a half-dozen, mostly older individuals (including myself), who have received the booster vaccine, and none (so far) have been symptomatically infected with COVID since that time.
While encouraging, every one of them (including myself) continues to wear a face mask in public, avoids crowds whenever possible, and uses hand sanitizer like its going out of style. Things, that most people aren't doing.
When fewer than 20% of the nation elects to get the booster, it is likely that the minority who do are more likely to take other precautions as well, and that may be skewing these VE estimates.
This MMWR report concludes with:
Findings from this analysis of national pharmacy testing data show that a bivalent mRNA booster dose provided added protection against symptomatic XBB/XBB.1.5 infection for at least the first 3 months after vaccination in persons who had previously received 2, 3, or 4 monovalent vaccine doses. All persons should stay up to date with recommended COVID-19 vaccines, including receiving a bivalent booster dose when eligible.
After 3 long years of COVID, we are moving increasingly towards treating the virus as an endemic disease, rather than an emergency. The FDA is considering recommending a yearly COVID shot alongside the annual fall flu shot (which fewer than 50% take), as are other countries (see UKHSA JCVI advises an autumn COVID-19 vaccine booster).
Whether the highly mutable SARS-CoV-2 virus settles down enough to make this workable - and people are willing to get the shot - remains to be seen.
While I try to be hopeful - between COVID and the other emerging threats out there (including H5N1) - I believe in hedging my bets. Which is why I inventoried my emergency supplies this week, and ordered another box of N95's.
I honestly don't see myself going barefaced in public anytime soon.
