Next Wave of COVID-19 Variants

New variants within the Omicron lineage are being reported in the US. How are they similar to BA.4/5 and BA4.6? Will the vaccines still work against these new variants?

Key takeaways:
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    The new BF.7, BQ.1 and BQ1.1, and XBB variants are all variations on an Omicron theme.
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    The bivalent booster is expected to work at least as well as the old (ancestral) booster.
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    Infections are still likely due to waning antibodies, but protection against severe disease is durable.
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    Antibodies protect against infection, memory T cells, and B cells protect against severe disease.
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    Both vaccination and prior infection stimulate the production of antibodies and T cells.
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    The interval of time between immune activations allows high-quality antibodies to be produced.
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    The flu and Covid-19 bivalent booster can be administered together, but more systemic side effects may be noticed.

The Centers for Disease Control and Prevention (CDC) monitors the genomic makeup of the spike protein to identify new variants. In the graphic below, which is from the CDC’s Variant Tracker, we notice that BF.7, BQ.1, and BQ1.1 (shades of green) are emerging variants in the Omicron lineage, together comprising approximately 20% of the circulating Omicron strains, and growing.

In Singapore, officials are carefully watching another variant, called Gryphon or XBB, which is a subvariant of Omicron BA.2 in circulation since August in at least 17 countries. It is now the dominant variant in Singapore, but in this highly vaccinated population, the Ministry of Health says severe disease remains low.

How well do we expect the new bivalent booster to work against new Omicron subvariants?

The new BA.4/5 bivalent booster, which is now authorized by the FDA for all children and adults ages 5 years and older, is expected to offer good protection against the new variants even if they are not a perfect match. This high degree of confidence in protection against severe disease is due to two very nimble defenders: T cells and memory B cells. How do they continue to battle new variants?

While neutralizing antibodies can prevent the virus from infecting cells, once SARS-CoV-2 invades a cell the memory T cells can respond and cause the cell to self-destruct. Long-lasting memory B cells can also be recruited to combat the virus with better-quality antibodies developed in response to a prior exposure (either vaccination or infection).

The new variant-specific boosters were selected for their increase in levels of neutralizing antibodies, but experts also questioned whether these laboratory findings would translate to real clinical differences. A recent modeling analysis suggests the answer is: probably not.

Paul Offit, MD, explains why boosting neutralizing antibodies may not exert much of a real-world clinical effect in an interview with MedPage Today correspondent Jeremy Faust, MD: “…back in December of 2020 — when you looked at the neutralizing antibody differences between Moderna and Pfizer — there was roughly a twofold greater neutralizing antibody response for Moderna than Pfizer, but that didn't matter in terms of protection against severe illness.”

Dr. Offit’s extensive experience in vaccine research and advocacy includes 26 years of developing a vaccine against pediatric diarrhea caused by rotavirus (RotaTeq). Offit serves as director of the Vaccine Education Center at the Children's Hospital of Philadelphia (CHOP), is an attending physician in the division of infectious diseases at CHOP, and the Maurice R. Hilleman Professor of Vaccinology at the Perelman School of Medicine at the University of Pennsylvania.

Who benefits most from Covid-19 boosting?

We can use existing research to better describe the group of people most likely to benefit from boosting antibodies. Monica Gandhi, MD, MPH, Professor of Medicine and Associate Division Chief (Clinical Operations/ Education) of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/San Francisco General Hospital considers a recent study published in The Lancet on October 15 to be “Probably (the) most ringing endorsement of vaccines (two-dose) published.”

The study was conducted among 30 million people in the UK to better understand who remained at risk despite having an initial booster dose. They found that compared to those aged 18 to 49 years, those who remained at excess risk were individuals at least 80 years of age, or those with 5 or more chronic medical conditions, kidney disease, or on immunosuppressants. For this special group of medically vulnerable people, getting a booster plus lining up prophylactic monoclonal antibodies (Evusheld) and arranging for treatment as appropriate if infected may be important lifesaving measures.

Those who had a prior Covid-19 infection were at reduced risk for serious disease upon reinfection, with those infected at least 9 months prior at the lowest risk of severe disease. Why? Recall that the memory B cells can develop high-quality antibodies in the germinal centers — this process takes time.

Can I combine the Covid-19 bivalent booster with the flu shot?

The CDC recommends getting both the flu shot and the Covid-19 booster, and getting both at once is acceptable. Seasonal influenza vaccination should be timed before the peak of flu season, typically in October or November. The CDC also recommends, however, that boosting against Covid-19 be at least 3 months following a previous infection to allow the body to develop a mature response to the last SARS-CoV-2 exposure. For example, if you had Omicron in early August, your Covid-19 bivalent booster should be at least two months after your last dose and three months after infection — in this case, early November.

While the administration of both flu and Covid-19 vaccines at the same time is authorized, there is some evidence that people who get both together have more systemic reactions. It might make sense, in the scenario just described, to separate the two vaccines by two weeks: flu shot by Halloween, then Covid-19 booster two weeks later (and in plenty of time to develop maximal immunity before Thanksgiving).

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