As Omicron Mutates, Researchers Compare Efficacy of Therapeutic Antibodies and Antivirals

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As the BA.4 and BA.5 Omicron subvariants become the dominant strains of COVID-19 around the world, researchers are evaluating just how well vaccines and therapies work against these extremely infectious strains. Here’s a look at some of the latest news on that front.

Comparing Therapeutic Antibodies and Antiviral Drugs Against Omicron

A Letter to the Editor in The New England Journal of Medicine described a study looking at how well different therapeutic antibodies and antiviral therapies work against the Omicron subvariants BA.2.12.1, BA.4 and BA.5. Currently, BA.4 and BA.5 are the dominant strains around the world.

Regeneron’s REGN10933 (casirivimab) lost neutralizing activity against all three, but the company’s REGN10987 (imdevimab) retained neutralizing activity against each. The combination of the two also inhibited all three strains even better.

AstraZeneca’s COV2-2197 (tixagevimab) had neutralizing activity against BA.2.12.1 but not against BA.4 or BA.5. The company’s COV2-2130 (cilgavimab) neutralized all three. The combination of the two inhibited all three.

AstraZeneca told BioSpace, "EVUSHELD is an investigational medicine used in adults and adolescents for pre-exposure prophylaxis for prevention of COVID-19. It consists of two investigational medicines, tixagevimab and cilgavimab. You receive one dose of EVUSHELD, consisting of two separate injections (tixagevimab and cilgavimab). EVUSHELD is given by a healthcare provider as two intramuscular injections, given one after the other. Because EVUSHELD is given as a combination, singling tixagevimab out vs. the combination is not in line with our FDA emergency use authorization or our trials."

“Of the FDA-approved monoclonal antibodies that we tested, only LYCoV1404 (marketed as bebtelovimab) efficiently neutralized BA.2.12.1, BA.4 and BA.5,” the authors wrote. Bebtelovimab was co-developed by AbCellera and Eli Lilly.

Of the antiviral drugs, Gilead’s remdesivir, Merck’s molnupiravir and Pfizer’s nirmatrelvir (marketed as Paxlovid) all showed similar efficacy against subvariants as against the original Wuhan wildtype strain. Against BA.2.12.1, efficacy was highest for molnupiravir and lowest for nirmatrelvir, with remdesivir in between. For BA.4, molnupiravir was highest, with nirmatrelvir very close and remdesivir a little lower. And for BA.5, the highest was nirmatrelvir followed closely by molnupiravir and then remdesivir.

“Our findings show that the selection of monoclonal antibodies to treat patients who are infected with Omicron variants should be carefully considered,” the authors of the study, from the National Institute of Infectious Diseases (Japan), University of Tokyo, Icahn School of Medicine at Mount Sinai (New York, NY), Johns Hopkins University and the University of Wisconsin-Madison said.

Vaxart’s Oral Vaccine Induces Long-Lasting Immune Response

South San Francisco-based Vaxart reported more Phase I data indicating that its spike/nucleocapsid (S+N) oral COVID-19 vaccine induced long-lasting mucosal IgA antibodies against the virus that causes COVID-19, as well as all tested coronaviruses. Earlier data showed it was well-tolerated and immunogenic. The new data suggests the vaccine can improve immune responses at mucosal surfaces. The data is not yet peer-reviewed.

Hypertension More than Doubles Risk of Hospitalization with Omicron

High blood pressure is one of the comorbidities associated with increased risk of COVID-19. New research out of Cedars-Sinai Medical Center in Los Angeles evaluated 912 COVID-19 patients likely infected with the Omicron variant who had received at least three doses of an mRNA vaccine, including 145 who were hospitalized.

The severe disease risk was higher in people who were older and had heart failure or kidney disease, as expected, but hypertension “was associated with the greatest magnitude of risk,” more than doubling the likelihood that they would require hospitalization. Even in generally healthy younger people with high blood pressure, there were “substantial and significant risks.”

Omicron Infection in Third Trimester Increases Risk of Preterm Delivery

An Israeli study of 2,753 pregnant patients who tested positive for COVID-19 Omicron infection compared to the same number of uninfected pregnant patients found the infections were associated with more preterm births. About half of the infected women caught the virus in the third trimester. In that group, preterm birth rates were 5.8% compared to 2.3% compared to uninfected women at the same stage of pregnancy.

“Women during their third trimester, specifically after 34 weeks of gestation, should practice social distancing and respiratory protection to reduce risk of adverse pregnancy outcomes,” the researchers wrote, adding that women in earlier stages of pregnancy should also be cautious.

Immunocompromised Shouldn’t Re-use Masks

A study out of Japan evaluated face mask hygiene for COVID-19 prevention. The small study surveyed 109 people on face mask usage and collected bacteria and fungi samples from both sides of their masks. The researchers also collected data on the type of masks and how long the people wore them. There were generally three types: non-woven, polyurethane and gauze/cloth. Polyurethane and gauze masks can be washed and re-used and still “effectively prevent infections,” the study stated. The non-woven masks are not washable and are designed for single use. The study did not find that longer duration of mask usage was associated with bacterial colony counts. It did, however, tie into increases in fungal colony counts.

“We propose that immunocompromised people should avoid repeated use of masks to prevent microbial infection,” the authors wrote. “Since masks can be a direct source of infection to the respiratory tract, digestive tract and skin, it is crucial to maintain their hygiene to prevent bacterial and fungal infections that can exacerbate COVID-19.”

Boosters Do Help Prevent Omicron Infection

A University of Washington School of Medicine study funded by the Bill & Melinda Gates Foundation indicated that although Omicron subvariants, particularly the latest, BA.5, are very good at evading the immune protection from vaccines or previous COVID-19 infections, booster shots do a good job at helping fend off infection. This supports other studies that suggest the same thing. BA.5 is now the dominant strain around the world because its spike protein binds to the host receptor more than six times better than the original wildtype Wuhan strain.

John Bowen, Ph.D., one of the study’s lead authors and a biochemist at the Veesler Lab at UW said, “We were able to look at essentially every single prominent vaccine platform in the world side by side and see that despite the scariness of this variant, all of these vaccines platforms are going to elicit solid immune responses.”

Another study out of Singapore found that the Pfizer-BioNTech vaccine was 82.7% effective against hospitalization for Omicron illness in children ages 5 to 11, and that was just with two shots. Two shots were 36.8% effective in preventing all infections in this age group and 63.5% effective against test-confirmed cases. The study analyzed data from 255,936 children 5 to 11 years of age from January 21 to April 8, 2022. In the country, vaccination of children in that age group began on Dec. 27, 2021, beginning with kids 9 to 11 and then extending to the younger group two weeks later.