A proud sports mom, Shantay Brown longs to pack into a crowded stadium for her son’s Ohio State football games and scream her face off over the action on the field.
But as with so many other simple pleasures in the age of Covid-19, nothing is that simple for Brown. The 47-year-old Missouri resident takes immunosuppressant medication for lupus. Consequently, her body has mounted virtually no antibody response to the coronavirus vaccine – leaving her in persistent peril.
Brown is among the estimated 3% of American adults who have immunosuppression, including transplant recipients and people with cancer and autoimmune disorders such as lupus.
For these millions, a vaccine-fueled sense of springtime liberation quickly plummeted into a summer of discontent, after the Centers for Disease Control and Prevention (CDC) said the vaccine might not protect them. They and their household members were advised to go right back to masking and social distancing. Last month, the Food and Drug Administration (FDA) cleared an extra vaccine dose for many.
So Brown was immediately intrigued when her rheumatologist at Washington University in St Louis, where she works as a laboratory technician, told her the FDA could soon grant emergency authorization for immunocompromised people to receive preventive injections of monoclonal antibodies.
“I trust the scientists and I feel like I don’t have a choice,” Brown said of the prospect of receiving antibodies as pre-exposure prophylaxis, or PrEP, against Sars-Cov-2. “It’s a no-brainer for me.”
Brown’s rheumatologist, Alfred Kim, said his immunocompromised patients “are frustrated because they’re seeing the world open up – maybe in some places too fast – and they can’t”.
Consequently, he said, their interest in antibody PrEP is “very high”.
“Ultimately, there will be a large group of immunocompromised people who will not mount a protective response with vaccines,” said Dorry Segev, an epidemiologist and transplant specialist at Johns Hopkins University who is leading a major study of extra vaccine shots for this population.
“For them, monoclonal antibodies as PrEP will likely be their best and possibly only chance for robust protection.”
Regeneron’s dual-antibody cocktail, Regen-Cov, which is covered by the federal government at $2,100 per dose, has emergency authorization for treatment of non-hospitalized patients within 10 days of Covid symptom onset. These antibodies, which remain effective against Delta, have proven powerful at reducing the risk of severe Covid, hospitalization and death.
In August, the FDA granted further emergency authorization to Regeneron’s cocktail for use as post-exposure prophylaxis, or PEP. Unvaccinated or immunocompromised people at risk of severe Covid who have been in close contact with someone who tested positive can receive a preventive infusion or subcutaneous injection of Regen-Cov, ideally within four days of exposure.
In the study supporting this authorization, participants were evenly randomized to receive a single injected dose of Regen-Cov or a placebo within 96 hours of a household member’s coronavirus diagnosis. The New England Journal of Medicine reported that of 1,505 participants who initially tested negative for Sars-Cov-2, the antibody injection lowered their risk of symptomatic infection by 81% over four weeks.
Regeneron is in talks with the FDA about securing emergency authorization for Regen-Cov as PrEP. The protocol would probably entail monthly injections; the cocktail’s half-life is approximately that long. Unvaccinated and immunocompromised individuals are already allowed to follow that protocol under the FDA’s PEP authorization, provided they live or work in an institutional setting, such as a nursing home or prison, where ongoing coronavirus exposure is expected.
AstraZeneca plans to apply for authorization this fall for its own prophylactic antibody cocktail – one that might provide as long as 12 months of protection. The company has contingent agreements with the US government to provide up to 700,000 doses.
On 20 August, AstraZeneca announced preliminary, non-peer-reviewed results from an advanced trial of its cocktail as PrEP among 5,172 initially unvaccinated and coronavirus-negative participants. The study, which randomized a third of participants to receive a placebo, is ongoing in the US and Europe. Thus far, a single intramuscular injection of the antibodies reduced symptomatic Covid risk by 77% compared with the placebo during the first one to five months of a planned 15 months of follow-up.
None of those who got the antibody cocktail, called AZD7442, have developed severe Covid or died, compared with three severe cases and two deaths in the placebo group.
Howard J Huang, a transplant pulmonologist at Houston Methodist hospital, said: “For individuals with weakened, suppressed or no immune response to vaccination” prophylactic antibody injections offer “a realistic alternative to perpetual isolation and risk for serious illness or death from Covid-19”.
Calling PrEP “a ray of hope” for his immunocompromised patients, Huang maintains such a confident outlook even though such individuals have only comprised 1.5% to 4% of the study populations in the key treatment and prevention trials of these antibodies.
Myron Cohen, a top coronavirus antibody researcher at the University of North Carolina at Chapel Hill and a leader of the prophylactic Regen-Cov study, said he “saw no reason to believe” immunosuppression would lessen the antibodies’ preventive power.
“They’ve proven very safe,” Cohen said of the cocktails, adding that he expects the FDA to authorize at least one as PrEP and that the pipeline for coronavirus antibody prophylactics is robust. “There are really no predictable side-effects from these drugs.”
Cohen stressed that PrEP would be meant to complement, not replace, vaccination.
‘I felt this huge relief’
As a public health strategy, PrEP has already revolutionized HIV prevention over the past decade. Some 300,000 HIV-negative Americans currently take antiretroviral pills that, when taken daily, nearly eliminate their risk of contracting that virus.
A rare early bird to the eagerly anticipated prophylactic revolution on the Covid front is Sheila Portington, a British expat and kidney transplantee living in Bolton Landing, New York. She suffered devastating anxiety after learning through participation in Segev’s study that she had no antibody response to the coronavirus vaccine.
“Your whole life just completely changes when you suddenly realize these vaccines aren’t working for you,” said Portington, 68. “I can’t even tell you how scary it is.”
Her nephrologist spent numerous hours securing her Regen-Cov as PrEP under compassionate use. She got her first monthly dose in August.
“The difference this made to me mentally is absolutely amazing,” said Portington, now comfortable planning a long-delayed visit to family in England. “When I stepped out of the doctor’s office, I felt this huge relief.’”
Janet Handal, 70, is a transplant recipient and New York City consultant who founded a 540-member Facebook group for immunocompromised people and an associated advocacy organization.
She said: “What people are looking for is to be able to resume a normal life and to go out in the community, go to concerts, eat indoors.”
Shantay Brown said PrEP would allow her to attend those all-important Ohio State games with greater confidence and ease. But she acknowledged that antibody injections wouldn’t make her invincible. So, she said, she would remain vigilant and keep her mask on.
“Which will stop me from screaming like I want to.”