Dr. Bob Wachter, chair of the department of medicine at University of California, San Francisco, has been saying for months that the two possible game-changers affecting the “uneasy new normal with Covid-19” are the introduction of effective oral antiviral medications to treat covid, or the introduction of a “really nasty new variant.” Today, Grand Rounds panelists discussed the possibility of both.
Omicron uncertainty and media frenzy
Omicron has “gone from a variant of interest, to a variant of concern, to a variant of mass panic in the space of a week, and the one thing we’re really short of is actual data,” said Dr. John P. Moore, professor of microbiology and immunology at Weill Cornell Medical College, who joked that, to figure out reality, “you might as well get a sheep, slaughter it and inspect the entrails.”
No one in South Africa is known to have been hospitalized or fallen seriously ill with omicron, and despite the media frenzy around it (which San Francisco health officials are refusing to participate in), it is possible that omicron will spread but not cause serious disease, and evolve to be more like the common cold, Moore said.
Moore also highlighted news articles from South Africa that reported omicron patients are not experiencing loss of smell or taste.
“That alone would say that there’s something funky about this variant,” he said.
Discussing a pre-print study looking at reinfection rates related to omicron, Moore said, “they’re seeing evidence that it is more capable of reinfecting people who’ve recovered from earlier infections; not a massive effect, but it’s statistically significant, according to these analyses.”
However, “we really need more time to digest this emerging information, understand the implications,” he said. “We’re seeing essentially panicky reactions from the media, certainly from members of the public, and to some extent from the [Biden] administration.”
Regarding omicron-specific boosters, Moore said that manufacturing and distributing millions of doses of a new booster is “a major policy decision, and you would hope that very serious data would justify doing that.” The bigger problem in the United States, however, is individuals’ refusal to get vaccinated in the first place.
Moore also drew attention to the frenzy around the Beta variant, which “was considered to be quite a scary variant with a high degree of antibody resistance,” which some feared would cause a surge this spring. But it never happened, he said. “Beta was squelched out by Delta. Well, that could happen to omicron.”
Omicron arose in South Africa during a time of low transmission in a less-vaccinated population, he said. However, infection rates in the United States are high, so the more important question is about whether omicron can outcompete Delta, unlike other variants. “And that’s just a complete unknown at the moment,” he said.
A key indicator that is important to monitor would be a surge of vaccinated people in the intensive care unit, he said. Both cases of omicron detected in the United States appear to be mild and are in vaccinated individuals, and though they are only two cases, and Moore doesn’t see a reason to change his behavior yet.
“Let’s try and keep a sense of perspective and react to events, instead of fearing that automatically what we’re going to see is fire and brimstone and hell break out in America,” he said. “We already are facing a delta-driven winter surge that is going to kill another 100,000 to 150,000 Americans.”
Dr. Annie Luetkemeyer, professor of medicine in UCSF’s Division of HIV, Infectious Diseases and Global Medicine, discussed two new oral antivirals in detail: Merck’s Molnupiravir and Pfizer’s Paxlovid.
Molnupiravir, which was named after Thor’s hammer in the “hope that this would end up really being a hammer against covid,” does not appear to be the all-powerful weapon the medical community hoped it would be, Luetkemeyer said.
The drug showed a 30 percent reduction in death or hospitalization compared to the placebo, and was “generally well tolerated,” she said. There is data for several variants, but not omicron.
Though it was approved for use in the United Kingdom for those over 18, and the FDA’s 13-10 vote this week recommended it be approved for emergency authorization use, concern remains about how the antiviral works to inhibit covid.
The drug disrupts SARS-CoV-2’s replication process by causing mutations in the virus’s RNA, but there is fear that the process it uses could cause mutations in human DNA. However, Luetkemeyer said that animal tests have not consistently been associated with worrisome abnormalities, except in pregnant rats, which is why the medication is not approved for pregnant women in the UK.
Luetkemeyer also discussed Paxlovid, another oral antiviral that has been submitted for FDA review. An interim report showed an 85 percent reduction in hospitalization and death for those treated with Paxlovid within five days of the appearance of symptoms. Clinical trial participants, like those in the Molnupiravir study, were not vaccinated against covid.
Experts don’t have a full analysis of data yet and the numbers could change, “but it certainly looks like a very promising trend,” Luetkemeyer said.
On an individual basis, the drugs will game-changers, she said. “Are we going to treat our way out of this as a society? I think the answer to that is: Very, very unlikely.”
Regarding omicron, Luetkemeyer doesn’t “expect there to be a lot of impact” on the new oral antiviral drugs, but certain monoclonal antibodies, molecules created in a lab to treat covid that are administered through an intravenous drip, could be affected.
“All of this is still in the realm of speculation, but it is not outside of what is plausible,” she said.
See our previous Grand Rounds coverage here.