Omicron forces us to rethink COVID-19 testing and treatments
By Tina Hesman Saey and Laura Sanders
New year, new variant. As 2022 gets under way, omicron, a fast-moving version of the virus that causes COVID-19, is well into its march across the world. As of January 11, a record-breaking total of 145,982 people were hospitalized in the United States with confirmed or suspected COVID-19. And hundreds of thousands of people are catching the coronavirus every day.
“There’s a lot of activity right now in the [United States], and we’re seeing that in terms of these astronomical numbers of new cases,” says infectious disease physician Preeti Malani of the University of Michigan in Ann Arbor. “Omicron is keeping us busy.”
Omicron’s unique biology is leading to headaches for both testing and treatments designed to keep people out of hospitals. Researchers are racing to understand omicron and this new phase of the pandemic (SN: 12/21/21). Answers can’t come soon enough.
The variant is more transmissible than previous versions of the coronavirus. Compared with delta, omicron is 160 percent to 200 percent more transmissible, one preliminary study from researchers in Germany and the United Kingdom estimates. That’s mainly because omicron replicates itself in the body and sickens people faster than delta. With delta, it takes about four days after infection for symptoms to appear. Omicron produces symptoms in about three days, researchers have learned from outbreaks in Oslo and Nebraska.
Fortunately, omicron seems less likely than previous versions of the coronavirus to cause deep lung infections that lead to serious complications, such as admissions to intensive care units, intubation and death. But the surge of cases means that vulnerable people, including the unvaccinated, immunocompromised, elderly and those with underlying health conditions, are still landing in hospital beds.
“Health care systems are really under stress,” Malani says.
The key to heading off collapse of health care systems is to prevent people from needing to visit emergency rooms and be admitted to the hospital in the first place. Testing and isolation of infected people has helped to stem the tide of previous waves of infection, but omicron is spreading quickly and tests of all kinds are in short supply. And as quick as rapid tests are, they may not catch someone with omicron before they become infectious. What’s more, some treatments, such as laboratory-made monoclonal antibodies, aren’t as effective against omicron as they were against other variants. Other treatments, including new antiviral pills, are scarce.
“It’s going to be a rough couple weeks for sure, and maybe longer,” Malani says.
Here’s a look at some of the challenges that omicron presents for testing and treatment.
Daily PCR testing and rapid antigen tests have helped many employers nip outbreaks in the bud by identifying infected employees and isolating them before they could pass the virus on to others, says Blythe Adamson, an infectious disease epidemiologist and economist. She founded Infectious Economics, a New York City–based company that helps businesses devise strategies to limit disease spread in workplaces.
But omicron has hampered those efforts. In a study conducted in December during the ongoing omicron surge, Adamson and colleagues tested people at five workplaces in New York City, Los Angeles and San Francisco with PCR tests that gave answers within eight hours. “This population was 100 percent vaccinated.… And they were highly boosted, so they were doing all the right things,” Adamson says. Yet employees were still getting infected and spreading the virus.
At the workplaces, “omicron outbreaks looked really different than delta outbreaks were looking before,” she says. “While daily PCR testing previous to omicron worked really well to pick up cases before they were infectious, we started noticing [with omicron] that people were slipping through the cracks. Transmissions were happening faster. People were becoming infectious faster and spreading it to other people.”
So rapid antigen tests were added to the mix. Even after finding a positive test, the researchers continued testing the employees daily, adding an unprecedented look at COVID-19 infections in the early stages and allowing the researchers to determine whether rapid antigen tests are still good for pinpointing when people with COVID-19 are infectious to others.
A few weeks ago, rapid antigen tests were considered quite good at saying whether a person is able to infect others, answering the question, “Are you infectious now?” (SN: 12/17/21). But new evidence from Adamson’s group and a study conducted at a walk-up test site in San Francisco calls that past stellar performance into question. “I’m no longer confident that that negative is as meaningful as it was two weeks ago,” says Bob Wachter, chair of the department of medicine at the University of California, San Francisco.
The trouble seems to be at the front end of an infection.
Adamson’s group found that on the first two days of infection, PCR tests, which detect viral RNA, diagnosed infections that the rapid antigen tests didn’t. That’s not unusual. In fact, in previous COVID-19 outbreaks with other variants, Adamson relied on PCR tests to catch infections before they became contagious. But in 28 of 30 omicron infections in the study, people were producing infectious levels of the virus, but the nasal swabs with rapid antigen tests weren’t picking up the contagious cases. In fact, in four verified instances, people who had negative rapid antigen tests spread the virus to others, Adamson and colleagues report January 4 at medRxiv.org. That work has not yet been peer reviewed by other scientists.
It matches other results, however. At a San Francisco walk-up testing site, the BinaxNOW rapid antigen test made by Abbott was able to pick up cases in which people had high levels of virus. But the test didn’t do as well when people were on the threshold of infectiousness, researchers at Unidos en Salud, a community partnership with academic institutions including UCSF, the Chan Zuckerberg Biohub and the University of California, Berkeley, report in a January 10 preprint posted at medRxiv.org.
One of the characteristics emerging about omicron specifically is where it lives in the body. Compared with previous variants, omicron seems to be more abundant in some upper respiratory areas, such as the throat, than in the nose, at least in the early days of an infection. That locale means that a nose swab may be missing omicron early on, before viral levels are high.
Adamson’s group found that in the first two days of infection, saliva swabs were better than nasal swabs at picking up infectious cases. By day three, particularly if people had symptoms, there was no difference in the ability of rapid antigen tests to detect the infection, regardless if the swab came from saliva or the nose, Adamson says. That bolsters preliminary evidence in a study from Hong Kong that found that saliva swabs are better for detecting omicron than nasal swabs are. That study appeared December 24 at medRxiv.org. It also has not been vetted by other scientists.
Recently, Wachter’s son had COVID-19 symptoms but tested negative on a standard home nose-swab test. Given the symptom list, Wachter wasn’t convinced. He planned to swab his son’s throat next. “As I think about going down to test my son this morning, I think I am going to stick it in his mouth before I stick it in his nose, which is kind of gross,” Wachter told Science News. He did anyway, and sure enough, that test was positive.
Available home tests haven’t been approved for this use, though, and the throat move isn’t endorsed by test makers or the U.S. Food and Drug Administration. In a January 8 tweet, the agency wrote, “Please don’t go sticking that #COVID19 testing swab down your throat.”
Also, says Joshua Gans, an economist at the University of Toronto who has been studying COVID-19 testing, “It’s difficult to swab your own throat because you have to swab where your tonsils are.” Not to mention that many people have a gag reflex when their throats are swabbed. Nevertheless, throat swabbing followed by swabbing the nose with that same cotton swab is recommended in the United Kingdom for rapid testing.
Eating or drinking before doing a throat swab may produce false positives on some rapid antigen tests, but has no effect on nasal swabs, researchers reported in October in Microbiology Spectrum. But, overall, false positives from antigen tests are rare, Gans and colleagues report January 7 in JAMA. Of course, that was with nasal swabs. The researchers didn’t test throat swabbing.
“The antigen tests aren’t perfect,” Malani says. “But they are pretty specific. If it’s positive, you’re positive.”
The problem now comes if you test negative on a rapid antigen test. With omicron, you can no longer be sure you’re not infectious, Adamson says. “You would not want to right now with omicron have a 300-person wedding where you test everyone with a rapid antigen. With the prevalence of omicron in the community, you would absolutely have a superspreading event.”
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Just as with previous versions of the virus, most people who are sick with omicron will recover on their own at home with standard hunker-down advice: Rest, fluids and fever-reducing medicine. But some people need more medical help, and omicron has changed that process. With omicron cases flooding hospitals and doctors’ offices, treatments are essential to prevent serious disease.
At first glance, help is at hand. In late December, two new oral pills were authorized by the FDA: molnupiravir from Merck and Paxlovid made by Pfizer. Both drugs and the antiviral drug remdesivir were designed to stop coronaviruses from copying themselves in the body. All three seem to hold up against omicron in lab tests, researchers reported in a preprint posted December 28 at bioRxiv.org, but there are no data yet to suggest how the drugs work in the real world, especially against the fast-moving variant.
Molnupiravir drops a person’s risk of hospitalization by about 30 percent (SN: 12/2/21). But because the drug works by introducing genetic mutations in viral RNA, there’s a chance molnupiravir might cause mutations in human genes too. That makes it an especially risky choice for women who are pregnant or might become pregnant, says Katherine Seley-Radtke, a medicinal chemist at the University of Maryland, Baltimore County. Lab animal studies have shown that high doses or prolonged use of the drug may cause genetic mutations or developmental problems in fetuses. There have been no long-term studies of molnupiravir’s effect on people.
Other antivirals have their own issues. Remdesivir is approved for use in hospitalized people, but recent evidence has suggested it can help high-risk people stay out of the hospital too, researchers reported December 22 in the New England Journal of Medicine. Remdesivir blocks viral replication by inserting a dummy RNA building block that stops RNA copying. The problem with that drug is that it must be given intravenously, though its maker, Gilead Sciences, is reportedly working on pill and inhaled forms of remdesivir.
Remdesivir has another drawback in that it has to be converted in the body to its active form. That works better for some people than others, and can affect how well the drug can keep the coronavirus in check, Seley-Radtke says.
For some people, the best choice for treatment may be Pfizer’s new antiviral pill. In clinical trials, Paxlovid, a combination medication which blocks a protein-cutting enzyme that the coronavirus needs to replicate itself, reduced hospitalization and death in high-risk people by 88 percent. It does not have the mutation concerns associated with molnupiravir, but it might introduce problems when given to people taking other drugs.
That’s because Paxlovid also contains a drug called ritonavir. Ritonavir blocks the action of enzymes that break down drugs, keeping levels of the virus inhibitor in the body high so that it can fight the virus. But those enzymes that ritonavir inhibits also process other drugs, so people might accidentally overdose on their other medications. Doctors and pharmacists need to keep a close eye out for such drug interactions when prescribing Paxlovid to patients, Seley-Radtke says.
There is a bigger hurdle for Paxlovid, though. There isn’t enough of it to go around, especially as hospitalizations surge. “It’s a classic situation of scarcity,” Wachter says. At UCSF, “we have a fair amount of the Merck drug. We have very little of Paxlovid,” he says.
“If I have a choice, the Pfizer drug seems like it’s better in every regard, better efficacy and easier to take,” Wachter says. “But for now, we are highly rationing it.” Many of the people who need the treatment the most are unvaccinated – a situation that “raises a whole bunch of moral questions, that they would jump ahead of the line of someone who made a better choice,” Wachter says. This rationing framework is “a hard thing to get your arms around, but not inconsistent with the way we do the rest of medicine,” hehe says. “We don’t treat a lung cancer patient differently depending on whether they smoked.”
Another hurdle for the antiviral drugs is that they work best if given very early in the infection, ideally within three days of symptoms starting. But omicron replicates faster than delta or other previous versions of the virus, perhaps making the window for treatment even shorter, Seley-Radtke says.
It’s unclear what that accelerated timeline means for another class of treatments, monoclonal antibodies. Omicron’s highly mutated spike protein is missing many of the targets that some monoclonal antibodies aim for. Two of the three monoclonal antibody treatments that have been authorized for use in the United States seem to falter with omicron. Of the three, only one, called sotrovimab, seems to incapacitate omicron’s spike protein. Derived from a person who survived a SARS-CoV infection in 2003, sotrovimab still recognizes omicron’s mutated spike protein and disarms it, laboratory tests suggest. That study, posted December 15 at medRxiv.org, has not been reviewed by other scientists.
But sotrivimab is exceedingly hard to get at the moment, Malani and Wachter say. “We basically have none, so that’s not on the list right now,” Wachter says. That scarcity and others “make the promise of these drugs potentially more theoretical than real,” he says.
Over time, COVID-19 tests and treatments will become more plentiful. The U.S. government has pledged to distribute half a billion rapid tests in the coming weeks, for instance. But omicron isn’t waiting.
“We’re stuck with now and the next month being quite horrible,” Wachter says. And as promising as some tests and treatments seem to be, logistics can still foil the plans. “Can I get a test? Can I find a doctor? Can I get a prescription? Does the pharmacy have the medicine?” Wachter says. “And all of those are like ‘No. No. Maybe. Keep calling back. Try a different pharmacy.’ In real life, this is all very hard.”
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