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Thursday, Aug 05, 2021

Pandemic Far From Over: Virus Mutations Add Urgency To Vaccination Effort

Pandemic Far From Over: Virus Mutations Add Urgency To Vaccination Effort

Research findings published in recent days have shown that vaccines will still likely work against mutated variants of the coronavirus.
The road to herd immunity from the coronavirus suddenly looks longer. The emergence of more transmissible, potentially vaccine-evading variants threatens to extend the global health disaster and make 2021 feel too much like 2020. A complicated mix of good news and bad news makes any forecast for the coming months fuzzy, but scientists have one clear and sobering message: The pandemic is a long way from over.

The mutation-laden variants are on the move, and that includes one first identified in South Africa and confirmed in a Baltimore-area adult, Maryland Gov. Larry Hogan, a Republican, said Saturday. It was the third known case in the United States of the variant, following two cases announced Thursday in South Carolina. The person in Maryland had no travel history, which is evidence of community transmission.

Research findings published in recent days have shown that vaccines will still likely work against mutated variants of the coronavirus. But they may not work as well, as the slippery virus continues to adapt to its new host, the human species. Scientists are ramping up genomic surveillance of the virus and vaccine makers are retooling their formulas in an attempt to keep pace with this morphing pathogen.

"We're very worried," said Francis Collins, director of the National Institutes of Health. "All it's going to take is a couple more mutations on top of that, and you're really going to have to start worrying."

There is also the issue of reinfection. Collins said Friday that he is troubled by information from the biotech company Novavax, maker of a vaccine that proved effective in clinical trials, that the new variant circulating in South Africa showed signs of eluding natural immunity among volunteers who had previously survived an infection with the more common coronavirus strain. The Novavax vaccine was strikingly less effective against that variant, called B.1.351, than against other strains.

"That is something I had not seen before," Collins said of the reinfection claim. "It is very tentative, and the numbers are not huge, but I would be alarmed if natural infection . . . is not sufficient to provide immunity."

All three of the most-scrutinized "variants of concern" - first identified in the United Kingdom, South Africa and Brazil - have arrived in the United States. As of midday Saturday there were more than 430 reported cases involving the U.K. variant, B.1.1.7, and one case, in Minnesota, of the Brazil variant, known as P.1., announced by authorities there Monday.

The mutations have complicated and likely extended the timeline for crushing the pandemic. A truism among epidemiologists is that herd immunity from a more transmissible virus requires a higher percentage of immunized people. Early in the pandemic, scientists estimated that around 70% of people would need to be vaccinated or have developed natural immunity to reach the threshold at which the virus would not freely circulate. That number now seems too low.

If a more transmissible strain becomes dominant, "that level of coverage needed for herd immunity would become higher, in the 80 to 85 percent range," Jay Butler, deputy director for infectious diseases at the Centers for Disease Control and Prevention, said Friday.

The latest bulletins about variants and the Novavax results in South Africa "really does make the prospect of herd immunity, at least before next winter, much less likely," said Christopher Murray, director of the University of Washington's Institute for Health Metrics and Evaluation.

The worrisome comments from experts come despite several positive developments on the vaccine front. Johnson & Johnson reported Friday that its one-dose vaccine was 66% effective in a large clinical trial in preventing moderate and severe disease. That vaccine is relatively easy to handle and, if authorized in coming weeks, will be another weapon to fight the pandemic.

Moreover, vaccines appear to work well against the B.1.1.7 variant that has spread explosively in southern England and led to drastic lockdowns.

But the good results come with asterisks. The J&J vaccine did not appear to prevent disease quite as well in South Africa and Latin America - places where problematic variants are spreading. And the Novavax data showed a dramatic drop in effectiveness against the B.1.351 variant circulating in South Africa.

The mutations have not changed the basic nature of the virus. The new variants spread from person to person and sicken people in the same manner as the more common coronavirus. Their spread can be inhibited by the same common-sense measures, like social distancing and mask-wearing.

So far there is limited evidence of changes in disease severity from these variants. The exception is the variant spreading in the United Kingdom, which may be roughly 30% more lethal, British scientists said recently, acknowledging their evidence is preliminary. There is no strong scientific evidence that B.1.351 or P.1, the variants identified in South Africa and Brazil, respectively, cause more severe disease.

Alessandro Sette, an immunologist at the La Jolla Institute for Immunology, also sees hopeful signs of lasting immunity to the virus. A paper he and colleagues published this month showed that post-infection immunity remained robust at eight months. Preliminary results suggest a large fraction of the immune response is mediated by T-cells that are not affected by the variants, he said, and both natural infection and vaccination induce this response.

"They would still be able to modulate disease severity," Sette said, suggesting that people infected a second time would likely have a milder disease.

That said, many scientists are convinced that the variants are more transmissible. They contain mutations that appear to enhance the virus's ability to bind to human receptor cells. One mutation, called E484K, which emerged independently in the variants seen in South Africa and Brazil, has shown signs of eluding antibodies produced either through the natural immune system or therapeutic drugs.

But there are limits to how much a virus can mutate without defanging itself, said Stanley Perlman, a virologist at the University of Iowa.

"It can't keep mutating because it's going to lose the properties of being an all-around transmissible and pathogenic virus," Perlman said. "You don't have an infinite number of ways to make yourself better."

Some scientists expect the punch of the virus will grow weaker over time. That has happened with other viruses, including the influenza virus that killed millions worldwide in 1918.

"We will not be for decades dealing with a pandemic," said epidemiologist Marc Lipsitch, of the Harvard T.H. Chan School of Public Health. "The concern is whether it will be a year or three years until we can make enough vaccines against enough strains to get this under control."

Paul Offit, a virologist and pediatrician at Children's Hospital of Philadelphia, said when he first saw the news about the efficacy of the Johnson & Johnson vaccine against the South African variant, it appeared "grim." But as he dug into the data, he saw that it was much more effective at preventing severe disease.

"If you can keep people out of the hospitals and out of morgues, that is of tremendous value," he said.

No vaccine is 100% effective, and even the flu vaccines are often just 50 to 60% effective, he noted, which is good enough to save countless lives.

The big question is whether SARS-CoV2 will mutate more like measles, also a single strand RNA virus, which has not drifted very far from when the first vaccine was introduced in 1963. Or will it be more like flu, another single-strand RNA virus, which changes so much that the vaccine has to be updated every year.

The mRNA vaccines in general, he said, are relatively easily reconstructed to battle new variants. The holdup is more likely to be the manufacturing and distributionof the retooled vaccines, Offit said.

Peter Marks, the head of the Food and Drug Administration division that oversees vaccines, said Friday that the agency will do what it can to speed the process. It won't require big clinical trials, for instance. Ratherthan studies of tens of thousands of people, the agency will mandate much smaller studies of a few hundred. The goal would be to ensure that the vaccines produce the desired immune response and to see whether the products cover just the new variants or the original virus as well as the new variation, he said.

"We would intend to be pretty nimble with this . . . so that we can get these variants covered as quickly as possible," Marks said on an American Medical Association webinar.

Another issue that could undermine plans to achieve herd immunity is vaccine hesitancy. New polls show that up to a third of the population in the United States is either unsure about getting vaccinated or firmly against it.

Numerous medical centers and first-responder groups have reported that only about half of employees eligible for vaccines have chosen to take them. The 1199 SEIU, the union that represents workers at hospitals, nursing homes and other care facilities in Maryland and the District of Columbia, said that only about 20% of those who work in nursing homes had agreed to get the vaccine. Maryland's acting health secretary said last week that it was a "surprise" that in the first few weeks the uptake in health care and nursing homes was 35 to 50% - rather than the 80 to 90% they expected.

The greater the unvaccinated pool, the greater the playing field for the virus to replicate and mutate, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said at a briefing Friday. "If you stop . . . the replication, viruses cannot mutate," he said, adding that this is the reason "to vaccinate as many people as possible, as quickly as possible."

The urgency of vaccination applies to everyone on the planet, disease experts point out. A mutation in any location will likely spread everywhere - something that happened earlier in the pandemic with a mutation called D614G that appears to have enhanced transmission.

"Vaccine nationalism is very clearly a problem," said Maria Sundaram, an epidemiologist at the University of Toronto. "The allure of being vaccinated and getting to normal is not quite reality because of the new variants and the underserved communities of the world not getting them."

But the alarms come at a time when the public may not be receptive to more dire warnings. As the number of infections and hospitalizations in the United States have dipped since the second week of January, governors and mayors have begun easing restrictions. People are eating indoors in restaurants in places formerly shuttered.

Infectious-disease experts warn that this is not a time to let down our guard.

"We have to understand we are going to live with this virus. That's the new normal," said Karin Michels, an epidemiologist at the University of California at Los Angeles. "I'm never going to sit on a plane for the next few years without being concerned."

She said she remains optimistic that the pandemic will be under greater controlbylate summer or fall if vaccinations continue increasing and community spread of the virus is drastically reduced.

Collins, the NIH director, said he sees best-case and worst-case scenarios.

Best case, he said, is that "people roll up their sleeves as quickly as possible to get to that 80 to 85 percent [vaccination rate] and no other strains emerge that are more resistant."

The worst case is that if people "continue to be irresponsible," more transmissible variants will rip across the country and potentially escape vaccines, treatments and naturally acquired immunity.

And then, he said, "we'd have to redesign a completely new vaccine all over again."
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