New study: COVID-19 is mutating, making antibody immunity and a vaccine more problematic (updated)

1
1658

I happened to catch this segment of The Last Word With Lawrence O’Donnell last night about the “uncertainty” of the current state of COVID-19 research. Dr. Naji Masri from Louisiana State University Medical School has been “keeping a video diary of life and death in New Orleans” for the show.

Dr. Masri reports that “Currently at our hospital we have two patients who were previously diagnosed and treated with COVID-19 and tested negative prior to discharge. They are now back testing positive. That’s scary.” “Now we have proof that what we thought was true immunity may not actually be protective. There’s a lot of people out there who subscribe to the theory that everyone should get this virus and therefore be protected from its effect, the so-called herd immunity theory, which clearly doesn’t hold water if patients like this can get reinfection. There’s other people that believe in immunity passports, that if you have been exposed to the virus that you should be getting a passport to roam around society freely. Well again, that has holes in that theory if patients like these can be reinfected.”

Dr. Masri’s two patients are at least anecdotal evidence that patients can be reinfected with COVID-19. It is possible that the tests the hospital administered were inaccurate. There has been a high rate of false-positive and false-negative tests because these tests have not been properly validated. See, Recovered patients who tested positive for COVID-19 likely not reinfected. Also, Coronavirus: Nobody has caught COVID-19 twice, scientists say.

But there may be another possible explanation. a new study reported in the LA Times raises a new challenge for vaccine researchers: the coronavirus is mutating. The original Wuhan strain is not the strain much of the world is currently infected with today. Scientists say a now-dominant strain of the coronavirus appears to be more contagious than original:

Scientists have identified a new strain of the coronavirus that has become dominant worldwide and appears to be more contagious than the versions that spread in the early days of the COVID-19 pandemic, according to a new study led by scientists at Los Alamos National Laboratory.

The new strain appeared in February in Europe, migrated quickly to the East Coast of the United States and has been the dominant strain across the world since mid-March, the scientists wrote.

In addition to spreading faster, it may make people vulnerable to a second infection after a first bout with the disease, the report warned.

The 33-page report was posted Thursday on BioRxiv, a website that researchers use to share their work before it is peer reviewed, an effort to speed up collaborations with scientists working on COVID-19 vaccines or treatments. That research has been largely based on the genetic sequence of earlier strains and might not be effective against the new one.

The mutation identified in the new report affects the now infamous spikes on the exterior of the coronavirus, which allow it to enter human respiratory cells. The report’s authors said they felt an “urgent need for an early warning” so that vaccines and drugs under development around the world will be effective against the mutated strain.

Wherever the new strain appeared, it quickly infected far more people than the earlier strains that came out of Wuhan, China, and within weeks it was the only strain that was prevalent in some nations, according to the report. The new strain’s dominance over its predecessors demonstrates that it is more infectious, according to the report, though exactly why is not yet known.

The coronavirus, known to scientists as SARS-CoV-2, has infected more than 3.5 million people around the world and caused more than 250,000 COVID-19 deaths since its discovery late last year.

The report was based on a computational analysis of more than 6,000 coronavirus sequences from around the world, collected by the Global Initiative for Sharing All Influenza Data, a public-private organization in Germany. Time and again, the analysis found the new version was transitioning to become dominant.

The Los Alamos team, assisted by scientists at Duke University and the University of Sheffield in England, identified 14 mutations. Those mutations occurred among the nearly 30,000 base pairs of RNA that other scientists say make up the coronavirus’s genome. The report authors focused on a mutation called D614G, which is responsible for the change in the virus’ spikes.

“The story is worrying, as we see a mutated form of the virus very rapidly emerging, and over the month of March becoming the dominant pandemic form,” study leader Bette Korber, a computational biologist at Los Alamos, wrote on her Facebook page. “When viruses with this mutation enter a population, they rapidly begin to take over the local epidemic, thus they are more transmissible.”

While the Los Alamos report is highly technical and dispassionate, Korber expressed some deep personal feelings about the implications of the finding in her Facebook post.

“This is hard news,” wrote Korber, “but please don’t only be disheartened by it. Our team at LANL was able to document this mutation and its impact on transmission only because of a massive global effort of clinical people and experimental groups, who make new sequences of the virus (SARS-CoV-2) in their local communities available as quickly as they possibly can.”

* * *

The report contains regional breakdowns of when the new strain of virus first emerged and how long it took to become dominant.

Italy was one of the first countries to see the new virus in the last week of February, almost at the same time that the original strain appeared. Washington was among the first states to get hit with the original strain in late February, but by March 15 the mutated strain dominated. New York was hit by the original virus around March 15, but within days the mutant strain took over. The team did not report results for California.

Scientists at major organizations working on a vaccine or drugs have told The Times that they are pinning their hopes on initial evidence that the virus is stable and not likely to mutate the way influenza virus does, requiring a new vaccine every year. The Los Alamos report could upend that assumption.

If the pandemic fails to wane seasonally as the weather warms, the study warns, the virus could undergo further mutations even as research organizations prepare the first medical treatments and vaccines. Without getting on top of the risk now, the effectiveness of vaccines could be limited. Some of the compounds in development are supposed to latch onto the spike or interrupt its action. If [vaccines] were designed based on the original version of the spike, they might not be effective against the new coronavirus strain, the study’s authors warned.

“We cannot afford to be blindsided as we move vaccines and antibodies into clinical testing,” Korber wrote on Facebook. “Please be encouraged by knowing the global scientific community is on this, and we are cooperating with each other in ways I have never seen … in my 30 years as a scientist.”

David Montefiori, a Duke University scientist who worked on the report said it is the first to document a mutation in the coronavirus that appears to make it more infectious.

Although the researchers don’t yet know the details about how the mutated spike behaves inside the body, it’s clearly doing something that gives it an evolutionary advantage over its predecessor and is fueling its rapid spread. One scientist called it a “classic case of Darwinian evolution.”

“D614G is increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread,” the study said.

Still unknown is whether this mutant virus could account for regional variations in how hard COVID-19 is hitting different parts of the world.

In the United States, doctors had begun to independently question whether new strains of the virus could account for the differences in how it has infected, sickened and killed people, said Alan Wu, a UC San Francisco professor who runs the clinical chemistry and toxicology laboratories at San Francisco General Hospital.

Medical experts have speculated in recent weeks that they were seeing at least two strains of the virus in the U.S., one prevalent on the East Coast and another on the West Coast, according to Wu.

“We are looking to identify the mutation,” he said, noting that his hospital has had only a few deaths out of the hundreds of cases it has treated, which is “quite a different story than we are hearing from New York.”

The Los Alamos study does not indicate that the new version of the virus is more lethal than the original. People infected with the mutated strain appear to have higher viral loads. But the study’s authors from the University of Sheffield found that among a local sample of 447 patients, hospitalization rates were about the same for people infected with either virus version.

Even if the new strain is no more dangerous than the others, it could still complicate efforts to bring the pandemic under control. That would be an issue if the mutation makes the virus so different from earlier strains that people who have immunity to them would not be immune to the new version.

If that is indeed the case, it could make “individuals susceptible to a second infection,” the study authors wrote.

It’s possible that the mutation changes the spike in some way that helps the virus evade the immune system, said Montefiori, who has worked on an HIV vaccine for 30 years. “It is hypothetical. We are looking at it very hard.

This new study undercuts the assumption that antibodies provide partial or total immunity from contracting COVID-19 again. I pointed out in an earlier post, WHO warning: ‘no evidence’ antibodies from COVID-19 protect from a second infection (excerpt):

There are a number of problems with this assumption. First, Coronaviruses are a large family of enveloped RNA viruses which include severe acute respiratory syndrome (SARS) (2002), Middle East respiratory syndrome (MERS) (2012), or coronavirus disease 19 (COVID-19) (2019). To date, there are no known treatments and no vaccine for these RNA viruses. How do SARS and MERS compare with COVID-These RNA viruses have not proven readily susceptible to the development of a vaccine, so the repeated public assertions that a vaccine may be available in as soon as 18 months is just false hope happy talk. (The mumps vaccine—considered the fastest ever approved—took four years to develop and adequately test for safety before approval for use).

* * *

Finally, the assumption that the presence of antibodies grants immunity to infection is now in doubt. WHO Warns You May Catch Coronavirus More Than Once:

Catching Covid-19 once may not protect you from getting it again, according to the World Health Organization, a finding that could jeopardize efforts to allow people to return to work after recovering from the virus.

“There is currently no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection,” the United Nations agency said in an April 24 statement.

The WHO guidance came after some governments suggested that people who have antibodies to the coronavirus could be issued an “immunity passport” or “risk-free certificate” that would allow them to travel or return to work, based on the assumption that they were safe from re-infection, according to the statement. People issued such a certificate could ignore public-health guidance, increasing the risk of the disease spreading further.

* * *

While there’s a consensus that the key to ending the coronavirus pandemic is establishing co-called herd immunity, there are many unknowns. One is whether researchers can develop a safe and effective vaccine. Another is how long people who’ve recovered have immunity; reinfection after months or years is common with other human coronaviruses. Finally, it’s not clear what percentage of people must be immune to protect the “herd.” That depends on the contagiousness of the virus.

The WHO said it’s reviewing the scientific evidence on antibody responses to coronavirus, but as yet no study has evaluated whether the presence of antibodies “confers immunity to subsequent infection by this virus in humans.” And while many countries are currently testing for antibodies, these studies aren’t designed to determine whether people recovered from the disease acquire immunity, the agency said.

Again, scientists have not successfully developed an antibody treatment or vaccine for the family of enveloped RNA viruses which include severe acute respiratory syndrome (SARS) (2002), Middle East respiratory syndrome (MERS) (2012), or coronavirus disease 19 (COVID-19) (2019).

Even if scientists do eventually succeed in developing a vaccine for a known strain of COVID-19, we now know that the virus is one that mutates, similar to the flu virus. The vaccine may not be effective against a new mutation strain of the virus. This virus is going to be with us for a long time.

UPDATE: Demonstrating the “uncertainty” that exists in coronavirus research, some infectious disease experts are now questioning the non-peer reviewed research from the scientists at Los Alamos Laboratory. The Problem With Stories About Dangerous Coronavirus Mutations (excerpt):

The paper has not yet been formally published or reviewed by other scientists. But on May 5, the Los Angeles Times wrote about it, claiming that “a now-dominant strain of the coronavirus could be more contagious than [the] original.” That story quickly went … well … viral.

But “the conclusions are overblown,” says Lisa Gralinski of the University of North Carolina, who is one of the few scientists in the world who specializes in coronaviruses. “To say that you’ve revealed the emergence of a more transmissible form of SARS-CoV-2 without ever actually testing it isn’t the type of thing that makes me feel comfortable as a scientist.” She and other virologists I’ve spoken with who were not involved in the Los Alamos research agree that the paper’s claims are plausible, but not justified by the evidence it presents. More important, they’re not convinced different strains of the coronavirus exist at all.

“We have evidence for one strain,” says Brian Wasik at Cornell University.

“I would say there’s just one,” says Nathan Grubaugh at Yale School of Medicine.

“I think the majority of people studying [coronavirus genetics] wouldn’t recognize more than one strain right now,” says Charlotte Houldcroft at the University of Cambridge.

Everyone else might be reasonably puzzled, given that news stories have repeatedly claimed there are two, or three, or even eight strains. This is yet another case of confusion in a crisis that seems riddled with them.

For a lengthy scientific explanation, read the full article.




1 COMMENT

  1. Bloomberg reports that scientists have created a monoclonal antibody that has neutralized the coronavirus in cell cultures. “Scientists Create Antibody That Defeats Coronavirus in Lab”, https://www.bloomberg.com/news/articles/2020-05-04/scientists-create-antibody-that-defeats-coronavirus-in-lab

    While that’s early in the drug development process — before animal research and human trials — the antibody may help prevent or treat Covid-19 and related diseases in the future, either alone or in a drug combination, according to a study published Monday in the journal Nature Communications.

    More research is needed to see whether the findings are confirmed in a clinical setting and how precisely the antibody defeats the virus, Berend-Jan Bosch of Utrecht University in the Netherlands and colleagues wrote in the paper.

    The antibody known as 47D11 targets the spike protein that gives the new coronavirus a crown-like shape and lets it enter human cells. In the Utrecht experiments, it didn’t just defeat the virus responsible for Covid-19 but also a cousin equipped with similar spike proteins, which causes Severe Acute Respiratory Syndrome, or SARS.

Leave a Reply