Virus Variants Doubtless Advanced Inside Folks With Weak Immune Programs

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The version of the coronavirus that surfaced in the UK late last year was shocking for many reasons. It just came when vaccines were giving a glimpse into the end of the pandemic and threatening to destroy those hopes. It was far more contagious than previous variants, resulting in a rapid increase in hospital stays. And perhaps the most surprising for scientists: a large constellation of mutations had apparently accumulated overnight.

A coronavirus usually gains mutations at a slow but steady pace of around two per month. This variant, known as B.1.1.7, had acquired 23 mutations that were not on the virus that was first identified in China. And 17 of these had evolved at once, some time after it had deviated from its youngest ancestor.

Experts said there is only one good hypothesis for this: at some point, the virus must have infected someone with a weak immune system so that it can adapt and develop in the person’s body for months before it is passed on to others. “It seems like the most likely explanation,” said Dr. Ravindra Gupta, a virologist at Cambridge University.

If so, the idea has implications for vaccination programs, especially in countries that have not yet started immunizing their populations. People with weakened immune systems – like cancer patients – should be among the first to be vaccinated, said Dr. Adam Lauring, virologist and infectious disease doctor at the University of Michigan. The faster this group is protected, the lower the risk that their bodies will become incubators for the world’s next charged mutant.

“We should literally and figuratively do our best to protect this population,” said Dr. Lauring.

That could be complicated, he added. For the same reason that these people don’t develop a strong immune response to the virus, vaccines may not work well for them. Therefore, they may need to be treated with monoclonal antibody cocktails as well, he said.

Like other viruses, the coronavirus collects mutations every time it replicates. The vast majority of these genetic disorders are minor and transitory. In most people, active infection only lasts about a week, not long enough for the virus to acquire more than one notable mutation, if any.

Mutations that make the coronavirus more contagious or allow it to evade the immune system are extremely rare, researchers reported in a study published in Science magazine last week. “But if they occur and can be transmitted, it’s open season right now,” said Katrina Lythgoe, an evolutionary biologist at Oxford University who led the study.

The virus can string several such mutations together over a period of months to years. Scientists can observe this slow evolution with the help of a molecular “clock” that tracks changes over time. However, in a person with a weak immune system, this timeline can be sped up significantly.

Several studies have shown that in some people with compromised immune systems, the virus can persist for more than eight months, providing ample time and opportunity to develop further.

Updated

March 15, 2021, 10:30 p.m. ET

“If we look at several points in time during this course of the infection and look at the virus population in this patient, we see each time that different variants come up with a high rate of fluctuation,” said Vincent Munster, virologist at the National Institute for Allergies and Infectious Diseases, one of the Conducted studies.

If one of these variants, which has received important mutations, is passed on to another person, it can spread rapidly through the population and appear to have come out of nowhere – as in the case of the variant that walled Britain and perhaps others that did identified in South Africa and Brazil.

“That’s a pretty decent hypothesis that they came from people with persistent infections,” said Dr. Lythgoe about the variants. “By keeping infection rates low, you reduce the number of immunocompromised people who are infected and reduce the likelihood of them occurring.”

“Immunocompromised” is a nebulous term that encompasses a wide range of diseases – from diabetes and rheumatoid arthritis to leukemia and lymphoma – and experts have disagreed on which diseases can lead to variants.

Some say the list should include the elderly as well as those taking drugs that suppress the immune system and anyone who doesn’t produce a robust set of antibodies.

“We learned from the vaccines that antibodies are important,” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh. “It is very important to keep tabs on people who are immunocompromised and do not have a fully functioning immune system.”

Dr. Lauring said he was most concerned about people with blood-related cancers like leukemia, but didn’t have serious concerns about taking drugs like Humira or Enbrel, which are used to treat rheumatoid arthritis.

“It’s another type of immunosuppression that I’m not sure would cause, but nobody really knows,” he said.

Some people with weak immune systems are known to transmit other viruses for long periods of time, noted Dr. Lauring. A man in England has rejected poliovirus for at least 28 years. Others had persistent norovirus or influenza infections.

“We’ve been looking into it for a long time,” he said. “But just like everything at Covid, we deal with it on a large scale.”

He and the other experts stressed that regardless of the risks, it is important not to stigmatize or blame people who have weakened immune systems. Instead, the focus should be on limiting exposure to the virus.

“Let’s get the vaccines into people, let’s distance ourselves well, let’s mask well,” said Dr. Duprex. “Anything we can do to stop the virus from spreading is really, really important.”