U.K. variant puts spotlight on immunocompromised patients’ role in the COVID-19 pandemic

Science Mag:

In June, Ravindra Gupta, a virologist at the University of Cambridge, heard about a cancer patient who had come into a local hospital the month before with COVID-19 and was still shedding virus. The patient was being treated for a lymphoma that had relapsed and had been given rituximab, a drug that depletes antibody-producing B cells. That made it hard for him to shake the infection with SARS-CoV-2.

Gupta, who studies how resistance to HIV drugs arises, became interested in the case and helped treat the patient, who died in August, 101 days after his COVID-19 diagnosis, despite being given the antiviral drug remdesivir and two rounds of plasma from recovered patients, which contained antibodies against the virus.

When Gupta studied genome sequences from the coronavirus that infected the patient, he discovered that SARS-CoV-2 had acquired several mutations that might have allowed it to elude the antibodies.

Now, his analysis, reported in a preprint on medRxiv earlier this month, has become a crucial puzzle piece for researchers trying to understand the importance of B.1.1.7, the new SARS-CoV-2 variant first found in the United Kingdom. That strain, which appears to spread faster than others, contains one of the mutations that Gupta found, and researchers believe B.1.1.7, too,

[They believe it] may have originated in an immunocompromised patient who had a long-running infection. “It’s a perfectly logical and rational hypothesis,” says infectious disease scientist Jeremy Farrar, director of the Wellcome Trust.

Scientists are still trying to figure out the effects of the mutations in B.1.1.7, whose emergence led the U.K. government to tighten coronavirus control measures and other countries in Europe to impose U.K. travel bans.

But the new variant, along with research by Gupta and others, has also drawn attention to the potential role in COVID-19 of people with weakened immune systems. If they provide the virus with an opportunity to evolve lineages that spread faster, are more pathogenic, or elude vaccines, these chronic infections are not just dangerous for the patients, but might have the potential to alter the course of the pandemic.

It’s still very unclear whether that is the case, but Farrar believes it’s important to ensure doctors take extra precautions when caring for such people: “Until we know for sure, I think, treating those patients under pretty controlled conditions, as we would somebody who has drug resistant tuberculosis, actually makes sense.”

Researchers’ concern mostly focuses on cancer patients being treated for chemotherapy and similar situations. “We don’t yet know about people who are immunocompromised because of HIV, for instance,” Farrar says.

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People with a weakened immune system may give the virus the opportunity to evolve, Gupta’s data show.

More evidence comes from a paper published in The New England Journal of Medicine on 3 December that described an immunocompromised patient in Boston infected with SARS-CoV-2 for 154 days before he died. Again, the researchers found several mutations, including N501Y.

“It suggests that you can get relatively large numbers of mutations happening over a relatively short period of time within an individual patient,” says William Hanage of the Harvard T.H. Chan School of Public Health, one of the authors. (In patients who are infected for a few days and then clear the virus, there simply is not enough time for this, he says.) When such patients are given antibody treatments for COVID-19 late in their disease course, there may already be so many variants present that one of them is resistant, Goldstein says.

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