A team of four doctors, experts in infectious diseases at Johns Hopkins University School of Medicine, are sounding a warning about Americans who remain most vulnerable to COVID-19 -- those with existing health conditions or the immunosuppressed.

They can harbor what the doctors call “evolving viral swarms” and could produce even more harmful variants of the coronavirus that would undermine the nation’s and the world’s efforts to break out of the 2-year-old pandemic.

The doctors, with expertise in virology and immunology, are Ashwin Balagopal, Andrew Karaba, Olivia Kates and Stuart Ray. They are speaking out about this particular concern.

Q. We’ve heard a lot about the risks that people with existing health conditions continue to face in the pandemic. Are they vulnerable even after vaccination?

Kates: Despite vaccinations, immunosuppressed people are at increased risk of severe COVID-19, complications from COVID-19, breakthrough infections and death. And their unique susceptibility to infection might explain the emergence of viral variants.

Q. How so? Let’s go over that.

Kates: The immune system has numerous tools to fight viruses: B cells produce antibodies that bind and neutralize infectious virus particles, and T cells recognize and kill virus-infected cells. In people with healthy immune systems, the replication of the coronavirus that causes COVID-19 appears to stop within about two weeks, when the B and T cells engage against the virus. But it’s a different story for people with immunosuppression that hampers B or T cells.

Q. These are people who’ve had other debilitating diseases and conditions, right?

Karaba: Right. They are less able to control coronavirus infection. The virus can replicate longer and more prolifically, persisting for months and accumulating genetic changes in an increasingly diverse swarm of offspring. An impaired immune response will still pick off many members of the swarm. But some members of the swarm are able to evade antibodies or T cells. They will escape and propagate. Therefore, in people with impaired immune systems, the coronavirus could evolve toward increasingly immune-resistant variants. That might be how omicron emerged. In these diverse swarms, the coronavirus could also undergo recombination.

Q. Let’s stop here for an explanation. What is recombination?

Ray: It’s when fragments of genetic material get swapped between two similar but not identical genomes, and that produces large and abrupt genetic changes. It’s believed to be what caused four influenza pandemics between 1918 and 2009 -- the shuffling of influenza’s genomic segments, most likely in waterfowl.

Q. And this happens in people with existing health conditions?

Ray: People with healthy immune systems are infected too briefly for recombination. But an immunosuppressed person might be infected for long enough with one variant to be exposed to a second one, allowing the two to coexist possibly in the same cell. Recombination between these two variants in one person could produce a new hybrid that could then be passed on to someone else.

Q. I assume you and your colleagues have seen this movie before.

Ray: The earliest COVID-19 coronavirus genomes bear evolutionary signatures of recombination. At least one ancestor of the virus emerged from recombination of two related coronaviruses. This might have been the evolutionary leap that enabled the virus to cross into humans. If more recombinations happen in humans, they’re most likely to occur in immunosuppressed people. A recombinant variant would not only endanger the vulnerable people carrying the infection, but it could also jeopardize our whole vaccination strategy.

Q. So, what do you and your colleagues think should be done about this?

Balagopal: We could borrow an idea from doctors who treat other infections like HIV and hepatitis C. For these viruses, doctors use a combination of antiviral drugs that rapidly reduce a patient’s viral burden. Just to note: They’ve found that using single antivirals can result in resistant variants. … So, in the cases of the coronavirus, we think antiviral clinical trials, combining medications, should be prioritized for immunosuppressed patients.

Q. Have you and your colleagues at Hopkins treated people this way?

Karaba: We have cared for many immunosuppressed patients with ongoing coronavirus replication for more than a month. In several of these patients, eliminating the virus required a combination of monoclonal antibodies and the first FDA-approved antiviral, remdesivir.

Q. Considering the threat of variants, this sounds pretty important.

Ray: The pandemic is ongoing despite major advances in the biomedical fight against the virus. The big worry about variants would be any that escape vaccine protection. That would require significant evolutionary change, and that’s what we’re talking about -- that’s the kind of change possible with recombination. So, we should be funding cooperative clinical trials of combination antivirals in immunosuppressed people. If not, we may fall short of the full potential of our biomedical advances, and we’ll remain just as vulnerable as the most vulnerable among us.


Dan Rodricks
Dan Rodricks is a longtime columnist for the Baltimore Sun. -- Ed.

(Baltimore Sun / Tribune Content Agency)