Yearlong infection spawned a striking mutation beyond SARS-CoV-2’s spike protein.

Colorized scanning electron micrograph of an apoptotic cell (purple) heavily infected with SARS-CoV-2 virus particles (green), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

A cancer survivor had the longest documented COVID-19 infection. Our lab helped investigate this novel case and was recently interviewed by JENNIFER COUZIN-FRANKEL at

Here’s what we learned:

She (Nussenblatt) asked for help from Elodie Ghedin, a molecular virologist who runs an NIH lab that studies the genomes of SARS-CoV-2 virus from infections. Ghedin and computational biologist Allison Roder sequenced samples from the patient and confirmed the virus had continued to replicate. Then, they compared those sequences with ones from the patient stored 10 months earlier.

“It was the same virus,” Ghedin says. The patient had been infected in 2020 by one of the first versions of SARS-CoV-2, which by early this year was no longer circulating. Samples from later in the infection allowed the team to trace how the virus evolved as her weakened immune system combated it. Nussenblatt, Ghedin, and their colleagues posted a report this month on the preprint server medRxiv and are submitting it for publication.

“There’s very few systematic studies of immune-suppressed patients and how long they continue to shed virus,” says Jonathan Li, an infectious disease specialist at Brigham and Women’s Hospital and Harvard Medical School. “We need to study them so we can help these patients and prevent the virus from mutating further.” With colleagues, Li published a case study in The New England Journal of Medicine about a 45-year-old immune-compromised man infected for about 5 months, who ultimately died of the disease in late summer 2020. “Even now,” Li says, more than 1 year later, “I still find places where that patient has continued to teach us.”

In Li’s patient, the virus developed mutations that are hallmarks of the Alpha, Gamma, and Delta variants of SARS-CoV-2, none of which had yet taken hold in the general population. Immune-suppressed patients “give you a window on how the virus explores the genetic space,” Ghedin says.

In the NIH patient, sequencing revealed two genetic deletions that caught the researchers’ eyes. One was in the RNA that codes for the spike protein, which helps the virus enter cells. Because of the spike protein’s critical role in how SARS-CoV-2 causes infection, mutations in that sequence have garnered a lot of interest. But it was the other that especially struck the team: a large deletion, almost 500 nucleotides out of the virus’ 30,000, that lay outside the spike sequence.

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