Scientists have just reported what's believed to be the longest-known COVID-19 infection, and it carries a warning for us all.
The case, reported by infectious disease specialists at the Amsterdam University Medical Center in The Netherlands, describes a now-deceased 72-year-old immunocompromised man who had COVID-19 for 613 days – so long the virus evolved into a new immune-evasive variant inside his body.
The man had received multiple COVID-19 vaccinations but his immune system had failed to mount a sufficiently protective response against the virus, which often happens in older people and immunocompromised individuals.
It's a good reminder of why we all stand to benefit from protecting each other --particularly the immunocompromised – from COVID-19 and other viral infections. People with weakened immune systems are at much greater risk of falling severely ill with COVID-19 and up to 13 times more likely to be hospitalized, even when triple vaccinated.
As this case shows, immune systems weakened by illness or suppressed by treatment also struggle to clear existing infections. The man previously had a stem cell transplant and later developed lymphoma, requiring treatment that destroyed the white cells responsible for producing virus-neutralizing antibodies.
"The duration of SARS-CoV-2 infection in this described case is extreme, but prolonged infections in immunocompromised patients are much more common compared to the general community," Amsterdam University Medical Center medical student Magda Vergouwe and colleagues said in a statement.
Vergouwe and her team will present the case at the 2024 European Society of Clinical Microbiology and Infectious Diseases Global Congress later this month. With their findings yet to be peer-reviewed, less detail has been shared about this case than previous reports of persistent COVID-19 infections that also lasted hundreds of days.
In those cases, doctors were able to select the right therapy for patients based on the specific variant of SARS-CoV-2 they had, confirmed by repeated genetic sequencing of the virus. For some infections, doctors avoided antibody therapies that newer variants had rendered ineffective in favor of other treatments, which ultimately helped their patients clear the virus.
The man in this current case was not so fortunate. He died in October 2023, some 20 months after contracting COVID-19, not from the virus but because his lymphoma had returned.
Routine genomic surveillance revealed the man was initially infected in February 2022 with the Omicron BA.1.17 variant. But within weeks of treatment, the virus mutated to become resistant to sotrovimab, a neutralizing antibody therapy.
Ever since scientists first started mapping out the genetic sequences of different SARS-CoV-2 variants, we've known this virus to be a shapeshifter that evades the immune system and thwarts treatments (but much slower than influenza does).
All told, genomic sequencing of 27 nasal and throat swabs collected between February 2022 and September 2023 showed the man's virus had accumulated an extra 50 mutations compared to Omicron BA.1 variants circulating at the time. This included deletions in one end of the SARS-CoV-2 spike protein, suggesting the virus could escape the immune system.
"This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals as unique SARS-CoV-2 viral variants may emerge due to extensive intra-host evolution," Vergouwe and colleagues write in their case summary.
"We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections given the potential public health threat of possibly introducing viral escape variants into the community."
No such transmission of the man's highly mutated variant to others in the community was documented or observed, the researchers said.
Transmissions of mutated infections have occurred in a handful of other cases, according to Massachusetts General Hospital infectious disease physician Jacob Lemieux who published a study earlier this year looking at persistent infections in more than 50 immunocompromised people.
Lemieux and colleagues found a spectrum of COVID-19 risk among individuals with poor immune systems, with those on immunosuppressant treatments for blood cancers or organ transplants taking the longest time to clear the virus.
"It's really important to try to identify the best ways to eradicate infection from persistently infected patients so that they can get better. But also, so that the risk of transmission is eliminated," Lemieux told STAT News' Elizabeth Cooney when the study was published in Science Translational Medicine in January.
However, there's still a lot that researchers don't know about how best to treat immunocompromised people with COVID-19, especially those with chronic infections.