William Hanage, PhD, discusses viral evolution, transmission risk, and clinical implications for immunocompromised patients.
A case study published in The Lancet Microbe describes one of the longest known persistent SARS-CoV-2 infections—lasting more than 750 days—in a person with advanced HIV-1 infection who was not receiving antiretroviral therapy and was not virally suppressed.
In an email Q&A with William P Hanage, PhD, associate professor of epidemiology at Harvard University and study coauthor, emphasized the broader implications for variant emergence.
“The convergent evolution shows how long-term infections allow the virus to explore ways to infect cells more efficiently, and adds to the evidence that more transmissible variants have emerged from such infections. Effectively treating such cases is hence a priority for both the health of the individual and the community.”
Between March 2021 and July 2022, researchers collected eight clinical specimens from the patient, who was presumed to have been initially infected in May 2020. Sequencing showed the viruses formed a monophyletic cluster within the B.1 lineage, with 68 consensus and 67 subconsensus single nucleotide variants identified. The intrahost evolutionary rate (6.74 × 10–4 substitutions per site per year) was similar to rates observed in community sequences.
A person with advanced HIV carried SARS-CoV-2 for more than 750 days, with 68 consensus and 67 subconsensus mutations observed.
10 nonsynonymous spike mutations matched positions seen in the omicron lineage, nine detected prior to November 2021.
Despite viral adaptation, no evidence of onward transmission was found, though findings emphasize the need for surveillance and treatment in persistent infections.
Despite intrahost evolution, no evidence of onward transmission was detected.
“The vast majority of persistent infections do not produce highly transmissible variants, in large part because adaptation to successfully replicate in an individual patient is quite different from adapting to successfully transmit to a new host,” Hanage explained. “Even though evolution to produce more transmissible variants is rare, it remains a risk. And that risk can be reduced by treating such infections.”
Notably, 10 nonsynonymous spike protein mutations matched positions later defining Omicron, with nine detected before November 2021. Nine of 18 substitutions were rare in global databases, suggesting little evidence of sustained transmission chains.
Hanage stressed that timely treatment and access to care remain critical for immunocompromised individuals.
“It is notable that the patient in this case did not receive antivirals or other therapies directed at SARS-CoV-2, and their HIV-1 infection was poorly controlled with persistently low CD4 counts. This illustrates the importance of adequate access to healthcare for all, because we have treatments for both viruses which could have resolved this infection.”
Investigators conclude that while persistent infections in immunocompromised hosts may rarely contribute to variant emergence, they remain a source of viral adaptation that requires close monitoring and appropriate treatment.
