New COVID studies show varied viral clearance time in patients with lower immunity

Two new studies show immune-compromised patients, including those with cancer and HIV, have varied times until they clear the virus, with some at increased risk for persistent COVID-19 infections.

Risks of prolonged infection

In the first study, published The Lancet Microbe, researchers assessed 150 immunocompromised patients with COVID-19 from five US healthcare systems in 2022, when the Omicron strain was dominant. The study authors wanted to measure how long the patients tested positive for COVID-19, as persistent infections had been widely reported by clinicians treating patients with compromised immune systems.

Moreover, immunocompromised patients with persistent viruses have been considered a possible source of mutated variants.

“We were specifically looking at who was at risk for prolonged infection, such that they never cleared the virus,” said lead study author Adam Lauring, MD, PhD in a press release. “In contrast to a lot of case reports, we were finding that very few people had prolonged infection.”

Only 8% had live viruses for more than 3 weeks

Nasal swab specimens were obtained about every 2 weeks from participants during the study. Almost all participants were fully vaccinated prior to infection, and 45% received the antiviral drug remdesivir between 90 days before and 7 days after enrollment.

Lauring’s team found that only 25% of patients tested positive on polymerase chain reaction (PCR) tests for 21 days or longer after onset of illness, and only 8% tested positive for live virus for 21 days or longer.

In all, the median time to last positive test overall was 9 days in immunocompromised patients.

The investigators noted differences in viral clearance among the patients. Of the 150 participants, 59 had a solid organ transplant with T-cell immunosuppression. Among that group, only 1 patient had an infection lasting longer than 56 days.

Participants living with HIV (5) and B-cell cancers (18) like leukemias and lymphomas were more likely to have prolonged infections.

Patients with non–B-cell malignancy (23) and autoimmune or autoinflammatory conditions (45) had a shorter time to viral clearance, with the latter group experiencing the shortest time to last positive test, at 4 days.

In patients with prolonged infections, there was limited evidence of dangerous virus mutations.

“In the few participants with prolonged infection, we found accumulation of mutations within the receptor binding domain; the most prominent alterations have rarely, if ever, been detected in subsequent SARS-CoV-2 sequences in global databases,” the authors wrote. “Mutations arising within patients who were immunocompromised were only weakly predictive of subsequent omicron mutations at a population scale.”

Severe immunocompromise led to prolonged infection

The second study, published in Science Translational Medicine, from researchers at Mass General Brigham, also highlights varied risk of persistent COVID-19 infection among immunocompromised patients, with patients who were more severely immunocompromised more likely to have prolonged infections.

Our results highlight the finding that the risk of chronic SARS-CoV-2 infection is not uniform across immunosuppressive conditions.

“Our results highlight the finding that the risk of chronic SARS-CoV-2 infection is not uniform across immunosuppressive conditions and provide clarity on which immunosuppression conditions predispose individuals to delayed SARS-CoV-2 RNA and culture clearance as well as viral evolution,” the authors wrote.

The 31 patients included in the study who had immune suppression deemed to be not severe, including those with autoimmune diseases receiving anti-tumor necrosis factor treatment, had similar viral shedding dynamics to non-immunocompromised participants.

In contrast, the median times to nasal SARS-CoV-2 RNA and culture clearance in people with severe immunosuppression were 72 and 40 days, respectively, the authors said.

“While our sample size is limited, these results provide reassurance that most patients with mild/moderate immunosuppression (including those on B-cell depleting therapy) will be able to clear the virus during the acute phase of infection,” said first author Yijia Li, PhD in a Mass General Brigham press release.