Prolonged SARS-CoV-2 infections impact quarter of immunocompromised patients
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Key takeaways:
- One-fourth of patients who were immunocompromised tested positive for COVID-19 21 days after initial detection.
- Within-host evolution rates were similar in those with short-term vs. long-term infection.
Approximately 25% of patients with COVID-19 who are immunocompromised remain positive for the disease 21 days or more from initial onset, according to data published in The Lancet Microbe.
In addition, although within-host evolutionary rates were similar across patients, infections longer than 56 days resulted in spike mutations distinct from others seen globally, the researchers wrote.
“A large number of case reports and case series have documented that a subset of patients who are immunocompromised are at risk for very prolonged infections, lasting hundreds of days,” Zoe Raglow, MD, of the University of Michigan, and colleagues wrote. “Because nearly all these studies are retrospective, with varying levels of ascertainment bias, prospective studies are needed to fully define this problem and those most at risk.
“Although the propagation of novel SARS-CoV-2 mutations is generally limited by host clearance and the stochastic dynamics of transmission, extended within-host replication in individuals who are immunocompromised allows the virus sufficient time to accumulate mutations,” they added. “If transmitted, these viruses will appear to have evolved at an accelerated rate, with more mutations per unit time.”
To analyze the risk factors for prolonged infection and subsequent within-host evolution, Raglow and colleagues recruited 150 immunocompromised adults with COVID-19 from five U.S. centers between April 2022 and October 2022, when the predominant variant was omicron. Eligible participants (39% male; median age, 60 years) were immunocompromised, and had a positive real-time reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 within the last 14 days.
The researchers collected nasal swabs from participants approximately every 2 weeks and analyzed them via viral culture and whole genome sequencing. Factors associated with the duration of infection were then examined in a Cox proportional hazards model. Participants were split into groups depending on if they were immunocompromised due to:
- B-cell malignancy or anti-B-cell therapy (n = 18);
- solid organ transplantation or hematopoietic stem cell transplantation (HSCT) (n = 59);
- non-B-cell malignancy (n = 23); or
- autoimmune or autoinflammatory conditions (n = 45).
Overall, 25% of participants demonstrated prolonged infection, defined as being real-time RT-PCR-positive after 21 days or longer, while 8% were culture-positive after 21 days. The highest risk for prolonged infection was seen among those with B-cell malignancy or taking B-cell-depleting therapies.
In five participants who were real-time RT-PCR positive for 75 to 207 days, 23 consensus de novo spike mutations were identified, 14 of which were in the receptor-binding domain. Few of the mutations were shared between the participants, and “none have been prevalent globally,” the researchers wrote. Rates of within-host evolution were “similar” between those with short-term vs. long-term infection, according to the researchers.
“In this prospective cohort of adults who were immunocompromised and had SARS-CoV-2 infection, duration of infection and evolution of SARS-CoV-2 were observed more frequently in patients with B-cell malignancy and B-cell depletion than in patients with other forms of immunocompromise,” Raglow and colleagues wrote.
“With extended viral replication, these individuals can accumulate substantial numbers of mutations in spike and elsewhere across the genome,” they added. “In our cohort, mutations arising within patients who were immunocompromised were only weakly predictive of subsequent omicron mutations at a population scale, suggesting that alternative genomic surveillance approaches might be more useful.”
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