Immunocompromised individuals, notably those with conditions like autoimmune deficiency syndrome (AIDS), exhibit increased susceptibility to SARS-CoV-2 infection, raising concerns about insufficient immunity and reduced vaccine efficacy. A recent prospective multicenter study, featured in The Lancet Microbe, explores the intrahost evolution of SARS-CoV-2 in immunocompromised patients and identifies risk factors for prolonged infections. The distinctive immunocompromised environment provides an extended timeframe for viral mutations, possibly contributing to the emergence of variants of concern (VOCs) like Alpha (B.1.1.7) and Omicron (BA.1).
The prospective and multicenter study led by Raglow et al., focusing on adult immunocompromised patients with recent Omicron infections, explored the impact of existing interventions on the evolution of highly mutated variants within this population. The study was conducted in five medical centers in the United States, and employed nasal specimens collected every two to four weeks for real-time reverse transcription polymerase chain reaction (RT-PCR) assays until consecutive negative results were obtained. Positive specimens underwent viral culture and whole genome sequencing.
The use of viral culture, ribonucleic acid (RNA) viral load, and sequence data analysis helped identify individuals who were at a higher risk of prolonged SARS-CoV-2 infection. It also helped evaluate the efficacy of antiviral treatments and understand the evolutionary dynamics of the virus in immunocompromised patients. The study showed that prolonged SARS-CoV-2 infection was uncommon in a diverse group of patients with moderate to severe immunocompromise. The within-host rate of evolution remained consistent in short- and long-term infections, indicating relatively restricted SARS-CoV-2 evolution across a wide array of immunocompromising conditions. The duration of the infectious period was identified as the primary differentiating factor among these patients.
During prolonged cases of infection, the researchers observed mutations in the viral receptor binding domain (RBD) and several substitutions in current or subsequent Omicron lineages. B-cell dysfunction or depletion, attributable to therapies such as anti-CD20 or anti-CD19, myeloma, or lymphoma, was identified as a significant risk factor. This finding supported previous case reports that underscored the crucial role of antibodies in clearing SARS-CoV-2. The study also drew parallels between prolonged viral replication in individuals with HIV infection and cases of extended infection in patients with COVID-19. Specifically, a patient with AIDS in the cohort experienced an infection period exceeding 200 days, despite receiving treatment. This patient had a low CD4 count of fewer than 50 cells/μL and uncontrolled HIV replication, highlighting the potential impact of impaired humoral immunity on the duration of infection.
The study further adds to the present understanding of SARS-CoV-2 infection dynamics in immunocompromised adults, particularly those affected by the Omicron variant. research underscores the need for ongoing investigation and emphasizes the intricate balance between viral dynamics, host immune responses, and therapeutic interventions in this vulnerable population.
Reference
Raglow Z, Surie D, Chappell JD, Zhu Y, Martin ET, Kwon JH, et al. SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis. The Lancet Microbe [Internet]. 2024 Jan 26 [cited 2024 Feb 1];0(0).