Persistent SARS-CoV-2 Infection in Immunocompromised Patients

Persistent SARS-CoV-2 infection in individuals with compromised immunity represents a critical challenge for both patient management and public health. Unlike the typical course of infection, which resolves within a fortnight, these patients may harbour replicating virus for months, driven by an inability to mount effective B-cell and T-cell responses. Prolonged viral replication fosters intrahost evolution, yielding mutations that can reduce antiviral efficacy, escape monoclonal antibodies and dampen vaccine-induced immunity. Clinically, persistent infection is associated with recurrent symptoms, extended viral shedding, and a heightened risk of long-COVID sequelae. The phenomenon is most often documented in patients with haematological malignancies, organ transplants or advanced HIV disease, where immunosuppressive therapies or viral-induced immune dysfunction impede clearance. Global surveillance indicates that such chronic infections, although infrequent, serve as potential reservoirs for the emergence of highly divergent lineages and may contribute to future outbreaks and novel variants of concern.

Research from Nature Portfolio

Recent community surveillance that incorporated longitudinal viral sequencing identified a small but significant proportion of infections persisting beyond 60 days, with viral loads rebounding intermittently. These cases demonstrated evidence of ongoing replication and, in some individuals, rapid accumulation of amino acid substitutions, including mutations later observed in variants of concern and at sites targeted by therapeutic antibodies. Another investigation tracked sequential persistent infections in immunocompromised hosts over several months, revealing not only intrahost evolution of an Omicron sublineage but also onward transmission of neutralisation-resistant variants. A further study consolidated genomic data from dozens of chronic infections to elucidate the drivers of adaptive evolution. It showed that viral rebound correlates strongly with the emergence of antibody-evasion mutations and that dynamic, polymorphic viral populations develop within patients, suggesting that selective pressures vary across anatomical niches in the host.

Persistent SARS-CoV-2 Infection in Immunocompromised Patients publication trend

The graph below shows the total number of articles in persistent sars-cov-2 infection in immunocompromised patients across all publications each year (not limited to Nature Index journals).

Technical terms

Persistent infection: ongoing replication of SARS-CoV-2 beyond the typical acute phase, often exceeding 30 days.

Immunocompromised: having an impaired or weakened immune system due to disease or immunosuppressive therapy.

Intrahost evolution: genetic diversification of the virus within a single host over time.

Neutralizing antibody: an antibody that binds to viral surface proteins to block infection of host cells.

Monoclonal antibody: a laboratory-produced antibody designed to target a specific viral epitope.

Viral rebound: the resurgence of viral load after an initial decline, indicating renewed replication.

References

1. Prevalence of persistent SARS-CoV-2 in a large community surveillance study. Nature (2024).
2. Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants. Nature Communications (2023).
3. SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape. Cell Host & Microbe (2022).
4. Drivers of adaptive evolution during chronic SARS-CoV-2 infections. Nature Medicine (2022).
5. Immunocompromised Patients with Protracted COVID-19: a Review of “Long Persisters”. Current Transplantation Reports (2022).