SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency, 2024, Li et al

SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency

Editor’s summary
Interrogating Infection in Immunosuppression. Individuals who are immunosuppressed remain at increased risk of severe COVID-19, but this heterogenous patient pool should not be considered a monolith. Here, Li et al. asked whether the extent of immunosuppression a person has influences their ability to develop immunity and clear SARS-CoV-2 infections.

The authors found that severe immunosuppression due to hematologic malignancy or transplant resulted in the longest time to viral clearance. These individuals also had evidence of increased intrahost viral evolution associated with resistance to antibody therapy and were marked by impaired humoral and T cell responses. Individuals with severe immunosuppression due to autoimmunity or B cell deficiency had, expectedly, impaired humoral responses but intact T cell responses, and those with nonsevere immunodeficiency had intact SARS-CoV-2–specific immunity mostly comparable to control participants.

Together, these results highlight the importance of considering the type and severity of immunosuppression an individual is experiencing when considering their antiviral immunity. —Courtney Malo

Abstract
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood.

In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups (P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2–specific humoral responses, whereas only the S-HT group had reduced T cell–mediated responses.

This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

https://www.science.org/doi/10.1126/scitranslmed.adk1599

 

This study should be interesting to anybody interested in viral persistence. I have wondered why the viral persistence researchers have largerly ignored immunocompromised patients for whom there is a lot of data that they can have a persistent infection for weeks or even months, but that there is seemingly no significant increase of LC risks amongst that group.