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Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
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Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
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Immunological dysfunction associated with SARS-CoV-2 persistence in immunocompromised patients.

Ida M Johannsen1,2, Line K Vibholm2, Giacomo S Frattari1,2

  • 1Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Clinical and Experimental Immunology
|April 10, 2026
PubMed
Summary

Immunocompromised patients with prolonged SARS-CoV-2 infections show impaired T cell activation and humoral responses. This suggests a dysregulated immune response needing targeted interventions to restore antiviral immunity.

Keywords:
COVID-19SARS-CoV-2T-cell responsesimmunocompromised hostscRNA-seq

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Area of Science:

  • Immunology
  • Virology
  • Genomics

Background:

  • Immunocompromised patients face persistent SARS-CoV-2 infections despite advances in COVID-19 management.
  • Investigating immunological factors is crucial for understanding prolonged viral clearance in this vulnerable group.

Purpose of the Study:

  • To identify immunological factors associated with time to viral clearance (TTC) of SARS-CoV-2 in immunocompromised individuals.
  • To compare immune responses between patients with short and long TTC.

Main Methods:

  • Integrated clinical data, SARS-CoV-2-specific humoral and cellular responses, and single-cell RNA transcriptomics.
  • Analyzed differential immune responses at diagnosis and during infection.

Main Results:

  • Prolonged infection linked to reduced SARS-CoV-2-specific humoral immunity and diminished CD4+/CD8+ T cell activation.
  • Baseline CD8+ cytotoxic T and NK cell engagement was higher in prolonged TTC, potentially compensating for impaired T cell function.
  • Impaired T cell functionality and exhaustion markers (NEAT1, CD52, IL12RB2) were enriched in patients with long TTC.

Conclusions:

  • Impaired viral clearance in immunocompromised patients stems from an actively engaged yet dysregulated immune response.
  • Findings highlight the complexity of immune dysfunction and the need for interventions targeting functional T cell activation.