Lymphopenia in patients affected by SARS-CoV-2 infection is caused by margination of lymphocytes in large bowel: an [18F]FDG PET/CT study

The study titled “Lymphopenia in patients affected by SARS-CoV-2 infection is caused by margination of lymphocytes in large bowel: an [18F]FDG PET/CT study” investigates the cause of lymphopenia in patients with newly diagnosed COVID-19.

Here’s a detailed summary:

Study Overview

  • Objective: To understand the cause of lymphopenia in COVID-19 patients by measuring [18F]FDG uptake in various tissues and correlating these measurements with hematological parameters.
  • Methods: The study involved 18 newly diagnosed COVID-19 patients. Regions of interest were drawn over major organs and specific areas of the bowel, and [18F]FDG PET/CT scans were used for analysis. Additionally, white blood cell scans with 99mTc-HMPAO-WBC were performed for some patients. Blood counts and lymphocyte subsets were measured at diagnosis and after recovery​​.

Key Findings

  1. Patient Characteristics and Symptoms:
    • Patients had moderate severity COVID-19 with primary symptoms being pulmonary issues and persistent fever. Treatment was well tolerated, and fever subsided between 3 to 9 days. All patients were discharged after testing negative twice for SARS-CoV-2​​.
  2. Imaging and Blood Count Results:
    • At diagnosis, patients showed significantly lower lymphocyte counts compared to controls and higher monocyte counts. [18F]FDG uptake was higher in the lungs, spleen, terminal ileum, caecum, and right colon. After recovery, these uptakes normalized except in the right colon​​.
  3. Lymphocyte Subset Analysis:
    • Severely lymphopenic patients had significantly lower CD3+ CD4+/CD45+ and CD16+ CD56+/CD45+ cells compared to moderately lymphopenic patients​​.
  4. Correlation of [18F]FDG Uptake and Lymphocytes:
    • Regression analyses indicated an inverse correlation between CD4+ lymphocytes and [18F]FDG uptake in the caecum and colon. Conversely, there was a direct correlation between CD8+ lymphocytes and [18F]FDG uptake in the lungs and bone marrow​​.
  5. Interpretation and Hypothesis:
    • The findings suggest that lymphopenia in COVID-19 patients is associated with large bowel inflammation. The hypothesis is that CD4+ lymphocytes migrate to peripheral lymphoid tissues in the bowel, contributing to inflammation​​.


  • Implications: The study presents a new hypothesis on the pathogenesis of lymphopenia in COVID-19 patients, suggesting a migration of CD4+ cells to the bowel as a contributing factor to inflammation.
  • Future Directions: Further studies investigating the trafficking of radiolabelled CD4+ cells in vivo are needed for direct confirmation. The findings open new avenues for understanding COVID-19’s impact on the immune system and developing therapeutic strategies​​.

This study provides a novel insight into the pathophysiology of lymphopenia in COVID-19, indicating a potential link with bowel inflammation and lymphocyte migration, thereby contributing to the growing body of knowledge on COVID-19’s systemic effects.

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