# Lymphocyte loss and plasmacytosis are associated with IL-6- and TNF-producing cells in the spleens of fatal COVID-19 cases

## TL;DR

The spleens of people who died from COVID-19 showed significant immune changes, including loss of lymphocytes and increased inflammation, which may contribute to severe disease outcomes.

## Contribution

This study identifies specific immune alterations in the spleen of fatal COVID-19 cases, linking them to inflammatory cytokine production and cell death.

## Key findings

- Fatal COVID-19 cases show lymphocyte depletion and plasma cell accumulation in the spleen.
- Increased numbers of IL-6- and TNF-producing cells correlate with splenic changes.
- Widespread cell death is observed in the spleens of COVID-19 patients.

## Abstract

The spleen undergoes changes during acute and chronic infections, which may contribute to immune dysregulation and disease aggravation. In fatal cases of COVID-19, pronounced splenic changes are noted. However, the role played by these alterations in patient mortality remains poorly understood. Objectives: We aim to characterize structural alterations and changes in splenic cell populations in fatal COVID-19 cases, as a potential substrate for immune dysfunction associated with bacterial coinfection and mortality in severe infectious diseases.

In this study, we characterized the histological and cellular changes observed in the spleens of nine patients who died from COVID-19. Spleens from five healthy individuals were used as a reference. Histopathological analysis and immunolabeling techniques were employed to evaluate tissue architecture, cell composition, cytokine production, and cell death.

COVID-19-associated changes included atrophy of the white pulp (WP), reduced cellular density in the red pulp (RP), and reticular fiber fragmentation. Leukocyte phenotyping revealed substantial lymphocyte depletion across all splenic compartments, accompanied by plasma cell accumulation. These alterations correlated with increased numbers of IL-6- and TNF-producing cells. Additionally, a high density of TUNEL-positive cells indicated widespread cell death in the spleens of COVID-19 patients.

These findings suggest that the spleen contributes to the inflammatory response in SARS-CoV-2 infection, acting both as a source of inflammatory cytokines as well as a site of leukocyte, particularly lymphocyte, death both in association with the exacerbated release of IL-6 and TNF.