Abstract
Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis.
Highlights
Dysregulated immune response to infection with SARS-coronavirus-2 (SARS-CoV-2) is the main driver of mortality in coronavirus disease 2019 (COVID-19) [1, 2]
We first quantified and localised SARS-CoV-2 in formalin-fixed paraffin embedded (FFPE) samples of oesophagus, stomach, duodenum, ileum, colon, lungs and spleen from 7 males and 2 females who died after being diagnosed with COVID-19 (Supplementary Table 1)
We showed that microanatomy of Peyer’s patches (PP) of COVID-19 patients was severely affected by the disease, which was independent of the local levels of viral RNA (Figure 6)
Summary
Dysregulated immune response to infection with SARS-coronavirus-2 (SARS-CoV-2) is the main driver of mortality in coronavirus disease 2019 (COVID-19) [1, 2]. Whilst respiratory dysfunction is common, symptoms involving the gastrointestinal (GI) tract has been identified, including vomiting and diarrhoea in 12% of the patients [3]. The receptor for SARS-CoV-2 angiotensin converting enzyme 2 (ACE2) is expressed on the luminal surface of epithelial cells throughout the GI tract. Disrupted Peyer’s Patches in Severe COVID-19 antibody responses that are fundamental for controlling virus replication or could be associated with persistent disease if ineffective [5, 6]. The consequences of SARS-CoV-2 infection on the GI immune system and the local ability to respond to viral infection in severe disease is currently unknown
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