Patterns of Inflammatory Cell Infiltration and Expression of STAT6 in the Lungs of Patients With COVID-19: An Autopsy Study

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 causes diffuse alveolar damage (DAD), lymphocyte infiltration in the lungs and a cytokine storm. In this study we examined inflammatory cell infiltrates and the expression of signal transducer and activator of transcription (STAT) 6 in the lungs of patients with coronavirus disease 2019 (COVID-19).Methods: Eighteen COVID-19 autopsy cases, 9 non-COVID cases with DAD, and 11 controls without lung diseases were included. Immunostainings for STAT6, CD3, CD4, CD8, CD68, and broad-spectrum keratins were performed. Results:The average age of COVID-19 patients was 64.4 ± 2.1 years. The disease duration was 7 to 53 days. The number of pneumocytes, macrophages or CD3 + T cells was significantly increased in the lungs of patients with COVID-19. Patients' age above 67 years, blood troponin levels > 0.2 ng/mL, platelet count > 100×10 9 /L, lung macrophages > 130/high-power field (HPF), CD3 + T cells > 145/HPF, CD8 + T cells <30/HPF, and CD8/CD4 ratio <1 were associated with shorter survival duration after onset of symptoms. In addition, STAT6 staining was much stronger in pneumocytes and lymphocytes in the lungs of patients with COVID-19 than non-COVID DAD patients or controls. Conclusion:Older age, high blood troponin level and platelet count, more macrophages and fewer CD8 + T cells in the lungs of COVID-19 were associated with poorer outcome. STAT6 expression was increased in pneumocytes and lymphocytes in the lungs of patients with COVID-19, implying a role of STAT6 in cytokine storms.

Lung Expression of Macrophage Markers CD68 and CD163, Angiotensin Converting Enzyme 2 (ACE2), and Caspase-3 in COVID-19

“…Pathomorphological studies of the lungs of those patients who died from COVID-19 showed the presence of pneumocytes, CD68+ macrophages, and CD3+ T cells with the activation of STAT6 expression in the inflammatory infiltrates [24]. Patients who died from COVID-19 showed a significant increase in CD4, CD68, and CD138 [25].…”

The Role of Toll-like Receptor-4 in Macrophage Imbalance in Lethal COVID-19 Lung Disease, and Its Correlation with Galectin-3

“…Patients with lethal COVID-19 associated with macrophage counts of >130/High Power Field (HPF) showed shorter survival time in an autopsy cohort studied by Cao W et al [40].…”

The role of the endothelium in severe acute respiratory syndrome coronavirus 2 infection and pathogenesis

“…This suggests that viral exposure may promote inflammation and cell permeability causing immune cell infiltration that exacerbates disease and can cause ARDS or viral pneumonia [12] . A study using immunostained lung samples from patients with diffuse alveolar damage (DAD) as a result of COVID-19 showed a significant increase in the number of pneumocytes, macrophages and CD3+ T cells compared to healthy controls and non-DAD-COVID patients [13] . An increased presence of macrophages and fewer CD8+ T cells were further associated with poor outcomes in all COVID-19 patients suggesting a role between the overactivated innate immune system and disease exacerbation [14] .…”