Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α

Abstract

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1β, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1β in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Mapping Biological Risks Related to Necropsy Activities: Old Concerns and Novel Issues for the Safety of Health Professionals

“…The results obtained certainly provide indications for the identification of operating methods capable of limiting the spread of pathogenic microorganisms in the work environment and minimizing the biological risk [48][49][50]. The performance of monitoring activities made it possible to characterize the different sources of risk, including new ones, to which the different operators are exposed [51].…”

Evaluation of postmortem pathological changes in the lung in SARS-CoV-2 RT-PCR positive cases

“…This finding supports the hypothesis of Huang JL et al [27], who stated that the SARS-CoV-2 virus directly or indirectly destructs the CD8 (+) T lymphocytes through impairment of cellular immunity or SARS-CoV-2 induced-mediators, but the mechanism is not clear yet. However, an immunohistochemical study by Frisoni P et al [24] reported that CD8 (+) T cells and CD20 (+) B cells were mainly found in the lung. They showed that the reason for this was that none of the patients in their study had received any treatment that would activate the immune system, for they died in an out-of-hospital setting [24].…”

“…However, an immunohistochemical study by Frisoni P et al [24] reported that CD8 (+) T cells and CD20 (+) B cells were mainly found in the lung. They showed that the reason for this was that none of the patients in their study had received any treatment that would activate the immune system, for they died in an out-of-hospital setting [24]. In our study, 45.7% (n=43) of the cases were hospitalized.…”

“…IL-6 alters the host defense through various immune-stimulating mechanisms such as altering antigen-dependent B lymphocyte differentiation, increasing IgG formation by B lymphocytes, and managing monocytes and their differentiation to macrophages [23]. IL-6 also activates complements and triggers coagulation [24]. Also, the level of serum SARS-CoV-2 nucleic acid is tightly related to exceedingly elevated levels of IL-6 [23].…”

Myocardial Pathology in COVID-19-Associated Cardiac Injury: A Systematic Review

“…The prevention or attenuation of the cytokine storm and endothelial cell activation may be helpful to mitigate cardiac involvement [55]. Indeed, a better understanding of cardiac involvement pathophysiology and the pathological pattern is needed and autoptic studies on COVID-19 deaths should be further promoted [13,56].…”