Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

Cristina Mondello; Salvatore Roccuzzo; Orazio Malfa; Daniela Sapienza; Patrizia Gualniera; Elvira Ventura Spagnolo; Nunzio Di Nunno; Monica Salerno; Cristoforo Pomara; Alessio Asmundo

doi:10.3389/fphar.2021.614586

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

Front Pharmacol. 2021 Apr 1:12:614586. doi: 10.3389/fphar.2021.614586. eCollection 2021.

Affiliations

¹ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
² Institute of Legal Medicine and Department of Surgical and Medical Sciences, University "Magna Graecia", Catanzaro, Italy.
³ Section of Legal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
⁴ Department of History, Society and Studies on Humanity, University of Salento, Lecce, Italy.
⁵ Department of Medical, Surgical and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy.

Abstract

Introduction: The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs. Methods: A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations. Results: A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung. Discussion: The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.

Keywords: COVID-19; SARS-CoV-2; autopsy; diffuse alveolar damage; hyperinflammatory state; immuno-thrombotic microangiopathy; pathological findings; systematic review.