An Insight into the Role of Postmortem Immunohistochemistry in the Comprehension of the Inflammatory Pathophysiology of COVID-19 Disease and Vaccine-Related Thrombotic Adverse Events: A Narrative Review

Abstract

On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of Diffuse Alveolar Damage (DAD) and a hypercoagulability state, frequently leading to Severe Acute Respiratory Syndrome (SARS) and multiorgan failure, particularly in old and severe-critically ill patients. In order to find effective therapeutic strategies, many efforts have been made aiming to shed light on the pathophysiology of COVID-19 disease. Moreover, following the late advent of vaccination campaigns, the need for the comprehension of the pathophysiology of the fatal, although rare, thrombotic adverse events has become mandatory as well. The achievement of such purposes needs a multidisciplinary approach, depending on a correct interpretation of clinical, biochemical, biomolecular, and forensic findings. In this scenario, autopsies have helped in defining, on both gross and histologic examinations, the main changes to which the affected organs undergo and the role in assessing whether a patient is dead “from” or “with” COVID-19, not to mention whether the existence of a causal link exists between vaccination and thrombotic adverse events. In the present work, we explored the role of postmortem immunohistochemistry, and the increasingly used ancillary technique, in helping to understand the mechanism underlying the pathophysiology of both COVID-19 disease and COVID-19 vaccine-related adverse and rare effects.

How the Innate Immune System of the Blood Contributes to Systemic Pathology in COVID-19-Induced ARDS and Provides Potential Targets for Treatment

“…From these cases of seriously ill COVD-19 patients, it was observed that the pulmonary tissue was infiltrated with immune cells ( 20 ). Initially, lymphocytes and macrophages were reported to be the dominating cell types ( 22 ), but later studies also showed that PMNs were important players ( 23 ). This discrepancy was probably due to that the latter observation were obtained in patients with earlier disease.…”

Autopsy Findings and Inflammatory Markers in SARS-CoV-2: A Single-Center Experience

“…8,9 The corresponding histological findings are represented by diffuse alveolar damage in exudative or proliferative stage, inflammatory cell infiltrates, squamous metaplasia, type 2 pneumocyte activation and fibrin microthrombi formation within pulmonary, cardiac, renal and hepatic circulation. [10][11][12][13] Postmortem examinations are the gold standard for understanding the pathophysiological pathways of diseases and the prime objective of the forensic autopsy is to provide answers about the cause of death. 14 In order to predict the prognosis of COVID-19 in a personalized approach, a set of time and cost-efficient biomarker signatures must be selected.…”

“…The corresponding histological findings are represented by diffuse alveolar damage in exudative or proliferative stage, inflammatory cell infiltrates, squamous metaplasia, type 2 pneumocyte activation and fibrin microthrombi formation within pulmonary, cardiac, renal and hepatic circulation. 10–13 …”

Dissecting Physiopathology of COVID-19

“…The articles included in this Special Issue are focused on prevention, diagnostics, signatures of the disease course, molecules involved, vaccine-related adverse effects, potential treatments, and short- and long-term consequences. There are 3 original research papers [ 2 , 3 , 4 ] and 11 review articles [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…The work by Chiara Stassi and colleagues [ 9 ] explores the significance of postmortem immunohistochemistry in understanding the pathophysiology of both COVID-19 and COVID-19 vaccine-related adverse rare effects. Maria Narożna and Błażej Rubiś [ 10 ], in their article, discuss the necessity of identification of novel strategies and markers as well as diagnostic methods in the fight against the COVID-19 pandemic.…”