Citation: Gheban-Ros , ca, I.-A.; Gheban, B.-A.; Pop, B.; Mironescu, D.-C.; Siserman, V.C.; Jianu, E.M.; Drugan, T.; Bolboac˘ a, S.D. Identification of Histopathological Biomarkers in Fatal Cases of Coronavirus Disease: A Study on Lung Tissue. Diagnostics 2023, 13, 2039. https://doi.org/10.3390/ diagnostics13122039 Academic Editor: Andreas Kjaer Received: 21 May 2023 Revised: 6 June 2023 Accepted: 9 June 2023 Published: 12 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). diagnostics Article Identification of Histopathological Biomarkers in Fatal Cases of Coronavirus Disease: A Study on Lung Tissue Ioana-Andreea Gheban-Ros , ca 1,2 , Bogdan-Alexandru Gheban 3,4, * , Bogdan Pop 5,6 , Daniela-Cristina Mironescu 7,8 , Vasile Costel Siserman 7,8 , Elena Mihaela Jianu 4 , Tudor Drugan 1 and Sorana D. Bolboacă 1, * 1 Department of Medical Informatics and Biostatistics, Iuliu Hat , ieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; andreea.gheban-rosca@umfcluj.ro (I.-A.G.-R.); tdrugan@umfcluj.ro (T.D.) 2 Clinical Hospital of Infectious Diseases, 400003 Cluj-Napoca, Romania 3 Rouen University Hospital—Charles-Nicolle, 76000 Rouen, France 4 Department of Histology, Iuliu Hat , ieganu University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania; marina.elena@umfcluj.ro 5 The Oncology Institute “Prof. Dr. Ion Chiricut , ă”, 400015 Cluj-Napoca, Romania; bogdan.pop@umfcluj.ro 6 Department of Anatomic Pathology, Iuliu Hat , ieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania 7 Institute of Legal Medicine, 400006 Cluj-Napoca, Romania; csiserman@umfcluj.ro (V.C.S.) 8 Department of Forensic Medicine, Iuliu Hat , ieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania * Correspondence: gheban.bogdan@umfcluj.ro (B.-A.G.); sbolboaca@umfcluj.ro (S.D.B.) Abstract: We aimed to evaluate the primary lung postmortem macro- and microscopic biomarkers and factors associated with diffuse alveolar damage in patients with fatal coronavirus (COVID-19). We retrospectively analyzed lung tissue collected from autopsies performed in Cluj-Napoca, Romania, between April 2020 and April 2021 on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examined 79 patients with confirmed SARS-CoV-2 infection, ages 34 to 96 years, split into two groups using the cut-off value of 70 years. Arterial hypertension (38%) and type 2 diabetes mellitus (19%) were the most common comorbidities with similar distribution between groups (p-values > 0.14). Macroscopically, bloody exudate was more frequently observed among patients < 70 years (33/36 vs. 29/43, p-value = 0.0091). Diffuse alveolar damage (53.1%) was similarly observed among the evaluated groups (p-value = 0.1354). Histopathological biomarkers of alveolar edema in 83.5% of patients, interstitial pneumonia in 74.7%, and microthrombi in 39.2% of cases were most frequently observed. Half of the evaluated lungs had an Ashcroft score of up to 2 and an alveolar air capacity of up to 12.5%. Bronchopneumonia (11/43 vs. 3/36, p-value = 0.0456) and interstitial edema (9/43 vs. 2/36, p-value = 0.0493) were significantly more frequent in older patients. Age (median: 67.5 vs. 77 years, p-value = 0.023) and infection with the beta variant of the virus (p-value = 0.0071) proved to be significant factors associated with diffuse alveolar damage. Keywords: histopathology biomarker; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); coronavirus disease (COVID-19); autopsy; lung 1. Introduction Severe acute respiratory coronavirus 2 (SARS-CoV-2) is known to produce coronavirus-19 (COVID-19), a pathology classified as a multisystemic disease [1] that primarily affects the lungs [2,3]. Upon entering the host organism, SARS-CoV-2 binds to the angiotensin- converting enzyme-2 (ACE2) receptor on the cell surface, allowing the virus to enter the cell and promote replication. The ACE2 receptors are expressed in several tissues, including the heart, lungs, and kidneys [4,5]. In mild cases of infection, SARS-CoV-2 primarily causes lower respiratory tract in- fections (LRTIs) and severe pneumonia. In advanced cases, the disease can lead to acute Diagnostics 2023, 13, 2039. https://doi.org/10.3390/diagnostics13122039 https://www.mdpi.com/journal/diagnostics