A histopathological analysis of extrapulmonary lesions in fatal coronavirus disease (COVID-19).

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues. MATERIALS AND METHODS: The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated. RESULTS: In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD. DISCUSSION: The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging. CONCLUSION: Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.

Immunohistochemical and Morphometric Analysis of Lung Tissue in Fatal COVID-19.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage.

The Influence of HLA Polymorphisms on the Severity of COVID-19 in the Romanian Population.

In this study, we aimed to investigate whether specific HLA alleles found in patients from Romania and the Republic of Moldova were associated with the severity of COVID-19 infection and its associated mortality. We analyzed the HLA alleles at the -A, -B, -C, -DRB1, and -DQB1 loci in a cohort of 130 individuals with severe and extremely severe forms of COVID-19, including 44 individuals who died. We compared these findings to a control group consisting of individuals who had either not been diagnosed with COVID-19 or had experienced mild forms of the disease. Using multivariate logistic regression models, we discovered that the B*27 and B*50 alleles were associated with an increased susceptibility to developing a severe form of COVID-19. The A*33 and C*15 alleles showed potential for offering protection against the disease. Furthermore, we identified two protective alleles (A*03 and DQB1*02) against the development of extremely severe forms of COVID-19. By utilizing score statistics, we established a statistically significant association between haplotypes and disease severity (p = 0.021). In summary, this study provides evidence that HLA genotype plays a role in influencing the clinical outcome of COVID-19 infection.

Identification of Histopathological Biomarkers in Fatal Cases of Coronavirus Disease: A Study on Lung Tissue.

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.