Gulubova Maya, Merhar Vesselina, Chonov Dimitar, Mitev Mitko, Pekova Lilia, Ananiev Julian
Department of Pathology, Medical Faculty, Trakia University, Stara Zagora, Bulgaria.
Department of Anatomy, Histology, Embryology and Pathology, Medical Faculty, University "Prof. Dr. Assen Zlatarov", Burgas, Bulgaria.
Ital J Pediatr. 2025 Jun 7;51(1):174. doi: 10.1186/s13052-025-01984-y.
BACKGROUND: COVID-19 is a complex disease caused by SARS-CoV-2. The molecular and cellular mechanisms of the disease are unclear and their study is one of the greatest challenges for the modern science. Since the lung is the biggest target for SARS-CoV-2, the studies on cellular and molecular changes in this organ are essential to establish the pathogenesis of the disease. To date there is increasing number of reports on the lung pathology of fatal COVID-19 and the results are mainly obtained by autopsies of elderly patients, since this age group shows highest mortality. Little is known about the progression of the disease in children and especially newborn and infants and, to our knowledge, there are no reports on the lung features of fatal COVID-19 in this age group. METHODS: In the present case study, we have investigated the lung morphological features in 11-months old infant who has died as a result of complications from COVID-19. Immunohistochemistry for immune cell markers and transmission electron microscopy for alveolocytes type II (ATII) are made. RESULTS: Immediate cause of the death was acute respiratory failure resulting from bilateral interstitial pneumonia and subsequent acute cardiovascular failure. The histopathology shows lung edema, hyaline membranes, airway mucus plugging and interstitial inflammation. On cellular level we have observed a substantial increase in the number of ATII cells. ATII cells were marked with cytokeratin 19, TTF1 and napsin A. Transmission elec-tron microscopy reveals ongoing apoptosis in these cells with a typical chromatin clustering and condensation towards the inner nuclear membrane. Immunohisto-chemistry shows significant increase of CD68+ macro-phages in the alveoli, increase of IL-6 in immune and stromal cells, moderate elevation of FOXP3+ and IL-17+ cells and expression of CD4+ and CD8+ cells in alveolar walls. Immune cell interactions are discussed in the sense of ongoing cytokine storm. CONCLUSIONS: Our findings highlight the complexity of COVID-19 lung affection, involving ATII cell hyperplasia, interstitial mononuclear cell infiltration and macrophages increase. The findings provide an additional knowledge on the pathophysiology of COVID-19 in the lung and can serve as a basis for investigation of molecular mechanisms of this disease.
背景：新冠病毒肺炎（COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的一种复杂疾病。该疾病的分子和细胞机制尚不清楚，对其进行研究是现代科学面临的最大挑战之一。由于肺是SARS-CoV-2的主要靶器官，因此对该器官细胞和分子变化的研究对于确定疾病的发病机制至关重要。迄今为止，关于致命性COVID-19肺病理学的报道越来越多，其结果主要来自老年患者的尸检，因为这一年龄组的死亡率最高。关于儿童尤其是新生儿和婴儿的疾病进展情况知之甚少，据我们所知，尚无关于该年龄组致命性COVID-19肺部特征的报道。 方法：在本病例研究中，我们调查了一名因COVID-19并发症死亡的11个月大婴儿的肺部形态特征。进行了免疫细胞标志物的免疫组织化学检测和II型肺泡上皮细胞（ATII）的透射电子显微镜检查。 结果：死亡的直接原因是双侧间质性肺炎导致的急性呼吸衰竭以及随后的急性心血管衰竭。组织病理学显示肺水肿、透明膜形成、气道黏液堵塞和间质炎症。在细胞水平上，我们观察到ATII细胞数量大幅增加。ATII细胞用细胞角蛋白19、甲状腺转录因子1（TTF1）和天冬氨酸蛋白酶A（napsin A）标记。透射电子显微镜显示这些细胞中存在持续的细胞凋亡，伴有典型的染色质向核内膜聚集和浓缩。免疫组织化学显示肺泡中CD68+巨噬细胞显著增加，免疫细胞和基质细胞中白细胞介素-6（IL-6）增加，叉头框蛋白3（FOXP3）+和白细胞介素-17（IL-17）+细胞中度升高，以及肺泡壁中CD4+和CD8+细胞表达。从持续的细胞因子风暴角度讨论了免疫细胞相互作用。 结论：我们的研究结果突出了COVID-19肺部病变的复杂性，包括ATII细胞增生、间质单核细胞浸润和巨噬细胞增加。这些发现为COVID-19肺部病理生理学提供了更多知识，并可作为该疾病分子机制研究的基础。
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