tetano
Editor, Senior Moderator
Ital J Pediatr
. 2025 Jun 7;51(1):174.
doi: 10.1186/s13052-025-01984-y. Histopathological examination of lung from infant with lethal COVID-19 with special attention on pneumocytes type II and the immune infiltrate: a case study
Maya Gulubova[SUP] 1 2 3 4 [/SUP], Vesselina Merhar[SUP] 5 [/SUP], Dimitar Chonov[SUP] 6 [/SUP], Mitko Mitev[SUP] 7 [/SUP], Lilia Pekova[SUP] 8 [/SUP], Julian Ananiev[SUP] 9 [/SUP]
Affiliations
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.
Keywords: Alveolar type II cells; Cytokine storm; IL-6; Immune cells; Infant; Pulmonary disease; SARS-CoV-2.
. 2025 Jun 7;51(1):174.
doi: 10.1186/s13052-025-01984-y. Histopathological examination of lung from infant with lethal COVID-19 with special attention on pneumocytes type II and the immune infiltrate: a case study
Maya Gulubova[SUP] 1 2 3 4 [/SUP], Vesselina Merhar[SUP] 5 [/SUP], Dimitar Chonov[SUP] 6 [/SUP], Mitko Mitev[SUP] 7 [/SUP], Lilia Pekova[SUP] 8 [/SUP], Julian Ananiev[SUP] 9 [/SUP]
Affiliations
- PMID: 40483512
- PMCID: PMC12145646
- 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.
Keywords: Alveolar type II cells; Cytokine storm; IL-6; Immune cells; Infant; Pulmonary disease; SARS-CoV-2.