Despite the official declaration of the pandemic’s end, new cases of COVID-19 persist, prompting a sustained effort in treatment management and vaccination programs [1,2]. While the majority of affected individuals are adults, children, too, are not immune to the impacts of this infectious disease . This article delves into the intricacies of COVID-19 in pediatric patients, focusing on the morphological features of lung involvement and virus-host interactions in this specific demographic.
Statistics reveal that only 3.6% of the total COVID-19 cases are children, with a mere 0.6–2.0% requiring intensive care unit admission . Despite these relatively low numbers, clinical observations highlight the potential severity of the disease in children, and fatalities are not unheard of .
The pediatric population with comorbidities, particularly those with oncological diseases, faces an elevated risk of severe COVID-19 outcomes, underscoring the importance of understanding the disease’s pathogenesis in this vulnerable group .
Importance of Postmortem Investigations
Postmortem investigations, commonly referred to as autopsies, serve as the “gold standard” for unraveling the pathogenesis of diseases [7,8]. While numerous studies have explored postmortem findings in adult COVID-19 cases, the data on pediatric cases remain notably scarce . The limited understanding of the pathological morphology in children with COVID-19 stems from the absence of concrete facts obtained through immunohistochemical investigations.
Challenges in Pediatric COVID-19 Pathogenesis Research
The paucity of data regarding the pathological morphology of COVID-19 in children poses a significant challenge in comprehending the disease’s pathogenesis in this demographic . Existing research predominantly relies on conjectures due to the dearth of concrete evidence. Understanding virus-host interactions is pivotal for elucidating the course and development of the infection, and this becomes even more crucial when dealing with pediatric cases .
Significance for Post-COVID Conditions
Beyond unraveling the mysteries of COVID-19 pathogenesis, investigating the morphological features of the disease in pediatric cases holds broader implications. It provides a foundation for understanding the development of post-COVID conditions, an area of increasing concern as the aftermath of the pandemic unfolds.
The primary objective of our study is to bridge the knowledge gap by identifying the morphological features of lung involvement and evaluating virus-host interactions in cases of COVID-19 among pediatric patients. This research aims to contribute valuable insights that can inform treatment strategies and enhance our understanding of the disease’s impact on the younger population.
The study delves into a comprehensive analysis of autopsy materials derived from three pediatric cases of COVID-19. By employing immunohistochemical and PCR investigations, we meticulously examined histological changes in the lungs, enabling a nuanced pathogenetic evaluation across various stages of the disease.
Patient 1, experiencing a 5-day duration of the disease, exhibited changes indicative of the early exudative phase of diffuse alveolar damage. In contrast, Patient 2, at the 20th day post-onset, displayed significant alterations, including dense serofibrinous exudate filling 95% of alveoli, hybrid clots in vessels, and pronounced T-lymphocytic inflammatory infiltration. Patient 3, with a 50-day disease duration, showed evident manifestations of diffuse alveolar damage, albeit with weakly positive expressions of nucleocapsid SARS-CoV-2 and CD95.
An intriguing finding is the substantial expression of SARS-CoV-2 antigens in the epithelia of both large and small bronchi in patients succumbing to the disease on the 6th and 20th days. This observation distinguishes SARS-CoV-2 from other highly pathogenic coronaviruses, as adults typically exhibit lower antigen expression in respiratory passages and higher expression in lung endothelia and macrophages. The results highlight a high viral load in pediatric upper respiratory passages and persistent virus expression in severe cases, aligning with existing literature.
The study confirms the upper respiratory passages as potential primary sites for virus replication after air-droplet infection. This is supported by the detection of SARS-CoV-2 in tracheal material, main bronchi, and lung tissue during postmortem PCR investigations in children. Additionally, a significant expression of SARS-CoV-2 antigens in endothelial cells of capillaries and larger vessels implies these cells as crucial targets for pathogenic influence.
Contradictions in existing literature regarding SARS-CoV-2 infection of endothelial cells are addressed in our study. While some argue against it, our findings suggest the virus’s presence in macrophages throughout various stages of infection, potentially indicating persistence and the likelihood of reactivation in children. The role of macrophages in restricting or exacerbating alveolar damage requires further exploration.
A consistent observation across cases is endothelial damage in vessels of different sizes. Histological and immunohistochemical investigations reveal increasingly destructive damage to capillary endothelia during prolonged COVID-19 cases. Endothelial cells, possessing ACE2 receptors, serve as conduits for virus distribution, adhering to and penetrating cells without causing cytopathic changes. The cytokine response becomes pivotal, potentially triggering destructive effects in infected cells.
The study highlights a significant expression of the apoptosis marker CD95 in bronchial epithelia, vessel endothelia, and macrophages, especially in early-stage cases. Apoptosis corpuscles, identified more abundantly in advanced cases, underline the role of apoptosis in COVID-19-related pediatric deaths. The spatial co-localization of SARS-CoV-2 nucleocapsid protein, CD95, and apoptosis corpuscles within different lung structures signifies their fundamental significance in understanding COVID-19 pathogenesis.
In conclusion, our findings provide crucial insights into the dynamic progression of COVID-19 in pediatric cases. The distinctive patterns observed in lung histopathology, viral distribution, and host response emphasize the need for further research to unravel the intricate interplay between SARS-CoV-2 and the pediatric respiratory system.
reference link : https://www.mdpi.com/1422-0067/24/23/16750