Unveiling the Pathological Mechanisms of Death Induced by SARS-CoV-2 Viral Pneumonia.

In this comprehensive study of 15 deceased patients with confirmed SARS-CoV-2 infection, spanning a time frame of 1 to 68 days from confirmation to death, autopsies were meticulously conducted with stringent safety measures. Clinical, laboratory, histopathological, and molecular analyses were integrated, shedding light on diverse pulmonary lesions, including acute inflammatory changes, vascular abnormalities, and aberrant regenerative processes. Immunohistochemical analysis, utilizing various markers, successfully identified the SARS-CoV-2 nucleocapsid antigen within infected tissue cells and also revealed what type of inflammatory cells are involved in COVID-19 pathogenesis. Molecular investigations through rt-qPCR revealed the persistent presence and varying quantities of viral genes, even after 68 days. Moreover, the viral nucleocapsid was present even in patients who died after 50 days of infection onset. Employing statistical analyses such as Chi-square and phi coefficient tests, significant associations among microscopic lesions and their correlation with molecular and immunohistochemical findings were elucidated. We could draw a map of what kind of lesions were a direct consequence of viral invasion and what lesions where secondary to the acute immunological response. This integrative approach enhances our understanding of the intricate relationships between pathological features, providing valuable insights into the multifaceted landscape of COVID-19 pathogenesis.

Rare splicing mutation in COL1A1 gene identified by whole exomes sequencing in a patient with osteogenesis imperfecta type I followed by prenatal diagnosis: A case report and review of the literature.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as dentinogenesis imperfecta, blue sclera and deafness. Over 90% of OI cases are caused by mutations in the COL1A1 and COL1A2 genes and the inheritance is autosomal dominant. METHODS: We present a case of a couple requesting genetic counseling, because the man was diagnosed with OI on a clinical and radiological basis and the woman was pregnant. Whole exomes sequencing (WES) was performed in order to identify the mutation (s), followed by prenatal diagnosis. RESULTS: WES identified a rare splicing mutation c.1155 + 1G > C in the COL1A1 gene recognized to be pathogenic and subsequently confirmed by next generation sequencing. The carrier state of the mutation was excluded for the fetus, so the pregnancy was further pursued and a healthy baby was born at term. CONCLUSIONS: WES is a new and effective technique for detecting pathogenic variants in monogenic diseases and it is preferable to use such a technique in diseases with genetic heterogeneity especially when time does not allow another time-consuming diagnostic technique such classical Sanger sequencing. WES offers possibility to expand the global spectrum of OI pathogenic variants enabling the diagnosis of the disease.