ABSTRACT
BACKGROUND: Pulmonary hypoperfusion is common in children with congenital heart diseases (CHDs) or pulmonary hypertension (PH) and causes adult pulmonary dysplasia. Systematic reviews have shown that some children with CHDs or PH have mitigated clinical outcomes with COVID-19. Understanding the effects of pulmonary hypoperfusion on postnatal alveolar development may aid in the development of methods to improve the pulmonary function of children with CHDs or PH and improve their care during the COVID-19 pandemic, which is characterized by cytokine storm and persistent inflammation. METHODS AND RESULTS: We created a neonatal pulmonary hypoperfusion model through pulmonary artery banding (PAB) surgery at postnatal day 1 (P1). Alveolar dysplasia was confirmed by gross and histological examination at P21. Transcriptomic analysis of pulmonary tissues at P7(alveolar stage 2) and P14(alveolar stage 4) revealed that the postnatal alveolar development track had been changed due to pulmonary hypoperfusion. Under the condition of pulmonary hypoperfusion, the cell-cell communication and axon guidance, which both determine the final number of alveoli, were lost; instead, there was hyperactive cell cycle activity. The transcriptomic results were further confirmed by the examination of axon guidance and cell cycle markers. Because axon guidance controls inflammation and immune cell activation, the loss of axon guidance may explain the lack of severe COVID-19 cases among children with CHDs or PH accompanied by pulmonary hypoperfusion. CONCLUSIONS: This study suggested that promoting cell-cell communication or supplementation with guidance molecules may treat pulmonary hypoperfusion-induced alveolar dysplasia, and that COVID-19 is less likely to cause a cytokine storm in children with CHD or PH accompanied by pulmonary hypoperfusion.
Subject(s)
COVID-19 , Hypertension, Pulmonary , Child , Infant, Newborn , Humans , Axon Guidance , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/pathology , Pandemics , COVID-19/metabolism , Pulmonary Alveoli/pathology , Hypertension, Pulmonary/metabolism , Cell CommunicationABSTRACT
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), also referred to as COVID-19, has spread to several countries and caused a serious threat to human health worldwide. Patients with confirmed COVID-19 infection spread the disease rapidly throughout the region. Multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL) are risk factors for COVID-19, although the molecular mechanisms underlying the relationship among MM, DLBCL, and COVID-19 have not been elucidated so far. In this context, transcriptome analysis was performed in the present study to identify the shared pathways and molecular indicators of MM, DLBCL, and COVID-19, which benefited the overall understanding of the effect of COVID-19 in patients with MM and DLBCL. Three datasets (GSE16558, GSE56315, and GSE152418) were downloaded from the Gene Expression Omnibus (GEO) and searched for the shared differentially expressed genes (DEGs) in patients with MM and DLBCL who were infected with SARS-CoV-2. The objective was to detect similar pathways and prospective medicines. A total of 29 DEGs that were common across these three datasets were selected. A protein-protein interaction (PPI) network was constructed using data from the STRING database followed by the identification of hub genes. In addition, the association of MM and DLBCL with COVID-19 infection was analyzed through functional analysis using ontologies terms and pathway analysis. Three relationships were observed in the evaluated datasets: transcription factor-gene interactions, protein-drug interactions, and an integrated regulatory network of DEGs and miRNAs with mutual DEGs. The findings of the present study revealed potential pharmaceuticals that could be beneficial in the treatment of COVID-19.