ABSTRACT
Thrombocytes (platelets) are the type of blood cells that are involved in hemostasis, thrombosis, etc. For the conversion of megakaryocytes into thrombocytes, the thrombopoietin (TPO) protein is essential which is encoded by the TPO gene. TPO gene is present in the long arm of chromosome number 3 (3q26). This TPO protein interacts with the c-Mpl receptor, which is present on the outer surface of megakaryocytes. As a result, megakaryocyte breaks into the production of functional thrombocytes. Some of the evidence shows that the megakaryocytes, the precursor of thrombocytes, are seen in the lung's interstitium. This review focuses on the involvement of the lungs in the production of thrombocytes and their mechanism. A lot of findings show that viral diseases, which affect the lungs, cause thrombocytopenia in human beings. One of the notable viral diseases is COVID-19 or severe acute respiratory syndrome caused by SARS-associated coronavirus 2 (SARS-CoV-2). SARS-CoV-2 caused a worldwide alarm in 2019 and a lot of people suffered because of this disease. It mainly targets the lung cells for its replication. To enter the cells, these virus targets the angiotensin-converting enzyme-2 (ACE-2) receptors that are abundantly seen on the surface of the lung cells. Recent reports of COVID-19-affected patients reveal the important fact that these peoples develop thrombocytopenia as a post-COVID condition. This review elaborates on the biogenesis of platelets in the lungs and the alterations of thrombocytes during the COVID-19 infection.
Subject(s)
COVID-19 , Thrombocytopenia , Humans , Blood Platelets/metabolism , COVID-19/metabolism , SARS-CoV-2 , Lung , Thrombocytopenia/complications , Thrombocytopenia/genetics , Thrombocytopenia/metabolismABSTRACT
The highly heterogeneous symptomatology and unpredictable progress of COVID19 triggered unprecedented intensive biomedical research and a number of clinical research projects. Although the pathophysiology of the disease is being progressively clarified, its complexity remains vast. Moreover, some extremely infrequent cases of thrombotic thrombocytopenia following vaccination against SARSCoV2 infection have been observed. The present study aimed to map the signaling pathways of thrombocytopenia implicated in COVID19, as well as in vaccineinduced thrombotic thrombocytopenia (VITT). The biomedical literature database, MEDLINE/PubMed, was thoroughly searched using artificial intelligence techniques for the semantic relations among the top 50 similar words (>0.9) implicated in COVID19mediated human infection or VITT. Additionally, STRING, a database of primary and predicted associations among genes and proteins (collected from diverse resources, such as documented pathway knowledge, highthroughput experimental studies, crossspecies extrapolated information, automated text mining results, computationally predicted interactions, etc.), was employed, with the confidence threshold set at 0.7. In addition, two interactomes were constructed: i) A network including 119 and 56 nodes relevant to COVID19 and thrombocytopenia, respectively; and ii) a second network containing 60 nodes relevant to VITT. Although thrombocytopenia is a dominant morbidity in both entities, three nodes were observed that corresponded to genes (AURKA, CD46 and CD19) expressed only in VITT, whilst ADAM10, CDC20, SHC1 and STXBP2 are silenced in VITT, but are commonly expressed in both COVID19 and thrombocytopenia. The calculated average node degree was immense (11.9 in COVID19 and 6.43 in VITT), illustrating the complexity of COVID19 and VITT pathologies and confirming the importance of cytokines, as well as of pathways activated following hypoxic events. In addition, PYCARD, NLP3 and P2RX7 are key potential therapeutic targets for all three morbid entities, meriting further research. This interactome was based on wildtype genes, revealing the predisposition of the body to hypoxiainduced thrombosis, leading to the acute COVID19 phenotype, the 'longCOVID syndrome', and/or VITT. Thus, common nodes appear to be key players in illness prevention, progression and treatment.
Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Artificial Intelligence , COVID-19/complications , COVID-19 Vaccines/adverse effects , Humans , SARS-CoV-2 , Thrombocytopenia/chemically induced , Thrombocytopenia/genetics , Thrombosis/genetics , Post-Acute COVID-19 SyndromeSubject(s)
COVID-19 Drug Treatment , Idiopathic Pulmonary Fibrosis/complications , Pyrazoles/therapeutic use , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/drug therapy , Janus Kinase 2/genetics , Janus Kinases/antagonists & inhibitors , Male , Nitriles , Oxygen Inhalation Therapy , Pyrimidines , Thrombocytopenia/diagnosis , Thrombocytopenia/geneticsABSTRACT
BACKGROUND: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection. OBJECTIVES: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. METHODS: Whole-exome sequencing was performed on both patients, and the impact of the identified variants was validated by functional assays using the patients' PBMCs. RESULTS: Each patient was found to have a unique heterozygous truncation variant in suppressor of cytokine signaling 1 (SOCS1). SOCS1 is an essential negative regulator of type I and type II IFN signaling. The patients' PBMCs showed increased levels of signal transducer and activator of transcription 1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II IFN-stimulated genes and proapoptotic genes. The enhanced IFN signature exhibited by the patients' unstimulated PBMCs parallels the hyperinflammatory state associated with multisystem inflammatory syndrome in children, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of multisystem inflammatory syndrome in children. CONCLUSIONS: Heterozygous loss-of-function SOCS1 mutations are associated with enhanced IFN signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias.