Περίληψη:
The highly heterogeneous symptomatology and unpredictable progress of
COVID-19 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 SARS-CoV-2 infection have
been observed. The present study aimed to map the signaling pathways of
thrombocytopenia implicated in COVID-19, as well as in vaccine-induced
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 COVID-19-mediated 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, high-throughput experimental studies,
cross-species 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
COVID-19 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 COVID-19 and thrombocytopenia. The calculated
average node degree was immense (11.9 in COVID-19 and 6.43 in VITT),
illustrating the complexity of COVID-19 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 wild-type genes,
revealing the predisposition of the body to hypoxia-induced thrombosis,
leading to the acute COVID-19 phenotype, the `long-COVID syndrome',
and/or VITT. Thus, common nodes appear to be key players in illness
prevention, progression and treatment.
Συγγραφείς:
Geronikolou, Styliani
Pavlopoulou, Athanasia
Mantzourani, Marina
and Chrousos, George
Takan, Isil
