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Heart, Lung and Circulation

Letter to the Editor Regarding “Pulmonary Embolism Prophylaxis in Patients With COVID-19: an Emerging Issue”, Heart Lung Circ. 2021;30(10):1435–41.

  • Salvatore Patanè
    Correspondence
    Corresponding author at: Cardiologia Ospedale San Vincenzo Taormina (Me) Azienda Sanitaria Provinciale di Messina, Contrada Sirina, 98039 Taormina (Messina), Italy.
    Affiliations
    Cardiologia Ospedale San Vincenzo Taormina (Me) Azienda Sanitaria Provinciale di Messina, Contrada Sirina, Taormina (Messina), Italy
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Published:November 03, 2021DOI:https://doi.org/10.1016/j.hlc.2021.10.008
      To the Editor,
      I read the article by Sanidas and colleagues [
      • Sanidas E.
      • Grassos C.
      • Papadopoulos D.
      • Velliou M.
      • Barbetseas J.
      Pulmonary embolism prophylaxis in patients with COVID-19: an emerging issue.
      ] with great interest and congratulate the authors on their excellent work. However, I would like to draw attention to several points. Recent findings suggest that SARS-CoV-2 controls the expression of host regulatory molecules such as miRNAs and transcription factors (TFs), often regulating gene expression at transcriptional and post-transcriptional levels and forming highly complex network interactions [
      • Khurana P.
      • Gupta A.
      • Sugadev R.
      • Sharma Y.K.
      • Varshney R.
      • Ganju L.
      nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.
      ]. Research has identified four miRNAs (hsa-mir-9-5p, hsa-mir-324-3p, hsa-mir-1827, and hsa-mir-1277-5p) and TFs (EP300, MYC, E2F1, and SP1) that co-regulate important target genes responsible for SARS-CoV-2 host invasion [
      • Khurana P.
      • Gupta A.
      • Sugadev R.
      • Sharma Y.K.
      • Varshney R.
      • Ganju L.
      nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.
      ]. Studies have found evidence supporting common molecular trajectories of SARS-CoV-2 with clotting, pulmonary embolism, pulmonary oedema, and systematic inflammation, showing both fibrinolysis as a major pathway leading to D-dimer increase and cytokines TGF-β and TNF-α as major regulators of fibrinolysis controlling proteins PAI-1 and plasminogen activators also highlighting the role of hsa-mir-9-5p, hsa-mir-324-3p, EP300, and SP1 on pulmonary embolism [
      • Khurana P.
      • Gupta A.
      • Sugadev R.
      • Sharma Y.K.
      • Varshney R.
      • Ganju L.
      nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.
      ]. It has also been reported that in the circulating exosomes of high D-dimer COVID-19 patients (cut-off 3 μg/mL) there is significant miR-424 upregulation and miR-103a, miR-145, and miR-885 downregulation. Exosomal miR-424 is an independent thromboembolic event predictor in COVID-19 patients [
      • Plowman T.
      • Lagos D.
      Non-coding RNAs in COVID-19: emerging insights and current questions.
      ,
      • Gambardella J.
      • Sardu C.
      • Morelli M.B.
      • Messina V.
      • Marfella R.
      • Maggi P.
      Exosomal microRNAs drive thromboembolism in COVID-19.
      ], whereas miR-103a independently regulates D-dimer levels [
      • Gambardella J.
      • Sardu C.
      • Morelli M.B.
      • Messina V.
      • Marfella R.
      • Maggi P.
      Exosomal microRNAs drive thromboembolism in COVID-19.
      ]. Furthermore, miR-885 targets von Willebrand factor and miR-145 targets tissue factor [
      • Plowman T.
      • Lagos D.
      Non-coding RNAs in COVID-19: emerging insights and current questions.
      ,
      • Gambardella J.
      • Sardu C.
      • Morelli M.B.
      • Messina V.
      • Marfella R.
      • Maggi P.
      Exosomal microRNAs drive thromboembolism in COVID-19.
      ], showing negative correlations with their respective targets [
      • Plowman T.
      • Lagos D.
      Non-coding RNAs in COVID-19: emerging insights and current questions.
      ]. The findings of Sanidas and colleagues [
      • Sanidas E.
      • Grassos C.
      • Papadopoulos D.
      • Velliou M.
      • Barbetseas J.
      Pulmonary embolism prophylaxis in patients with COVID-19: an emerging issue.
      ] add significant information to previously published data; however, also evaluating these aspects would be useful for better understanding of the interplay between pulmonary embolism in patients with COVID-19 and its complex regulatory network.

      Conflict of Interest

      None declared.

      References

        • Sanidas E.
        • Grassos C.
        • Papadopoulos D.
        • Velliou M.
        • Barbetseas J.
        Pulmonary embolism prophylaxis in patients with COVID-19: an emerging issue.
        Heart Lung Circ. 2021; 30: 1435-1441
        • Khurana P.
        • Gupta A.
        • Sugadev R.
        • Sharma Y.K.
        • Varshney R.
        • Ganju L.
        nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.
        ExRNA. 2020; 2: 16
        • Plowman T.
        • Lagos D.
        Non-coding RNAs in COVID-19: emerging insights and current questions.
        Non-coding RNA. 2021; 7: 54
        • Gambardella J.
        • Sardu C.
        • Morelli M.B.
        • Messina V.
        • Marfella R.
        • Maggi P.
        Exosomal microRNAs drive thromboembolism in COVID-19.
        Circulation. 2020; 142: A221

      Linked Article

      • Pulmonary Embolism Prophylaxis in Patients With COVID-19: An Emerging Issue
        Heart, Lung and CirculationVol. 30Issue 10
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          Severe acute respiratory syndrome (SARS)-CoV-2 virus disease (coronavirus disease 2019; COVID-19) is associated with increased coagulation activity, resulting in an excessive risk of venous thromboembolism (VTE) and poor prognosis. The most common manifestation of VTE is pulmonary embolism (PE), with approximately one in five hospitalised patients being at risk. These reports led to the empirical use of prophylactic anticoagulation, even in the absence of established or clinically suspected disease.
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