The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases

Viruses. 2021 Sep 23;13(10):1904. doi: 10.3390/v13101904.

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

Keywords: COVID-19; DOACs; LMWH; Long-COVID-19; PARs; anticoagulants.

Publication types

  • Case Reports

MeSH terms

  • Anticoagulants / therapeutic use
  • Blood Coagulation / drug effects
  • Blood Coagulation Disorders / drug therapy
  • COVID-19 / complications*
  • COVID-19 Drug Treatment
  • Endothelial Cells
  • Factor Xa Inhibitors / therapeutic use
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Inflammation / drug therapy
  • Male
  • Middle Aged
  • Post-Acute COVID-19 Syndrome
  • SARS-CoV-2 / pathogenicity
  • Systemic Inflammatory Response Syndrome / drug therapy
  • Systemic Inflammatory Response Syndrome / immunology
  • Systemic Inflammatory Response Syndrome / physiopathology*
  • Thrombosis / drug therapy
  • Thrombosis / immunology
  • Thrombosis / physiopathology*

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Heparin, Low-Molecular-Weight