The Potential of Low Molecular Weight Heparin to Mitigate Cytokine Storm in Severe COVID‐19 Patients: A Retrospective Cohort Study

Abstract

On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID-19) as a global pandemic. However, specific anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID-19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group (P = 0.011). Likewise, changes in the levels of D-dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group (P = 0.035). Remarkably, IL-6 levels were significantly reduced after LMWH treatment (P = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti-inflammatory effect and attenuate in part the "cytokine storm" induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical study. On March 11, 2020, the World Health Organization (WHO) declared its assessment of coronavirus disease 2019 (COVID-19) as a global pandemic. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is characterized by a long incubation period, high infectivity, and multiple routes of transmission. 1,2 However, no effective medicines are currently available, so patients are treated symptomatically. A better understanding of the mechanisms of pathological changes will help to screen potential drugs out of the currently available medications. Several clinical studies revealed that cytokine storms are important mechanisms underlying disease exacerbation and death of patients with COVID-19. 3-5 Particularly, IL-6 levels in severely ill patients were significantly higher than in mild cases. 6 IL-6 is one of the core cytokines, 7 contributing to many of the key symptoms of cytokine storm, such

COVID-19 associated thrombotic thrombocytopenic purpura (TTP) ; A case series and mini-review

“…Heparin exhibits anti-inflammatory effects by neutralizing damage associated cellular proteins, thereby stabilizing endothelial cell membrane, decreasing vascular leakage, and thrombus formation [36] , [37] . A report from China, administration of low molecular weight heparin reduced the IL-6 levels and improved anti-coagulation indices [38] .…”

Antithrombotic and Anti-Inflammatory Effects of Fondaparinux and Enoxaparin in Hospitalized COVID-19 Patients: The FONDENOXAVID Study

“…10,[25][26][27] Standard treatment for COVID-19 in fact is based on the administration of several kind of drugs with multiple actions, in order to reduce inflammatory damage (ie, antivirals, immunomodulants, antibiotics, steroids, antithrombotics). Due to their pharmacological properties, heparinoids can fight SARS-CoV2 in multiple ways: a specific antiviral action of heparin toward SARS-CoV2 has been found in vitro and in vivo, 10,[23][24][25][26][27] as well a specific anti-inflammatory action of heparinoids and fondaparinux. 28,29 Of course, these additional properties should be added to the well-known antithrombotic actions of both drugs.…”

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease

“…Elevated blood levels of cytokines and chemokines have been reported in patients with COVID-19 infection [ [4] , [5] , [6] , [7] ] that trigger a pro-inflammatory environment and severe tissue damage, thereby contributing to the adverse outcomes of this disease [ 8 ]. Inflammatory disease progression is usually associated with the production of reactive oxygen species (ROS) followed by oxidative stress [ 9 ].…”