As reviewed in paragraph 3, COVID-19 is frequently associated with thrombotic complications, both in the venous and arterial circulations. Endothelial dysfunction induced by SARS-CoV-2 infection results in a pro-thrombotic state leading to occlusion and microthrombi formation in COVID-19 patients, encouraging the use of prophylactic or even therapeutic anti-coagulation therapies. First, all hospitalized COVID-19 patients should have coagulation tests performed on admission, as it can provide useful prognosis information and help guide the anticoagulant therapy [
64,
82,
83]. Tang et al. demonstrated that the use of prophylactic anticoagulant therapy was associated with a decreased mortality in COVID-19 patients [
84]. In various national or international guidelines, it has been admitted that all confirmed or suspected COVID-19 patients admitted to the hospital should be treated with venous thrombosis event prophylaxis, in the absence of contra-indication [
83,
85]. The dose of anticoagulation for prophylaxis has also been increased by many teams to “intermediate intensity” doses such as 0.5 mg/kg twice a day of enoxaparin, using a risk-adapted strategy based on levels of D-dimer, fibrinogen, ICU location, obesity, or other factors associated with increased risk [
85,
86]. The concept of using full-dose anticoagulation in COVID-19 patients for preventing microvascular thrombosis during severe infection has been also considered [
85]. To date, data are scarce to support either one or the other strategy. Moreover, heparin exhibits non-anticoagulant effects as abilities to bind to inflammatory cytokines, to inhibit neutrophil chemotaxis and leukocyte migration through the endothelium, to neutralize the positively charged peptide complement factor C5a, and to sequester acute phase proteins [
87,
88]. Thus, heparin anti-inflammatory functions may also be relevant in COVID-19 patients. Furthermore, Wang et al. have also reported the use of fibrinolytic agent, tissue plasminogen activator, in 3 critically ill patients, with a transient improvement of their respiratory status [
89]. Eculizumab is a human monoclonal antibody designed to bind to the complement protein C5 with high affinity prevents the generation of the terminal complement complex C5b-9, which is involved in cell lysis [
90]. Complement inhibition has been shown to be an effective therapeutic target in hematological and neuroinflammatory diseases [
91,
92]. An Italian preliminary report of four severe COVID-19 patients treated by eculizumab recovered after treatment [
93]. Currently, two French studies are testing eculizumab in SARS-CoV-2 infection, hypothesizing that complement activation may be a key player in COVID-19 infection-related EC dysfunction and multi-organ failure (Clinical Trials
NCT04346797 and
NCT04355494).