On December 31, 2019, an outbreak of pneumonia caused by a novel coronavirus named SARS-CoV-2 was detected in the city of Wuhan (China). From a clinical point of view, infected patients could present with anything from mild upper respiratory tract symptoms to severe pneumonia associated with respiratory distress syndrome that could progress to severe respiratory failure and death of the patient.

Although this new disease mainly affects the respiratory tract, several observational studies suggest that SARS-CoV-2 (COVID-19) infection predisposes patients to thrombotic events in the vein; pulmonary embolism (PE) is the most frequent among them.1–7 This increase in pulmonary thrombotic manifestations has been observed in the autopsies of patients infected in the SARS-CoV and MERS-CoV epidemics of 2003 and 2012, respectively.8

The physiopathology that links PE and SARS-CoV-2 infection is not well known, though it seems to be related to a state of hypercoagulability. Recent studies have demonstrated that D-dimer levels greater than 1,000 ng/mL in patients with COVID-19 constitute a prognostic factor that is relevant to mortality.9 The systemic inflammatory response and endothelial damage associated with viral infection could activate coagulation, with an increase in thrombin generation and a decrease in the organism’s natural anticoagulants. Years ago, the term “immunothrombosis” was coined to describe this correlation between the immune system and the coagulation system as a response to infection designed to prevent its propagation.

SARS-CoV-2 penetrates alveolar epithelial cells through the angiotensin-converting enzyme 2 (ACE2) surface receptor.10 Viral replication triggers the activation of the complement system, with formation of C3a and C5a, which are able to recruit neutrophils, macrophages, lymphocytes, and monocytes that in turn are responsible for the massive release of proinflammatory cytokines (IL-1, IL-6, IL-8, and interferon-γ). These favor the expression of the tissue factor (TF) of thrombomodulin and endothelial adhesion molecules and also activate fibrinolysis, among other effects.11

Furthermore, SARS-CoV-2 infects endothelial cells that express ACE2. This endothelial damage activates the TF, which generates thrombin from prothrombin by means of activated factor X action. The activated circulating platelets coagulate and provide an appropriate phospholipid surface for the adhesion of different compounds in the coagulation cascade, with the generation of a large amount of thrombin.

Recently, Ciceri et al. have proposed the acronym MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) to designate this pulmonary thrombotic microangiopathy or thrombosis in situ.12 In concordance with this pathophysiological hypothesis, fibrin clots have been found in small pulmonary artery vessels in the autopsies of patients who have died due to COVID-19.13

For this reason, it would be interesting to learn the incidence of deep vein thrombosis (DVT) in patients with COVID-19 and PE. According to published series, the presence of concomitant DVT varies between 35%–45% in patients with PE.14 Though 20% of patients with PE can present with undiagnosed DVT, the studies by Poissy et al.4 and Lodigiani et al.6 observed an incidence of DVT of 13.6% and 10%, respectively, in patients with COVID-19 and PE. The published case series of patients with COVID-19 and DVT are shown in Table 1.

In conclusion, the severe respiratory failure that patients with COVID-19 develop may partially be explained by pulmonary thrombotic microangiopathy that is the consequence of an exaggerated immune response in the host. The coagulopathy in these patients has led to the proposal of different antithrombotic strategies, especially in severe patients admitted to intensive care units (ICU). Although we do not know the best antithrombotic strategy, low-molecular-weight heparins at prophylactic or intermediate doses should be indicated in these patients (except when contraindicated). Therapeutic anticoagulation should be reserved for cases in which thrombosis is observed or suspected.15

Randomized controlled trials are needed to determine the suitability of primary thromboprophylaxis beyond discharge from the hospital and the optimal duration of anticoagulant treatment in patients with PE.