Venous thromboembolism and COVID-19 patients: An ongoing story.

In December 2019, China reported the first cluster of severe acute respiratory syndrome due to a new coronavirus 2 (SARS-CoV-2) [1], [2]. The disease rapidly spread into a global pandemic of public health emergency worldwide leading to more than 1,400,000 deaths with 60 millions of persons affected by the disease (data from November 25, 2020), leading to major health and economic consequences and 2 worldwide lockdowns. The characteristics of COVID-19 pneumopathy appeared atypical due to the dissociation between initial well-conserved lung compliance and the severity of hypoxemia, due to disruption of pulmonary vasoregulation and local thrombogenesis [3]. Several publications reported thrombotic complications in series of severe COVID-19 patients with great variability [4].

For this reason, we decided to assess the prevalence and characteristics of PE, diagnosed by computed tomography pulmonary angiography (CTPA), in a large series of 1042 hospitalized patients hospitalized in two large hospitals in Paris [5]. The aim of this study was to estimate the incidence and clinical characteristics of symptomatic PE in a large population of consecutive COVID-19 patients admitted for acute respiratory syndrome in regular wards or in Intensive Care Units (ICU). The main results of this study can be summarized below:

CTPA was performed in 269 patients (25·8%) for PE suspicion; 59 patients were diagnosed with PE corresponding to an incidence of PE in this COVID-19 population of 5·6%. If we consider only the 269 patients who had had a CTPA, the prevalence of PE was 21·2%;

almost half of the PE events were diagnosed on the day of admission;

BMI, history of venous or arterial thrombosis were not associated with PE occurrence;

invasive mechanical ventilation increased significantly the risk of PE;

PE patients exhibited more extensive lung lesions due to SARS-CoV-2 than controls;

the risk of PE was 5 times higher in patients with D-Dimers above 2500 ng/mL;

no association between deaths and occurrence of PE was observed in this COVID-19 population.

At odds with the initial reports, more recent publications on larger populations seem to show a lower incidence of VTE, mainly in the largest series [6]. Our study, based on a population of 1042 COVID-19 patients hospitalized during the first wave between March 1 and April 20, found a PE prevalence of 5.6%, which is probably underestimated, as CTPA was mainly performed if the patients had signs of PE or worsening oxygen dependence. This rate of PE remains a very high incidence as it is 3 times higher than the 1.7% incidence of PE observed in the prospective PROTECT trial evaluating dalteparin versus unfractionated heparin in ICU [7]. Furthermore, compared to the incidence of PE in the more recent trials of thromboprophylaxis in acutely ill medical patients, this prevalence is 10 times higher.

The accurate estimation of VTE incidence in patients hospitalized for COVID-19 is unclear, as literature data report incidences between 4.8% and 85% [4], [5], [6]. This large variability can be due to the selection of patients, the type of events analyzed (DVT/PE), the systematic screening for VTE or not, and the use of thromboprophylaxis. In a recent meta-analysis the incidence of PE was 12.1% (95% CI; 8.4–16.4) and 7.1% for DVT (95% CI 5.3–9.1). The incidence of total VTE in studies with systematic screening was 3 times higher than in those based on clinical diagnosis (33.1% vs. 9.8%), and the pooled incidence of VTE was 7.1% for patients admitted to the ward and 27.9% in the ICU (two third of the events being VTE) [4]. Interestingly, after exclusion of catheter-associated thrombosis and isolated distal DVT the incidence of DVT was 6.2% (95% CI, 4.1–8.7) and after exclusion of isolated subsegmental PE the incidence of PE was 5.5% (95% CI; 4.0–7.1), almost similar to the rate we found. Another large French multicentric study found a PE prevalence of 8.3% [6]. Recently in a large series of 4244 critically ill adults, a 9% rate of proven PE was found, that is also underestimated as CTPA was not performed in all patients [8]. Another recent study on smaller number of patients, found a similar rate of PE (11.8%) in COVID-19 patients [9]. Finally, a recent Swiss study of 443 patients, found a prevalence of PE of 6.3% and a total rate of VTE of 9.3%, with also a high rate of diagnosis made at admission [10].

The ongoing story of VTE in COVID-19 is not finished as we still need to evaluate more accurately the true rate of PE and DVT, through systematic assessment of patients and prognostic factors associated with thrombosis. The task will be facilitated by a better awareness of the disease and larger prescription of systematic thromboprophylaxis in hospitalized patients [11]. Finally, it will also be an opportunity to decipher the physiopathology of thrombosis associated with SARS-CoV-2 infection, that could allow a better understanding of inflammation induced coagulopathy.

Disclosure of interest

The author declares that he has no competing interest.