Thrombosis and thromboembolism related to COVID‐19: A clarion call for obtaining solid estimates from large‐scale multicenter data

Abstract

The clinical spectrum of coronavirus disease 2019 (COVID‐19) is wide, ranging from minor, nonspecific symptoms to severe pneumonia, acute respiratory distress syndrome, multiorgan involvement, and shock. In severe cases, the acute systemic inflammatory response, coagulation activation, and diffuse endothelial damage may, in combination with hypoxia, immobilization, and underlying risk factors, result in potentially life‐threatening venous and arterial thrombotic events. The first data from single‐center retrospective studies suggest that thrombotic events are a key aspect of COVID‐19‐associated morbidity and mortality. We have planned and will be launching the COvid REgistry on THROMBOSIS (CORE‐THROMBOSIS), a large online registry of previously or currently hospitalized patients with COVID‐19. The study aims to (i) determine the rate of acute thrombotic events in consecutive hospitalized patients with coronavirus (COVID‐19); (ii) investigate the current use and trends in thromboprophylaxis regimens; and (iii) describe the use of imaging tests for the detection of cardiovascular events in patients with COVID‐19.

The clinical spectrum of coronavirus disease 2019 (COVID‐19) is wide, ranging from minor, nonspecific symptoms to severe pneumonia, acute respiratory distress syndrome, multiorgan involvement, and shock. ¹ , ² , ³ In severe cases, the cytokine storm following the viral infection precipitates an acute systemic inflammatory response and diffuse endothelial damage, which may, in combination with hypoxia, immobilization, and underlying risk factors, result in potentially life‐threatening venous and arterial thrombotic events. ⁴ , ⁵ , ⁶ In fact, clinical and laboratory findings reported in patients with COVID‐19 since the beginning of this outbreak frequently include hemostatic abnormalities, which have been associated with an unfavorable in‐hospital outcome in preliminary reports. ⁷ , ⁸ , ⁹ Physicians involved in the care of patients with COVID‐19 in large‐volume centers keep emphasizing that they have “never seen so many patients with deep vein thrombosis or pulmonary embolism” as they do right now. First retrospective studies appear to support this assumption, ¹⁰ , ¹¹ , ¹² , ¹³ although it is currently debated whether the thrombosis risk among severely ill COVID‐19 patients requiring intensive care is significantly higher than that in patients with sepsis and shock related to other bacterial or viral pathogens. ¹⁴ , ¹⁵ , ¹⁶ In parallel, evidence is beginning to accumulate on cardiac injury, cardiovascular mortality, ¹⁷ , ¹⁸ and stroke ¹⁰ in COVID‐19.

Taken together, the first publications summarized above suggest that thrombotic events are a key aspect of COVID‐19‐associated morbidity and mortality. ¹⁶ It is therefore now imperative to move beyond individual and small‐group observations to systematic large‐scale data collection at a multinational level. Randomized controlled trials, or even single‐arm prospective management studies for diagnosing and managing thrombosis and thromboembolism in the hospital setting, are at least theoretically the best way to generate high‐level evidence, but they appear unfeasible at the present stage for several reasons. First, performing serial diagnostic tests, such as computed tomography coronary angiography, as part of study protocols may pose insurmountable logistical challenges to emergency and radiology departments of hospitals overwhelmed by admissions during the outbreak. Second, the large majority of patients with COVID‐19 are, and will increasingly be, expected to enter treatment trials targeted at the viral disease itself, and competition for patients will be counterproductive for all those involved in these efforts. Finally, a purely prospective trial will essentially miss the very large number of patients hospitalized over the past months during the first wave of the infection. In light of all the above, we have planned and will be launching in the next few days COvid REgistry on THROMBOSIS (CORE‐THROMBOSIS), a large online registry of previously or currently hospitalized patients with COVID‐19. The study aims to (i) determine the rate of acute arterial or venous thrombotic events in consecutive hospitalized patients with coronavirus (COVID‐19); (ii) investigate the current use and trends in thromboprophylaxis regimens; and (iii) describe the use of imaging tests for the detection of cardiovascular events in patients with COVID‐19. The electronic case report form of the study will include strictly anonymized data, permitting rapid, nonbureaucratic approval by local ethics committees and online data entry. Past “closed” as well as current and future cases will be included, and participating investigators will commit themselves to do their best to not miss any case of confirmed arterial or venous thrombosis related to COVID‐19 in their institution. Being purely observational and having a user‐friendly, fast‐to‐complete data entry form, CORE‐THROMBOSIS will not devour the time of clinical researchers or study teams, and it will not interfere with any parallel therapeutic trials or even other registries. We believe that by including a large number of both prevalent and incident cases within a short time period, CORE‐THROMBOSIS will provide observational but nevertheless representative data on the magnitude of the problem, and it will enable us to formulate robust hypotheses to be tested in future prophylaxis and management trials.

We ask interested investigators to join this effort and actively participate in CORE‐THROMBOSIS by contacting us at s.barco@uni‐mainz.de.

RELATIONSHIP DISCLOSURE

SB reports personal fees from Biocompatibles Group UK and Bayer HealthCare, nonfinancial support from Bayer HealthCare and Daiichi Sankyo, outside the submitted work. SVK reports grants and nonfinancial support from Bayer AG, grants and personal fees from Boehringer Ingelheim, personal fees from Bayer AG, grants and personal fees from Actelion, grants and personal fees from Daiichi‐Sankyo, grants and personal fees from Biocompatibles Group UK, personal fees from Pfizer–Bristol‐Myers Squibb, and grants and personal fees from MSD, outside the submitted work.

Barco S, Konstantinides SV. Thrombosis and thromboembolism related to CsOVID‐19: A clarion call for obtaining solid estimates from large‐scale multicenter data. Res Pract Thromb Haemost. 2020;4:741–743. 10.1002/rth2.12364