Letter in response to article in journal of infection: “Cardiovascular complications in COVID-19: A systematic review and meta-analysis”

To the Editor,

We read with great interest the systematic review and meta-analysis by Kunutsor and Laukkanen, which was recently published in the Journal of Infection and attempted to investigate the cardiovascular complications of coronavirus disease 2019 (COVID-19).¹ The authors investigated and reported the pooled incidence for cardiac arrhythmia, heart failure, cardiomyopathy, disseminated intravascular coagulation, cardiac arrest, acute coronary syndrome, stroke, and among these pulmonary embolism (PE) and venous thromboembolism (VTE). The authors report an extensive search that included three databases (MEDLINE, Embase, Cochrane Library) with the last search date reported as of May 27^th, 2020. The proposed search term combinations included “Pulmonary Embolism” and “Venous Thromboembolism”, however, the authors identified only one study reporting on VTE and PE.

There are several limitations regarding the systematic review and meta-analysis of PE and VTE complications. First, the authors should have clarified how they defined VTE in their study since VTE, by definition, includes both PE and deep vein thrombosis (DVT). Second, the study by Klok et al. has been updated with 65 PE events and a total of 75 thrombotic events.² Third, to our knowledge, there are at least nine studies published before May 27th, 2020 that we identified on a similar search on May 26th, 2020 and that report extractable data on the incidence of PE and DVT and that the authors failed to include.2., 3., 4., 5., 6., 7., 8., 9., 10. Cui et al. (published on April 9th, 2020) reported a lower extremity DVT incidence of 25% (n = 20/81).³ Tavazzi et al. (published on April 22nd, 2020) reported a DVT incidence of 14.8% (n = 8/54) in mechanically ventilated patients admitted in an intensive care unit (ICU), despite being on anticoagulant prophylaxis.⁴ Leonard-Lorant et al. (published on April 23rd, 2020) investigated the results of pulmonary computed tomography scans in 106 patients diagnosed with COVID-19 and reported a PE incidence of 30% (n = 32/106).⁵ Middeldorp et al. (published May 5th, 2020) investigated the incidence of VTE (DVT, PE, other venous thromboses) in hospitalized patients with COVID-19 treated with standard of care anticoagulant prophylaxis and reported a cumulative incidence of 16%, 33%, and 42% on days 7, 14, and 21, respectively.⁶ Poissy et al. (published on April 24th, 2020) recruited 107 patients admitted in the ICU and identified 22 cases of PE with a 20.4% cumulative incidence on day 15 after ICU admission.⁷ Thomas et al. (published on April 25th, 2020) reported a cumulative VTE incidence of 27% in 63 COVID-19 patients in the ICU.⁸ In a multicenter prospective study, Helms et al. (published on May 4th, 2020) included COVID-19 patients admitted in four ICUs in two French centers and documented a PE incidence of 25% (n = 25/99).⁹ Last but not least, Ren et al. (published on May 15th, 2020) reported a lower extremity DVT incidence of 85.4% (n = 41/48).¹⁰

Based on the abundance of studies reporting on VTE incidence, the findings of this systematic review and meta-analysis should be considered with caution. The standard thromboprophylaxis doses seem inadequate to prevent VTE in critical or severe COVID-19, contributing to an unacceptably high rate of thromboembolic events. Ongoing prospective randomized trials (NCT04401293, NCT04359277) are already enrolling patients and will hopefully elucidate the role of higher heparin doses for the prevention of thromboembolic events in COVID-19. Future, well-designed systematic reviews that include the constantly increasing literature on VTE will provide further insights into the actual incidence of COVID-19 associated DVT and PE.

Declaration of Competing Interest

The authors state that they have no competing interests.