Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients
Authors: Warrior Surbhi , Behrens Elizabeth , Thomas Joshua , Rajakumar Priya , Gezer Sefer , Venugopal Parameswaran , Jain Shivi 
Published: February 2021

Background
The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.
Methods
A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.
Results
Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p&lt;.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p&lt;0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p&lt;.0001), and Remdesivir 72% (p&lt;.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).
Conclusion
In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.

Disclosures
No relevant conflicts of interest to declare.