Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the incidence of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate the synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival.
This was a secondary analysis of a retrospective cohort. Patients included in this study were older than 18 years of age and admitted for severe COVID-19 pneumonia between March to June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was performed to assess hazard ratio.
In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [HR =2.92 (95% CI 1.54, 5.55 P< 0.0001)]. The was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P<0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups. (P 0.40). There was no higher risk in high dose versus low dose
[RR=0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for DVT/PE between methylprednisolone for > 7 days and < 7 days was statistically significant. (RR=5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR=1.81 95% CI 0.994 to 3.294) (P=0.0522). There was no difference in 30 days in hospital survival between high dose with prophylactic or therapeutic heparin (HR=0.827 95% CI 0.514 to 1.33) (P=0.4335).
Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.