Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study

ABSTRACT

Objectives To evaluate the impact of low molecular weight heparin (LMWH) on the outcome of patients with SARS-CoV-2 pneumonia. Methods Prospective observational study including consecutive patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (4th March-30th April 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe ARDS. LMWH, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox-regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent Propensity-score (PS) was calculated and a PS-matching performed for each treatment variable. Results Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) hydroxychloroquine, 201 (63.8%) proteases inhibitors, 150 (47.6%) doxycycline, 141 (44.8%) steroids, 42 (13.3%) macrolides, 40 (12.7%) baricitinib, 13 (4.1%) tocilizumab, and 13 (4.1%) remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (HR 0.36 [95% CI 0.21-0.6], p<0.001) and composite endpoint (HR 0.61 [95% CI 0.39-0.95], p=0.029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in Covid-19. Randomized controlled trials are warranted to confirm these preliminary findings.