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. 2021 May 31;11(1):11334.
doi: 10.1038/s41598-021-90713-6.

Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia

Alessandra Vergori  1 , Patrizia Lorenzini  2 , Alessandro Cozzi-Lepri  3 , Davide Roberto Donno  4 , Gina Gualano  5 , Emanuele Nicastri  6 , Fabio Iacomi  7 , Luisa Marchioni  8 , Paolo Campioni  9 , Vincenzo Schininà  9 , Stefania Cicalini  2 , Chiara Agrati  10 , Maria Rosaria Capobianchi  11 , Enrico Girardi  12 , Giuseppe Ippolito  13 , Francesco Vaia  14 , Nicola Petrosillo  4 , Andrea Antinori #  2 , Fabrizio Taglietti #  3   4 ; ReCOVeRI Study Group
Collaborators, Affiliations

Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia

Alessandra Vergori et al. Sci Rep. .

Abstract

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50-77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2-26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7-15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51-3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03-2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

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Conflict of interest statement

The corresponding author is responsible for submitting a competing interests statement on behalf of all authors of the paper. Alessandra Vergori, Patrizia Lorenzini, Alessandro Cozzi lepri, Davide Roberto Donno, Emanuele Nicastri, Gina Gualano, Fabio Iacomi, Luisa Marchioni, Paolo Campioni, Vincenzo Schininà, Stefania Cicalini, Chiara Agrati, Maria Rosaria Capobianchi, Enrico Girardi, Giuseppe Ippolito, Francesco Vaia, Nicola Petrosillo, Andrea Antinori and Fabrizio Taglietti have no competing interests that might be perceived to influence the results and/or discussion reported in this paper. Outside of this submitted work: Alessandra Vergori received institutional grant from Gilead Sciences, personal fees and travel grant from Janssen, personal fee from MSD; Andrea Antinori has served as a paid consultant to Gilead Sciences, Janssen-Cilag, Merck and ViiV Healthcare and received research institutional grants from Gilead Sciences, Janssen-Cilag and ViiV Healthcare; Enrico Girardi received institutional grants for Gilead Sciences and Mylan, personal fees from Gilead Sciences and ViiV; Nicola Petrosillo received personal fees from Shionogi Ltd, MSD, Becton &Dickinson, Pfizer and Cepheid. The other co-authors declare no conflicts of interests outside the submitted work.

Figures

Figure 1
Figure 1
Scatterplot and regression line representing the correlation between (a) D-dimer and Padua score and between (b) D-dimer and PaO2/FiO2.
Figure 2
Figure 2
(a) Estimated probability of mechanical invasive oro-tracheal intubation/death (OTI/death) according to pLMWH exposure in the study population and stratified by PaO2/FiO2 ratio at admission (b) > 300 mmHg and (c) ≤ 300 mmHg. pLMWH prophylactic low molecular weight heparin, OTI/death oro-tracheal intubation/death.
See this image and copyright information in PMC

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