key: cord-0757500-n9i55f8b
authors: Stessel, Björn; Peeters, Jeroen; Bruckers, Liesbeth; Nulens, Marijke; Callebaut, Ina; Poelaert, Jan; Dubois, Jasperina
title: Bacterial surinfection and venous thromboembolism in critically ill ICU patients with COVID-19: What is the relationship?
date: 2021-08-27
journal: Thromb Res
DOI: 10.1016/j.thromres.2021.08.023
sha: 1d61aff498d2cee9a6b375b66752cfb216ebb8ea
doc_id: 757500
cord_uid: n9i55f8b

nan

due to the current Coronavirus disease 2019 (COVID-19/SARS-CoV-2) pandemic. The vast majority of patients with severe COVID-19 initially presents with single organ failure, i.e. hypoxemic respiratory failure (1) . A growing body of research suggests that severe COVID-19 infection, despite routinely low dose pharmacological venous thromboembolism (VTE) prophylaxis with Low Molecular Weight Heparins (LMWH), is associated with a high incidence of thromboembolic phenomena (2, 3) . Acute bacterial infection is another well-described cause of venous thromboembolism (4, 5) . Bacterial coinfection is relatively infrequent in hospitalized patients with COVID-19 but more common in critically ill patients (8.1%) (6) . We wondered if there is, independently from the causal relationship between SARS-CoV-2 and elevated thrombosis risk, also a superimposed clear association between bacterial co-infection in COVID-19 patients admitted to the ICU and thrombosis risk. In view of the fact that many of those patients suffer from multiple episodes of co-infections, it would be additionally interesting to assess whether an association between total number of co-infection episodes and thrombosis risk could be found. Therefore, we investigated if there is a relationship between the number of diagnosed VTEs and the number of episodes of bacterial co-infections in COVID-19 patients admitted to the ICU.

In this monocentric, investigator-initiated, longitudinal, retrospective, observational cohort study, all patients diagnosed with COVID-19 pneumonia and admitted to the ICU department of the Jessa Hospital, Hasselt, Belgium from 13th March 2020 until 17th October 2020 were enrolled. This study was approved by the ethical committee of Jessa Hospital on 14th April 2021 (2021037) and registered on clinicaltrials.gov (NCT04877808). In light of the urgent need to collect data in the ongoing pandemic, written informed consent was waived. Only laboratory-confirmed patients were local, e.g PEs which could be expected in hospitalized patients due to pneumonia a, but DVTs, which is in contradiction with previous literature (11) , might suggest that the mechanism responsible for the increased risk is systemic.

A second more controversial hypothesis to explain these results might be that COVID-19 ICU patients suffering from VTE are more at risk to develop bacterial co-infections (i.e. reverse causation), for instance: simply by prolonging hospitalization. The formation of thrombi stimulated by a COVID-19

infection might also create a perfect breeding ground for bacteria (12) . A thrombus can be infected via a distant, typically unidentified source of bacteremia and the poor antibiotic penetration of large size thrombi carry the risk of recurrent episodes of bacteremia (12) . In line with this hypothesis might micro-embolization of thrombi in the pulmonary vascular bed also explain the higher incidence of pneumonia in COVID-19 patients with VTE.

Finally, a third bystander may also cause both VTE and bacterial coinfections. For instance, a more severe COVID-19 disease or pre-existing comorbidities may independently increase the risk of both bacterial infection and VTE.

This study contains some limitations. First, the exact timing of diagnosis of VTE and bacterial coinfection episodes was not recorded. Therefore, we cannot draw firm conclusions regarding the temporal association between bacterial co-infections and VTE formation. Second, pulmonary embolisms were not systematically screened, potentially underestimating the presence of thromboembolic events. Finally, the mono-centric design of this study may limit the generalizability of these results.

In conclusion, our study suggests that, independently from the causal relationship between SARS-CoV-2 and elevated thrombosis risk, a superimposed clear association between bacterial co-infection and thrombosis risk is present in patients with a severe COVID-19 infection admitted to the ICU.

J o u r n a l P r e -p r o o f

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

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