Characteristics and outcomes of Acute Respiratory Distress Syndrome related to COVID-19 in Belgian and French Intensive Care Units according to antiviral strategies. The COVADIS multicenter observational study

  1. David Grimaldi
  2. Nadia Aissaoui
  3. Gauthier Blonz
  4. Giuseppe Carbutti
  5. Romain Courcelle
  6. Stephane Gaudry
  7. Alain D’hondt
  8. Julien Higny
  9. Geoffrey Horlait
  10. Sami Hraiech
  11. Laurent Lefebvre
  12. Francois Lejeune
  13. Andre Ly
  14. Michael Piagnerelli
  15. Bertrand Sauneuf
  16. Nicolas Serck
  17. Thibaud Soumagne
  18. Piotr Szychowiak
  19. Julien Textoris
  20. Benoit Vandenbunder
  21. Christophe Vinsonneau
  22. Jean-Baptiste Lascarrou
  23. for the COVADIS study group
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Abstract

Background

Limited data are available for antiviral therapy efficacy especially for the most severe patients under mechanical ventilation suffering from Covid-19 related Acute Respiratory Distress Syndrome (ARDS).

Methods

Observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, comparing antiviral strategies (none, hydroxychloroquine (HCQ), lopinavir/ritonavir (L/R), others (combination or remdesivir). The primary end-point was the day-28 ventilator free days (VFD), patients which died before d28 were considered as having 0 VFD. The variable was dichotomized in patients still ventilated or dead at day 28 vs patients being extubated and alive at day 28 (VFD = or >0).

Results

We analyzed 376 patients (80 with standard of care (SOC), 49 treated with L/R, 197 with HCQ, and 50 others). The median number of d28-VFD was 0 (IQR 0-13) and was different across the different groups (P=0.01), the SOC patients having the highest d28-VFD. A multivariate logistic regression including antiviral strategies, showed that age (OR 0.95 CI95%:0.93-0.98), male gender (OR 0.53 CI95%:0.31-0.93), Charlson score (OR 0.85 CI95%:0.73-0.99) and plateau pressure (OR 0.94 CI95%:0.88-0.99) were associated with having 0 d28-VFD whereas P/F ratio (OR 1.005 CI95%:1.001-1.010) was associated with having ≥1 d28-VFD (ie. being extubated and alive). Acute kidney injury (AKI) was frequent (64%), its incidence was different across the patients’ groups (P=0.01). In a post-hoc logistic multivariate regression apart from demographics characteristics and comorbidities, the use of L/R (administered to 81 of 376 patients was associated with occurrence of AKI (OR 2.07 CI95%:1.17-3.66) and need for renal replacement therapy (RRT).

Conclusion

In this observational study of moderate to severe Covid-19 ARDS patients, we did not observed a benefit of treating patients with any specific antiviral treatment. We observed an association between L/R treatment and occurrence of AKI and need for RRT.

Take home message

Any specific COVID-19 antiviral treatment is associated with higher ventilator free days at day 28 as compared to no antiviral treatment for patient in ICU under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of acute kidney injury.

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COVID-19: Insights from ARDS cohort: no signal of efficacy for antiviral treatments. Lopinavir/ritonavir may be associated with AKI and need for RRT.

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