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 multicentre observational study
Authors: Grimaldi David , Aissaoui Nadia , Blonz Gauthier , Carbutti Giuseppe , Courcelle Romain , Gaudry Stephane , Gaultier Aurelie , D’hondt Alain , Higny Julien , Horlait Geoffrey , Hraiech Sami , Lefebvre Laurent , Lejeune Francois , Ly Andre , Piagnerelli Michael , Sauneuf Bertrand , Serck Nicolas , Soumagne Thibaud , Szychowiak Piotr , Textoris Julien , Vandenbunder Benoit , Vinsonneau Christophe , Lascarrou Jean- Baptiste ,   for the COVADIS study group, Biston Patrick , Colin Gwenhael , de Maere Oriane , Ebstein Nathan , Ehrmann Stephan , Foret Frederic , Haentjens Lionel , Helbert Thibault , Mesland Jean-Baptiste , Monard Celine , Mongardon Nicolas , Ottavy Gregoire , Pasau Thomas , Piton Gael , Ponzetto Ester , Sejourne Caroline , Snacken Morgane , Souloy Xavier , Sylvestre Aude , Tartrat Nicolas , Vanbrussel Cedric 
Published: October 2020

Abstract
Background
Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS).

Methods
Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into “patients still ventilated or dead at day 28” versus “patients weaned and alive at day 28”.

Results
We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0–13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18–1.25); OR 0.96 (0.47–2.02) and OR 1.43 (0.53–4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16–5.59).

Conclusion
In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT.
Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement.
Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT