Impact of medical care, including use of anti-infective agents, on prognosis of COVID-19 hospitalized patients over time
Authors: COVID-19 RPC Team
Ghilas Boussaid
Véronique Perronne
Pierre Moine
Christine Lawrence
Jean-Claude Alvarez
Christian Perronne
Frédérique Bouchand
Djillali Annane
Isabelle Vaugier
Benjamin Davido
Pierre De Truchis
Frédéric Barbot
Thibaud Lansaman
Azzam Saleh-Mghir
Journal: International Journal of Antimicrobial Agents (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Covid-19; azithromycin; hydroxychloroquine; pneumonia.
Affiliations: Maladies Infectieuses, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France. Electronic address: ., Université Paris-Saclay, UVSQ, Erphan, 78000, Versailles, France., Centre d'Investigation Clinique (Inserm CIC 1429), Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France., Rééducation fonctionnelle, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France., Pharmacie Hospitalière, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France., EOH, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France., Pharmaco-toxicologie, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France., Réanimation médicale, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France., Maladies Infectieuses, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches, France.

Abstract:  Introduction: The effect of anti-infective agents in COVID-19 is unclear. The impact of changes in practice on prognosis over time has not been evaluated. Methods: Single center, retrospective study in adults hospitalized in a medicine ward for COVID-19 from March 5th to April 25th 2020. Patient characteristics were compared between two periods (before/after March 19th) considering French guidelines. The aim of the study was to evaluate how medical care impacted unfavorable outcome, namely admission to intensive care unit (ICU) and/or death. Results: A total of 132 patients were admitted: mean age 59.0±16.3 years; mean C-reactive protein (CRP) level 84.0±71.1 mg/L; 46% had a lymphocyte count &lt;1000/mm3. Prescribed anti-infective agents were lopinavir-ritonavir (n=12), azithromycin (AZI) (n=28) and AZI combined with hydroxychloroquine (HCQ) (n=52). There was a significant decrease in ICU admission, from 43% to 12%, between the two periods (P&lt;0.0001). Delays until transfer to ICU were similar between periods (P=0.86). Pulmonary computerized tomography (CT)-scans were performed significantly more often with time (from 50% to 90%, P&lt;0.0001), and oxygen-dependency (53% vs 80%, P=0.001) and prescription of AZI±HCQ (from 25% to 76%, P&lt;0.0001) were also greater over time. Multivariate analyses showed a reduction of unfavorable outcome in patients receiving AZI±HCQ (hazard ratio [HR]=0.45, 95% confidence interval [CI: 0.21-0.97], P=0.04), particularly among an identified category of individuals (lymphocyte ≥1000/mm3 or CRP ≥100 mg/L). Conclusion: The present study showed a significant decrease in admission to ICU over time, which was probably related to multiple factors, including a better indication of pulmonary CT-scan, oxygen therapy, and a suitable prescription of anti-infective agents. 

Retracted: No

PubPeer comments:
 This paper (Davido and al) describes a study where patients have been admitted in ICU from March 5th to April 25th 2020. To mitigate the occurence of side effects, authors mentioned that * In addition, our experience does not report any serious side effect of this combination therapy as long as we take the necessary caution and perform follow-up ECG using a conventional dose of HCQ, as proposed by Borba et al. [24].* Borba and al describe a study which recruited participants from March 23th 2020 to April 5th, 2020 . Borba and al has been published on April 24th, 2020, the day before the final completion date of the study of Davido and all. [Source: ClinicalTrials.gov] Could the authors explain how they were able to follow the safety recommendations of a study (Borba and al) not yet started ? And from an article not yet published ? ,