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Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome

Hraiech et al., Ann. Intensive Care, doi:10.1186/s13613-020-00678-4
May 2020  
  Source   PDF   All Studies   Meta AnalysisMeta
Mortality 65% Improvement Relative Risk Mortality (b) -376% Viral clearance -3% HCQ for COVID-19  Hraiech et al.  ICU PATIENTS Is very late treatment with HCQ beneficial for COVID-19? Retrospective 32 patients in France Lower mortality with HCQ (not stat. sig., p=0.21) Hraiech et al., Ann. Intensive Care, May 2020 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter et al. show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
This study is excluded in the after exclusion results of meta analysis: very late stage, ICU patients.
risk of death, 64.7% lower, RR 0.35, p = 0.21, treatment 2 of 17 (11.8%), control 5 of 15 (33.3%), NNT 4.6, day 38 +- 7.
risk of death, 376.5% higher, RR 4.76, p = 0.49, treatment 2 of 17 (11.8%), control 0 of 15 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), day 6 from ARDS.
risk of no viral clearance, 2.9% higher, RR 1.03, p = 1.00, treatment 14 of 17 (82.4%), control 8 of 10 (80.0%), day 6 from treatment.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hraiech et al., 24 May 2020, retrospective, France, peer-reviewed, 8 authors, average treatment delay 7.0 days.
This PaperHCQAll
Abstract: (2020) 10:63 Hraiech et al. Ann. Intensive Care LETTER TO THE EDITOR Open Access Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS‑CoV‑2‑related acute respiratory distress syndrome Sami Hraiech1,2* , Jérémy Bourenne2,3, Khaldoun Kuteifan4, Julie Helms5, Julien Carvelli2,3, Marc Gainnier2,3, Ferhat Meziani5 and Laurent Papazian1,2 The current international outbreak of respiratory illness due to SARS-CoV-2 and named Covid-19 can evolve to severe progressive pneumonia and acute respiratory distress syndrome (ARDS), multiorgan failure, and death. Up to now, there are no specific therapeutic agents for coronavirus infections. Lopinavir–ritonavir treatment recently failed to demonstrate any significant outcome benefit, but the study was underpowered to rule out clinically meaningful treatment effects, and the intervention was started a median of 13 days after symptoms onset [1]. In vitro inhibition of virus spread has been reported with chloroquine prior to or after SARS-CoV-2 infection [2]. Hydroxychloroquine has been found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro [3] and a recent report suggested that 70% of 20 non-ICU hydroxychloroquine-treated patients had negative PCR results in nasopharyngeal samples at day 6 (D6) post-inclusion [4] and in all the 6 patients treated with hydroxychloroquine and azithromycin combination (hydroxychloroquine–azithromycin) [4]. In order to evaluate these results in intensive care unit (ICU) patients, we retrospectively assessed in moderate-to-severe ARDS the efficacy of hydroxychloroquine–azithromycin combination regarding viral disappearance at both day 6 of the treatment and day 6 of evolution of ARDS as compared *Correspondence: sami.hraiech@ap‑ 1 Assistance Publique ‑ Hôpitaux de Marseille, Hôpital Nord, Médecine Intensive Réanimation, Hôpital Nord, 13015 Marseille, France Full list of author information is available at the end of the article with patients treated with lopinavir–ritonavir and a control group without any anti-viral treatment. Forty-five patients were included, 17 receiving the combination of hydroxychloroquine 600 mg and azithromycin 500 then 250 mg daily, 13 receiving lopinavir– ritonavir 800 mg daily and 15 who did not receive any anti-viral treatment (controls). Patients were admitted to 4 ICUs in 2 different regions of France from March 2nd to March 31st. In one ICU, they received hydroxychloroquine–azithromycin as a usual policy while this combination was maintained if started prior to admission in the second ICU (the other patients receiving lopinavir–ritonavir). Controls were treated in 2 other ICUs with antibiotics targeting bacterial community acquired pneumonia only. In all patients, nasopharyngeal PCR for SARS-CoV-2 were performed at the time of diagnosis and then regularly during ICU stay in order to assess viral clearance. Results of PCR were qualitative at the beginning of the pandemic, then quantitative and expressed by the PCR cycle threshold (CT). Data were expressed as mean ± the standard deviation or median with interquartile range for the quantitative variables, and as numbers and percentages for the categorical variables. Groups were compared using the Chi-square or Fisher’s exact test for categorical characteristics, and using the Student’s t test or Mann–Whitney U test for continuous ones. A two-sided p value of less than..
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Late treatment
is less effective
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