Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS‐CoV‐2 infection: A retrospective cohort study
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Abstract
As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID‐19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent‐to‐treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30‐day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30‐day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50‐4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID‐19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID‐19.
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SciScore for 10.1101/2020.06.05.20123299: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The study was approved by hospital’s ethical committee (Comitato Etico Interaziendale Area 1), and all of the study patients gave their written informed consent to the administration of off-label treatment (informed consent was waived in the case of those undergoing mechanical ventilation).
Consent: The study was approved by hospital’s ethical committee (Comitato Etico Interaziendale Area 1), and all of the study patients gave their written informed consent to the administration of off-label treatment (informed consent was waived in the case of those undergoing mechanical ventilation).Randomization not detected. Blinding not detected. Power Analysis not … SciScore for 10.1101/2020.06.05.20123299: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The study was approved by hospital’s ethical committee (Comitato Etico Interaziendale Area 1), and all of the study patients gave their written informed consent to the administration of off-label treatment (informed consent was waived in the case of those undergoing mechanical ventilation).
Consent: The study was approved by hospital’s ethical committee (Comitato Etico Interaziendale Area 1), and all of the study patients gave their written informed consent to the administration of off-label treatment (informed consent was waived in the case of those undergoing mechanical ventilation).Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The data were analysed using SAS software, version 9.4, and a p-value of < 0.05 was considered statistically significant. SASsuggested: (SASqPCR, RRID:SCR_003056)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has a number of limitations. Firstly, given the emergency context in which it was carried out, it was impossible to include a control group, and so we cannot exclude the possibility that the patients whose status improved after LPV/r+HCQ treatment would have improved regardless of any treatment. Secondly, a relatively large proportion of our patients received other experimental treatments during the study period, and this is clearly a confounding factor when analysing the efficacy LPV/r+HCQ: however, as there was no between-group difference in the proportion of patients who received other treatments, it is likely that this had no impact on our analysis of the effect that the time of starting treatment had on COVID-19 outcomes. Thirdly, the treatment’s virological efficacy (i.e. the reduction in viral load in nasopharyngeal secretions) could not be assessed because there was no regular monitoring of the presence of SARSCoV-2 genome on nasopharyngeal swabs and the RT-PCR available in our microbiology department only provides qualitative data. Finally, the study was conducted in the ever-changing scenario created by the dramatic escalation of the epidemic in Northern Italy. The Infectious Diseases Department of Luigi Sacco Hospital acts as a north Italian reference centre for infectious diseases. Consequently, our findings concerning the potential use of LPV/r+HCQ relate to hospitalised patients in the early wave of the Italian pandemic and may not extend inferred to o...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
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