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(In adult patients admitted to hospital with confirmed COVID-19) does (lopinavir–ritonavir) lead to (reduced mortality and/or reduced length of stay and/or reduced time to improvement)?
A 52-year-old man presented to the ED with a 9-day history of coryzal symptoms including sore throat and fever, after 5 days developed a dry cough and shortness of breath on exertion. His shortness of breath had become more severe over the last 24 hours, now breathless at rest and complaining of right-sided pleuritic chest pain. Chest X-ray and blood result findings were highly suspicious of COVID-19 and this was confirmed on PCR testing. With ongoing research into novel therapies for COVID-19, you wonder if lopinavir–ritonavir would reduce mortality or length of hospital stay for this patient.
A search of EMBASE (1974 to 2020 week 22) using Ovid interface, Medline (1946 to 3 June 2020) using Ovid interface and PubMed as well as the Cochrane Library and Google Scholar was carried out to ensure no missing relevant material
(Lopinavir-Ritonavir OR Lopinavir-Ritonavir OR Kaletra OR exp Ritonavir/ OR exp Lopinavir/) AND ((Covid-19 OR coronavirus OR Severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR 2019 novel coronavirus OR 2019-nCoV or coronavirus disease 2019)).af. LIMIT to (2019 -Current and human and English language).
The searches returned 166 papers of which 5 were clinically relevant (see table 1).
Lopinavir/ritonavir, a protease inhibitor previously used in treatment of HIV has been suggested as a potentially effective treatment for COVID-19. Initial evidence in vitro showed promising results with Choy et al 6 showing inhibition on viral replication. Most of the literature in humans thus far is descriptive. The only high-level evidence is the randomised controlled trial by Cao et al published in the NEJM. This showed no significant difference in time to clinical improvement or 28-day mortality when compared with a control. Modified intention-to-treat analysis did show marginal improvement in length of stay (15 days vs 16 days) when patients excluded from the treatment group after death prior to administration of medication. There is some observational evidence that treatment with antivirals may shorten viral shedding and, separately, prolonged viral shedding has been shown to be an independent risk factor for mortality. There is, however, no significant causative relationship thus demonstrated between lopinavir–ritonavir treatment and the outcomes in the clinical question.
Clinical bottom line
There is no current evidence to support the use of lopinavir–ritonavir in COVID-19 to improve clinical outcomes.
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