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in just a few hours&#44; to a rare wave of pessimism among the groups of professionals in charge of making decisions in many hospitals&#46; This was reflected in heated discussions via WhatsApp and other forums&#44; leading to the abrupt removal of lopinavir&#47;ritonavir from the treatment protocols of several large centers in our country&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Nevertheless&#44; the result of the information from a trial such as that one must be taken cautiously and analyzed with a critical&#44; rigorous eye&#46; The work suffers from various methodological problems in the design and in patient recruitment related to the urgent nature of the work&#46; The authors themselves recognize these aspects in the discussion&#46; Patient assignment was not blind and the desirable placebo control was not able to be established for patients who did not receive the drug in said study&#46; Likewise&#44; plasma levels of lopinavir&#47;ritonavir were not able to be determined and could have been compromised in critical patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">On the other hand&#44; the study lacks power for outcomes that are secondary in the design&#44; but which are important&#44; such as mortality&#46; Assuming the same premises as for the principal variable&#44; between 200 and 860 additional patients would have been needed in each arm to demonstrate differences&#46; In addition&#44; although the overall benefit was weak&#44; a close reading allows for observing how the use of lopinavir&#47;ritonavir could point towards a trend in mortality reduction if it is used in the first 12 days&#46; Among patients treated earlier&#44; the primary objective was indeed achieved&#44; with respective mortality of 15&#37; versus 27&#37; in each arm&#46; What&#8217;s more&#44; the other secondary aims&#44; such as a stay in the intensive care unit &#40;5 days of difference&#41; and the percentage of patients who developed ARDS &#40;12&#37; versus 24&#37;&#41;&#44; were also improved&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In our opinion&#44; the fundamental issue is that patients were treated too late &#40;median of 13 days from onset of symptoms&#41; and in monotherapy&#46; Therefore&#44; although it did not achieve the primary aim&#44; the results indicate that the treated group could progress better&#46; Therefore&#44; it remains to be determined if the use of lopinavir&#47;ritonavir in the earliest phases and&#47;or in combination with other potentially active drugs would benefit patients or not&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nevertheless&#44; we are aware of the lack of trust that protease inhibitors and their limited in vitro activity generate and in their clinical efficacy in this novel coronavirus and in others &#40;SARS-CoV&#44; MERS-CoV&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The controversial results of this study had already in part been anticipated in another Chinese study&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which did not demonstrate a benefit to treatment with lopinavir&#47;ritonavir and abidol&#46; Furthermore&#44; Janssen has reported unpublished data on the inefficacy of darunavir&#47;cobicistat in the treatment of 30 patients with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Even so&#44; while awaiting new evidence or consolidated alternative therapies&#44; it seems prudent to continue using the optimize form of the few drugs we do have available&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In catastrophic times&#44; it is important to keep a cool head and even keel when it comes to making decisions that may determine a patient&#8217;s prognosis&#46;</p></span>"
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Correspondence
Whether to make decisions "on the fly" regarding treatment for SARS-CoV-2 infection
Tomar o no tomar «decisiones en caliente» respecto al tratamiento de la infección por SARS-CoV-2
V. Abril López de Medranoa,
Corresponding author
, E. Merino de Lucasb, M. Salavert Lletíc
a Consorcio Hospital General Universitario de Valencia, Valencia, Spain
b Hospital General Universitario de Alicante, Alicante, Spain
c Hospital Universitario y Politécnico La Fe, Valencia, Spain

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