Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis

Abstract

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.

Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis

“…Ten articles from Medrxiv/Google Scholar were added, so 29 articles were included, of which 25 were observational studies, one was an interventional non-randomized study and three were RCT. These studies included 27 articles for hydroxychloroquine [ [14] , [15] , [16] , [17] , [18] , [19] , 23 , 24 , 36 , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] ] and 12 articles for hydroxychloroquine + azithromycin [ 18 , 36 , 41 , 42 , 47 , 48 , 50 , 51 , [57] , [58] , [59] , [60] ]. For chloroquine, after searching PubMed, Cochrane Review, Embase and Web of Science, 449 articles were identified.…”

“…Ten studies were conducted in the USA [ 15 , 18 , 23 , 41 , 42 , 49 , 50 , 53 , 56 , 58 ], four in Spain [ 16 , 17 , 44 , 57 ], seven in France [ 13 , 24 , 46 , 48 , 54 , 59 , 60 ], one in the UK [ 40 ], two in Italy [ 43 , 65 ], one in China [ 14 ], one in Brazil [ 51 ] and three in several other countries (USA, Canada, Italy and Spain) [ 39 , 47 , 52 ]. Twenty-two articles were published [ [13] , [14] , [15] , 17 , 18 , 24 , 39 , 41 , 43 , 44 , 46 , 47 , [49] , [50] , [51] , [52] , [53] , [54] , 56 , 57 , 59 , 60 , 65 ] and six articles were preprints [ 16 , 23 , 40 , 42 , 48 , 58 ]. Mean daily dose of hydroxychloroquine ranged from 333 mg/day to 945 mg/day.…”

“…Among the observational studies, fourteen articles had a moderate or serious risk of bias [ [13] , [14] , [15] , [16] , [17] , [18] , 41 , 42 , 44 , [46] , [47] , [48] , 56 , 58 ] and eleven studies had a critical risk of bias [ 23 , 43 , 49 , 50 , [52] , [53] , [54] , 57 , 59 , 60 , 65 ]. Eleven observational studies did not report adjusted effect sizes to control confusion and selection bias [ 23 , 24 , 43 , 44 , 49 , 53 , 54 , 57 , 59 , 60 , 65 ]. Quality of studies was lowered by the lack of information about the assignment of treatment, the time between start of follow up and start of intervention, some unbalanced co-intervention with other antiviral and antibiotic drugs and imbalance between groups for confounders such as co-morbidities and age.…”

Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results

“…This finding indicates that the use of hydroxychloroquine at this stage of disease would be not useful. Randomized controlled trials are required to show whether this drug could be useful in ICU patients admitted for Covid-19 [15] .…”

Covid-19 Therapy: What Have We Learned In 8 Months?

“…A case study of a patient, treated with Lopinavir/Ritonavir for chronic HIV demonstrate that the treatment failed not only to prevent SARS-CoV-2 infection, but also failed to prevent rapid progression to severe pneumonia [85]. Also a retrospective study did not confirm the efficacy of Lopinavir/Ritonavir in COVID19 treatment compared to standard care [100]. Also the comparison of effectiveness of Lopinavir/Ritonavir to Arbidol demonstrate the superiority of Arbidol in COVID-19 treatment [203].…”