• Lammers A J J AJJ Isala, Zwolle, The Netherlands. Electronic address: a.j.j.lammers@isala.nl., R M Brohet, R E P Theunissen, C Koster, R Rood, D W M Verhagen, K Brinkman, R J Hassing, A Dofferhoff, R El Moussaoui, G Hermanides, J Ellerbroek, N Bokhizzou, H Visser, M van den Berge, H Bax, D F Postma, and P H P Groeneveld.
• Isala, Zwolle, The Netherlands. Electronic address: a.j.j.lammers@isala.nl.
• Int. J. Infect. Dis. 2020 Dec 1; 101: 283-289.

BackgroundThe global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 has resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28-day mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward.MethodsA nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ, CQ, or no treatment. We compared the outcomes between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the intensive care unit (ICU).ResultsThe analysis included 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity-matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID ward. However, HCQ was associated with a significantly decreased risk of transfer to the ICU (hazard ratio (HR) = 0.47, 95% CI = 0.27-0.82, p =  0.008) when compared with controls. This effect was not found in the CQ group (HR = 0.80, 95% CI = 0.55-1.15, p =  0.207), and remained significant after competing risk analysis.ConclusionThe results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ - but not CQ - is associated with a 53% reduction in risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28-day, all-cause mortality only; therefore, additional prospective data on the early effects of HCQ in preventing transfer to the ICU are still needed.Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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