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Lammers AJJ, Brohet RM, Theunissen REP, Koster C, Rood R, Verhagen DWM, Brinkman K, Hassing RJ, Dofferhoff A, El Moussaoui R, Hermanides G, Ellerbroek J, Bokhizzou N, Visser H, van den Berge M, Bax H, Postma DF, Groeneveld PHP. Early Hydroxychloroquine but not Chloroquine use reduces ICU admission in COVID-19 patients. Int J Infect Dis. 2020 Sep 29:S1201-9712(20)32175-5. doi: 10.1016/j.ijid.2020.09.1460. Epub ahead of print. PMID: 33007454; PMCID: PMC7524430.

Background: The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 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.

Methods: A 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 or CQ, or no treatment. We compared the outcome between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the Intensive Care Unit (ICU).

Results: The analysis contained 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. HCQ however was associated with a significant decreased risk of transfer to the ICU (Hazard ratio (HR) = 0.47, 95%CI = 0.27-0.82, p = 0.008), when compared to 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.

Conclusion: The 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 53% decreased risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28 days all-cause mortality only, therefore additional prospective data on the early effect of HCQ in preventing transfer to the ICU is still needed.

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