Early Hydroxychloroquine but not Chloroquine use reduces ICU admission in COVID-19 patients

Lammers, A.J.J.; Brohet, R. M.; Theunissen, R.E.P.; Koster, C.; Rood, R.; Verhagen, D.W.M.; Brinkman, K.; Hassing, R. J.; Dofferhoff, A.; el Moussaoui, R.; Hermanides, G.; Ellerbroek, J.; Bokhizzou, N.; Visser, H.; van den Berge, M.; Bax, H.; Postma, D. F.; Groeneveld, P.H.P.

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.