Abstract
Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80–1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83–1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75–1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57–1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials.Trial Registration: Clinicaltrials.gov Identifier: NCT04347993
Highlights
The global pandemic caused by a novel coronavirus [severe acute respiratory syndrome (SARS)-CoV-2] and its disease, COVID-19, has led to infection in over 15.8 million individuals and more than 640,000 deaths as of July 25, 2020 [1, 2]
One empirical treatment for COVID-19 which has received attention is hydroxychloroquine, an antimalarial drug repurposed in recognition of its anti-inflammatory properties in the treatment of autoimmune conditions
Causal inferences on effectiveness of treatments are challenging, but confounding effects can be partially mitigated via statistical methods [27, 28]. Understanding these limitations, but with the urgency for evaluating potential therapeutic approaches during the current COVID-19 pandemic, we established an observational database within a 13-hospital network spanning New Jersey using an integrated electronic health record (EHR) system (EPIC; Verona, WI). In this observational cohort study we report our survival outcomes with hydroxychloroquine and tocilizumab among hospitalized patients with COVID-19
Summary
The global pandemic caused by a novel coronavirus [severe acute respiratory syndrome (SARS)-CoV-2] and its disease, COVID-19, has led to infection in over 15.8 million individuals and more than 640,000 deaths as of July 25, 2020 [1, 2]. One empirical treatment for COVID-19 which has received attention is hydroxychloroquine, an antimalarial drug repurposed in recognition of its anti-inflammatory properties in the treatment of autoimmune conditions. Hydroxychloroquine and its analogue, chloroquine, demonstrate suppression of SARS-CoV-2 replication in vitro, with hydroxychloroquine demonstrating greater potency [5, 6]. The immunomodulatory effects are thought to be due to the accumulation of the drug in lymphocytes and macrophages leading to reduction of proinflammatory cytokines, including type I interferons, tumor necrosis factor alpha, and interleukin-6 [9]. Other anti-inflammatory effects may be related to inhibition of signaling pathways [11]
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