Camostat Mesylate but Not Hydroxychloroquine May Reduce Severity of Organ Failure in COVID-19 Sepsis: A Case-Control Study

Abstract

Background: The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). COVID-19 may take a severe course, resulting in sepsis, and antivirals are urgently needed to combat the disease. However, at present, only drugs developed against other diseases are available including the Malaria drug hydroxychloroquine but their therapeutic efficacy is unclear. Camostat mesylate, a clinically-proven protease inhibitor for treatment of pancreatitis, was shown to block SARS-CoV-2 entry into lung cells. Whether camostat mesylate dampens COVID-19 induced sepsis and the associated organ failure is unknown. Here we compare clinical courses of critically ill COVID-19 patients treated with either camostat mesylate or hydroxychloroquine. Methods: Eleven COVID-19 patients with organ failure were treated in intensive care unit (ICU) at our institution. Five patients (group 1) received hydroxychloroquine and six patients (group 2) camostat mesylate. Clinical disease status was assessed by Simplified Acute Physiology Score (SAPS) II and Sequential/ Sepsis-related Organ Failure Assessment (SOFA) score at day 1, 3 and 8. Viral load was determined from nasopharyngeal swabs. Findings: Patient age ranged from 45 to 76 years, all but one had histories of chronic disease and cardiovascular risk factors. Median symptomatic period was 2-10 days before being transferred to ICU. No differences in SAPS II scores or SOFA scores were observed upon ICU admission. In group 1, SOFA and SAPS II scores remained elevated (2 patients died) while in group 2 SOFA and SAPS II score decreased from 9 to 4 points (1 patient died). The decline in disease severity for group 2 was paralleled by a decline in inflammatory markers, which was not observed in group 1. The virus load in the nasopharynx was variable between patients, did not correlate with organ failure and no marked differences were observed between groups 1 and 2. Interpretation: The severity of COVID-19 sepsis markedly decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed upon hydroxychloroquine treatment. Camostat mesylate thus warrants further evaluation within randomized clinical studies. Funding Statement: Authors were employed at the University of Gottingen or at the Infection Biology Unit of the German Primate Center (Leibniz Institute for Primate Research). All expenses were covered by publicly funded institutions. Stefan Pohlmann received funding from the German Federal Ministry of Education and Research (BMBF), RAPID Fund (#01KI1723D). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Compassionate use was approved by our local ethical committee at the University of Gottingen.