Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Timothy M. Uyeki; Karl J. Erlandson; George Korch; Michael O'Hara; Michael Wathen; Jean Hu-Primmer; Sally Hojvat; Erik J. Stemmy; Armen Donabedian

Disclosures

Emerging Infectious Diseases. 2016;22(7):e1-e11. 

In This Article

Abstract and Introduction

Abstract

Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures.

Introduction

From September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO).[1] Most infections (75%) have been identified in Saudi Arabia.[2] Zoonotic transmission from exposure to MERS-CoV–infected Arabian camels, known as dromedaries, or their raw milk and limited, nonsustained human-to-human transmission have been reported, including large outbreaks in healthcare facilities.[3–5] The recovery of infectious MERS-CoV in virus cultures of specimens from bed sheets, bedrails, intravenous fluid hangers, and radiograph equipment indicates the potential for fomite transmission of the virus in hospitals providing care for MERS-CoV patients.[6] However, sustained human-to-human transmission has not been documented, and some case-patients have no identified source of exposure to MERS-CoV. As of April 2016, a total of 26 countries had reported locally acquired or exported cases from the Arabian Peninsula, including 2 cases in the United States identified during May 2014 in healthcare personnel who became ill after working in Saudi Arabia.[7,8] A traveler who visited Saudi Arabia, Qatar, the United Arab Emirates, and Bahrain and then returned to South Korea infected with MERS-CoV in mid-2015 triggered 184 MERS-CoV cases, resulting in 38 deaths in multiple health facilities and 1 additional case in a person who traveled to China.[9,10]

Human infections with MERS-CoV are expected to continue to occur on the Arabian Peninsula because of the prevalence of MERS-CoV in dromedaries and the cultural importance of these camels (i.e., for food, milk, and racing purposes) in the region. During the 2003 outbreak of severe acute respiratory syndrome (SARS) in China, civet cats, the suspected reservoir of SARS coronavirus (SARS-CoV), were culled aggressively; no outbreaks were identified after 2004. In contrast, culling of camels is culturally impractical in the Middle East, and MERS-CoV zoonotic infections of humans have continued since 2012.

The potential for emergence of MERS-CoV mutations that could facilitate sustained community transmission and global dissemination cannot be predicted. No vaccines against or specific treatments for human infection with SARS-CoV, MERS-CoV, or other coronaviruses have been approved. Since 2013, efforts have focused on furthering development of animal models, vaccines, and therapies against MERS-CoV.[11,12] In this report, we update the current state of development for MERS-CoV medical countermeasures, including regulatory challenges in the United States, and draw attention to areas in immediate need of increased infrastructure support for development of these countermeasures.

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