Surface–Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012–2018

Neeltje van Doremalen; Michael Letko; Robert J. Fischer; Trenton Bushmaker; Jonathan Schulz; Claude K. Yinda; Stephanie N. Seifert; Nam Joong Kim; Maged G. Hemida; Ghazi Kayali; Wan Beom Park; Ranawaka A.P.M. Perera; Azaibi Tamin; Natalie J. Thornburg; Suxiang Tong; Krista Queen; Maria D. van Kerkhove; Young Ki Choi; Myoung-don Oh; Abdullah M. Assiri; Malik Peiris; Susan I. Gerber; Vincent J. Munster

Disclosures

Emerging Infectious Diseases. 2021;27(12):3052-3062. 

In This Article

Abstract and Introduction

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV) was detected during 2012 and continues to cause outbreaks as a result of frequent spillover from dromedary camels to humans. Human infection with MERS-CoV has a mortality rate of ≈35%, and the virus has spread to 27 countries.[1] Approximately 41% of human MERS-CoV infections in Saudi Arabia are primary, resulting from direct camel-to-human transmission.[2] To date, MERS-CoV has been detected in camels in Burkina Faso, Egypt, Ethiopia, Jordan, Kenya, Morocco, Nigeria, Saudi Arabia, Senegal, Sudan, Tunisia, and Uganda.[3–11]

Human-to-human transmission of MERS-CoV primarily occurs in hospital settings and within households.[12] Epidemiologic studies have mapped indirect patient contact within hospitals, providing evidence for aerosol-mediated and hospital-worker–mediated spread.[13–16] The largest outbreak of infection with MERS-CoV outside the Middle East occurred when 1 traveler from the Middle East brought MERS-CoV to South Korea, resulting in 185 subsequent infections.[17]

Coronaviruses have large, nonsegmented, positive-sense RNA genomes. The 1% nucleotide sequence variation reported between various MERS-CoV isolates collected in the Middle East and North Africa is equivalent to 300 nt changes in the 30-kB viral genome.[18] Many of these changes are nonsynonymous and distributed throughout the viral genome. Even single amino acid changes in MERS-CoV can alter viral replication,[19] and deletions in MERS-CoV have been shown to attenuate pathology in an animal model.[18] These findings underscore the need for characterizing how MERS-CoV genetic variation alters viral replication, pathogenicity, and stability.

We tested a broad panel of viral isolates collected from humans and camels, representing every major geographic region that has had MERS-CoV outbreaks and spanning from early to contemporary outbreaks. Because MERS-CoV spreads within households and hospitals, we characterized viral phenotypes with immediate implications for public health. We focused on environmental stability in aerosols as well as surface stability on common materials found in hospitals, replication kinetics in immortalized human cell lines and primary human airway epithelial cultures, and pathogenicity in a transgenic mouse model our laboratory developed to test vaccine efficacy.[20] For environmental stability studies, we included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enable better comparison of these findings with those of previously published stability studies.[21]

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