SARS and MERS: recent insights into emerging coronaviruses

Key Points

  • Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that can cause severe respiratory disease in humans. Although disease progression is fairly similar for SARS and MERS, the case fatality rate of MERS is much higher than that of SARS.

  • Comorbidities have an important role in SARS and MERS. Several risk factors are associated with progression to acute respiratory distress syndrome (ARDS) in SARS and MERS cases, especially advanced age and male sex. For MERS, additional risk factors that are associated with severe disease include chronic conditions such as diabetes mellitus, hypertension, cancer, renal and lung disease, and co-infections.

  • Although the ancestors of SARS-CoV and MERS-CoV probably circulate in bats, zoonotic transmission of SARS-CoV required an incidental amplifying host. Dromedary camels are the MERS-CoV reservoir from which zoonotic transmission occurs; serological evidence indicates that MERS-CoV-like viruses have been circulating in dromedary camels for at least three decades.

  • Human-to-human transmission of SARS-CoV and MERS-CoV occurs mainly in health care settings. Patients do not shed large amounts of virus until well after the onset of symptoms, when patients are most probably already seeking medical care. Analysis of hospital surfaces after the treatment of patients with MERS showed the ubiquitous presence of infectious virus.

  • Our understanding of the pathogenesis of SARS-CoV and MERS-CoV is still incomplete, but the combination of viral replication in the lower respiratory tract and an aberrant immune response is thought to have a crucial role in the severity of both syndromes.

  • The severity of the diseases that are caused by emerging coronaviruses highlights the need to develop effective therapeutic measures against these viruses. Although several treatments for SARS and MERS (based on inhibition of viral replication with drugs or neutralizing antibodies, or on dampening the host response) have been identified in animal models and in vitro studies, efficacy data from human clinical trials are urgently required.

Abstract

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.

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Figure 1: SARS-CoV and MERS-CoV structure and replication.
Figure 2: The emergence of SARS-CoV and MERS-CoV.
Figure 3: Evasion of the innate immune response by SARS-CoV and MERS-CoV.

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Acknowledgements

The work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health.

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Correspondence to Vincent J. Munster.

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The authors declare no competing financial interests.

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Glossary

Nosocomial transmission

Transmission of an infectious agent by staff, equipment or the environment in a health care setting.

Proofreading

The correction of errors that are acquired during the replication of DNA or RNA.

ER–Golgi intermediate compartment

(ERGIC). A cellular compartment that facilitates transport between the endoplasmic reticulum (ER) and the Golgi complex.

Super spreaders

Infected individuals who each infect a disproportionately large number of secondary cases.

Acute respiratory distress syndrome

(ARDS). A life-threatening condition in which the accumulation of fluid and inflammatory cells in the lungs decreases the exchange of oxygen and carbon dioxide to dangerously low levels.

Collaborative Cross mouse

One of a panel of recombinant inbred mouse strains derived from a genetically diverse set of founder strains and designed for the analysis of complex traits.

Perivascular cuffing

The aggregation of leukocytes around blood vessels.

Type I IFNs

(Type I interferons). A group of IFNs, including IFNα and IFNβ, with immune-modulating and antiviral functions.

RNAi

A biological process in which small RNA molecules induce the degradation of specific mRNA molecules, thereby inhibiting gene expression.

Minireplicon systems

Systems in which a DNA molecule is produced that contains the viral leader and trailer sequences, with an assayable reporter replacing the viral ORFs. When combined with the expression of viral proteins in trans, this system can be used to model the viral life cycle without the necessity of using infectious virus.

Ribavirin

A broadly active antiviral nucleoside analogue with several direct and indirect mechanisms of action; mainly used for the treatment of hepatitis C, in combination with interferon.

Pegylated

Having polyethylene glycol (PEG) attached, to a drug for example; this moiety improves the solubility, decreases the immunogenicity and increases the stability, of the drug of interest, thereby allowing a reduced dosing frequency to be used.

Peptidomimetics

Compounds that mimic biologically active peptides or proteins.

Anaphylatoxin C5a

A complement-activated molecule that is important for the recruitment to and activation of inflammatory cells in the lungs.

Subunit vaccines

Vaccines that contain immunogenic parts of a pathogen rather than the entire pathogen.

DNA vaccines

Vaccines based on the direct introduction of a plasmid encoding an antigen; following in situ production of this antigen, an immune response is mounted against it.

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de Wit, E., van Doremalen, N., Falzarano, D. et al. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 14, 523–534 (2016). https://doi.org/10.1038/nrmicro.2016.81

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