Medusa's Ugly Head Again: From SARS to MERS-CoV
Authors: Trish M. Perl, Allison McGeer, Connie Savor Price
Journal: Annals of Internal Medicine (2014)

Editorials18 March 2014Medusa's Ugly Head Again: From SARS to MERS-CoVFREETrish M. Perl, MD, MSc, Allison McGeer, MD, and Connie Savor Price, MDTrish M. Perl, MD, MScFrom Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland; Mount Sinai Hospital, Toronto, Ontario, Canada; and University of Colorado School of Medicine, Denver, Colorado., Allison McGeer, MDFrom Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland; Mount Sinai Hospital, Toronto, Ontario, Canada; and University of Colorado School of Medicine, Denver, Colorado., and Connie Savor Price, MDFrom Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland; Mount Sinai Hospital, Toronto, Ontario, Canada; and University of Colorado School of Medicine, Denver, Colorado.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-0096 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Eleven years ago, a novel coronavirus, the severe acute respiratory syndrome coronavirus (SARS-CoV), emerged, causing respiratory illness characterized by relatively high mortality and high rates of transmission in hospitals. The SARS virus taught the scientific community the value of unprecedented collaboration. In February 2013, a similar yet novel coronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV), was identified. At this writing, approximately 200 cases have been reported and many more are probably undetected (1). Like SARS, MERS-CoV infection causes severe respiratory disease for which there is no effective therapy. In this issue of Annals, Arabi and colleagues (2) report a consecutive series of 12 patients with severe respiratory failure, carbon dioxide retention, and extrapulmonary manifestations of sepsis requiring intensive care. One third of cases were hospital-acquired, and 68% of the patients died. Although an intensive search for antivirals continues, a gap remains between this serious disease and effective therapy. Evaluation of the potential effectiveness of convalescent serum therapy and therapeutic drug options is needed to improve our response to emerging diseases.In Arabi and colleagues’ case series, all patients had comorbid illness that may have increased susceptibility to infection. Similar to SARS, MERS-CoV affects middle-aged persons and spares children. However, preexisting chronic illness is more common in patients with severe MERS-CoV–associated pneumonia than in those with SARS: Rates of diabetes, renal disease, and heart disease are 68%, 49%, and 28%, respectively, in patients with MERS versus 24%, 2.6%, and 10%, respectively, among those with SARS (3). Carefully designed case–control studies are essential to determine the exposures that lead to infection. Such studies could identify potential preventive strategies and, when coupled with translational studies of genetic and other biological factors, could further define the key factors modulating disease severity.Of note in Arabi and colleagues’ report (and similar to SARS) is the nosocomial transmission among close contacts, with 33% of the cases associated with health care. Other reports from Jordan (4), the United Kingdom (5), and the Al-Hasa province of Saudi Arabia (6) implicated health care transmission in an even greater proportion of cases. In the Al-Hasa report, epidemiologic analysis suggested that 91% of reported cases resulted from transmission in health care facilities. Genomic analysis subsequently identified close phylogenetic clustering of MERS-CoV isolates consistent with human-to-human transmission (7). Although the investigations of Arabi and colleagues and others (4, 5) have found a relatively low risk for MERS-CoV infection and illness in exposed health care personnel, 30 of the first 161 reported MERS-CoV case patients were health care providers and new cases continue to occur in this population (8).Analysis to date suggests that MERS-CoV does not yet have pandemic potential. A model based on published data used the rate of MERS-CoV introduction into the population in the Jordan and Al-Hasa outbreaks to calculate the basic reproductive number (R0)—that is, the number of secondary cases per index case in a fully susceptible population (9). For MERS-CoV, R0 is estimated to be between 0.60 (95% CI, 0.42 to 0.80) and 0.69 (CI, 0.50 to 0.92). At first blush, this is comforting: Prepandemic SARS virus had an R0 of 0.8. However, we must keep in mind both the rapid evolution that occurred with SARS and that it emerged in a much more densely populated region. Given the right environment and a crowded part of the world, MERS-CoV might propagate more readily.As with SARS, we are indebted to international collaboration and a ProMED post that alerted the world to a new virus on 15 September 2012. Early recognition allowed the World Health Organization and other public health authorities to enhance surveillance and develop mitigation strategies. To date, all cases have been directly or indirectly linked to travel to or residence in countries in the Arabian Peninsula. How long will this last, given minimal data on specific exposure risks for infection and persistent health care transmission?The question remains of whether MERS-CoV infection is occurring due to repeated introductions from an animal reservoir with subsequent limited transmission in humans or from sustained human-to-human transmission, with most cases being subclinical disease in patients without underlying medical conditions. Camels and bats have been implicated as potential reservoirs, but most case patients have not been exposed to these animals and the search for the source of human exposure continues (10, 11). As reported cases of MERS-CoV increase, we must not lose sight of the most important lesson of SARS: the value of transparency in reporting and of effective international collaboration in public health and research.Does health care transmission continue because of failure to adhere to infection control practices or despite practices previously believed to be adequate to control the transmission of infection? The concentration of vulnerable patients, the frequent movement of patients, and the many daily contacts make health care facilities the perfect breeding ground for MERS-CoV transmission. This, in combination with known imperfect adherence to routine infection prevention practices, suggests that early recognition of possible MERS-CoV infection is critical. Intensive surveillance for cases combined with the use of standard, contact, and droplet precautions for persons with suspected or confirmed disease aborted the Al-Hasa outbreak (6). Because we know little about how the virus is transmitted, it is not surprising that the Centers for Disease Control and Prevention and the World Health Organization disagree on the need for airborne isolation. Data are unavailable to discount either approach.Arabi and colleagues provide a stark reminder of lessons learned from SARS. Infection with MERS-CoV causes respiratory failure with extrapulmonary organ dysfunction for which there is no effective treatment. Mortality remains high. Health care–associated MERS-CoV transmission to patients, workers, and visitors remains significant but is underplayed. Focus on the health care setting may prevent continued human-to-human transmission among at-risk patients. We applaud these brave authors for providing independent data and enhancing the scientific collaborations that MERS-CoV has created. Globalization and emerging viruses combine to demand new levels of scientific transparency and collaboration to effectively protect populations, a change we must all strive to achieve.Trish M. Perl, MD, MScJohns Hopkins University School of Medicine and Bloomberg School of Public HealthBaltimore, MarylandAllison McGeer, MDMount Sinai HospitalToronto, Ontario, CanadaConnie Savor Price, MDUniversity of Colorado School of MedicineDenver, ColoradoReferences1. Cauchemez S, Fraser C, Van Kerkhove MD, Donnelly CA, Riley S, Rambaut A, et al. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility. Lancet Infect Dis. 2014;14:50-6. [PMID: 24239323] CrossrefMedlineGoogle Scholar2. Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-97. LinkGoogle Scholar3. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13:752-61. [PMID: 23891402] CrossrefMedlineGoogle Scholar4. Hijawi B, Abdallat M, Sayaydeh A, Alqasrawi S, Haddadin A, Jaarour N, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J. 2013;19 Suppl 1 S12-8. [PMID: 23888790] CrossrefMedlineGoogle Scholar5. Health Protection Agency (HPA) UK Novel Coronavirus Investigation Team. Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, February 2013. Euro Surveill. 2013;18:20427. [PMID: 23517868] MedlineGoogle Scholar6. Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA, et al; KSA MERS-CoV Investigation Team. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-16. [PMID: 23782161] CrossrefMedlineGoogle Scholar7. Cotten M, Watson SJ, Kellam P, Al-Rabeeah AA, Makhdoom HQ, Assiri A, et al. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet. 2013;382:1993-2002. [PMID: 24055451] CrossrefMedlineGoogle Scholar8. The WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013;5:. [PMID: 24270606] MedlineGoogle Scholar9. Breban R, Riou J, Fontanet A. Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk. Lancet. 2013;382:694-9. [PMID: 23831141] CrossrefMedlineGoogle Scholar10. Reusken C, Ababneh M, Raj V, Meyer B, Eljarah A, Abutarbush S, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. Euro Surveill. 2013;18:. [PMID: 24342516] CrossrefMedlineGoogle Scholar11. Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, et al. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill. 2013;18:pii=20574. [PMID: 24079378] CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment James F. Burris, MDDepartment of Veterans Affairs, Washington DC12 June 2014 Two Heads Are Better Than One A recent editorial (1) that referenced the ancient Greek myth of Medusa in its title but not in its text discussed some similarities and differences in the SARS and MERS-CoV coronaviruses. Medusa, one of the Gorgons, had writhing snakes instead of hair and a face so terrifying that it turned to stone anyone who looked into it. She was slain by Perseus, who avoided looking into her face by watching only her reflection in his mirrored shield.A perhaps even more apt classical allusion for the challenges posed by these two coronaviruses (and perhaps others yet to come) is the Lernaean Hydra. This somewhat reptilian beast had multiple heads, and each time one was cut off two more grew in its place, making the monster progressively more dangerous the more it was attacked. One of the Labors of Hercules was to slay this beast, which he finally accomplished by cauterizing each neck with a torch after cutting off its head. We may need the clinical equivalent of a lightsaber to meet the challenges posed by the many-headed coronaviruses.Classical allusions become more and more hazardous both to the one who alludes and to the audience as fewer and fewer of us have had enough of a classical education to carry the old myths around in our working memory, but they can still serve to make a point and enliven a text.James F. Burris, MDWashington, DC1. Perl TM, McGeer A, Price CS. Medusa’s Ugly Head Again: From SARS to MERS-CoV. Ann Intern Med 2014; 160: 432-433. Author, Article, and Disclosure InformationAuthors: Trish M. Perl, MD, MSc; Allison McGeer, MD; Connie Savor Price, MDAffiliations: From Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland; Mount Sinai Hospital, Toronto, Ontario, Canada; and University of Colorado School of Medicine, Denver, Colorado.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0096.Corresponding Author: Trish M. Perl, MD, MSc, Department of Epidemiology and Infection Prevention, Johns Hopkins Medicine, 600 North Wolfe Street, Osler 327A, Baltimore, MD 21287-5425; e-mail, tperl@jhmi.edu.Current Author Addresses: Dr. Perl: Department of Epidemiology and Infection Prevention, Johns Hopkins Medicine, 600 North Wolfe Street, Osler 327A, Baltimore, MD 21287-5425.Dr. McGeer: Mount Sinai Hospital, Microbiology/Room 210, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.Dr. Price: Denver Health and Hospital, MC-4000, Denver, CO 80238.This article was published online first at www.annals.org on 28 January 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoClinical Course and Outcomes of Critically Ill Patients With Middle East Respiratory Syndrome Coronavirus Infection Yaseen M. Arabi , Ahmed A. Arifi , Hanan H. Balkhy , Hani Najm , Abdulaziz S. Aldawood , Alaa Ghabashi , Hassan Hawa , Adel Alothman , Abdulaziz Khaldi , and Basel Al Raiy Metrics Cited byEvaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV VaccineLessons from the public health response to EbolaThe discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) 18 March 2014Volume 160, Issue 6Page: 432-433KeywordsEpidemiologyHealth careHealth care facilitiesInfectious diseasesMortalityPrevention, policy, and public healthPulmonary diseasesRespiratory failureSARS coronavirusUpper respiratory tract infections ePublished: 18 March 2014 Issue Published: 18 March 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...