MEDUSA’S UGLY HEAD AGAIN: FROM SARS TO MERS-COV16
Trish M. Perl,17Allison McGeer,18and Connie Savor Price19
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 (Cauchemez et al., 2014). Like SARS, MERS-CoV infection causes severe respiratory disease for which there is no effective therapy. In this issue of Annals, Arabi and colleagues (2014) 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 (Assiri et al., 2013b). 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
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16 Reprinted from Annals of Internal Medicine. Originally published as Perl TM, McGeer A, Price CS. Medusa’s Ugly Head Again: From SARS to MERS-CoV. Ann Intern Med. 2014;160:432-433. doi:10.7326/M14-0096. Available online at: http://annals.org/article.aspx?articleId=1817261&guestAccessKey=fbdb7e96-15f9-4c71-b29a-c502e4e787ba.
17 Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland.
18 Mount Sinai Hospital, Toronto, Ontario, Canada.
19 University of Colorado School of Medicine, Denver, Colorado.
health care. Other reports from Jordan (Hijawi et al., 2013), the United Kingdom (HPA, 2013), and the Al-Hasa province of Saudi Arabia (Assiri et al., 2013a) 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 (Cotton et al., 2013). Although the investigations of Arabi and colleagues and others (Assiri et al., 2013a; Hijawi et al., 2013; HPA, 2013) 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 (WHO MERS-CoV Research Group, 2013).
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 (Breban et al., 2013). 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 (Perera et al., 2013; Reusken et al., 2013). 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 (Assiri et al., 2013a). 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.
References
Arabi, Y. M., A. A. Arifi, H. H. Balkhy, H. Najm, A. S. Aldawood, A. Ghabashi, H. Hawa, A. Alothman, A. Khaldi, and B. Al Raiy. 2014. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Annals of Internal Medicine 160(6):389-397.
Assiri, A., A. McGeer, T. M. Perl, C. S. Price, A. A. Al Rabeeah, D. A. Cummings, Z. N. Alabdullatif, M. Assad, A. Almulhim, H. Makhdoom, H. Madani, R. Alhakeem, J. A. Al-Tawfiq, M. Cotten, S. J. Watson, P. Kellam, A. I. Zumla, and Z. A. Memish. 2013a. Hospital outbreak of Middle East respiratory syndrome coronavirus. New England Journal of Medicine 369(5):407-416.
Assiri, A., J. A. Al-Tawfiq, A. A. Al-Rabeeah, F. A. Al-Rabiah, S. Al-Hajjar, A. Al-Barrak, H. Flemban, W. N. Al-Nassir, H. H. Balkhy, R. F. Al-Hakeem, H. Q. Makhdoom, A. I. Zumla, and Z. A. Memish. 2013b. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infectious Diseases 13(9):752-761.
Breban, R., J. Riou, and A. Fontanet. 2013. Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk. Lancet 382(9893):694-699.
Cauchemez, S., C. Fraser, M. D. Van Kerkhove, C. A. Donnelly, S. Riley, A. Rambaut, V. Enouf, S. van der Werf, and N. M. Ferguson. 2014. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility. Lancet Infectious Diseases 14(1):50-56.
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