流行病学
2012 年报告了第一例 MERS 病例——沙特阿拉伯吉达一名 60 岁的老年患者。[1]Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814-1820. http://www.nejm.org/doi/full/10.1056/NEJMoa1211721#t=article http://www.ncbi.nlm.nih.gov/pubmed/23075143?tool=bestpractice.com 该患者死于重症肺炎和多器官功能衰竭。此后,又报告了许多个别病例或群发病例,其中大多数都是在阿拉伯半岛及其周边国家/地区获得该病毒,尤其是在沙特阿拉伯、阿拉伯联合酋长国(阿联酋)、阿曼、卡塔尔和约旦。
与前往这些国家/地区旅行有关的病例,往往限于少数人的小规模群发病例,[14]Puzelli S, Azzi A, Santini MG, et al. Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013. Euro Surveill. 2013;18:20564. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20564 http://www.ncbi.nlm.nih.gov/pubmed/23987829?tool=bestpractice.com [15]Kraaij-Dirkzwager M, Timen A, Dirksen K, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands, May 2014. Euro Surveill. 2014;19:20817. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20817 http://www.ncbi.nlm.nih.gov/pubmed/24906375?tool=bestpractice.com [16]Guery B, Poissy J, el Mansouf L, et al. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet. 2013;381:2265-2272. http://www.ncbi.nlm.nih.gov/pubmed/23727167?tool=bestpractice.com [17]Abroug F, Slim A, Ouanes-Besbes L, et al. Family cluster of Middle East respiratory syndrome coronavirus infections, Tunisia, 2013. Emerg Infect Dis. 2014;20:1527-1530. http://www.ncbi.nlm.nih.gov/pubmed/25148113?tool=bestpractice.com 除了 2015 年韩国发生的一次大规模暴发(报告了 186 例病例)[18]Lee SI. Costly lessons from the 2015 Middle East respiratory syndrome coronavirus outbreak in Korea. J Prev Med Public Health. 2015;48:274-276. https://www.jpmph.org/journal/view.php?doi=10.3961/jpmph.15.064 http://www.ncbi.nlm.nih.gov/pubmed/26639740?tool=bestpractice.com [19]Hui DS, Perlman S, Zumla A. Spread of MERS to South Korea and China. Lancet Respir Med. 2015;3:509-510. http://www.ncbi.nlm.nih.gov/pubmed/26050550?tool=bestpractice.com [20]Ha KM. A lesson learned from the MERS outbreak in South Korea in 2015. J Hosp Infect. 2016;92:232-234. http://www.ncbi.nlm.nih.gov/pubmed/26601605?tool=bestpractice.com 以及 2017 年利雅得(沙特阿拉伯)的超级传播事件(其中 44 起病例均与一名急性肾衰竭患者有关)。[11]Amer H, Alqahtani AS, Alzoman H, et al. Unusual presentation of Middle East respiratory syndrome coronavirus leading to a large outbreak in Riyadh during 2017. Am J Infect Control. 2018 Apr 13. pii: S0196-6553(18)30146-9. http://www.ncbi.nlm.nih.gov/pubmed/29661625?tool=bestpractice.com 2014 年,美国报道了两起病例,均为来自沙特阿拉伯的旅行者。[21]Centers for Disease Control and Prevention. MERS in the US. September 2017 [internet publication]. http://www.cdc.gov/coronavirus/mers/us.html 自此以后,美国再未报道任何病例。自 2012 年以来,英国已报道了 5 例实验室确诊病例,最近一例报道于 2018 年 8 月。[22]Public Health England. MERS-CoV case in England. August 2018 [internet publication]. https://www.gov.uk/government/news/mers-cov-case-in-england 其他出现旅行相关病例的国家包括法国、意大利、希腊、土耳其、黎巴嫩、德国、奥地利、荷兰、中国、马来西亚、泰国、菲律宾和埃及。韩国于 2018 年 9 月报告了一例病例:患者为韩国国民,在前往科威特后经迪拜返回韩国。21 名接触者目前正在接受主动监测。[23]World Health Organization. Disease outbreak news. Middle East respiratory syndrome coronavirus (MERS-CoV) infection – Republic of Korea. September 2018 [internet publication]. http://www.who.int/csr/don/12-september-2018-mers-republic-of-korea/en/
截至 2018 年 8 月底,全球范围内 27 个国家/地区自 2012 年以来报道了共 2248 例实验室确诊病例,其中包括 798 例死亡病例(病死率为 35.5%)。大多数病例来自沙特阿拉伯(1871 例)。50-59 岁年龄组人群获得原发性感染的风险最高。[24]World Health Organization. MERS situation update. August 2018 [internet publication]. http://www.emro.who.int/pandemic-epidemic-diseases/mers-cov/mers-situation-update-august-2018.html
World Health Organization (WHO): disease outbreak news external link opens in a new window
在报道的病例中,98% 为成年人(定义为年龄>14 岁)。[8]Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, 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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com 尽管已有报告显示,在成人群体中,感染可发生于不同的年龄组,但患者的中位年龄范围为 50 至 67 岁。[4]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. http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-humans-2/ http://www.ncbi.nlm.nih.gov/pubmed/24270606?tool=bestpractice.com [9]Al-Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59:160-165. https://academic.oup.com/cid/article/59/2/160/2895452/Middle-East-Respiratory-Syndrome-Coronavirus-A http://www.ncbi.nlm.nih.gov/pubmed/24723278?tool=bestpractice.com [25]Omrani AS, Saad MM, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14:1090-1095. http://www.ncbi.nlm.nih.gov/pubmed/25278221?tool=bestpractice.com 年龄≥50 岁患者死亡的风险更高。[5]Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-alpha-2a or IFN-beta-1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129-2132. http://www.ncbi.nlm.nih.gov/pubmed/25900158?tool=bestpractice.com [26]Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301-306. http://www.ijidonline.com/article/S1201-9712(14)01622-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25303830?tool=bestpractice.com 一项队列研究表明死亡率随着年龄的增加而增加,在>60 岁的患者中高达 75%。[8]Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, 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;13:752-761. http://www.ncbi.nlm.nih.gov/pubmed/23891402?tool=bestpractice.com 大多数病例为男性。[24]World Health Organization. MERS situation update. August 2018 [internet publication]. http://www.emro.who.int/pandemic-epidemic-diseases/mers-cov/mers-situation-update-august-2018.html 儿童感染的情况罕见,但原因不明。[12]Memish ZA, Al-Tawfiq JA, Assiri A, et al. Middle East respiratory syndrome coronavirus disease in children. Pediatr Infect Dis J. 2014;33:904-906. http://www.ncbi.nlm.nih.gov/pubmed/24763193?tool=bestpractice.com [13]Khuri-Bulos N, Payne DC, Lu X, et al. Middle East respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to September 2012. Clin Microbiol Infect. 2014;20:678-682. http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)61157-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/24313317?tool=bestpractice.com
大多数病例是人际间传播(而非骆驼与人之间传播)的结果,确诊病例的高峰出现于医院暴发期间。[6]Oboho IK, Tomczyk SM, Al-Asmari AM, et al. 2014 MERS-CoV outbreak in Jeddah - a link to health care facilities. N Engl J Med. 2015;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [7]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [27]Alenazi TH, Al Arbash H, El-Saed A, et al. Identified transmission dynamics of Middle East respiratory syndrome coronavirus infection during an outbreak: implications of an overcrowded emergency department. Clin Infect Dis. 2017;65:675-679. http://www.ncbi.nlm.nih.gov/pubmed/28575307?tool=bestpractice.com 据病例记录显示,传播呈现家族聚集性。[17]Abroug F, Slim A, Ouanes-Besbes L, et al. Family cluster of Middle East respiratory syndrome coronavirus infections, Tunisia, 2013. Emerg Infect Dis. 2014;20:1527-1530. http://www.ncbi.nlm.nih.gov/pubmed/25148113?tool=bestpractice.com [28]Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:309-318. https://academic.oup.com/cid/article/58/3/309/340555/Executive-Summary-2013-IDSA-Clinical-Practice http://www.ncbi.nlm.nih.gov/pubmed/24421306?tool=bestpractice.com [29]Memish ZA, Zumla AI, Al-Hakeem RF, et al. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;368:2487-2494. http://www.nejm.org/doi/full/10.1056/NEJMoa1303729#t=article http://www.ncbi.nlm.nih.gov/pubmed/23718156?tool=bestpractice.com 然而,报告显示,更常见的传播形式为医院内(例如血液透析室、重症监护病房、内科病房)暴发。[6]Oboho IK, Tomczyk SM, Al-Asmari AM, et al. 2014 MERS-CoV outbreak in Jeddah - a link to health care facilities. N Engl J Med. 2015;372:846-854. http://www.nejm.org/doi/full/10.1056/NEJMoa1408636#t=article http://www.ncbi.nlm.nih.gov/pubmed/25714162?tool=bestpractice.com [7]Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-416. http://www.nejm.org/doi/full/10.1056/NEJMoa1306742#t=article http://www.ncbi.nlm.nih.gov/pubmed/23782161?tool=bestpractice.com [29]Memish ZA, Zumla AI, Al-Hakeem RF, et al. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;368:2487-2494. http://www.nejm.org/doi/full/10.1056/NEJMoa1303729#t=article http://www.ncbi.nlm.nih.gov/pubmed/23718156?tool=bestpractice.com [30]Omrani AS, Matin MA, Haddad Q, et al. A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case. Int J Infect Dis. 2013;17:e668-e672. http://www.ijidonline.com/article/S1201-9712(13)00225-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/23916548?tool=bestpractice.com [31]Memish ZA, Cotten M, Watson SJ, et al. Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study. Int J Infect Dis. 2014;23:63-68. http://www.ijidonline.com/article/S1201-9712(14)01451-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/24699184?tool=bestpractice.com [32]Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59:1225-1233. https://academic.oup.com/cid/article/59/9/1225/419021/Hospital-Associated-Outbreak-of-Middle-East http://www.ncbi.nlm.nih.gov/pubmed/24829216?tool=bestpractice.com [33]Shehata MM, Gomaa MR, Ali MA, et al. Middle East respiratory syndrome coronavirus: a comprehensive review. Front Med. 2016;10:120-136. http://www.ncbi.nlm.nih.gov/pubmed/26791756?tool=bestpractice.com
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