病史和体格检查
关键诊断因素
所有确诊病例均于症状出现前 14 天内在中东居住或旅行。[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 [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 [76]Reuss A, Litterst A, Drosten C, et al. Contact investigation for imported case of Middle East respiratory syndrome, Germany. Emerg Infect Dis. 2014;20:620-625. https://wwwnc.cdc.gov/eid/article/20/4/13-1375_article http://www.ncbi.nlm.nih.gov/pubmed/24655721?tool=bestpractice.com [77]Bialek SR, Allen D, Alvarado-Ramy F, et al. First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014. MMWR Morb Mortal Wkly Rep. 2014;63:431-436. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm http://www.ncbi.nlm.nih.gov/pubmed/24827411?tool=bestpractice.com 这包括阿拉伯半岛(巴林、科威特、阿曼、卡塔尔、沙特阿拉伯、阿拉伯联合酋长国、也门)及其周边国家(伊拉克;伊朗;以色列、约旦河西岸和加沙;约旦;黎巴嫩;叙利亚)。
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
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
40% 至 98% 的病例报告出现此症状。[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 [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 [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
老年患者、免疫功能低下患者、孕妇,以及患有终末期肾病、糖尿病或血色病的患者,可能不会出现发热;[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 因此,即使没有发热,也不应排除对 MERS 进行检查。[85]Shalhoub S, Al-Zahrani A, Simhairi R, et al. Successful recovery of MERS CoV pneumonia in a patient with acquired immunodeficiency syndrome: a case report. J Clin Virol. 2015;62:69-71. http://www.ncbi.nlm.nih.gov/pubmed/25542475?tool=bestpractice.com
54% 至 86% 的病例报告出现此症状。通常为干咳;但 23% 至 36% 的患者出现咳痰。[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 [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 [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
报道出现于60% 至 72% 的病例。[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 [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 [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
其他诊断因素
报道出现于7% 至 17% 的病例。[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 [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 [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
报道出现于7% 至 26% 的病例。[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 [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 [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
报道出现于17% 至 24% 的病例。[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 [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
报道出现于7% 至 21% 的病例。[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 [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 [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
常伴有发热。
非特异性症状在一些病例中得以报道。[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 [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 [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 [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 [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
非特异性症状在一些病例中得以报道。[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 [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 [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 [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 [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
非特异性症状在一些病例中得以报道。[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 [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 [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 [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 [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
非特异性症状在一些病例中得以报道。[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 [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 [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 [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 [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
非特异性症状在一些病例中得以报道。[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 [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 [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 [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 [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
非特异性症状在一些病例中得以报道。[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 [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 [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 [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 [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
某些病例有此表现,包括急性呼吸窘迫患者。
某些病例有此表现,包括急性呼吸窘迫患者。
某些病例有此表现,包括急性呼吸窘迫患者。
可能提示肺炎。
可能提示肺炎。
可能还会闻及支气管呼吸音。
危险因素
所有确诊病例均于症状出现前 14 天内在中东居住或旅行。[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 [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 [76]Reuss A, Litterst A, Drosten C, et al. Contact investigation for imported case of Middle East respiratory syndrome, Germany. Emerg Infect Dis. 2014;20:620-625. https://wwwnc.cdc.gov/eid/article/20/4/13-1375_article http://www.ncbi.nlm.nih.gov/pubmed/24655721?tool=bestpractice.com [77]Bialek SR, Allen D, Alvarado-Ramy F, et al. First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014. MMWR Morb Mortal Wkly Rep. 2014;63:431-436. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm http://www.ncbi.nlm.nih.gov/pubmed/24827411?tool=bestpractice.com 这包括阿拉伯半岛(巴林、科威特、阿曼、卡塔尔、沙特阿拉伯、阿拉伯联合酋长国、也门)及其周边国家(伊拉克;伊朗;以色列、约旦河西岸和加沙;约旦;黎巴嫩;叙利亚)。
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
病毒通过感染者的呼吸道飞沫(如咳嗽、打喷嚏)或与感染者密切接触而发生传播。但不排除通过空气传播或污染物传播的可能性。[62]Kim SH, Chang SY, Sung M, et al. Extensive viable Middle East respiratory syndrome (MERS) coronavirus contamination in air and surrounding environment in MERS isolation wards. Clin Infect Dis. 2016;63:363-369. https://academic.oup.com/cid/article/63/3/363/2595016/Extensive-Viable-Middle-East-Respiratory-Syndrome http://www.ncbi.nlm.nih.gov/pubmed/27090992?tool=bestpractice.com 潜伏期为 2 至 14 天,传播发生在有症状阶段或潜伏阶段。[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 [63]Centers for Disease Control and Prevention. MERS clinical features. September 2017 [internet publication]. http://www.cdc.gov/coronavirus/mers/clinical-features.html
所有在中东以外确诊的患者都与前 14 天在中东旅行过的人有所接触。[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 [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 [76]Reuss A, Litterst A, Drosten C, et al. Contact investigation for imported case of Middle East respiratory syndrome, Germany. Emerg Infect Dis. 2014;20:620-625. https://wwwnc.cdc.gov/eid/article/20/4/13-1375_article http://www.ncbi.nlm.nih.gov/pubmed/24655721?tool=bestpractice.com [77]Bialek SR, Allen D, Alvarado-Ramy F, et al. First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014. MMWR Morb Mortal Wkly Rep. 2014;63:431-436. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm http://www.ncbi.nlm.nih.gov/pubmed/24827411?tool=bestpractice.com
目前认为单峰骆驼是主要的动物宿主。[36]Omrani AS, Shalhoub S. Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn? J Hosp Infect. 2015;91:188-196. http://www.ncbi.nlm.nih.gov/pubmed/26452615?tool=bestpractice.com
确切的传播方式尚不清楚,人们认为传播途径为直接或间接接触单峰骆驼(例如挤骆驼奶,接触骆驼鼻腔分泌物、尿液或粪便)或食用骆驼产品(例如未经巴氏消毒的骆驼奶,未加工或未煮熟的骆驼肉)。
骆驼与人之间的传播最有力证据来自沙特阿拉伯的一项研究,该研究从患者和他的一只骆驼中分离出病毒,发现基因组几乎相同。[58]Memish ZA, Cotten M, Meyer B, et al. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis. 2014;20:1012-1015. https://wwwnc.cdc.gov/eid/article/20/6/14-0402_article http://www.ncbi.nlm.nih.gov/pubmed/24857749?tool=bestpractice.com [59]Azhar EI, El-Kafrawy SA, Farraj SA, et al. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014;370:2499-2505. http://www.nejm.org/doi/full/10.1056/NEJMoa1401505#t=article http://www.ncbi.nlm.nih.gov/pubmed/24896817?tool=bestpractice.com
一项病例对照研究发现,与骆驼接触是一项危险因素。[61]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?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 岁的患者,症状表现更重、结局更劣,且死亡风险更高。[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
据报道, 65% 至 87% 的确诊病例为糖尿病患者,与重症感染有关。[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 [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 [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
在入住重症监护病房的 12 名危重患者队列中,糖尿病是最常见的共患病。[78]Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-397. http://annals.org/aim/article/1817260/clinical-course-outcomes-critically-ill-patients-middle-east-respiratory-syndrome http://www.ncbi.nlm.nih.gov/pubmed/24474051?tool=bestpractice.com
将其确定为病例对照研究中的风险因素。[61]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
约 33% 的确诊病例中可见报道(相比之下,最初疑似感染,但后来检测结果呈阴性的患者中,其发生率为 7%)。[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
据报道,患有终末期肾病的患者会发生严重感染,并且临床结局更劣。[78]Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-397. http://annals.org/aim/article/1817260/clinical-course-outcomes-critically-ill-patients-middle-east-respiratory-syndrome http://www.ncbi.nlm.nih.gov/pubmed/24474051?tool=bestpractice.com 一项病例系列事件报道显示,慢性肾功能损害患者死亡率为 100%,其中包括 8 名正在接受血液透析的患者。[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
这可能与接受血液透析的终末期肾病患者发生的免疫失调有关。[79]Deenitchina SS, Ando T, Okuda S, et al. Cellular immunity in hemodialysis patients: a quantitative analysis of immune cell subsets by flow cytometry. Am J Nephrol. 1995;15:57-65. http://www.ncbi.nlm.nih.gov/pubmed/7872366?tool=bestpractice.com
将其确定为病例对照研究中的风险因素。[61]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
在一项病例对照研究中,确诊感染患者的中位 BMI 为 32,而对照组为 27.8。[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
据研究报告,这与几个病例系列事件报道中的严重感染和临床结局较差相关。[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 [78]Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389-397. http://annals.org/aim/article/1817260/clinical-course-outcomes-critically-ill-patients-middle-east-respiratory-syndrome http://www.ncbi.nlm.nih.gov/pubmed/24474051?tool=bestpractice.com
将其确定为病例对照研究中的风险因素。[61]Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49-55. https://wwwnc.cdc.gov/eid/article/22/1/15-1340_article http://www.ncbi.nlm.nih.gov/pubmed/26692185?tool=bestpractice.com
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