J Korean Med Assoc 2015 June; 58(6): Received: June 12, 2015 Accepted: June 15, 2015 Corresponding author: Jae Wook Choi

Special contribution J Korean Med Assoc 2015 June; 58(6): 487-497 pissn 1975-8456 / eissn 2093-5951 http://dx.doi.org/10.5124/jkma.2015.58.6.487 한국메르스감염의역학현황과공중보건학적대응조치방향 최재욱 1-4* 김경희 1* 조용민 1 김상후 1,3 고려대학교 1 환경의학연구소, 2 보건대학원, 3 의과대학예방의학교실, 4 대한의사협회의료정책연구소 Current epidemiological situation of Middle East respiratory syndrome coronavirus clusters and implications for public health response in South Korea Jae Wook Choi, MD 1-4* Kyung Hee Kim, PhD 1* Yong Min Cho, PhD 1 Sang Hoo Kim, MD 1,3 1 Institute for Occupational and Environmental Health, 2 Graduate School of Public Health, 3 Department of Preventive Medicine, College of Medicine, Korea University, Seoul, 4 Research Institute for Healthcare Policy, Korean Medical Association, Seoul, Korea Since May 20, 2015, when the first case of Middle East respiratory syndrome (MERS) in South Korea was confirmed, the cluster case in South Korea has grown to become the largest observed case following Saudi Arabia within the span of one month. Akin to what was observed in the Middle East, confirmed cases were infected through nosocomial transmission where the cluster is largely limited to patients, healthcare workers, and visitors to patients in healthcare facilities with confirmed cases. A major difference from the outbreaks in the Arabian Peninsula has been the large number of tertiary transmission cases in South Korea, which had reached forty cases by June 12. This observation may suggest that despite the lack of genetic mutation of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea, the virus may be behaving differently from that of the Middle East. The higher infectiousness of super-spreaders in South Korea also suggests that this assertion should be under further investigation. Suggestions of inadequate triage in emergency rooms, particularly at Samsung Medical Center which accounts for the most nosocomial infection with 60 cases, have been made by several organizations as the basis for this rapid spread. This, however, does not account for the fact that triage was impossible to implement, since the presence of MERS-CoV in South Korea was unknown during the index patient s stay at the healthcare facilities. This paper aims to identify the key factors in the amplified spread of MERS-CoV in South Korea. The first is the initial failure to confirm diagnosis promptly and to isolate the index case after confirmation of MERS in hospital and the lack of detail in tracking potential exposures in the community of the index case before isolation. The second is the early inadequate measures the Korea Centers for Disease Control and Prevention took in categorizing close contacts. Due to inconsistencies in defining what constitutes close contact, a number of cases were neglected from quarantine and were not subjected to investigation. Finally, confirmed or potential MERS patients were admitted for treatment and observation at medical facilities without adequate disease control measures or rooms, such as ventilated single rooms or airborne precaution rooms. Due to the rigid position that MERS-CoV cannot be transmitted via airborne means, infection control measures has so far neglected evidence that smaller droplets (aerosol) containing the virus can act similar to airborne agents, which may account for the widespread and rapid transmission in a emergency room and a patient s room in hospital. Although the South Korean government expects newly confirmed cases to abate in the coming few weeks, without stringent implementation of clearly defined guidelines to control further transmissions, the cessation of the current trend may continue for an extended period. Additionally, due to the high infection rate of super-spreaders in South Korea, efforts to screen for potential super-spreaders and a thorough investigation of those confirmed to be super-spreaders should be done to quickly identify source of infection, to potentially lower the number of secondary, tertiary transmissions and prevent possible quaternary transmissions. Key words: Middle East respiratory syndrome coronavirus; Communicable diseases; Super spreader; Epidemiology; Precautionary principle 한국메르스감염의역학현황과공중보건학적대응조치방향 487

J Korean Med Assoc 2015 June; 58(6): 487-497 Received: June 12, 2015 Accepted: June 15, 2015 Corresponding author: Jae Wook Choi E-mail: shine@korea.ac.kr *These authors contributed equally to this work. Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 서론 2015 년 5 월 20 일, 한국에서중동호흡기증후군 (Middle East respiratory syndrome, MERS; 메르스 ) 첫확진자가발생한직후부터급속한증가세로번지고있다. 6월 12일현재, 메르스확진자 126명, 사망자 11명, 격리자 3,680명으로증가하였다 [1] (Figure 1). 사우디아라비아 ( 확진자 1,028명, 사망 451명 ) 에이어세계 2위의메르스발병국이되었다 [2]. 226명의메르스확진자중남성이 74명, 여성이 52명이며, 남성은 40대에서, 여성은 50대에서많은확진자가발생하였다. 10대에서도 1명의남성환자가보고되었다 (Figure 2). 2015년 6월 12일현재, 확진자로보고된 126명의환자들중최초환자로부터감염된것으로판단되는 2차감염자는 30명으로전체의 24% 인반면, 3차감염자는 94명 (74%) 이다. 또한환자와동일한병동에입원하였던확진자가 62명 (49%), 환자의가족혹은보호자 22명 (17%) 외에도환자가입원한병원에방문하였거나체류하였던방문자중에서감염확진자도 31명 (25%) 에이르고있다 (Figure 3). 메르스감염자가발생한병원은서울강남에위치한삼성서울병원이 60명으로가장많고, 평택성모병원이 36명으로그뒤를잇고있다. 슈퍼전파자로추정되는 1번, 14번, 16번환자중 1번환자는확진전인 5월 15일과 17일각각평택성모병원과삼성서울병원에입원하였다. 평택성모병원에서는 5월 20일이후 36명의환자가확진되었다. 또한 14번환자는 27일에삼성서울병원에내원하였으며삼성서울병원은 6월 4일, 1명의환자가발견된이후급격한환자의증가를나타내어현재까지 60명의환자가보고되었다. 16번환자는 5월 25일에대전에위치한대청병원, 그리고 28일에마찬가지로대전에위치한건양대학교병원에입원하였으며, 이두병원에서 6월 1일부터 6월 12일까지총 17명의환자가감염된것으로보고하고있다 (Figure 4). 한국내메르스확진자들은의료기관내방문및체류환자들을중심으로한감염특성을보이고있다. 이는 2014년사우디아라비아 Jeddah의메르스환자들의주요감염경로라고알려진슈퍼전파자와병원내감염과유사한감염경로의특성을보이고있다 [3]. 이러한특성으로판단컨대, 최초감염자와추정슈퍼전파자의병원내격리가가장중요하며향후 감염성질환관리및대책 에있어서차단과격리의중요한기준이라고할수있다. 그러나, 한국보건당국과일부전문가들은 MERS-CoV의공기전파가능성을부정하고직접접촉에의한전파가능성만을인정하고있다. 이에본저자들은 MERS-CoV의비말전파와공기전파에대한체과학적검토와한국내역학현황을분석하여향후차단과격리범위에대한공중보건학적대응조치를제시하고자한다. 에어로졸, 비말의과학적정의에대한논란 에어로졸 (aerosol) 은미세한고체또는액체방울이기체에떠다니는것을의미하며대체로크기는 0.001 μm에서 100 μm 이다 [4]. 과학적인정의에따르면장시간동안먼거리를부유할수있는작은크기의에어로졸은공기운반입자 (airborne) 으로분류하고그에비해크기가큰에어로졸은비말 (droplet) 로분류한다 [5]. 즉, 에어로졸에의한전파는직접접촉에의한비말전파와공기전파의두가지형태로일어날수있다는것이다. 비말전파는일반적으로재채기, 기침, 대화할때또는숨을내쉴때이루어지는데, 이것을 1차에어로졸화라고한다 [6]. 그에반해공기전파는비말의수분이증발하면서남기는 <5 μm 의비말핵이퍼지면서전파되는것인데, 비말핵은가벼우며공기중에장시간부유할수있기때문에특히위험할수있다 [7]. 비말은표면에정착한후에도진동또는기류등에의 488 대한의사협회지

Choi JW et al. Current epidemiological situation of MERS-CoV clusters in South Korea 140 Quarantine cases 4,000 Confirmed case (person) 120 100 80 60 40 20 0 Accumulated confirmed cases 122 126 3,500 Accumulated deaths 108 3,000 95 87 2,500 2,000 64 1,500 50 42 1,000 36 30 24 25 500 18 13 15 2 3 3 3 3 3 5 5 7 2 3 4 5 7 9 10 11 0 May 20 22 24 26 28 30 June 1 3 5 7 9 11 Quarantine case (person) Figure 1. Number of confirmed patients, deaths and quarantines with Middle East respiratory syndrome coronavirus in South Korea (20 May to 12 June, 2015). 90-99 Female Male 90-99 80-89 70-79 60-69 50-59 40-49 30-39 20-29 10 11 9 5 5 2 3 2 9 11 15 16 17 80-89 70-79 60-69 50-59 40-49 30-39 20-29 10-19 1 10-19 0-9 0-9 24 22 20 18 16 14 12 10 8 6 4 2 0 2 4 6 8 10 12 14 16 18 20 22 24 Figure 2. Number of confirmed patients with Middle East respiratory syndrome coronavirus for age and gender in South Korea (20 May to 12 June, 2015). 해바이러스가다시공기중으로들어가는 2차에어로졸화또는재부유 (resuspension) 를일으킬수있다 [6,8]. 비말과비말핵은구형입자의직경에따라공기중에떠돌아다니는시간이달라지는데 Tellier [9] 에의하면비말발생장소로부터 3 m 이동범위내침강하는데 100 μm의입자는 4분 20초, 10 μm는 17분, 5 μm는 62분그리고 3 μm 미만은거의침강하지않고공기중에부유한다고한다. 또한, 공기중의비말은생성중에전하를가지게되어서로같은극성의성질을띠게되는데, 이때문에각입자간에척력이발생하여입자의공기중확산이일어날수있다고보고한바있다 [10]. 이와관련하여환기시스템과공기의흐름은중증급성호흡기증후군 (severe acute respiratory syndrome, SARS), 인플루엔자같은전염병의공기전파와깊은연관이있다 [11]. 입자의호흡기출입경로, 증발정도에따른비말의크기변화, 기류에의한입자의이동경로등에따라감염이결정되기때문에크기에따른공기운반입자와비말의분류에관해서는지속적인연구가필요하다 [5,12]. 호흡기내에서분열되거나증식되는대다수병원체는특정환경이충족되면공기전파와비슷한양상을보일수있다는연구결과가보고되었다 [13]. 이와관련된실험연구로 Chao 등 [14] 은비말이평균적으로기침을할때는 11.7 m/s, 말을할때는 3.9 m/s 의빠른속도로퍼지는것을보고한바있다. 비말의평균크기는기침을할때 13.5 μm, 말을할때 16 μm이며, 관찰된비말중 5 μm 미만의작은비말도존재한다. 이러한작은크기의비말의경우빠르게증발되어더작은크기의비말핵 (droplet nuclei) 을남겨공기의흐름을따라장시간부유하 한국메르스감염의역학현황과공중보건학적대응조치방향 489

J Korean Med Assoc 2015 June; 58(6): 487-497 4th infection (1,1%) 3rd infection (94,74%) Visit or stay in hospital (31,75%) Medical personnel (10,8%) 1st patient (1,1%) 2nd infection (30,24%) Family or caregiver (22,17%) 1st patient (1,1%) Hospital acquired infection (hospitalized with patient) (62,49%) Figure 3. Classification of transmission with route of Middle East respiratory syndrome coronavirus among of all confirmed patients in South Korea (20 May to 12 June, 2015). (A) Classification followed the transmission steps of 126 confirmed patients. (B) Classification followed the characteristics of 126 confirmed patients. A B 며널리퍼지는것으로보고하였다. 더나아가비말핵은입자가작기때문에오랫동안공기에떠다닐뿐만아니라하부호흡기에깊숙이침투될수있다. 앞서기술한연구결과를요약하자면, 5 μm 크기미만비말또는비말핵은공기전파의가능성이있다는것이다. 그러나, 2014년 12월질병관리본부가발간한 중동호흡기증후군 (MERS) 관리지침 (2판) 은밀접접촉자를 확진또는의심환자와신체적접촉을한자 ( 또는환자가증상이있는동안 2 m 이내의공간에 1시간이상함께머문자 ) 로정의하여, 에어로졸에의한공기중전파의원내감염가능성을고려하지않았다. 결과적으로본지침에따른밀접접촉자의격리에관한한국의보건복지부와질병관리본부의대응조치가불충분하였음을시사한다 [15]. 미국질병통제예방센터 (Centers for Disease Control and Prevention, CDC) 는밀접접촉 (close contact) 의기준을 1) 6 ft (2 m) 이내접촉또는가운, 장갑, 호흡기, 고글등의개인보호장비 (personal protective equip- 25 Hospitalization 87 in KUH of 64 86 patient no. 16 63 85 20 62 84 61 83 60 82 Hospitalization 59 81 in SMC of patient no. 14 58 80 15 57 79 Hospitalization Hospitalization patient no. 1 in DCH of 55 77 108 121 in SMC of 56 78 122 (17th, May) patient no. 16 54 76 107 120 in MHP (15th, May) 53 75 106 119 10 52 74 105 118 51 73 104 117 50 72 95 103 116 25 49 71 94 102 115 b) 13 24 36 42 48 70 93 101 114 5 12 23 30 35 41 47 69 92 100 113 11 22 29 b) 34 40 46 68 91 99 112 126 10 b) 18 21 28 33 39 45 67 90 98 111 125 b) 2 5 7 9 15 17 20 27 32 38 44 66 89 97 110 124 b) b) 1 3 4 6 8 14 16 19 26 31 b) 37 43 65 88 96 109 123 20 21 22 23 24 25 26 27 28 29 30 31 1 2 4 5 6 7 8 9 10 11 May June 1st patient Bahrain 1 MHP Pyeongtaek 36 YCS Seoul 1 SCA Asan 1 KUH Daejeon 9 DCH Daejeon 8 SMC Seoul 60 MHY Seoul 1 AMC Seoul 1 HMC Hwaseong 4 GMP Pyeongtaek 3 BHP Pyeongtaek 1 Total 126 Seoul Hwaseong Pyeongtaek Asan Daejeon Figure 4. Date of confirmation for Middle East respiratory syndrome coronavirus and distribution of hospitals and locations where patients infected (number of each box means patient number) in South Korea (20 May to 12 June, 2015). MHP, St. Mary s Hospital in Pyeongtaek; YCS, 365 Yeollin Clinic in Seoul; SCA, Seoul Clinic in Asan; KUH, Konyang University Hospital in Daejeon; DCH, Daecheong Hospital in Daejeon; SMC, Samsung Medical Center in Seoul; MHY, St. Mary s Hospital Yeouido in Seoul; AMC, Asan Medical Center in Seoul; HMC, Hallym University Medical Center in Hwaseoung; GMP, Goodmorning Hospital in Pyeongtaek; BHP, Bagae Hospital in Pyeongtaek. Red bold represents the suspected super spreader. Death; b) Complete recovery. 490 대한의사협회지

Choi JW et al. Current epidemiological situation of MERS-CoV clusters in South Korea ment) 를착용하지않은상태에서장기간동안입원실또는같은치료공간안에머무른의료진이나가족의경우 ; 2) 가운, 장갑, 호흡기, 고글등의보호장비를착용하지않은상태에서기침과같은전염성분비물과직접접촉한사람을의미한다 고정의한다 [16]. 한국질병관리본부의중동호흡기증후군 (MERS) 대응지침 2판 (2014년 12월 ) 은 2015년 5월 24일까지사용하였으며, 미국 CDC의밀접접촉기준중개인보호장비를착용하지않은상태에서장기간동안입원실또는같은치료공간안에머무른의료진이나가족의경우를제외하였다. 결과적으로이러한기준은입원실또는같은치료공간내에머무른의료진과가족중 2 m 이내공간에머무른사람만접촉관리대상에포함하고그보다훨씬많은입원실과응급실의접촉관리대상자를놓치는결과를초래한원인이되었다. 또한, 관리지침서 (2판) 의여러곳에서밀접접촉자의정의가전반적으로일정하지않고접촉거리와시간등의세부기준이불분명한것을지적할수있다. Azhar 등 [17] 에따르면 2013 년 10월 19일메르스에감염된낙타와접촉한사람에게 10월 26일증상이발생하였다. 이후 10월 31일중증의증상으로발전하였으며, 11월 6일같은환자에게서 MERS-CoV가검출되었다. 또한, MERS- CoV에감염된낙타를사육하던낙타농장에서공기샘플을사흘간 (11월 7일, 8일, 9일 ) 채취하여분석한결과, 11월 7일 MERS-CoV에감염된남성과공기샘플의 MERS-CoV의유전자단편이서로일치하는것을확인한바있다. 6월 5일자 Nature News[18] 는병원내호흡이어려운환자들에게 MERS-CoV 전파가이루어진것이이번한국에서메르스감염의큰이유라고보도한바있다. 병원내자가호흡이곤란한환자들이호흡보조 (aid breathing) 를받을때폐에서에어로졸이발생할수있으며그에어로졸에바이러스가포함되어전파될수있다. MERS-CoV는일반적으로폐하부를침범하여감염되기때문에보통사람들은기침을해도 MERS-CoV가밖으로나오지않기때문에폐렴환자등호흡보조가필요한중증의환자에서는언제든에어로졸형태로 MERS-CoV가전파될수있다는것을의미한다. 세계보건기구 (World Health Organization, WHO) 는메르스환자 치료시 aerosol-generating medical procedures (AGMPs) 가에어로졸을발생할수있다고보고하고이에대한 공기전파주의 (airborne precaution) 를권고하고있다 [19]. 요약하자면, 병원과같은제한된공간내에서메르스감염자들에게 AGMPs( 인공호흡기와기관내삽관, 가래제거 ) 등을수행하는경우와 MER-CoV의공기전파가능성을인정하고입원실또는같은치료공간안에머무른모든사람들을밀접접촉대상자로관리하는것이시급하다. 한국슈퍼전파자의역학적특성 감염전파자의개인적특성을고려한팔레토법칙의양상이많은감염성질환유행에서발견되었다 [20]. 이는전체감염자중 20% 가유행원인의 80% 를차지한다는가설이며개인별전파력이동일하지않다는의미를가지고있다. 이와같이다른감염전파자에비해상대적으로많은숫자의 2차감염자를발생시키는감염자를슈퍼전파자 (super spreader) 로정의하며 [21], 현대감염병유행의중요한특성이다. 슈퍼전파자는다양한감염성질환유행에서발견되었다. 2003년중국베이징에서발생한 SARS의경우총 77명의환자중 66명은 2차감염을일으키지않았으나 3명의환자가각각 10명이넘는 2차감염자를발생시켰다 [22]. 싱가폴에서는 2003년 SARS에감염된전체 238명중 206명의병원감염자가운데 5명의슈퍼전파자가발생하여한명이최대 37명까지전파시킨사례가있었다 [23-25]. 반면, 베트남의경우격리입원기간동안전체 33명의 SARS 감염자중슈퍼전파자가관찰되지않았으며, 추가적인 2차감염자또한발생하지않았다 [26]. 슈퍼전파는병원이라는특수한환경에서일어날가능성이크다는보고가있다. 2014년 Jeddah에서 MERS-CoV 양성으로나온케이스와병원기록을모두분석한연구에서는증상을보인 191명메르스양성환자중 20.9% 가의료진이었으며의료진이아닌나머지 151명의 97.3% 가증상발현 14일전병원에다녀간경험이있다. 따라서 2014년 Jeddah 메르스 2차감염은병원에서현저하게증가했으며 MERS- 한국메르스감염의역학현황과공중보건학적대응조치방향 491

J Korean Med Assoc 2015 June; 58(6): 487-497 Table 1. Super-spreading events are shaped by host, pathogen, and environmental factors Event component Factor Example Host Physiological factor Susceptibility Behavioral factor Immunological factor Pathogen Transmissibility Virulence Co-infection Environment Crowdedness Size of the crowd Misdiagnosis Hospital transfer Ventilation Modified from Stein RA. Int J Infect Dis 2011;15:e510-e513 [31]. Often, more than one factor may be implicated in the same outbreak. CoV에쉽게감염될수있는환자를감별하는것이중요하다고보고하였다. 슈퍼전파를발생시키는원인은아직까지명확하지않으나, 최근연구에서동시감염이중요한관리요인임을알려졌다. 1960년대미국에서유행한신생아포도상구균감염사례에서슈퍼전파자들은공통적으로상기도감염증상을보였고 [27], 1983년같은지역의포도상구균성피부감염사례에서도동일한결과가나타났다 [28]. 또한 2005년미국웨이크포레스트대학에서지원자 11명을대상으로한실험연구는 rhinovirus 감염이포도상구균보균자의감염력을최소 2배에서최대 34배까지증가시키는결과를보여주었다 [29]. 동시감염이감염력을증가시키는메커니즘이명확하게밝혀지지는않았으나 Sherertz 등 [30] 은포도상구균의체내균락 (colony) 존재와상기도감염이비강의협소와유체역학적특성을초래하고결과적으로비말의에어로졸화증가와환자의비말분출을증가시켰다고주장하였다. 그밖에도숙주, 병인및환경요인에따라슈퍼전파자의발생위험을추정해볼수있다. Table 1은현재까지발생한슈퍼전파발생사례를토대로관련요인을기술한자료이다 [31]. 메르스는 WHO [32] 가 Cauchemez 등 [33] 의연구결과를인용하여보고한기초감염재생산수 (R0) 가 0.8-1.3이었으나, 이미우리나라에서 63명이상을감염시킨슈퍼전파추정사례가발생하고있다. 이들의발생양상을분석하여슈퍼전파가능의심사례를빠른시일내찾아조치하는것이야말로이번메르스감염전파관리의핵심이라고볼수있다. Li 등 [34] 은감염병증상이발현된시점으로부터입원 이 4일이상지연될경우슈퍼전파의발생가능성이높아진다고주장하였다. 이번국내메르스유행에서도슈퍼전파의양상이나타나고있다. 따라서슈퍼전파자의발생양상을분석하여이들을적시에찾아조치하는것이야말로이번메르스유행관리의핵심사안이라고볼수있다. 한국내최초 MERS-CoV 감염자가내원하였던서울의한병원과아산의한병원에서 2명의의료진을통한 2차감염이일어났으며, 평택성모병원에서 27건의 2차감염을초래하였다. 1번환자로부터감염된것으로판단되는 15번환자는경기도화성의한림대학교병원으로이동, 의료인을포함한 4명의 3차감염자를발생시킨것으로보인다. 또한메르스확산에있어주요한슈퍼전파자로추정되는 14번환자의경우평택성모병원에서확진판정을받은후삼성서울병원으로이동한환자이며, 6월 12일현재까지삼성서울병원에서발생한 60명과평택굿모닝병원 3명의 3차감염원인을제공한것으로여겨진다. 마찬가지로평택성모병원의 16번환자는대전에소재한두병원 ( 건양대학교병원, 대청병원 ) 에서 17명의환자에대한전파를야기하였다 (Figure 5). 이러한역학적현황을볼때, 향후추가적인슈퍼전파자의감염과당분간 3차감염자의추가보고가이어질가능성이있으며대량의 4차감염자발생가능성에대한우려를주목할필요가있다. 한국과중동에서발병한메르스환자의특성 Table 2는한국에서발생하는메르스의발병양상과사우디아라비아의발병양상의차이를정리한내용이다 [35-37]. Breban 등 [35] 은여러명의환자가 2차감염을시키지않고한환자가다수에게 2차감염을시킨다는가정하에서 prepandemic SARS 기초감염재생산수 (basic reproduction number, R0) 는 0.8인반면 MERS-CoV의 R0는 0.69 (95% CI, 0.50-0.92) 라고보고하였으며, 한환자가소수에게 2차감염을시키고그러한환자가여러명이있다는가정하에서는 MERS-CoV의 R0는 0.60 (0.42-0.80) 로보고한바있다. 최초메르스환자가병원에서발생했을때한국보건복지부 492 대한의사협회지

Choi JW et al. Current epidemiological situation of MERS-CoV clusters in South Korea Primary infection Secondary infection Tertiary infection Patient with uncertain pathway Hospitalized with Confirmed patient Family or caregiver Medical personnel Cured patient Deceased patient Suspected super spreader Secondary infection route Tertiary infection route Patient with uncertain pathway Figure 5. Distribution of transmission of Middle East respiratory syndrome coronavirus clusters and suspected super spreader in South Korea (20 May to 12 June, 2015). Table 2. Differences between Middle East respiratory syndrome outbreak in the Middle East and South Korea The Middle East South Korea Virus transmissibility (basic 0.6-0.69[35] reproduction number) Maximum of 63 patients transmitted from a suspected no. 14 super spreaders Maximum transmission distance and time required Less than 2 m, more than an hour Unknown Fever (>38 ) Common Underlying disease Comorbidity 45 (96%), diabetes 32 1) Hypertension (10 patients, (68%), chronic kidney disease 23 17.2%), diabetes (8 patients, (49%), hypertension 16 (34%) chronic 13.7%),cancer (7 patients, cardiac disease 13 (28%), chronic 12.0%), chronic lung disease lung disease 12 (26%), etc.[36] (10.3%), etc.[37] 을 적용하여 기초감염재생산수를 잠정 적으로 산출하였다. 6월 11일을 기준으 로 126명의 확진자중 감염경로가 파악 이 되지 않은 1명의 환자를 제외한 후 2 세대까지의 기초감염재생산수를 산출한 Not common 결과 약 4.0명으로 추정되었다. 이는 현 재까지 보고된 극히 제한적인 역학자료 를 바탕으로 계산된 추정치이며 향후 정 확한 자료를 바탕으로 추가적인 연구가 Basic reproduction number of Middle East respiratory syndrome coronavirus in Korea is not yet available because of the lack of epidemiologic data. 필요하다. 한국에서 확진자가 증가하면 서 메르스 감염환자들의 일반적인 증상 는 기존 기초감염재생산수 0.6-0.8 자료에 근거하여 우리나 인 고열을 보이지 않는 경우에서 MERS-CoV 양성 확진을 라에서 감염력이 높지 않을 것이라고 발표하였으며[15,38], 진단받는 경우가 발생하였다. 또한, 고위험군 집단이 취약집 이로 인하여 슈퍼관리자에 대한 관리 필요성을 간과한 것으 단으로 알려져 있었으나, 한국의 메르스 감염자 중 36.2%는 로 보인다. 본 연구자들은 Breban 등[35]의 첫 번째 연구가설 기저질환이 없는 건강한 사람들이었다. Assiri 등[36]은 사우 한국 메르스 감염의 역학현황과 공중보건학적 대응조치 방향 493

J Korean Med Assoc 2015 June; 58(6): 487-497 디아라비아에서발생한 47명의 MERS-CoV 감염환자에대해역학적 임상적특성을분석하여메르스확진환자의기저질환을동반상병 45명 (96%), 당뇨병 32명 (68%), 만성신장질환 23명 (49%), 고혈압 16명 (34%) 만성심질환 13명 (28%), 만성폐질환 12명 (26%) 등의순으로보고한바있다. 한국보건복지부의발표자료에따르면한국내메르스확진자 45명을분석한결과, 기저질환이없는건강한사람은 21명 (36.2%) 이라고발표하였다. 또한, 메르스확진자의기저질환은고혈압 10명 (17.2%), 당뇨병 8명 (13.7%), 암 7명 (12.0%), 만성폐질환 6명 (10.3%) 등의순으로보고하였다 [37]. 결론및공중보건학적대응시사점 Azhar 등 [17] 이보고한메르스감염환자가소유한낙타농장에서환자의동일한 MERS-CoV 입자가발견되었으나 MERS-CoV 입자가감염력을갖고있는지에대해서는아직명확한증거는없다. 메르스의공기매개여부와공기중에떠있는상황에서 MERS-CoV 의감염력이얼마나지속되는지등에대한과학적인근거는아직충분하지않은상황이다. 그럼에도불구하고본저자들이 병원내공기전파가능성을배제해서는안된다 고주장하는이유는다음과같다. 감염성질환의원인과경로등이과학적으로엄밀하게입증된증거가없는경우라하더라도예견가능한연구보고들을토대로 precautionary principle 에의거하여공중보건학적예방관리대책를수립하고시행하는것이가장중요한기본원리이기때문이다. Harriman 등 [39] 과미국 CDC [40] 는 입원환자에대한감염예방관리권고 (Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV) 를통해병원전파경로등에관한정보가과학적으로확실하지않은상황에서는 precautionary principle에따라모든메르스감염환자들에대해 airborne precautions( 예 : 수술용마스크가아닌 N-95 마스크, 보호의및고글등 ) 을권고하고있다. SARS는발병당시비말감염으로간주하였으나비행기안에서감염자좌석기준 7줄앞에자리했던승객이감염되거나, 같은호텔의같은층을사용했던손님중환자가다수발생한사례, 홍콩의한아파트단지에서 1,000명이상의발병사례가보고되는등, 각종관련사례들이보고되어공기감염으로감염될수있다고판단하였다 [6]. 그러나, 상기 SARS의경우는지역사회에서의공기감염을위험성을강조하고자한것이다. SARS와메르스는모두병원내공기감염의위험성인정과그에따른 airborne precaution의적용은일치하나, 메르스의경우 SARS와는달리지역사회에서의공기감염위험성에대한명백한역학적증거가없는것은사실이다. 따라서메르스가지역사회내에서는공기감염의우려가없다고하는것은적절하다. 그러나병원내제한된공간내에서의비말과에어로졸의공기전파에의한감염가능성을입증할수있는다양한역학적그리고실험적연구결과들을고려할때, MERS-CoV의병원내공기감염의가능성을부정하는것은부적절하다. 2015년 6월 12일현재까지한국내발병양상과역학자료를분석한결과, 한국내메르스감염의초기대응에있어서문제점, 최초환자의격리와실패그리고소위슈퍼감염자로부터의 2차감염의증가에대한본저자들의견해는다음과같다. 첫째, 국내메르스첫환자발생직후, 2014년 12월작성된매뉴얼 중동호흡기증후군 (MERS) 관리지침 (2판) [15] 에따라대응을하였으나결과적으로선제적인격리차단대응이실패한것으로보인다. 메르스대응지침 (2판) 에따르면밀접접촉자의기준을 의심환자와신체적접촉을한자 ( 또는환자가증상이있는동안 2 m 이내의공간에 1시간이상함께머문자 ) 로한정함으로인하여, 작은크기의비말혹은에어로졸의동일공간내 ( 의료기관내 ) 공기전파로인한 2차감염자의발생을차단하지못한원인이되었다. 실제이는 14번환자로부터삼성서울병원응급실내의료인력과방문환자가감염되는계기가되었다. 둘째, 밀접접촉자들에대한격리차단의실패이다. 미국 CDC [41] 는메르스감염자혹은접촉자중병원입원이필요하지않은사람들에대한자가격리실행지침 (Im- 494 대한의사협회지

Choi JW et al. Current epidemiological situation of MERS-CoV clusters in South Korea plementing home care and isolation or quarantine of people not requiring hospitalization for MERS-CoV) 을통해의료전문가는자가격리이전에주또는지방보건부와의관리자들과점검후주거환경이자가격리에적당한지그리고 CDC interim guidance를따를수있는환경인지평가하여야한다고기술하고있다. 그러나, 한국은자가격리를실시하기전에밀접접촉자들의주거환경요인등을사전에검토하거나격리자에대한교육과지원이이루어지지않았다. 2015년 6월 3일자 Nature News는한국에서 MERS- CoV에처음감염된 68세남성은 5월 11일부터확진받은 5월 20일전까지의시간동안다른네곳의병원을방문하였으며그로인해병원내 MERS-CoV 확산을초래한것으로보고하였으며 [18], The Lancet News(2015년 6월 13일 ) [42] 는밀접접촉자중의한사람이자가격리지시를거부하고중국을방문한사실을언급하면서밀접접촉자에대한격리관리가적절하지않았음을지적한바있다. 셋째, 무엇보다도한국에서의가장중요하고치명적인문제점은슈퍼전파자에대한추가적인감염차단과격리실패이었다. 결과적으로최초환자 (1번환자, index case) 에대한병원내격리실패로 27명의 2차감염발생, 14번환자는응급실내체류 3일간격리조치가이루어지지않아 63명추가감염발생그리고 16번환자는 17명에게메르스 2차감염을전파하는상황을초래하였다. 넷째, 2차병원내감염성질환관리체계의미흡한역량과미흡한환기시설등의환경적요인이다. 유럽질병예방통제센터 (European Centre for Disease Prevention and Control) [2] 는한국내메르스감염환자의확산원인으로호흡기증상을보이는환자가응급실내원시여행력확보등의미흡한환자분류체계임을보고하였다. 또한, The Lancet News (2015년 6월 13일 )[42] 는한국에서의메르스발생은중동이외의지역에서일어난가장큰규모의집단발병사례로이는사우디아라비아의사례와마찬가지로불충분한병원감염관리역량이한국에서의전파의주요원인으로보고한바있다. 다섯째, 에어로졸과미세비말로인한공기매개전파가능성을배제하고비말에의한직접접촉감염경우만을고려한것은초동대응단계에서최초환자의격리가실패를하게된 가장중요한원인이었다고추정된다. 그러나현재까지한국정부는메르스확진자가집단발생한병원내에서공기전파의가능성을부인하고비말의직접접촉으로인한감염만을공식적으로인정하고있다. 이와같은감염방식에대한정부의지나친경직적인기준으로인하여직접접촉에의한감염의심자이외의추가적감염의심자가관리되지않을가능성이여전히존재한다. 마지막으로, 정부의미흡한위기관리소통이라고할수있다. 대응초기의료기관에게메르스확진환자의정보와, 경유병원과확진병원등에대한정보공개가지연되어또다른 2차, 3차감염이발생하였다. 실제, 삼성서울병원의경우응급실내음압격리병실과선별진료소가있음에도불구하고, MERS-CoV 감염환자의접촉여부에대한정보공유가신속하고투명하게되지않아응급실내에서의격리가시행되지않았다. 따라서한국-WHO 메르스합동평가단이권고한바와같이, 효과적인위기관리소통체계가시급히필요하다 [43]. 한국내메르스감염자의확산에대한본연구자들의견해는현재까지알려진제한된역학자료를토대로도출한잠정적인연구결과이다. 향후한국에서 MERS-CoV 감염에관한추가적인역학연구정보들과관련연구결과들이도출된다면본연구자들의견해는지지되거나수정될수있다. 그럼에도불구하고본연구자들의견해는 감염성질환예방및관리에있어사전예방원칙 의중요성을강조하고현시점에서시급한공중보건학적대응관리의방향을제언하는데의의가있다. Acknowledgement We would like to thank the researchers at the Institute for Occupational and Environmental Health at Korea University (Seung-Hun Ryu, Eunsun Lee, Jiwook Park, Minjoo Ku, Min Soo Kim, Byeo Ri Lee, Jiwon Moon, Minhee Kim, and Tinyami Eric Tandi) for their academic support. 한국메르스감염의역학현황과공중보건학적대응조치방향 495

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