原創 張秀月/李詩文 SIFIC感染官微
證實說話和咳嗽可產生氣溶膠或空氣中檢測到病毒RNA，並不能證明COVID-19是基於氣溶膠傳播的…
Viewpoint：Airborne Transmission of SARS-CoV-2
Theoretical Considerations and Available Evidence
觀點: SARS-CoV-2病毒的空氣傳播：理論考慮與現有證據
翻譯：張秀月 李詩文（中國醫科大學附屬盛京醫院 院內感染管理辦公室）
致謝：感謝世界衛生組織傳染病流行病學及感染控制合作中心、香港大學公共衛生學院高級護士程棣研女士對本文的推薦、翻譯審校與指導。
原文通訊作者：Michael Klompas，醫學博士，公共衛生碩士，哈佛醫學院和哈佛朝聖者衛生保健研究所，人口醫學部。401 Park Dr，Ste 401，Boston，MA 02215(mklompas@bwh. harvard.edu).
2019年冠狀病毒病(COVID-19)大流行再次喚醒了長期以來的爭論，即包括嚴重急性呼吸綜合症冠狀病毒2（SARS-CoV-2）在內的常見呼吸道病毒在多大程度上通過呼吸道飛沫、氣溶膠傳播。飛沫（droplets）通常被描述為較大的顆粒（>5μm），在重力作用下，通常在距離感染源3到6英尺的範圍內迅速降落到地面；氣溶膠（aerosols）是在空氣中迅速蒸發的較小顆粒（≤5μm），足夠小、足夠輕的飛沫核可以持續在空氣中懸浮數小時（類似於花粉）。
確定SARS-CoV-2在傳播過程中是飛沫主導還是氣溶膠主導具有重要意義。如果SARS-CoV-2主要通過呼吸道飛沫傳播，那麼戴上醫用口罩、面屏（face shields），或與其他人保持6英尺的距離，就足以防止傳播。但是，如果SARS-CoV-2由能夠長時間懸浮在空氣中的氣溶膠攜帶，那麼醫用口罩就不足以防止傳播（因為氣溶膠既能穿透又能繞行通過口罩），面屏也只能提供部分保護（因為面屏和佩戴者面部有開放的縫隙），而6英尺的隔離距離也無法防止懸浮在空氣中或隨氣流移動的氣溶膠。
實驗數據支持SARS-CoV-2即使在未執行產生氣溶膠的診療操作（如插管或無創正壓通氣）的情況下也可通過氣溶膠傳播（即空氣傳播）的可能性。研究人員已經證明，說話和咳嗽會產生大小不等的飛沫和氣溶膠的混合物，這些分泌物可以一同傳播長達27英尺，SARS-CoV-2在空氣中懸浮並存活數小時是可能的，可以從醫院的空氣樣本中檢測到SARS-CoV-2 RNA。通風不良會延長氣溶膠在空氣中停留的時間[1]。
顯示出與之前的流感病毒和其他常見呼吸道病毒有許多相同的特徵。這些數據為可能的SARS-CoV-2通過氣溶膠傳播提供了有用的理論框架，但尚不清楚的是這些特徵在多大程度上可導致感染的發生。證實說話和咳嗽可產生氣溶膠或空氣中檢測到病毒RNA，並不能證明COVID-19是基於氣溶膠傳播的；感染還取決於暴露的途徑、接種物的大小、暴露的持續時間以及宿主的防禦能力。
儘管實驗數據表明存在基於氣溶膠傳播的可能性，但關於正常的日常生活中人群感染率和傳播數據很難用基於氣溶膠的遠距離傳播進行解釋。首先，在採取防控措施阻止其傳播前，COVID-19的再生數（也稱傳染數）估計約為2.5，這意味著每個COVID-19感染者平均會再感染2-3人。這種傳染數與流感相似，而與眾所周知的通過氣溶膠傳播的麻疹病毒有很大的不同，後者的傳染數接近18。考慮到大多數COVID-19感染者在大約1周內會發生傳播，基於大多數人在正常情況下在7天內會有大量的互動、人群聚集和個人接觸，所以2-3的傳染數是相當小的。或者是造成感染所需的SARS-CoV-2病毒數量遠遠大於麻疹，亦或是氣溶膠不是主要的傳播方式。
同樣，SARS-CoV-2的續發率也很低。評估COVID-19確診患者密切接觸者病例序列報告僅有約5%的接觸者受到感染。然而，即使如此低的感染率也不是均勻分布在密切接觸者之間，而是取決於接觸的持續時間和強度。這種風險在家庭成員中最高，他們的傳播範圍在10%~40%之間[2-4]。密切但不太持久的接觸，如分享一頓飯與大約7%的繼發感染率相關，而購物人群之間路過性互動與0.6%的續發率相關[4]。
在不知情的情況下，單獨戴口罩或不使用任何個人防護用品時衛生保健人員的續發率也很低，傳播研究表明低於3%（在這些傳播研究中少數記錄在案的、感染的衛生保健人員感染與執行產生氣溶膠的診療操作或長時間暴露未持續佩戴口罩相關）[5-6]。SARS-CoV-2感染者可能會持續產生飛沫和氣溶膠，但其中大多數排放物不會感染其他人。這種模式似乎更符合分泌物迅速降落在感染者周圍小半徑內的地面，而不是攜帶病毒的氣溶膠持續數小時懸浮在面部水平、被鄰近的任何人吸入導致傳播。一個例外情況可以是在通風不良的空間裡長時間接觸感染者，使得原本微不足道的攜帶病毒的氣溶膠積聚。
氣溶膠傳播的支持者引用了詳細記錄在案的合唱團參與者、餐館顧客和共用封閉室內空間工作人員的感染聚集案例。然而，基於SARS-CoV-2的傳染數，這些事件似乎是例外而不是規則。此外，通過回顧研究很難確定感染事件發生之前、期間和之後可能發生的所有的潛在風險的人與人之間的互動行為。不應低估病毒在封閉環境中通過多種機制在緊密聯繫的群體中廣泛、迅速傳播的潛在能力。使用噬菌體標記實驗表明，病毒可以在數小時內從一個受汙染的門把手或1名感染者的手傳播給整個辦公樓的人員和設備[7]。這些告誡也是推測性的，並不排除氣溶膠傳播的可能性，尤其是在擁擠、通風不良的空間，但確實為這些聚集提供了潛在的替代解釋。
也許最實際的衡量氣溶膠與飛沫傳播相對重要性的標尺是研究針對氣溶膠與飛沫進行呼吸防護對應的有效性。如果呼吸道病毒主要通過氣溶膠傳播，N95呼吸器及其等效物將比單獨使用醫用口罩更具保護性。最近的一項薈萃分析提出了這一說法[8]。然而，薈萃分析並不是基於對N95呼吸器和醫用口罩的直接比較，而是基於兩個獨立分析的事後貝葉斯分析，一個是N95呼吸器對未佩戴口罩，另一個是醫用口罩對未佩戴口罩。
與未佩戴口罩相比，N95呼吸器和醫用口罩都具有保護性；但是，鑑於每種比較的源研究高度不同，因此比較分析這兩種呼吸道防護的有效性便值得懷疑。納入的研究是小型的、異質的病例對照研究，雖對可能的混雜因素進行了變量調整，但結果各不相同，置信區間很寬。
此外，在這項薈萃分析的10項研究中有9項涉及SARS冠狀病毒和中東呼吸症候群病毒，而不是SARS-CoV-2。從4個隨機試驗中直接比較、推斷N95呼吸器和醫用口罩的防護有效性將比從其他病毒推斷SARS-CoV-2呼吸道保護的有效性更有意義。隨機試驗中，未發現兩者在確診的衛生保健人員非嚴重急性呼吸綜合症冠狀病毒（non– SARS coronavirus）感染和流感感染率上存在差異[9]。
總的來說，目前對SARS-CoV-2傳播的認識仍然有限。目前還沒有完善的實驗數據來證明或反駁SARS-CoV-2的飛沫傳播與氣溶膠傳播。然而，證據似乎與SARS-CoV-2氣溶膠傳播不一致，特別是在通風良好的空間。這在實踐中意味著，與其他人保持6英尺的距離，並在不可能相隔6英尺的情況下戴上醫用口罩、高質量布質口罩或面屏（用於傳染源控制和呼吸道保護），應足以降低SARS-CoV-2的傳播（基於經常性手部衛生、環境清潔以及優化室內通風基礎上）。
可以肯定的是，生物學系統中很少有絕對的存在，人們既會產生飛沫，也會產生氣溶膠，不同傳播可能會在一定程度內發生，甚至醫用口罩也可能對氣溶膠起到一定的防護作用[6,10]。我們不可能得出這樣的結論：氣溶膠傳播從未發生過，而且很多人更傾向于謹慎行事，尤其是在醫療保健環境中照顧疑似或確診的COVID-19患者時，這是完全可以理解的。然而，現有證據表明，遠距離氣溶膠傳播並不是SARS-CoV-2傳播的主要方式。
原文於2020年7月13日在線發布Opinion jama.com：doi:10.1001/jama.2020.12458，©美國醫學會，版權所有。
利益衝突披露：克洛帕斯博士報告從美國疾病控制和預防中心獲得資助；並從UpToDate收取個人費用。沒有其他需披露的信息。
英文原文
Viewpoint：Airborne Transmission of SARS-CoV-2
Theoretical Considerations and Available Evidence
The coronavirus disease 2019 (COVID-19) pandemic has reawakened the long-standing debate about the extent to which common respiratory viruses, including the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), are transmitted via respiratory droplets vs aerosols. Droplets are classically described as larger entities (>5 μm) that rapidly drop to the ground by force of gravity, typically within 3 to 6 feet of the source person. Aerosols are smaller particles (≤5 μm) that rapidly evaporate in the air, leaving behind droplet nuclei that are small enough and light enough to remain suspended in the air for hours (analogous to pollen).
Determining whether droplets or aerosols predominate in the transmission of SARS-CoV-2 has critical implications. If SARS-CoV-2 is primarily spread by respiratory droplets, wearing a medical mask, face shield, or keeping 6 feet apart from other individuals should be adequate to prevent transmission. If, however, SARSCoV-2 is carried by aerosols that can remain suspended in the air for prolonged periods, medical masks would be inadequate (because aerosols can both penetrate and circumnavigate masks), face shields would provide only partial protection (because there are open gaps between the shield and the wearer’s face), and 6 feet of separation would not provide protection from aerosols that remain suspended in the air or are carried by currents.
Experimental data support the possibility that SARSCoV-2 may be transmitted by aerosols (so-called airborne transmission) even in the absence of aerosol generating procedures (such as intubation or noninvasive positive pressure ventilation). Investigators have demonstrated that speaking and coughing produce a mixture of both droplets and aerosols in a range of sizes, that these secretions can travel together for up to 27 feet, that it is feasible for SARS-CoV-2 to remain suspended in the air and viable for hours, that SARS-CoV-2 RNA can be recovered from air samples in hospitals, and that poor ventilation prolongs the amount of time that aerosols remain airborne.1
Many of these same characteristics have previously been demonstrated for influenza and other common respiratory viruses. These data provide a useful theoretical framework for possible aerosol-based transmission for SARS-CoV-2, but what is less clear is the extent to which these characteristics lead to infections. Demonstrating that speaking and coughing can generate aerosols or that it is possible to recover viral RNA from air does not prove aerosol-based transmission; infection depends as well on the route of exposure, the size of inoculum, the duration of exposure, and host defenses.
Notwithstanding the experimental data suggesting the possibility of aerosol-based transmission, the data on infection rates and transmissions in populations during normal daily life are difficult to reconcile with long range aerosol-based transmission. First, the reproduction number for COVID-19 before measures were taken to mitigate its spread was estimated to be about 2.5, meaning that each person with COVID-19 infected an average of 2 to 3 other people. This reproduction number is similar to influenza and quite different from that of viruses that are well known to spread via aerosols such as measles, which has a reproduction number closer to 18. Considering that most people with COVID-19 are contagious for about 1 week, a reproduction number of 2 to 3 is quite small given the large number of interactions, crowds, and personal contacts that most people have under normal circumstances within a 7-day period. Either the amount of SARSCoV-2 required to cause infection is much larger than measles or aerosols are not the dominant mode of transmission.
Similarly, the secondary attack rate for SARS-CoV-2 is low. Case series that have evaluated close contacts of patients with confirmed COVID-19 have reported that only about 5% of contacts become infected. However, even this low attack rate is not spread evenly among close contacts but varies depending on the duration and intensity of contact. The risk is highest among household members, in whom transmission rates range between 10% and 40%.2-4 Close but less sustained contact such as sharing a meal is associated with a secondary attack rate of about 7%, whereas passing interactions among people shopping is associated with a secondary attack rate of 0.6%.4
The secondary attack rate among health care workers who unknowingly care for a patient with COVID-19 while wearing face masks alone or not using any personal protective equipment is also low; transmission studies suggest less than 3% (and the few health care worker infections that were documented in these transmission studies were associated with aerosol-generating procedures or prolonged exposures with inconsistent use of facemasks).5,6 People infected with SARS-CoV-2may be producing both droplets and aerosols on a constant basis but most of these emissions are not infecting other people. This pattern seems more consistent with secretions that fall rapidly to the ground within a narrow radius of the infected person rather than with virus-laden aerosols that remain suspended in the air at face level for hours where they can be inhaled by anyone in the vicinity. An exception may be prolonged exposure to an infected person in a poorly ventilated space that allows otherwise insignificant amounts of virus-laden aerosols to accumulate.
Proponents of aerosol-based transmission cite well documented clusters of infections among choir participants, restaurant patrons, and office workers sharing closed indoor spaces. However, based on the reproduction number for SARS-CoV-2, these events appear to be the exception rather than the rule. Furthermore, it is difficult to determine in retrospect all the potential person to-person interactions that may have happened before, during, and immediately following these events. The potential capacity of viruses to spread widely and rapidly among tightly packed groups within closed environments via multiple mechanisms should not be underestimated. Experiments using labeled phages show that viruses can spread from a single contaminated door handle or the hands of 1 infected person to people and equipment throughout an office building within hours.7 These caveats are also speculative and do not exclude the possibility of aerosol-based transmission, particularly in crowded poorly ventilated spaces, but do provide potential alternative explanations for these clusters.
Perhaps the most practical gauge of the relative importance of aerosols vs droplets are studies on the relative effectiveness of respiratory protection targeting aerosols vs droplets. If respiratory viruses are predominantly spread via aerosols, N95 respirators and their equivalents would be more protective than medical masks alone. A recent meta-analysis made this claim.8 However, the meta-analysis was not based on direct comparisons of N95 respirators vs medical masks but rather on a post hoc bayesian analysis of 2 independent analyses, one onN95 respirators vs no masks and the other on medical masks vs no masks.
Both N95 respirators and medical masks were protective compared with no masks; however, the validity of then comparing these 2 analyses is questionable given the highly divergent source studies for each comparison. The included studies were small, heterogeneous case-control studies that variably adjusted for possible confounders, had disparate results, and wide confidence intervals.
Moreover, 9 of the 10 studies in this meta-analysis8 involved SARS coronavirus 1 and Middle East respiratory syndrome virus rather than SARS-CoV-2. To extrapolate about the effectiveness of respiratory protection for SARS-CoV-2 from other viruses, it would make more sense to extrapolate from the 4 randomized trials that have directly compared N95 respirators vs medical masks and found no difference between them in the rates of confirmed non– SARS coronavirus infections and influenza infections among health care workers.9
All told, current understanding about SARS-CoV-2 transmission is still limited. There are no perfect experimental data proving or disproving droplet vs aerosol-based transmission of SARSCoV-2. The balance of evidence, however, seems inconsistent with aerosol-based transmission of SARS-CoV-2 particularly in well ventilated spaces. What this means in practice is that keeping 6-feet apart from other people and wearing medical masks, high-quality cloth masks, or face shields when it is not possible to be 6-feet apart (for both source control and respiratory protection) should be adequate to minimize the spread of SARS-CoV-2 (in addition to frequent hand hygiene, environmental cleaning, and optimizing indoor ventilation).
To be sure, there are rarely absolutes in biological systems, people produce both droplets and aerosols, transmission may take place along a spectrum, and even medical masks likely provide some protection against aerosols.6,10 It is impossible to conclude that aerosol-based transmission never occurs and it is perfectly understandable that many prefer to err on the side of caution, particularly in health care settings when caring for patients with suspected or confirmed COVID-19. However, the balance of currently available evidence suggests that long-range aerosol-based transmission is not the dominant mode of SARS-CoV-2 transmission.
ARTICLE INFORMATION
Published Online: July 13, 2020. doi:10.1001/jama.2020.12458
Conflict of Interest Disclosures: Dr Klompas reported receiving grants from the US Centers for Disease Control and Prevention; and receiving personal fees from UpToDate. No other disclosures were reported.
REFERENCES
1. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: potential implications for reducing transmission of COVID-19. JAMA. 2020;323(18):1837-1838. doi:10.1001/jama. 2020.4756
2. Cheng HY, Jian SW, Liu DP, Ng TC, Huang WT, Lin HH; Taiwan COVID-19 Outbreak Investigation Team. Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset. JAMA Intern Med. Published online May 1, 2020. doi:10.1001/jamainternmed.2020.2020
3. Rosenberg ES, Dufort EM, Blog DS, et al; New York State Coronavirus 2019 Response Team. COVID-19 testing, epidemic features, hospital outcomes, and household prevalence, New York State-March 2020. Clin Infect Dis. Published online May 8, 2020. doi:10.1093/cid/ciaa549
4. Chen Y, Wang AH, Yi B, et al. Epidemiological characteristics of infection in COVID-19 close contacts in Ningbo. Article in Chinese. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(5):667-671.
5. Heinzerling A, Stuckey MJ, Scheuer T, et al. Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient—Solano County, California, February 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):472-476. doi:10. 15585/mmwr.mm6915e5
6. Ng K, Poon BH, Kiat Puar TH, et al. COVID-19 and the risk to health care workers: a case report. Ann Intern Med. 2020;172(11):766-767. doi:10.7326/ L20-0175
7. Reynolds KA, Beamer PI, Plotkin KR, Sifuentes LY, Koenig DW, Gerba CP. The healthy workplace project: reduced viral exposure in an office setting. Arch Environ Occup Health. 2016;71(3):157-162. doi: 10.1080/19338244.2015.1058234
8. Chu DK, Akl EA, Duda S, Solo K, Yaacoub S, Schünemann HJ; COVID-19 Systematic Urgent Review Group Effort (SURGE) Study Authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020;395(10242):1973-1987. doi:10.1016/S0140-6736(20)31142-9
9. Bartoszko JJ, Farooqi MAM, Alhazzani W, Loeb M. Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: a systematic review and meta-analysis of randomized trials. Influenza Other Respir Viruses. 2020;14(4):365-373. doi:10.1111/irv.12745
10. Dharmadhikari AS, Mphahlele M, Stoltz A, et al. Surgical face masks worn by patients with multidrug-resistant tuberculosis: impact on infectivity of air on a hospital ward. Am J Respir Crit Care Med. 2012;185(10):1104-1109. doi:10.1164/ rccm.201107-1190OC
Michael Klompas, MD, MPH Harvard Medical School and Harvard Pilgrim Health Care Institute, Department of Population Medicine, Boston, Massachusetts; and Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.
Meghan A. Baker, MD, ScD Harvard Medical School and Harvard Pilgrim Health Care Institute, Department of Population Medicine, Boston, Massachusetts; and Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.
Chanu Rhee, MD, MPH Harvard Medical School and Harvard Pilgrim Health Care Institute, Department of Population Medicine, Boston, Massachusetts; and Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.
Corresponding Author: Michael Klompas, MD, MPH, Harvard Medical School and Harvard Pilgrim Health Care Institute, Department of Population Medicine, 401 Park Dr, Ste 401, Boston, MA 02215 (mklompas@bwh. harvard.edu).
Opinion jama.com (Reprinted) JAMA Published online July 13, 2020 E1 © 2020 American Medical Association. All rights reserved.
原標題：《證實說話和咳嗽可產生氣溶膠，並不能證明COVID-19是基於氣溶膠傳播》
閱讀原文