An analysis of publicly available data on infections from the new coronavirus, SARS-CoV-2, that causes the respiratory illness COVID-19 yielded an estimate of 5.1 days for the median disease incubation period, according to a new study led by researchers at Johns Hopkins Bloomberg School of Public Health.
This median time from exposure to onset of symptoms suggests that the 14-day quarantine period used by the U.S. Centers for Disease Control and Prevention for individuals with likely exposure to the coronavirus is reasonable.
The analysis suggests that about 97.5 percent of people who develop symptoms of SARS-CoV-2 infection will do so within 11.5 days of exposure.
The researchers estimated that for every 10,000 individuals quarantined for 14 days, only about 101 would develop symptoms after being released from quarantine.
The findings will be published online March 9 in the journal Annals of Internal Medicine.
For the study, the researchers analyzed 181 cases from China and other countries that were detected prior to February 24, were reported in the media, and included likely dates of exposure and symptom onset.
Most of the cases involved travel to or from Wuhan, China, the city at the center of the epidemic, or exposure to individuals who had been to Hubei, the province for which Wuhan is the capital.
The CDC and many other public health authorities around the world have been using a 14-day quarantine or active-monitoring period for individuals who are known to be at high risk of infection due to contact with known cases or travel to a heavily affected area.
“Based on our analysis of publicly available data, the current recommendation of 14 days for active monitoring or quarantine is reasonable, although with that period some cases would be missed over the long-term,” says study senior author Justin Lessler, an associate professor in the Bloomberg School’s Department of Epidemiology.
The global outbreak of SARS-CoV-2 infection emerged in December 2019 in Wuhan, a city of 11 million in central China, and has resulted in 95,333 officially confirmed cases around the world and 3,282 deaths from pneumonia caused by the virus, according to the World Health Organization’s March 5 Situation Report.
The majority of the cases are from Wuhan and the surrounding Hubei province, although dozens of other countries have been affected, including the U.S., but chiefly South Korea, Iran, and Italy.
An accurate estimate of the disease incubation period for a new virus makes it easier for epidemiologists to gauge the likely dynamics of the outbreak, and allows public health officials to design effective quarantine and other control measures.
Quarantines typically slow and may ultimately stop the spread of infection, even if there are some outlier cases with incubation periods that exceed the quarantine period.
Lessler notes that sequestering people in a way that prevents them from working has costs, both personal and societal, which is perhaps most obvious when health care workers and first responders like firefighters are quarantined.
The CDC and many other public health authorities around the world have been using a 14-day quarantine or active-monitoring period for individuals who are known to be at high risk of infection due to contact with known cases or travel to a heavily affected area.
The new estimate of 5.1 days for the median incubation period of SARS-CoV-2 is similar to estimates from the earliest studies of this new virus, which were based on fewer cases.
This incubation period for SARS-CoV-2 is in the same range as SARS-CoV, a different human-infecting coronavirus that caused a major outbreak centered in southern China and Hong Kong from 2002-04.
For MERS-CoV, a coronavirus that has caused hundreds of cases in the Middle East, with a relatively high fatality rate, the estimated mean incubation period is 5-7 days.
Human coronaviruses that cause common colds have mean illness-incubation periods of about three days.
Lessler and colleagues have published an online tool that allows public health officials and members of the public to estimate how many cases would be caught and missed under different quarantine periods.
“The incubation period of COVID-19 from publicly reported confirmed cases: estimation and application” was written by co-first authors Stephen Lauer and Kyra Grantz, and Qifang Bi, Forrest Jones, Qulu Zheng, Hannah Meredith, Andrew Azman, Nicholas Reich, and Justin Lessler.
Funding: Support for the research was provided by CDC (NU2GGH002000), the National Institute of Allergy and Infectious Diseases (R01 AI135115), the National Institute of General Medical Sciences (R35 GM119582), and the Alexander von Humboldt Foundation.
Possible transmission routes of 2019-nCoV in dental clinics
Since 2019-nCoV can be passed directly from person to person by respiratory droplets, emerging evidence suggested that it may also be transmitted through contact and fomites43,48.
In addition, the asymptomatic incubation period for individuals infected with 2019-nCov has been reported to be ~1–14 days, and after 24 days individuals were reported, and it was confirmed that those without symptoms can spread the virus4,5,49.
To et al. reported that live viruses were present in the saliva of infected individuals by viral culture method43. Furthermore, it has been confirmed that 2019-nCov enters the cell in the same path as SARS coronavirus, that is, through the ACE2 cell receptor25.
2019-nCoV can effectively use ACE2 as a receptor to invade cells, which may promote human-to-human transmission11.
ACE2+ cells were found to be abundantly present throughout the respiratory tract, as well as the cells morphologically compatible with salivary gland duct epithelium in human mouth.
ACE2+ epithelial cells of salivary gland ducts were demonstrated to be a class early targets of SARS-CoV infection50, and 2019-nCoV is likely to be the same situation, although no research has been reported so far.
Dental patients and professionals can be exposed to pathogenic microorganisms, including viruses and bacteria that infect the oral cavity and respiratory tract.
Dental care settings invariably carry the risk of 2019-nCoV infection due to the specificity of its procedures, which involves face-to-face communication with patients, and frequent exposure to saliva, blood, and other body fluids, and the handling of sharp instruments.
The pathogenic microorganisms can be transmitted in dental settings through inhalation of airborne microorganisms that can remain suspended in the air for long periods51, direct contact with blood, oral fluids, or other patient materials52, contact of conjunctival, nasal, or oral mucosa with droplets and aerosols containing microorganisms generated from an infected individual and propelled a short distance by coughing and talking without a mask53,54, and indirect contact with contaminated instruments and/or environmental surfaces50.
Infections could be present through any of these conditions involved in an infected individual in dental clinics and hospitals, especially during the outbreak of 2019-nCoV (Fig. 1).
The airborne spread of SARS-Cov (severe acute respiratory syndrome coronavirus) is well-reported in many literatures. The dental papers show that many dental procedures produce aerosols and droplets that are contaminated with virus55.
Thus, droplet and aerosol transmission of 2019-nCoV are the most important concerns in dental clinics and hospitals, because it is hard to avoid the generation of large amounts of aerosol and droplet mixed with patient’s saliva and even blood during dental practice53.
In addition to the infected patient’s cough and breathing, dental devices such as high-speed dental handpiece uses high-speed gas to drive the turbine to rotate at high speed and work with running water.
When dental devices work in the patient’s oral cavity, a large amount of aerosol and droplets mixed with the patient’s saliva or even blood will be generated.
Particles of droplets and aerosols are small enough to stay airborne for an extended period before they settle on environmental surfaces or enter the respiratory tract.
Thus, the 2019-nCoV has the potential to spread through droplets and aerosols from infected individuals in dental clinics and hospitals.
A dental professional’s frequent direct or indirect contact with human fluids, patient materials, and contaminated dental instruments or environmental surfaces makes a possible route to the spread of viruses53.
In addition, dental professionals and other patients have likely contact of conjunctival, nasal, or oral mucosa with droplets and aerosols containing microorganisms generated from an infected individual and propelled a short distance by coughing and talking without a mask.
Effective infection control strategies are needed to prevent the spread of 2019-nCoV through these contact routines.
Contaminated surfaces spread
Human coronaviruses such as SARS-CoV, Middle East Respiratory Syndrome coronavirus (MERS-CoV), or endemic human coronaviruses (HCoV) can persist on surfaces like metal, glass, or plastic for up to a couple of days51,56.
Therefore, contaminated surfaces that are frequently contacted in healthcare settings are a potential source of coronavirus transmission. Dental practices derived droplets and aerosols from infected patients, which likely contaminate the whole surface in dental offices.
In addition, it was shown at room temperature that HCoV remains infectious from 2 h up to 9 days, and persists better at 50% compared with 30% relative humidity. Thus, keeping a clean and dry environment in the dental office would help decrease the persistence of 2019-nCoV.
Infection controls for dental practice
Dental professionals should be familiar with how 2019-nCoV is spread, how to identify patients with 2019-nCoV infection, and what extra-protective measures should be adopted during the practice, in order to prevent the transmission of 2019-nCoV.
Here we recommend the infection control measures that should be followed by dental professionals, particularly considering the fact that aerosols and droplets were considered as the main spread routes of 2019-nCoV. Our recommendations are based on the Guideline for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (the 5th edition) (http://www.nhc.gov.cn/yzygj/s7653p/202002/3b09b894ac9b4204a79db5b8912d4440.shtml), the Guideline for the Prevention and Control of Novel Coronavirus Pneumonia in Medical Institutes (the 1st edition) (http://www.nhc.gov.cn/yzygj/s7659/202001/b91fdab7c304431eb082d67847d27e14.shtml), and the Guideline for the Use of Medical Protective Equipment in the Prevention and Control of Novel Coronavirus Pneumonia (http://www.nhc.gov.cn/yzygj/s7659/202001/e71c5de925a64eafbe1ce790debab5c6.shtml) released by the National Health Commission of the People’s Republic of China, and the practice experience in West China Hospital of Stomatology related to the outbreak of 2019-nCoV transmission.
First of all, dental professionals should be able to identify a suspected case of COVID-19. To date that this paper was drafted, the National Health Commission of the People’s Republic of China has released the 5th edition of the Guideline for the Diagnosis and Treatment of Novel Coronavirus Pneumonia.
In general, a patient with COVID-19 who is in the acute febrile phase of the disease is not recommended to visit the dental clinic. If this does occur, the dental professional should be able to identify the patient with suspected 2019-nCoV infection, and should not treat the patient in the dental clinic, but immediately quarantine the patient and report to the infection control department as soon as possible, particularly in the epidemic period of 2019-nCoV.
The body temperature of the patient should be measured in the first place. A contact-free forehead thermometer is strongly recommended for the screening. A questionnaire should be used to screen patients with potential infection of 2019-nCoV before they could be led to the dental chair-side.
These questions should include the following:
(1) Do you have fever or experience fever within the past 14 days?
(2) Have you experienced a recent onset of respiratory problems, such as a cough or difficulty in breathing within the past 14 days?
(3) Have you, within the past 14 days, traveled to Wuhan city and its surrounding areas, or visited the neighborhood with documented 2019-nCoV transmission?
(4) Have you come into contact with a patient with confirmed 2019-nCoV infection within the past 14 days?
(5) Have you come into contact with people who come from Wuhan city and its surrounding areas, or people from the neighborhood with recent documented fever or respiratory problems within the past 14 days?
(6) Are there at least two people with documented experience of fever or respiratory problems within the last 14 days having close contact with you?
(7) Have you recently participated in any gathering, meetings, or had close contact with many unacquainted people?
If a patient replies “yes” to any of the screening questions, and his/her body temperature is below 37.3 °C, the dentist can defer the treatment until 14 days after the exposure event. The patient should be instructed to self-quarantine at home and report any fever experience or flu-like syndrome to the local health department.
If a patient replies “yes” to any of the screening questions, and his/her body temperature is no less than 37.3 °C, the patient should be immediately quarantined, and the dental professionals should report to the infection control department of the hospital or the local health department.
If a patient replies “no” to all the screening questions, and his/her body temperature is below 37.3 °C, the dentist can treat the patient with extra- protection measures, and avoids spatter or aerosol-generating procedures to the best.
If a patient replies “no” to all the screening questions, but his/her body temperature is no less than 37.3 °C, the patient should be instructed to the fever clinics or special clinics for COVID-19 for further medical care.
Fecal–oral transmission has been reported for 2019-nCoV, which underlines the importance of hand hygiene for dental practice. Although appropriate hand hygiene is the routine prerequisite for dental practice, hand-washing compliance is relatively low, which imposes a great challenge to the infection control during the epidemic period of 2019-nCoV transmission.
Reinforcement for good hand hygiene is of the utmost importance. A two-before-and-three-after hand hygiene guideline is proposed by the infection control department of the West China Hospital of Stomatology, Sichuan University, to reinforce the compliance of hand washing. Specifically, the oral professionals should wash their hands before patient examination, before dental procedures, after touching the patient, after touching the surroundings and equipment without disinfection, and after touching the oral mucosa, damaged skin or wound, blood, body fluid, secretion, and excreta. More caution should be taken for the dental professionals to avoid touching their own eyes, mouth, and nose.
Personal protective measures for the dental professionals
At present, there is no specific guideline for the protection of dental professionals from 2019-nCoV infection in the dental clinics and hospitals. Although no dental professional has been reported to acquire 2019-nCoV infection to the date the paper was drafted, the last experience with the SARS coronavirus has shown vast numbers of acquired infection of medical professionals in hospital settings57.
Since airborne droplet transmission of infection is considered as the main route of spread, particularly in dental clinics and hospitals, barrier-protection equipment, including protective eyewear, masks, gloves, caps, face shields, and protective outwear, is strongly recommended for all healthcare givers in the clinic/hospital settings during the epidemic period of 2019-nCoV.
Based on the possibility of the spread of 2019-nCoV infection, three-level protective measures of the dental professionals are recommended for specific situations.
(1) Primary protection (standard protection for staff in clinical settings). Wearing disposable working cap, disposable surgical mask, and working clothes (white coat), using protective goggles or face shield, and disposable latex gloves or nitrile gloves if necessary.
(2) Secondary protection (advanced protection for dental professionals). Wearing disposable doctor cap, disposable surgical mask, protective goggles, face shield, and working clothes (white coat) with disposable isolation clothing or surgical clothes outside, and disposable latex gloves.
(3) Tertiary protection (strengthened protection when contact patient with suspected or confirmed 2019-nCoV infection). Although a patient with 2019-nCoV infection is not expected to be treated in the dental clinic, in the unlikely event that this does occur, and the dental professional cannot avoid close contact, special protective outwear is needed.
If protective outwear is not available, working clothes (white coat) with extra disposable protective clothing outside should be worn. In addition, disposable doctor cap, protective goggles, face shield, disposable surgical mask, disposable latex gloves, and impermeable shoe cover should be worn.
Mouthrinse before dental procedures
A preoperational antimicrobial mouthrinse is generally believed to reduce the number of oral microbes. However, as instructed by the Guideline for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (the 5th edition) released by the National Health Commission of the People’s Republic of China, chlorhexidine, which is commonly used as mouthrinse in dental practice, may not be effective to kill 2019-nCoV. Since 2019-nCoV is vulnerable to oxidation, preprocedural mouthrinse containing oxidative agents such as 1% hydrogen peroxide or 0.2% povidone is recommended, for the purpose of reducing the salivary load of oral microbes, including potential 2019-nCoV carriage. A preprocedural mouthrinse would be most useful in cases when rubber dam cannot be used.
Rubber dam isolation
The use of rubber dams can significantly minimize the production of saliva- and blood-contaminated aerosol or spatter, particularly in cases when high-speed handpieces and dental ultrasonic devices are used.
It has been reported that the use of rubber dam could significantly reduce airborne particles in ~3-foot diameter of the operational field by 70%58.
When rubber dam is applied, extra high-volume suction for aerosol and spatter should be used during the procedures along with regular suction59. In this case, the implementation of a complete four-hand operation is also necessary.
If rubber dam isolation is not possible in some cases, manual devices, such as Carisolv and hand scaler, are recommended for caries removal and periodontal scaling, in order to minimize the generation of aerosol as much as possible.
The high-speed dental handpiece without anti-retraction valves may aspirate and expel the debris and fluids during the dental procedures. More importantly, the microbes, including bacteria and virus, may further contaminate the air and water tubes within the dental unit, and thus can potentially cause cross-infection.
Our study has shown that the anti-retraction high-speed dental handpiece can significantly reduce the backflow of oral bacteria and HBV into the tubes of the handpiece and dental unit as compared with the handpiece without anti-retraction function60.
Therefore, the use of dental handpieces without anti-retraction function should be prohibited during the epidemic period of COVID-19. Anti-retraction dental handpiece with specially designed anti-retractive valves or other anti-reflux designs are strongly recommended as an extra preventive measure for cross-infection59.
Therefore, the use of dental handpieces without anti-retraction function should be prohibited during the epidemic period of COVID-19. Anti-retraction dental handpiece with specially designed anti-retractive valves or other anti-reflux designs are strongly recommended as an extra preventive measure for cross-infection.
Disinfection of the clinic settings
Medical institutions should take effective and strict disinfection measures in both clinic settings and public area. The clinic settings should be cleaned and disinfected in accordance with the Protocol for the Management of Surface Cleaning and Disinfection of Medical Environment (WS/T 512-2016) released by the National Health Commission of the People’s Republic of China. Public areas and appliances should also be frequently cleaned and disinfected, including door handles, chairs, and desks. The elevator should be disinfected regularly. People taking elevators should wear masks correctly and avoid direct contact with buttons and other objects.
Management of medical waste
The medical waste (including disposable protective equipment after use) should be transported to the temporary storage area of the medical institute timely. The reusable instrument and items should be pretreated, cleaned, sterilized, and properly stored in accordance with the Protocol for the Disinfection and Sterilization of Dental Instrument (WS 506-2016) released by the National Health Commission of the People’s Republic of China.
The medical and domestic waste generated by the treatment of patients with suspected or confirmed 2019-nCoV infection are regarded as infectious medical waste. Double-layer yellow color medical waste package bags and “gooseneck” ligation should be used. The surface of the package bags should be marked and disposed according to the requirement for the management of medical waste.
Cite this article
Peng, X., Xu, X., Li, Y. et al. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci 12, 9 (2020). https://doi.org/10.1038/s41368-020-0075-9
- 1.Zhu, N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2001017 (2020).
- 2.Wang, C., Horby, P. W., Hayden, F. G. & Gao, G. F. A novel coronavirus outbreak of global health concern. Lancet 395, 470–473 (2020).
- 3.Liu, T. et al. Transmission dynamics of 2019 novel coronavirus (2019-nCoV). The Lancet. Available at SSRN: https://ssrn.com/abstract=3526307 (2020).
- 4.Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).
- 5.Guan, W.-j. et al. Clinical characteristics of 2019 novel coronavirus infection in China. Preprint at https://www.medrxiv.org/content/10.1101/2020.02.06.20020974v1 (2020).
- 6.Wang, D. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA https://doi.org/10.1001/jama.2020.1585 (2020).
- 7.Chen, N. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395, 507–513 (2020).
- 8.Chan, J. F.-W. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395, 514–523 (2020).
- 9.Li, Q. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2001316 (2020).
- 10.Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature https://doi.org/10.1038/s41586-020-2008-3 (2020).
- 11.Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature https://doi.org/10.1038/s41586-020-2012-7 (2020).
- 12.Gorbalenya, A. E. et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses—a statement of the Coronavirus Study Group. Preprint at https://www.biorxiv.org/content/10.1101/2020.02.07.937862v1 (2020).
- 13.Fehr, A. R. & Perlman, S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol. 1282, 1–23 (2015).
- 14.Gorbalenya, A., Enjuanes, L., Ziebuhr, J. & Snijder, E. Nidovirales: evolving the largest RNA virus genome. Virus Res. 117, 17–37 (2006).
- 15.Nakagawa, K., Lokugamage, K. G. & Makino, S. in Advances in Virus Research (ed John Ziebuhr) vol. 96, 165–192 (Academic Press, 2016).
- 16.Fan, Y., Zhao, K., Shi, Z.-L. & Zhou, P. Bat coronaviruses in China. Viruses 11, 210 (2019).
- 17.Perlman, S. & Netland, J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat. Rev. Microbiol. 7, 439–450 (2009).
- 18.Weiss, S. & Leibowitz, J. Coronavirus pathogenesis. Adv. Virus Res. 81, 85–164 (2011).
- 19.Yin, Y. & Wunderink, R. G. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology 23, 130–137 (2018).
- 20.Holmes, K. V. SARS-associated coronavirus. N. Engl. J. Med. 348, 1948–1951 (2003).
- 21.Falsey, A. R. & Walsh, E. E. Novel coronavirus and severe acute respiratory syndrome. Lancet 361, 1312–1313 (2003).
- 22.The Lancet. MERS-CoV: a global challenge. Lancet 381, 1960 (2013).
- 23.Al-Tawfiq, J. A., Zumla, A. & Memish, Z. A. Coronaviruses: severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus in travelers. Curr. Opin. Infect. Dis. 27, 411–417 (2014).
- 24.Song, Z. et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses https://doi.org/10.3390/v11010059 (2019).
- 25.de Wit, E., van Doremalen, N., Falzarano, D. & Munster, V. J. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 14, 523–534 (2016).
- 26.Al-Tawfiq, J. A., Zumla, A. & Memish, Z. A. Coronaviruses: severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus in travelers. Curr. Opin. Infect. Dis. 27, 411–417 (2014).
- 27.Bai, Y., Nie, X. & Wen, C. Epidemic prediction of 2019-nCoV in Hubei province and comparison with SARS in Guangdong province. The lancet. Available at SSRN: https://ssrn.com/abstract=3531427 (2020).
- 28.Liu, P., Chen, W. & Chen, J.-P. Viral metagenomics revealed sendai virus and coronavirus infection of malayan pangolins (Manis javanica). Viruses 11, 979 (2019).
- 29.Wahba, L. et al. Identification of a pangolin niche for a 2019-nCoV-like coronavirus through an extensive meta-metagenomic search. Preprint at https://www.biorxiv.org/content/10.1101/2020.02.08.939660v2 (2020).
- 30.Li, F. Structure, function, and evolution of coronavirus spike proteins. Annu. Rev. Virol. 3, 237–261 (2016).
- 31.Hantak, M. P., Qing, E., Earnest, J. T. & Gallagher, T. Tetraspanins: architects of viral entry and exit platforms. J. Virol. 93, e01429–e01417 (2019).
- 32.Belouzard, S., Millet, J. K., Licitra, B. N. & Whittaker, G. R. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4, 1011–1033 (2012).
- 33.Wan, Y., Shang, J., Graham, R., Baric, R. S. & Li, F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J. Virol. https://doi.org/10.1128/jvi.00127-20 (2020).
- 34.Chai, X. et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. Preprint at https://www.biorxiv.org/content/10.1101/2020.02.03.931766v1 (2020).
- 35.Fan, C., Li, K., Ding, Y., Lu, W. L. & Wang, J. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. Preprint at https://www.medrxiv.org/content/10.1101/2020.02.12.20022418v1 (2020).
- 36.Hoffmann, M. et al. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. Preprint at https://www.biorxiv.org/content/10.1101/2020.01.31.929042v1.full (2020).
- 37.Huang, Q. & Herrmann, A. Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV). Preprint at https://www.biorxiv.org/content/10.1101/2020.02.01.930537v1 (2020).
- 38.Lei, C. et al. Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig. Preprint at https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2 (2020).
- 39.Tian, X. et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg. Microbes. Infect. 9, 382–385. https://doi.org/10.1080/22221751.2020.1729069 (2020).
- 40.Zhao, Y. et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. Preprint at https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1 (2020).
- 41.Guy, J. L., Lambert, D. W., Warner, F. J., Hooper, N. M. & Turner, A. J. Membrane-associated zinc peptidase families: comparing ACE and ACE2. Biochim. Biophysi. Acta 1751, 2–8 (2005).
- 42.Lu, C.-W., Liu, X.-F. & Jia, Z.-F. 2019-nCoV transmission through the ocular surface must not be ignored. The Lancet https://doi.org/10.1016/S0140-6736(20)30313-5 (2020).
- 43.To, K. K.-W. et al. Consistent detection of 2019 novel coronavirus in saliva. Clin. Infect. Diseases https://doi.org/10.1093/cid/ciaa149 (2020).
- 44.Belser, J. A., Rota, P. A. & Tumpey, T. M. Ocular tropism of respiratory viruses. Microbiol. Mol. Biol. Rev. 77, 144–156 (2013).
- 45.Rothe, C. et al. Transmission of 2019-nCoV infection from an asymptomatic contact in germany. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2001468 (2020).
- 46.Wax, R. S. & Christian, M. D. Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Canadian Journal of Anesthesia/Journal canadien d’anesthésie https://doi.org/10.1007/s12630-020-01591-x (2020).
- 47.Holshue, M. L. et al. First Case of 2019 Novel coronavirus in the United States. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2001191 (2020).
- 48.Rodriguez-Morales, A. J., MacGregor, K., Kanagarajah, S., Patel, D. & Schlagenhauf, P. Going global – Travel and the 2019 novel coronavirus. Travel. Med. Infect. Dis. 101578, https://doi.org/10.1016/j.tmaid.2020.101578 (2020).
- 49.Backer, J. A., Klinkenberg, D. & Wallinga, J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro. Surveill. https://doi.org/10.2807/1560-7917.Es.2020.25.5.2000062 (2020).
- 50.Liu, L. et al. Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques. J. Virol. 85, 4025–4030 (2011).
- 51.Kampf, G., Todt, D., Pfaender, S. & Steinmann, E. Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents. J. Hosp. Infect. https://doi.org/10.1016/j.jhin.2020.01.022 (2020).
- 52.Chen, J. Pathogenicity and transmissibility of 2019-nCoV—a quick overview and comparison with other emerging viruses. Microb. Infect. https://doi.org/10.1016/j.micinf.2020.01.004 (2020).
- 53.Cleveland, J. L. et al. Transmission of blood-borne pathogens in US dental health care settings: 2016 update. J. Am. Dent. Assoc. (1939) 147, 729–738 (2016).
- 54.Harrel, S. K. & Molinari, J. Aerosols and splatter in dentistry: a brief review of the literature and infection control implications. J. Am. Dent. Assoc. (1939) 135, 429–437 (2004).
- 55.Wei, J. & Li, Y. Airborne spread of infectious agents in the indoor environment. Am. J. Infect. Control 44, S102–S108 (2016).
- 56.Otter, J. A. et al. Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination. J. Hosp. Infect. 92, 235–250 (2016).
- 57.Seto, W. H. et al. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet 361, 1519–1520 (2003).
- 58.Samaranayake, L. P., Reid, J. & Evans, D. The efficacy of rubber dam isolation in reducing atmospheric bacterial contamination. ASDC J. Dent. Child 56, 442–444 (1989).
- 59.Samaranayake, L. P. & Peiris, M. Severe acute respiratory syndrome and dentistry: a retrospective view. J. Am. Dent. Assoc. (1939) 135, 1292–1302 (2004).
- 60.Hu, T., Li, G., Zuo, Y. & Zhou, X. Risk of hepatitis B virus transmission via dental handpieces and evaluation of an anti-suction device for prevention of transmission. Infect. Control Hosp. Epidemiol. 28, 80–82 (2007).
- 61.Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science eabb2507, https://doi.org/10.1126/science.abb2507 (2020).
- 62.The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Chinese Journal of Epidemiology 41, 145–151 (2020).
This study was supported by the Emergency Project of Sichuan University (0082604151013, XZ).
Johns Hopkins University