COVID-19: What do we know?

Abstract

•Evidence regarding the provision of orthodontic care during the COVID-19 pandemic is examined. Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1World Health OrganizationAdvice on the use of masks in the context of COVID-19.https://apps.who.int/iris/bitstream/handle/10665/332293/WHO-2019-nCov-IPC_Masks-2020.4-eng.pdfGoogle Scholar Preliminary assessments suggest the virus is highly transmittable and infectious,2Liu J. Liao X. Qian S. Yuan J. Wang F. Liu Y. et al.Community transmission of severe acute respiratory syndrome coronavirus 2, Shenzhen, China, 2020.Emerg Infect Dis. 2020; 26: 1320-1323Crossref PubMed Scopus (97) Google Scholar, 3Chan J.F. Yuan S. Kok K.H. To K.K. Chu H. Yang J. 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. 2020; 395: 514-523Abstract Full Text Full Text PDF PubMed Scopus (2001) Google Scholar, 4Li Q. Guan X. Wu P. Wang X. Zhou L. Tong Y. et al.Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia.N Engl J Med. 2020; 382: 1199-1207Crossref PubMed Scopus (2990) Google Scholar, 5Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (7960) Google Scholar, 6Burke R.M. Midgley C.M. Dratch A. Fenstersheib M. Haupt T. Holshue M. et al.Active monitoring of persons exposed to patients with confirmed COVID-19 - United States, January-February 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 245-246Crossref PubMed Scopus (84) Google Scholar, 7Coronavirus disease 2019 (COVID-19) situation report – 73.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200402-sitrep-73-covid-19.pdf?sfvrsn=5ae25bc7_6Google Scholar with similarities in nosocomial and super-spreading events seen with severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) in 2003.8Chen Y.C. Huang L.M. Chan C.C. Su C.P. Chang S.C. Chang Y.Y. et al.SARS in hospital emergency room.Emerg Infect Dis. 2004; 10: 782-788Crossref PubMed Google Scholar Patients infected with SARS-CoV-2 display a wide range of host responses including no symptoms, mild nonrespiratory symptoms, severe respiratory illness, or organ dysfunction and death.1World Health OrganizationAdvice on the use of masks in the context of COVID-19.https://apps.who.int/iris/bitstream/handle/10665/332293/WHO-2019-nCov-IPC_Masks-2020.4-eng.pdfGoogle Scholar,5Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (7960) Google Scholar The American Association of Orthodontists Council on Scientific Affairs was charged with examining the literature to determine the best evidence for questions pertaining to COVID-19 and its impact on the practice of orthodontics. Transmission of SARS-CoV-2 is not fully understood, but preliminary evidence supports transmission of the virus between humans by (1) direct inhalation of airborne virus contained in infectious bioaerosol produced from an infected patient (ie, bioaerosol from coughing, sneezing, talking, exhaling breath, or mechanical aerosolization of infected salivary or respiratory secretions are potential routes of transmission), or (2) indirect transfer to the mouth, nose, or eyes from surfaces contaminated with virus-laden salivary or respiratory secretions or the settling of the airborne virus.1World Health OrganizationAdvice on the use of masks in the context of COVID-19.https://apps.who.int/iris/bitstream/handle/10665/332293/WHO-2019-nCov-IPC_Masks-2020.4-eng.pdfGoogle Scholar,9Scheuch G. Breathing is enough: for the spread of influenza virus and SARS-CoV-2 by breathing only.J Aerosol Med Pulm Drug Deliv. 2020; 33: 230-234Crossref Scopus (2) Google Scholar Recent evidence suggests that transmission of SARS-CoV-2 is possible from presymptomatic, symptomatic, and asymptomatic patients.10Wu D. Wu T. Liu Q. Yang Z. The SARS-CoV-2 outbreak: what we know.Int J Infect Dis. 2020; 94: 44-48Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar, 11Wölfel R. Corman V.M. Guggemos W. Seilmaier M. Zange S. Müller M.A. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (851) Google Scholar, 12Yu P. Zhu J. Zhang Z. Han Y. A familial cluster of infection associated with the 2019 novel coronavirus indicating possible person-to-person transmission during the incubation period.J Infect Dis. 2020; 221: 1757-1761Crossref PubMed Scopus (164) Google Scholar, 13Lauer S.A. Grantz K.H. Bi Q. Jones F.K. Zheng Q. Meredith H.R. et al.The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application.Ann Intern Med. 2020; 172: 577-582Crossref PubMed Scopus (767) Google Scholar, 14Kimball A. Hatfield K.M. Arons M. James A. Taylor J. Spicer K. et al.Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - King County, Washington, March 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 377-381Crossref PubMed Google Scholar, 15He X. Lau E.H.Y. Wu P. Deng X. Wang J. Hao X. et al.Temporal dynamics in viral shedding and transmissibility of COVID-19.Nat Med. 2020; 26: 672-675Crossref PubMed Scopus (459) Google Scholar, 16Byambasuren O. Cardona M. Bell K. Clark J. McLaws M.L. Glasziou P. Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis.medRxiv. 2020; (Epub)Google Scholar, 17Arons M.M. Hatfield K.M. Reddy S.C. Kimball A. James A. Jacobs J.R. et al.Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility.N Engl J Med. 2020; 382: 2081-2090Crossref PubMed Scopus (284) Google Scholar, 18Luo L. Liu D. Liao X. Wu X. Jing Q. Zheng J. et al.Modes of contact and risk of transmission in COVID-19 among close contacts.medRxiv. 2020; (Epub)Google Scholar, 19Hu Z. Song C. Xu C. Jin G. Chen Y. Xu X. et al.Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China.Sci China Life Sci. 2020; 63: 706-711Crossref PubMed Scopus (260) Google Scholar, 20Huang R. Xia J. Chen Y. Shan C. Wu C. A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China.Lancet Infect Dis. 2020; 20: 534-535Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 21Pan X. Chen D. Xia Y. Wu X. Li T. Ou X. et al.Asymptomatic cases in a family cluster with SARS-CoV-2 infection.Lancet Infect Dis. 2020; 20: 410-411Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 22Wang Y. Tong J. Qin Y. Xie T. Li J. Li J. et al.Characterization of an asymptomatic cohort of SARS-COV-2 infected individuals outside of Wuhan, China.Clin Infect Dis. 2020; (Epub)Google Scholar, 23Wei W.E. Li Z. Chiew C.J. Yong S.E. Toh M.P. Lee V.J. Presymptomatic transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 411-415Crossref PubMed Scopus (0) Google Scholar, 24Cheng H.Y. Jian S.W. Liu D.P. Ng T.C. Huang W.T. Lin H.H. et al.Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset.JAMA Intern Med. 2020; 180: 1156-1163Crossref Scopus (61) Google Scholar, 25Furukawa N.W. Brooks J.T. Sobel J. Evidence supporting transmission of severe acute respiratory syndrome coronavirus 2 while presymptomatic or asymptomatic.Emerg Infect Dis. 2020; 26: e201595Crossref Scopus (47) Google Scholar, 26Bai Y. Yao L. Wei T. Tian F. Jin D.Y. Chen L. et al.Presumed asymptomatic carrier transmission of COVID-19.JAMA. 2020; 323: 1406-1407Crossref PubMed Scopus (958) Google Scholar The proportion of asymptomatic patients to symptomatic patients varies with age, and children are less likely to exhibit clinical symptoms than adults.27World Health OrganizationCoronavirus disease 2019 (COVID-19): situation report, 73.https://apps.who.int/iris/handle/10665/331686Date accessed: July 27, 2020Google Scholar Estimates of infected asymptomatic patients range from 6% to 41%.14Kimball A. Hatfield K.M. Arons M. James A. Taylor J. Spicer K. et al.Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - King County, Washington, March 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 377-381Crossref PubMed Google Scholar The mechanism of asymptomatic transmission (direct or indirect) is not clear, and the extent of this phenomena is not exactly known, but is estimated to be low compared with transmission from symptomatic patients.18Luo L. Liu D. Liao X. Wu X. Jing Q. Zheng J. et al.Modes of contact and risk of transmission in COVID-19 among close contacts.medRxiv. 2020; (Epub)Google Scholar,24Cheng H.Y. Jian S.W. Liu D.P. Ng T.C. Huang W.T. Lin H.H. et al.Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset.JAMA Intern Med. 2020; 180: 1156-1163Crossref Scopus (61) Google Scholar,28Park S.Y. Kim Y.M. Yi S. Lee S. Na B.J. Kim C.B. et al.Coronavirus disease outbreak in call center, South Korea.Emerg Infect Dis. 2020; 26: 1666-1670Crossref PubMed Scopus (53) Google Scholar,29Chaw L. Koh W.C. Jamaludin S.A. Naing L. Alikhan M.F. Wong J. SARS-CoV-2 transmission in different settings: analysis of cases and close contacts from the Tablighi cluster in Brunei Darussalam.medRxiv. 2020; (Epub)Google Scholar Viral shedding, detected by viral RNA assay of nasopharyngeal secretions, has been reported in patients fully recovered from SARS-CoV-2 infection,30Young B.E. Ong S.W.X. Kalimuddin S. Low J.G. Tan S.Y. Loh J. et al.Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore.JAMA. 2020; 323: 1488-1494Crossref PubMed Scopus (491) Google Scholar, 31Long Q.X. Tang X.J. Shi Q.L. Li Q. Deng H.J. Yuan J. et al.Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.Nat Med. 2020; 26: 1200-1204Crossref PubMed Scopus (159) Google Scholar, 32Zhang J.F. Yan K. Ye H.H. Lin J. Zheng J.J. Cai T. SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge.Int J Infect Dis. 2020; 97: 212-214Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 33Zheng K.I. Wang X.B. Jin X.H. Liu W.Y. Gao F. Chen Y.P. et al.A case series of recurrent viral RNA positivity in recovered COVID-19 Chinese patients.J Gen Intern Med. 2020; 35: 2205-2206Crossref Scopus (9) Google Scholar however it is not known how the detection of viral RNA is related to transmissible (replication-competent) virus,34Theel E.S. Slev P. Wheeler S. Couturier M.R. Wong S.J. Kadkhoda K. The role of antibody testing for SARS-CoV-2: is there one?.J Clin Microbiol. 2020; 58: e00797-e00820Crossref PubMed Scopus (30) Google Scholar,35Guidance for dental settings.https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.htmlGoogle Scholar and no studies have reported transmission from patients fully recovered from COVID-19.36Duration of isolation and precautions for adults with COVID-19.https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.htmlGoogle Scholar Proximity to symptomatic patients appear to be the most significant risk factor for contracting the virus, and prolonged close contact with a symptomatic individual increases the risk.37Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19).https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdfDate accessed: July 27, 2020Google Scholar,38COVID-19 National Emergency Response CenterEpidemiology and Case Management TeamKorea Centers for Disease Control and PreventionCoronavirus disease-19: summary of 2,370 contact investigations of the first 30 cases in the Republic of Korea.Osong Public Health Res Perspect. 2020; 11: 81-84Crossref Scopus (15) Google Scholar Although there is not yet a consensus on the mode of transmission during close contact, studies indicate indoor venues with crowded spaces requiring prolonged close personal contact (ie, high-risk spaces) appear to be the source of super-spreading events and suggest airborne transmission is likely under these conditions.39Althouse B.M. Wenger E.A. Miller J.C. Scarpino S.V. Allard A. Hebert-Dufresne L. et al.Stochasticity and heterogeneity in the transmission dynamics of SARS-CoV-2.2020: arXivGoogle Scholar Even though airborne transmission is strongly suspected, we lack an understanding of exactly how this occurs.40Kutter J.S. Spronken M.I. Fraaij P.L. Fouchier R.A. Herfst S. Transmission routes of respiratory viruses among humans.Curr Opin Virol. 2018; 28: 142-151Crossref PubMed Scopus (85) Google Scholar Airborne virus (∼0.1 μm) travels in droplets produced by coughing, sneezing, talking, exhaling, or by bioaerosol generated during certain medical and dental procedures (aerosol-generating procedures [AGPs]). Airborne droplets from a respiratory or salivary origin are distinguished by size, from large (>5 μm) to small (<5 μm). Large droplets (eg, from sneezing, AGPs) tend to settle on surfaces or unprotected mucosa of close contacts and may be the source of direct or indirect virus transmission (also termed droplet transmission).41Judson S.D. Munster V.J. Nosocomial transmission of emerging viruses via aerosol-generating medical procedures.Viruses. 2019; 11: 940Crossref Scopus (70) Google Scholar In experimentally simulated aerosolization of SARS-CoV-2, the virus maintains viability on surfaces for up to 72 hours, indicating indirect (droplet) transmission can occur long after droplets establish contact with surfaces.42Fears A.C. Klimstra W.B. Duprex P. Hartman A. Weaver S.C. Plante K.C. et al.Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions.medRxiv. 2020; (Epub)PubMed Google Scholar, 43van Doremalen N. Bushmaker T. Morris D.H. Holbrook M.G. Gamble A. Williamson B.N. et al.Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.N Engl J Med. 2020; 382: 1564-1567Crossref PubMed Scopus (1681) Google Scholar, 44Chin A.W.H. Chu J.T.S. Perera M.R.A. Hui K.P.Y. Yen H.L. Chan M.C.W. et al.Stability of SARS-CoV-2 in different environmental conditions.Lancet Microbe. 2020; 1: e10Abstract Full Text Full Text PDF PubMed Google Scholar In contrast, small droplets (eg, from coughing, talking, exhaling, or AGPs) produced by similar experimental aerosolization can evaporate into “droplet nuclei” and remain in the air for many hours.42Fears A.C. Klimstra W.B. Duprex P. Hartman A. Weaver S.C. Plante K.C. et al.Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions.medRxiv. 2020; (Epub)PubMed Google Scholar,43van Doremalen N. Bushmaker T. Morris D.H. Holbrook M.G. Gamble A. Williamson B.N. et al.Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.N Engl J Med. 2020; 382: 1564-1567Crossref PubMed Scopus (1681) Google Scholar,45Stadnytskyi V. Bax C.E. Bax A. Anfinrud P. The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission.Proc Natl Acad Sci U S A. 2020; 117: 11875-11877Crossref PubMed Scopus (73) Google Scholar, 46Somsen G.A. van Rijn C. Kooij S. Bem R.A. Bonn D. Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission.Lancet Respir Med. 2020; 8: 658-659Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 47Asadi S. Wexler A.S. Cappa C.D. Barreda S. Bouvier N.M. Ristenpart W.D. Aerosol emission and superemission during human speech increase with voice loudness.Sci Rep. 2019; 9: 2348Crossref PubMed Scopus (99) Google Scholar The amount of viable SARS-CoV-2 in droplet nuclei remains unclear, but in subjects infected with other respiratory viruses, such as influenza, experiments comparing coughing and breathing suggest an equivalent production of viral RNA and replication-competent virus, detected at close range (<12-in).48Gralton J. Tovey E.R. McLaws M.L. Rawlinson W.D. Respiratory virus RNA is detectable in airborne and droplet particles.J Med Virol. 2013; 85: 2151-2159Crossref PubMed Scopus (0) Google Scholar,49Lindsley W.G. Blachere F.M. Beezhold D.H. Thewlis R.E. Noorbakhsh B. Othumpangat S. et al.Viable influenza A virus in airborne particles expelled during coughs versus exhalations.Influenza Other Respir Viruses. 2016; 10: 404-413Crossref PubMed Scopus (0) Google Scholar Although this has not been adequately studied for SARS-CoV-2, similar findings might be anticipated.50Johnson G.R. Morawska L. Ristovski Z.D. Hargreaves M. Mengersen K. Chao C.Y.H. et al.Modality of human expired aerosol size distributions.J Aerosol Sci. 2011; 42: 839-851Crossref Scopus (67) Google Scholar, 51Chen W. Zhang N. Wei J. Yen H.-L. Li Y. Short-range airborne route dominates exposure of respiratory infection during close contact.Build Environ. 2020; 176: 106859Crossref Scopus (14) Google Scholar, 52Jones R.M. Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care.J Occup Environ Hyg. 2020; 17: 408-415Crossref Scopus (5) Google Scholar Moreover, saliva can be aerosolized during AGPs and is a known source of SARS-CoV-2 in infected patients.53Azzi L. Carcano G. Gianfagna F. Grossi P. Gasperina D.D. Genoni A. et al.Saliva is a reliable tool to detect SARS-CoV-2.J Infect. 2020; 81: e45-50Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar A timeline suggesting when infected patients are most contagious has been informed by studies assessing viral shedding of COVID-19 patients by 2 methods: detection of SARS-CoV-2 RNA and SARS-CoV-2 replication in cultured cells.54WHO Scientific brief: criteria for releasing COVID-19 patients from isolation.https://www.who.int/news-room/commentaries/detail/criteria-for-releasing-covid-19-patients-from-isolationGoogle Scholar Viral RNA can be detected 1-3 days before the onset of COVID-19 symptoms, with the highest viral load in the upper respiratory tract occurring near the onset of symptoms followed by a decreasing viral load that is time-dependent based on disease severity. Viral RNA is shed for 1-2 weeks in asymptomatic cases and 3 or more weeks for mild to moderate cases of COVID-19.11Wölfel R. Corman V.M. Guggemos W. Seilmaier M. Zange S. Müller M.A. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (851) Google Scholar,15He X. Lau E.H.Y. Wu P. Deng X. Wang J. Hao X. et al.Temporal dynamics in viral shedding and transmissibility of COVID-19.Nat Med. 2020; 26: 672-675Crossref PubMed Scopus (459) Google Scholar,31Long Q.X. Tang X.J. Shi Q.L. Li Q. Deng H.J. Yuan J. et al.Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.Nat Med. 2020; 26: 1200-1204Crossref PubMed Scopus (159) Google Scholar,55To K.K. Tsang O.T.Y. Leung W.S. Tam A.R. Wu T.C. Lung D.C. et al.Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study.Lancet Infect Dis. 2020; 20: 565-574Abstract Full Text Full Text PDF PubMed Scopus (557) Google Scholar, 56Weiss A. Jellingsø M. Sommer M.O.A. Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: a systematic review and meta-analysis.EBioMedicine. 2020; 58: 102916Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 57COVID-19 Investigation TeamClinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.Nat Med. 2020; 26: 861-868Crossref PubMed Scopus (0) Google Scholar, 58Liu W.D. Chang S.Y. Wang J.T. Tsai M.J. Hung C.C. Hsu C.L. et al.Prolonged virus shedding even after seroconversion in a patient with COVID-19.J Infect. 2020; 81: 318-356Google Scholar, 59Zou L. Ruan F. Huang M. Liang L. Huang H. Hong Z. et al.SARS-CoV-2 viral load in upper respiratory specimens of infected patients.N Engl J Med. 2020; 382: 1177-1179Crossref PubMed Scopus (1142) Google Scholar, 60Lescure F.X. Bouadma L. Nguyen D. Parisey M. Wicky P.H. Behillil S. et al.Clinical and virological data of the first cases of COVID-19 in Europe: a case series.Lancet Infect Dis. 2020; 20: 697-706Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 61Pan Y. Zhang D. Yang P. Poon L.L.M. Wang Q. Viral load of SARS-CoV-2 in clinical samples.Lancet Infect Dis. 2020; 20: 411-412Abstract Full Text Full Text PDF PubMed Scopus (277) Google Scholar More severe symptoms require a longer time to reduce viral load.11Wölfel R. Corman V.M. Guggemos W. Seilmaier M. Zange S. Müller M.A. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (851) Google Scholar,15He X. Lau E.H.Y. Wu P. Deng X. Wang J. Hao X. et al.Temporal dynamics in viral shedding and transmissibility of COVID-19.Nat Med. 2020; 26: 672-675Crossref PubMed Scopus (459) Google Scholar,19Hu Z. Song C. Xu C. Jin G. Chen Y. Xu X. et al.Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China.Sci China Life Sci. 2020; 63: 706-711Crossref PubMed Scopus (260) Google Scholar,56Weiss A. Jellingsø M. Sommer M.O.A. Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: a systematic review and meta-analysis.EBioMedicine. 2020; 58: 102916Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar,62Zhou R. Li F. Chen F. Liu H. Zheng J. Lei C. et al.Viral dynamics in asymptomatic patients with COVID-19.Int J Infect Dis. 2020; 96: 288-290Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 63Widders A. Broom A. Broom J. SARS-CoV-2: the viral shedding vs infectivity dilemma.Infect Dis Health. 2020; 25: 210-215Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 64Xu K. Chen Y. Yuan J. Yi P. Ding C. Wu W. et al.Factors associated with prolonged viral RNA shedding in patients with coronavirus disease 2019 (COVID-19).Clin Infect Dis. 2020; 71: 799-806Crossref PubMed Scopus (0) Google Scholar, 65Qi L. Yang Y. Jiang D. Tu C. Wan L. Chen X. et al.Factors associated with the duration of viral shedding in adults with COVID-19 outside of Wuhan, China: a retrospective cohort study.Int J Infect Dis. 2020; 96: 531-537Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Reduction in viral load is accompanied by increases in neutralizing antibodies.11Wölfel R. Corman V.M. Guggemos W. Seilmaier M. Zange S. Müller M.A. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (851) Google Scholar The findings from a limited number of studies evaluating virus viability during the course of COVID-19 illness suggest it is rare to find infected symptomatic patients shedding viable virus after 9 days of symptom onset.11Wölfel R. Corman V.M. Guggemos W. Seilmaier M. Zange S. Müller M.A. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (851) Google Scholar,17Arons M.M. Hatfield K.M. Reddy S.C. Kimball A. James A. Jacobs J.R. et al.Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility.N Engl J Med. 2020; 382: 2081-2090Crossref PubMed Scopus (284) Google Scholar,57COVID-19 Investigation TeamClinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.Nat Med. 2020; 26: 861-868Crossref PubMed Scopus (0) Google Scholar,66Bullard J. Dust K. Funk D. Strong J.E. Alexander D. Garnett L. et al.Predicting infectious SARS-CoV-2 from diagnostic samples.Clin Infect Dis. 2020; (Epub)Crossref PubMed Google Scholar, 67Centers for Disease Control and PreventionCoronavirus Disease 2019 (COVID-19). Duration of isolation and precautions for adults with COVID-19.https://www.cdc.gov/coronavirus/2019-ncov/community/strategy-discontinue-isolation.htmlGoogle Scholar, 68La Scola B. Le Bideau M. Andreani J. Hoang V.T. Grimaldier C. Colson P. et al.Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards.Eur J Clin Microbiol Infect Dis. 2020; 39: 1059-1061Crossref PubMed Scopus (41) Google Scholar A study of nursing home residents found viral RNA and viable virus in presymptomatic and asymptomatic subjects.17Arons M.M. Hatfield K.M. Reddy S.C. Kimball A. James A. Jacobs J.R. et al.Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility.N Engl J Med. 2020; 382: 2081-2090Crossref PubMed Scopus (284) Google Scholar Taken together, these data suggest viral shedding, detected by viral RNA, may be an indicator of SARS-CoV-2 transmissibility before the onset of COVID-19 symptoms, but not later in the course of COVID-19 illness. However, measuring virus viability is more complex and may not be as sensitive as RNA detection.11Wölfel R. Corman V.M. Guggemos W. Seilmaier M. Zange S. Müller M.A. et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; 581: 465-469Crossref PubMed Scopus (851) Google Scholar,69World Health OrganizationLaboratory biosafety guidance related to coronavirus disease (COVID-19).https://www.who.int/publications/i/item/laboratory-biosafety-guidance-related-to-coronavirus-disease-2019-(covid-19)Google Scholar It is clear that additional studies are needed to correlate viral RNA detection and transmissibility of viable virus.68La Scola B. Le Bideau M. Andreani J. Hoang V.T. Grimaldier C. Colson P. et al.Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards.Eur J Clin Microbiol Infect Dis. 2020; 39: 1059-1061Crossref PubMed Scopus (41) Google Scholar Important factors characterizing airborne SARS-CoV-2 transmission remain unknown: (1) the presence of the virus within the spectrum of droplet sizes contained within the human bioaerosol of infected subjects; (2) the proportion of small bioaerosol droplets that evaporate to droplet nuclei; (3) the half-life of viable virus in droplet nuclei; (4) the inhalation dose of the virus required to cause infection; (5) the timeline of when infected patients are most contagious; and (6) the role of environmental conditions play in airborne transport and virus viability.70Wei J. Li Y. Airborne spread of infectious agents in the indoor environment.Am J Infect Control. 2016; 44: S102-S108Abstract Full Text Full Text PDF Scopus (79) Google Scholar Studies evaluating airborne transmission from patients with COVID-19 illness undergoing medical care that includes AGPs and medical care without AGPs (non-AGPs) have not revealed a clear consensus on the risk of airborne transmission of SARS-CoV-2.71Brurberg K.G. Fretheim A. Aerosol generating procedures in health care, and COVID-19. Norwegian Institute of Public Health, Oslo, Norway2020Google Scholar Airborne transmission of viable SARS-CoV-2 virus during medical AGPs on infected patients is suggested from previous studies of SARS-CoV-1 but has not been confirmed.71Brurberg K.G. Fretheim A. Aerosol generating procedures in health care, and COVID-19. Norwegian Institute of Public Health, Oslo, Norway2020Google Scholar In situations where health care workers wearing personal protective equipment (PPE) attend to patients with COVID-19 and do not perform medical AGPs, direct airborne transmission of replication-competent SARS-CoV-2 has not been confirmed.72WHO Scientific brief: transmission of SARS-CoV-2: implications for infection prevention precautions.https://apps.who.int/iris/bitstream/handle/10665/333114/WHO-2019-nCoV-Sci_Brief-Transmission_modes-2020.3-eng.pdfGoogle Scholar The results of hospital studies evaluating aerosolization of body fluids and respiratory droplets of SARS-CoV-1 infected patients generated during certain medical AGPs (tracheal intubation, noninvasive ventilation, bronchoscopy, etc.), suggest that airborne transmission of SARS-CoV-2 may be possible during these procedures.72WHO Scientific brief: transmission of SARS-CoV-2: implications for infection prevention precautions.https://apps.who.int/iris/bitstream/handle/10665/333114/WHO-2019-nCoV-Sci_Brief-Transmission_modes-2020.3-eng.pdfGoogle Scholar However, the “possibility” is not clearly defined. High-quality studies using consistent methodology to assess virus transmissibility during medical AGPs are lacking.71Brurberg K.G. Fretheim A. Aerosol generating procedures in health care, and COVID-19. Norwegian Institute of Public Health, Oslo, Norway2020Google Scholar A 2012 systematic review of 5 case-control studies and 5 retrospective cohort studies on the transmissibility of SARS-CoV-1 during medical AGPs found a weak association with tracheal intubation across multiple studies and could draw no conclusions regarding other medical AGPs.73Tran K. Cimon K. Severn M. Pessoa-Silva C.L. Conly J. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.PLoS One. 2012; 7: e35797Crossref PubMed Scopus (496) Google Scholar Subsequent studies on SARS-CoV-1 transmissibility during medical AGPs produced variable results.41Judson S.D. Munster V.J. Nosocomial transmission of emerging viruses via aerosol-generating medical procedures.Viruses.