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      Particle sizes of infectious aerosols: implications for infection control

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      , MD a , *
      The Lancet. Respiratory Medicine
      Elsevier Ltd.

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          Summary

          The global pandemic of COVID-19 has been associated with infections and deaths among health-care workers. This Viewpoint of infectious aerosols is intended to inform appropriate infection control measures to protect health-care workers. Studies of cough aerosols and of exhaled breath from patients with various respiratory infections have shown striking similarities in aerosol size distributions, with a predominance of pathogens in small particles (<5 μm). These are immediately respirable, suggesting the need for personal respiratory protection (respirators) for individuals in close proximity to patients with potentially virulent pathogens. There is no evidence that some pathogens are carried only in large droplets. Surgical masks might offer some respiratory protection from inhalation of infectious aerosols, but not as much as respirators. However, surgical masks worn by patients reduce exposures to infectious aerosols to health-care workers and other individuals. The variability of infectious aerosol production, with some so-called super-emitters producing much higher amounts of infectious aerosol than most, might help to explain the epidemiology of super-spreading. Airborne infection control measures are indicated for potentially lethal respiratory pathogens such as severe acute respiratory syndrome coronavirus 2.

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          Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

          To the Editor: A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic. 1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus. 2 We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates. SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter (Figure 1A). SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces (Figure 1A), although the virus titer was greatly reduced (from 103.7 to 100.6 TCID50 per milliliter of medium after 72 hours on plastic and from 103.7 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). The stability kinetics of SARS-CoV-1 were similar (from 103.4 to 100.7 TCID50 per milliliter after 72 hours on plastic and from 103.6 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). On copper, no viable SARS-CoV-2 was measured after 4 hours and no viable SARS-CoV-1 was measured after 8 hours. On cardboard, no viable SARS-CoV-2 was measured after 24 hours and no viable SARS-CoV-1 was measured after 8 hours (Figure 1A). Both viruses had an exponential decay in virus titer across all experimental conditions, as indicated by a linear decrease in the log10TCID50 per liter of air or milliliter of medium over time (Figure 1B). The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours and 95% credible intervals of 0.64 to 2.64 for SARS-CoV-2 and 0.78 to 2.43 for SARS-CoV-1 (Figure 1C, and Table S1 in the Supplementary Appendix). The half-lives of the two viruses were also similar on copper. On cardboard, the half-life of SARS-CoV-2 was longer than that of SARS-CoV-1. The longest viability of both viruses was on stainless steel and plastic; the estimated median half-life of SARS-CoV-2 was approximately 5.6 hours on stainless steel and 6.8 hours on plastic (Figure 1C). Estimated differences in the half-lives of the two viruses were small except for those on cardboard (Figure 1C). Individual replicate data were noticeably “noisier” (i.e., there was more variation in the experiment, resulting in a larger standard error) for cardboard than for other surfaces (Fig. S1 through S5), so we advise caution in interpreting this result. We found that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic. 3,4 Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed). These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, 5 and they provide information for pandemic mitigation efforts.
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            Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

            To the Editor: The novel coronavirus (2019-nCoV) from Wuhan is currently causing concern in the medical community as the virus is spreading around the world. 1 Since identification of the virus in late December 2019, the number of cases from China that have been imported into other countries is on the rise, and the epidemiologic picture is changing on a daily basis. We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient. A 33-year-old otherwise healthy German businessman (Patient 1) became ill with a sore throat, chills, and myalgias on January 24, 2020. The following day, a fever of 39.1°C (102.4°F) developed, along with a productive cough. By the evening of the next day, he started feeling better and went back to work on January 27. Before the onset of symptoms, he had attended meetings with a Chinese business partner at his company near Munich on January 20 and 21. The business partner, a Shanghai resident, had visited Germany between January 19 and 22. During her stay, she had been well with no signs or symptoms of infection but had become ill on her flight back to China, where she tested positive for 2019-nCoV on January 26 (index patient in Figure 1) (see Supplementary Appendix, available at NEJM.org, for details on the timeline of symptom development leading to hospitalization). On January 27, she informed the company about her illness. Contact tracing was started, and the above-mentioned colleague was sent to the Division of Infectious Diseases and Tropical Medicine in Munich for further assessment. At presentation, he was afebrile and well. He reported no previous or chronic illnesses and had no history of foreign travel within 14 days before the onset of symptoms. Two nasopharyngeal swabs and one sputum sample were obtained and were found to be positive for 2019-nCoV on quantitative reverse-transcriptase–polymerase-chain-reaction (qRT-PCR) assay. 2 Follow-up qRT-PCR assay revealed a high viral load of 108 copies per milliliter in his sputum during the following days, with the last available result on January 29. On January 28, three additional employees at the company tested positive for 2019-nCoV (Patients 2 through 4 in Figure 1). Of these patients, only Patient 2 had contact with the index patient; the other two patients had contact only with Patient 1. In accordance with the health authorities, all the patients with confirmed 2019-nCoV infection were admitted to a Munich infectious diseases unit for clinical monitoring and isolation. So far, none of the four confirmed patients show signs of severe clinical illness. This case of 2019-nCoV infection was diagnosed in Germany and transmitted outside Asia. However, it is notable that the infection appears to have been transmitted during the incubation period of the index patient, in whom the illness was brief and nonspecific. 3 The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak. In this context, the detection of 2019-nCoV and a high sputum viral load in a convalescent patient (Patient 1) arouse concern about prolonged shedding of 2019-nCoV after recovery. Yet, the viability of 2019-nCoV detected on qRT-PCR in this patient remains to be proved by means of viral culture. Despite these concerns, all four patients who were seen in Munich have had mild cases and were hospitalized primarily for public health purposes. Since hospital capacities are limited — in particular, given the concurrent peak of the influenza season in the northern hemisphere — research is needed to determine whether such patients can be treated with appropriate guidance and oversight outside the hospital.
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              Respiratory virus shedding in exhaled breath and efficacy of face masks

              We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.
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                Author and article information

                Contributors
                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                Elsevier Ltd.
                2213-2600
                2213-2619
                24 July 2020
                24 July 2020
                Affiliations
                [a ]Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
                Author notes
                [* ]Correspondence to: Dr Kevin P Fennelly, Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA kevin.fennelly@ 123456nih.gov
                Article
                S2213-2600(20)30323-4
                10.1016/S2213-2600(20)30323-4
                7380927
                32717211
                b139058d-0614-4a7f-9ecf-7e097a031e41
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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