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1.
Clin Infect Dis ; 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-2017760

ABSTRACT

BACKGROUND: SARS-CoV-2 epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. METHODS: We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. RESULTS: We enrolled 49 seronegative cases (mean days post onset 3.8 ±2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 45% of fine (≤5 µm), 31% of coarse (>5 µm) aerosols, and 65% of fomite samples overall and in all samples from four alpha-variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. CONCLUSION: SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

2.
Indoor Air ; 32(6): e13064, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1909399

ABSTRACT

The exhalation of aerosols during musical performances or rehearsals posed a risk of airborne virus transmission in the COVID-19 pandemic. Previous research studied aerosol plumes by only focusing on one risk factor, either the source strength or convective transport capability. Furthermore, the source strength was characterized by the aerosol concentration and ignored the airflow rate needed for risk analysis in actual musical performances. This study characterizes aerosol plumes that account for both the source strength and convective transport capability by conducting experiments with 18 human subjects. The source strength was characterized by the source aerosol emission rate, defined as the source aerosol concentration multiplied by the source airflow rate (brass 383 particle/s, singing 408 particle/s, and woodwind 480 particle/s). The convective transport capability was characterized by the plume influence distance, defined as the sum of the horizontal jet length and horizontal instrument length (brass 0.6 m, singing 0.6 m and woodwind 0.8 m). Results indicate that woodwind instruments produced the highest risk with approximately 20% higher source aerosol emission rates and 30% higher plume influence distances compared with the average of the same risk indicators for singing and brass instruments. Interestingly, the clarinet performance produced moderate source aerosol concentrations at the instrument's bell, but had the highest source aerosol emission rates due to high source airflow rates. Flute performance generated plumes with the lowest source aerosol emission rates but the highest plume influence distances due to the highest source airflow rate. Notably, these comprehensive results show that the source airflow is a critical component of the risk of airborne disease transmission. The effectiveness of masking and bell covering in reducing aerosol transmission is due to the mitigation of both source aerosol concentrations and plume influence distances. This study also found a musician who generated approximately five times more source aerosol concentrations than those of the other musicians who played the same instrument. Despite voice and brass instruments producing measurably lower average risk, it is possible to have an individual musician produce aerosol plumes with high source strength, resulting in enhanced transmission risk; however, our sample size was too small to make generalizable conclusions regarding the broad musician population.


Subject(s)
Air Pollution, Indoor , COVID-19 , Respiratory Aerosols and Droplets , Singing , Aerosols/analysis , Air Pollution, Indoor/analysis , COVID-19/transmission , Humans , Music , Pandemics , Respiratory Aerosols and Droplets/virology
3.
Microbiol Spectr ; 10(2): e0012822, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1752767

ABSTRACT

Saliva is an attractive sample for detecting SARS-CoV-2. However, contradictory reports exist concerning the sensitivity of saliva versus nasal swabs. We followed close contacts of COVID-19 cases for up to 14 days from the last exposure and collected self-reported symptoms, midturbinate swabs (MTS), and saliva every 2 or 3 days. Ct values, viral load, and frequency of viral detection by MTS and saliva were compared. Fifty-eight contacts provided 200 saliva-MTS pairs, and 14 contacts (13 with symptoms) had one or more positive samples. Saliva and MTS had similar rates of viral detection (P = 0.78) and substantial agreement (κ = 0.83). However, sensitivity varied significantly with time since symptom onset. Early on (days -3 to 2), saliva had 12 times (95% CI: 1.2, 130) greater likelihood of viral detection and 3.2 times (95% CI: 2.8, 3.8) higher RNA copy numbers compared to MTS. After day 2 of symptoms, there was a nonsignificant trend toward greater sensitivity using MTS. Saliva and MTS demonstrated high agreement making saliva a suitable alternative to MTS for SARS-CoV-2 detection. Saliva was more sensitive early in the infection when the transmission was most likely to occur, suggesting that it may be a superior and cost-effective screening tool for COVID-19. IMPORTANCE The findings of this manuscript are increasingly important with new variants that appear to have shorter incubation periods emerging, which may be more prone to detection in saliva before detection in nasal swabs. Therefore, there is an urgent need to provide the science to support the use of a detection method that is highly sensitive and widely acceptable to the public to improve screening rates and early detection. The manuscript presents the first evidence that saliva-based RT-PCR is more sensitive than MTS-based RT-PCR in detecting SARS-CoV-2 during the presymptomatic period - the critical period for unwitting onward transmission. Considering other advantages of saliva samples, including the lower cost, greater acceptability within the general population, and less risk to health care workers, our findings further supported the use of saliva to identify presymptomatic infection and prevent transmission of the virus.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Nasopharynx , SARS-CoV-2/genetics , Saliva , Specimen Handling/methods
4.
Clin Infect Dis ; 74(10): 1722-1728, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1707710

ABSTRACT

BACKGROUND: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading events suggest that aerosols play an important role in driving the coronavirus disease 2019 (COVID-19) pandemic. To better understand how airborne SARS-CoV-2 transmission occurs, we sought to determine viral loads within coarse (>5 µm) and fine (≤5 µm) respiratory aerosols produced when breathing, talking, and singing. METHODS: Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing. RESULTS: Thirteen participants (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic and 1 presymptomatic patient. Viral loads ranged from 63-5821 N gene copies per expiratory activity per participant, with high person-to-person variation. Patients earlier in illness were more likely to emit detectable RNA. Two participants, sampled on day 3 of illness, accounted for 52% of total viral load. Overall, 94% of SARS-CoV-2 RNA copies were emitted by talking and singing. Interestingly, 7 participants emitted more virus from talking than singing. Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative. CONCLUSIONS: Fine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in SARS-CoV-2 transmission. Exposure to fine aerosols, especially indoors, should be mitigated. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging; whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an urgent enquiry necessitating larger-scale studies.


Subject(s)
COVID-19 , Singing , Aerosols , Humans , RNA, Viral/genetics , SARS-CoV-2 , Viral Load
5.
Clin Infect Dis ; 73(11): e3983-e3984, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1575091
6.
Front Public Health ; 9: 747894, 2021.
Article in English | MEDLINE | ID: covidwho-1528873

ABSTRACT

Eighteen months into the COVID-19 pandemic, and as the world struggles with global vaccine equity, emerging variants, and the reality that eradication is years away at soonest, we add to notion of "layered defenses" proposing a conceptual model for better understanding the differential applicability and effectiveness of precautions against SARS-CoV-2 transmission. The prevailing adaptation of Reason's Swiss cheese model conceives of all defensive layers as equally protective, when in reality some are more effective than others. Adapting the hierarchy of controls framework from occupational safety provides a better framework for understanding the relative benefit of different hazard control strategies to minimize the spread of SARS-CoV-2.


Subject(s)
COVID-19 , Occupational Health , Humans , Pandemics/prevention & control , SARS-CoV-2 , Safety Management
7.
Biosens Bioelectron ; 197: 113803, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1517063

ABSTRACT

We report the rapid detection of SARS-CoV-2 in infected patients (mid-turbinate swabs and exhaled breath aerosol samples) in concentrations as low as 60 copies/mL of the virus in seconds by electrical transduction of the SARS-CoV-2 S1 spike protein antigen via SARS-CoV-2 S1 spike protein antibodies immobilized on bilayer quasi-freestanding epitaxial graphene without gate or signal amplification. The sensor demonstrates the spike protein antigen detection in a concentration as low as 1 ag/mL. The heterostructure of the SARS-CoV-2 antibody/graphene-based sensor is developed through a simple and low-cost fabrication technique. Furthermore, sensors integrated into a portable testing unit distinguished B.1.1.7 variant positive samples from infected patients (mid-turbinate swabs and saliva samples, 4000-8000 copies/mL) with a response time of as fast as 0.6 s. The sensor is reusable, allowing for reimmobilization of the crosslinker and antibodies on the biosensor after desorption of biomarkers by NaCl solution or heat treatment above 40 °C.


Subject(s)
Biosensing Techniques , COVID-19 , Graphite , Humans , SARS-CoV-2
8.
Ann Intern Med ; 174(12): 1710-1718, 2021 12.
Article in English | MEDLINE | ID: covidwho-1506230

ABSTRACT

Policies to prevent respiratory virus transmission in health care settings have traditionally divided organisms into Droplet versus Airborne categories. Droplet organisms (for example, influenza) are said to be transmitted via large respiratory secretions that rapidly fall to the ground within 1 to 2 meters and are adequately blocked by surgical masks. Airborne pathogens (for example, measles), by contrast, are transmitted by aerosols that are small enough and light enough to carry beyond 2 meters and to penetrate the gaps between masks and faces; health care workers are advised to wear N95 respirators and to place these patients in negative-pressure rooms. Respirators and negative-pressure rooms are also recommended when caring for patients with influenza or SARS-CoV-2 who are undergoing "aerosol-generating procedures," such as intubation. An increasing body of evidence, however, questions this framework. People routinely emit respiratory particles in a range of sizes, but most are aerosols, and most procedures do not generate meaningfully more aerosols than ordinary breathing, and far fewer than coughing, exercise, or labored breathing. Most transmission nonetheless occurs at close range because virus-laden aerosols are most concentrated at the source; they then diffuse and dilute with distance, making long-distance transmission rare in well-ventilated spaces. The primary risk factors for nosocomial transmission are community incidence rates, viral load, symptoms, proximity, duration of exposure, and poor ventilation. Failure to appreciate these factors may lead to underappreciation of some risks (for example, overestimation of the protection provided by medical masks, insufficient attention to ventilation) or misallocation of limited resources (for example, reserving N95 respirators and negative-pressure rooms only for aerosol-generating procedures or requiring negative-pressure rooms for all patients with SARS-CoV-2 infection regardless of stage of illness). Enhanced understanding of the factors governing respiratory pathogen transmission may inform the development of more effective policies to prevent nosocomial transmission of respiratory pathogens.


Subject(s)
Infection Control/methods , Respiratory Tract Infections/transmission , Respiratory Tract Infections/virology , Aerosols , COVID-19/prevention & control , COVID-19/transmission , COVID-19/virology , Cross Infection/prevention & control , Cross Infection/virology , Health Policy , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Influenza, Human/prevention & control , Influenza, Human/transmission , Influenza, Human/virology , Masks , Personnel, Hospital , SARS-CoV-2 , United States/epidemiology , Ventilation
9.
Clin Infect Dis ; 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-1406471

ABSTRACT

BACKGROUND: SARS-CoV-2 epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. METHODS: We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. RESULTS: We enrolled 49 seronegative cases (mean days post onset 3.8 ±2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 45% of fine (≤5 µm), 31% of coarse (>5 µm) aerosols, and 65% of fomite samples overall and in all samples from four alpha-variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. CONCLUSION: SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

11.
Clin Infect Dis ; 74(10): 1722-1728, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1345720

ABSTRACT

BACKGROUND: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading events suggest that aerosols play an important role in driving the coronavirus disease 2019 (COVID-19) pandemic. To better understand how airborne SARS-CoV-2 transmission occurs, we sought to determine viral loads within coarse (>5 µm) and fine (≤5 µm) respiratory aerosols produced when breathing, talking, and singing. METHODS: Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing. RESULTS: Thirteen participants (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic and 1 presymptomatic patient. Viral loads ranged from 63-5821 N gene copies per expiratory activity per participant, with high person-to-person variation. Patients earlier in illness were more likely to emit detectable RNA. Two participants, sampled on day 3 of illness, accounted for 52% of total viral load. Overall, 94% of SARS-CoV-2 RNA copies were emitted by talking and singing. Interestingly, 7 participants emitted more virus from talking than singing. Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative. CONCLUSIONS: Fine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in SARS-CoV-2 transmission. Exposure to fine aerosols, especially indoors, should be mitigated. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging; whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an urgent enquiry necessitating larger-scale studies.


Subject(s)
COVID-19 , Singing , Aerosols , Humans , RNA, Viral/genetics , SARS-CoV-2 , Viral Load
13.
Influenza Other Respir Viruses ; 15(3): 331-335, 2021 05.
Article in English | MEDLINE | ID: covidwho-1119238

ABSTRACT

Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections.


Subject(s)
COVID-19/prevention & control , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , Acute Disease , Adolescent , Adult , Cohort Studies , Female , Humans , Male , Physical Distancing , Prevalence , Young Adult
14.
Nat Commun ; 12(1): 6, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1007633

ABSTRACT

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19 Testing , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Microarray Analysis/methods , Middle East Respiratory Syndrome Coronavirus/immunology , Neutralization Tests , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology
17.
Nat Med ; 26(6): 981, 2020 06.
Article in English | MEDLINE | ID: covidwho-617429

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

18.
Nat Commun ; 11(1): 2800, 2020 05 29.
Article in English | MEDLINE | ID: covidwho-419772

ABSTRACT

Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1-4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Environmental Microbiology , Patients' Rooms , Pneumonia, Viral/virology , Adult , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Cross-Sectional Studies , Female , Hospitals , Humans , Male , Middle Aged , Pandemics , Particle Size , Particulate Matter/analysis , Particulate Matter/chemistry , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , SARS-CoV-2 , Time Factors
19.
Environ Int ; 142: 105832, 2020 09.
Article in English | MEDLINE | ID: covidwho-381748

ABSTRACT

During the rapid rise in COVID-19 illnesses and deaths globally, and notwithstanding recommended precautions, questions are voiced about routes of transmission for this pandemic disease. Inhaling small airborne droplets is probable as a third route of infection, in addition to more widely recognized transmission via larger respiratory droplets and direct contact with infected people or contaminated surfaces. While uncertainties remain regarding the relative contributions of the different transmission pathways, we argue that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors. Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public.


Subject(s)
Air Microbiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Aerosols , Betacoronavirus , COVID-19 , Crowding , Disinfection/instrumentation , Filtration , Humans , Inhalation Exposure , SARS-CoV-2 , Ventilation
20.
Nat Med ; 26(5): 676-680, 2020 05.
Article in English | MEDLINE | ID: covidwho-203367

ABSTRACT

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.


Subject(s)
Coronavirus Infections/transmission , Masks/virology , Pneumonia, Viral/transmission , Respiratory Tract Infections/transmission , Aerosols/isolation & purification , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Exhalation/physiology , Humans , Orthomyxoviridae/isolation & purification , Orthomyxoviridae/pathogenicity , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , RNA, Viral/isolation & purification , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology , Virus Shedding
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