Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 87 Records) |
Query Trace: Hy C [original query] |
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Comparative diagnostic utility of SARS-CoV-2 rapid antigen and molecular testing in a community setting
Kim AE , Bennett JC , Luiten K , O'Hanlon JA , Wolf CR , Magedson A , Han PD , Acker Z , Regelbrugge L , McCaffrey KM , Stone J , Reinhart D , Capodanno BJ , Morse SS , Bedford T , Englund JA , Boeckh M , Starita LM , Uyeki TM , Carone M , Weil A , Chu HY . J Infect Dis 2024 BACKGROUND: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. METHODS: This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). RESULTS: From February to December 2022, 5,757 participants reported 17,572 Ag-RDT results and completed 12,674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR-positive. Overall sensitivity and specificity were 53.0% (95% CI: 49.6-56.4%) and 98.8% (98.5-99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4 to 7 days post-symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥2 (68.5%) and ≥4 (75.8%) days after an initial Ag-RDT-negative result. CONCLUSION: Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high-risk for SARS-CoV-2 infection. |
Remote surveillance and detection of SARS-CoV-2 transmission among household members in King County, Washington
Emanuels A , Casto AM , Heimonen J , O'Hanlon J , Chow EJ , Ogokeh C , Rolfes MA , Han PD , Hughes JP , Uyeki TM , Frazar C , Chung E , Starita LM , Englund JA , Chu HY . BMC Infect Dis 2024 24 (1) 309 BACKGROUND: Early during the COVID-19 pandemic, it was important to better understand transmission dynamics of SARS-CoV-2, the virus that causes COVID-19. Household contacts of infected individuals are particularly at risk for infection, but delays in contact tracing, delays in testing contacts, and isolation and quarantine posed challenges to accurately capturing secondary household cases. METHODS: In this study, 346 households in the Seattle region were provided with respiratory specimen collection kits and remotely monitored using web-based surveys for respiratory illness symptoms weekly between October 1, 2020, and June 20, 2021. Symptomatic participants collected respiratory specimens at symptom onset and mailed specimens to the central laboratory in Seattle. Specimens were tested for SARS-CoV-2 using RT-PCR with whole genome sequencing attempted when positive. SARS-CoV-2-infected individuals were notified, and their household contacts submitted specimens every 2 days for 14 days. RESULTS: In total, 1371 participants collected 2029 specimens that were tested; 16 individuals (1.2%) within 6 households tested positive for SARS-CoV-2 during the study period. Full genome sequences were generated from 11 individuals within 4 households. Very little genetic variation was found among SARS-CoV-2 viruses sequenced from different individuals in the same household, supporting transmission within the household. CONCLUSIONS: This study indicates web-based surveillance of respiratory symptoms, combined with rapid and longitudinal specimen collection and remote contact tracing, provides a viable strategy to monitor households and detect household transmission of SARS-CoV-2. TRIAL REGISTRATION IDENTIFIER: NCT04141930, Date of registration 28/10/2019. |
Utilizing a university testing program to estimate relative effectiveness of monovalent COVID-19 mRNA booster vaccine versus two-dose primary series against symptomatic SARS-CoV-2 infection
Bennett JC , Luiten KG , O'Hanlon J , Han PD , McDonald D , Wright T , Wolf CR , Lo NK , Acker Z , Regelbrugge L , McCaffrey KM , Pfau B , Stone J , Schwabe-Fry K , Lockwood CM , Guthrie BL , Gottlieb GS , Englund JA , Uyeki TM , Carone M , Starita LM , Weil AA , Chu HY . Vaccine 2024 Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies. |
Effectiveness of bivalent mRNA COVID-19 vaccines in preventing SARS-cov-2 infection in children and adolescents aged 5 to 17 years
Feldstein LR , Britton A , Grant L , Wiegand R , Ruffin J , Babu TM , Briggs Hagen M , Burgess JL , Caban-Martinez AJ , Chu HY , Ellingson KD , Englund JA , Hegmann KT , Jeddy Z , Lauring AS , Lutrick K , Martin ET , Mathenge C , Meece J , Midgley CM , Monto AS , Newes-Adeyi G , Odame-Bamfo L , Olsho LEW , Phillips AL , Rai RP , Saydah S , Smith N , Steinhardt L , Tyner H , Vandermeer M , Vaughan M , Yoon SK , Gaglani M , Naleway AL . Jama 2024 331 (5) 408-416 IMPORTANCE: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. OBJECTIVE: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. EXPOSURE: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. MAIN OUTCOME AND MEASURES: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. RESULTS: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. CONCLUSION AND RELEVANCE: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations. |
Changing social contact patterns among US workers during the COVID-19 pandemic: April 2020 to December 2021
Kiti MC , Aguolu OG , Zelaya A , Chen HY , Ahmed N , Batross J , Liu CY , Nelson KN , Jenness SM , Melegaro A , Ahmed F , Malik F , Omer SB , Lopman BA . Epidemics 2023 45 100727 Non-pharmaceutical interventions minimize social contacts, hence the spread of respiratory pathogens such as influenza and SARS-CoV-2. Globally, there is a paucity of social contact data from the workforce. In this study, we quantified two-day contact patterns among USA employees. Contacts were defined as face-to-face conversations, involving physical touch or proximity to another individual and were collected using electronic self-kept diaries. Data were collected over 4 rounds from 2020 to 2021 during the COVID-19 pandemic. Mean (standard deviation) contacts reported by 1456 participants were 2.5 (2.5), 8.2 (7.1), 9.2 (7.1) and 10.1 (9.5) across round 1 (April-June 2020), 2 (November 2020-January 2021), 3 (June-August 2021), and 4 (November-December 2021), respectively. Between round 1 and 2, we report a 3-fold increase in the mean number of contacts reported per participant with no major increases from round 2-4. We then modeled SARS-CoV-2 transmission at home, work, and community settings. The model revealed reduced relative transmission in all settings in round 1. Subsequently, transmission increased at home and in the community but remained exceptionally low in work settings. To accurately parameterize models of infection transmission and control, we need empirical social contact data that capture human mixing behavior across time. |
Burden of respiratory syncytial virus-associated acute respiratory infections during pregnancy
Kenmoe S , Chu HY , Dawood FS , Milucky J , Kittikraisak W , Matthewson H , Kulkarni D , Suntarattiwong P , Frivold C , Mohanty S , Havers F , Li Y , Nair H . J Infect Dis 2023 INTRODUCTION: With the licensure of maternal RSV vaccines in Europe and USA, data are needed to better characterize the burden of respiratory syncytial virus (RSV)-associated acute respiratory infections (ARI) in pregnancy. This study aims to determine among pregnant individuals the proportion of ARI testing positive for RSV and RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal outcomes. METHODS: We conducted a systematic review following PRISMA 2020 guidelines using five databases (Medline, Embase, Global Health, Web of Science and Global Index Medicus) and included additional unpublished data. Pregnant individuals with respiratory infections who had respiratory samples tested for RSV were included. We used a random-effects meta-analysis to generate overall proportions and rate estimates across studies. RESULTS: Eleven studies with pregnant individuals recruited between 2010 and 2022 were identified, most of which recruited pregnant individuals in community, inpatient and outpatient settings. Among 8126 pregnant individuals, the proportion with respiratory infections that tested positive for RSV ranged from 0.9% to 10.7%, with a meta-estimate of 3.4% (95% CI: 1.9; 54). The pooled incidence rate of RSV infection episodes among pregnant individuals was 26.0 (15.8; 36.2) per 1000 person-years. RSV hospitalization rates reported in two studies were 2.4 and 3.0 per 1000 person-years. Of five studies that ascertained RSV-associated deaths among 4708 pregnant individuals, no deaths were reported. Three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in odds of miscarriage, stillbirth, low birth weight, and small for gestational age. RSV-positive pregnant individuals had higher odds of preterm delivery (odds ratio 3.6 [1.3; 10.3]). CONCLUSION: Data on RSV-associated hospitalization incidence rates are limited but available estimates are lower than those reported in older adults and young children. As countries debate whether to include RSV vaccines in maternal vaccination programs, which are primarily intended to protect infants, this information could be useful in shaping vaccine policy decisions. |
Risk of subsequent respiratory virus detection after primary virus detection in a community household study - King County, Washington 2019-2021
Heimonen J , Chow EJ , Wang Y , Hughes JP , Rogers J , Emanuels A , O'Hanlon J , Han PD , Wolf CR , Logue JK , Ogokeh CE , Rolfes MA , Uyeki TM , Starita L , Englund JA , Chu HY . J Infect Dis 2023 BACKGROUND: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. METHODS: We retrospectively analyzed data from a longitudinal household cohort study from October 2019-June 2021. Enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swabs; after April 2020, participants with ARI or laboratory-confirmed SARS-CoV-2 and their household members self-collected nasal swabs. Specimens were tested via multiplex RT-PCR for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. RESULTS: Rhinovirus was the most frequently detected pathogen in study specimens (n=406, 9.5%). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8, 14.8%) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days following primary detection; risk varied by primary virus: parainfluenza, rhinovirus, and respiratory syncytial virus were statistically significant. CONCLUSIONS: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection. |
A Remote Household-Based Approach to Influenza Self-Testing and Antiviral Treatment (preprint)
Heimonen J , McCulloch DJ , O'Hanlon J , Kim AE , Emanuels A , Wilcox N , Brandstetter E , Stewart M , McCune D , Fry S , Parsons S , Hughes JP , Jackson ML , Uyeki TM , Boeckh M , Starita LM , Bedford T , Englund JA , Chu HY . medRxiv 2021 2021.02.01.21250973 Background Households represent important settings for transmission of influenza and other respiratory viruses. Current influenza diagnosis and treatment relies upon patient visits to healthcare facilities, which may lead to under-diagnosis and treatment delays. This study aimed to assess the feasibility of an at-home approach to influenza diagnosis and treatment via home testing, telehealth care, and rapid antiviral home delivery.Methods We conducted a pilot interventional study of remote influenza diagnosis and treatment in Seattle-area households with children during the 2019-2020 influenza season using pre-positioned nasal swabs and home influenza tests. Home monitoring for respiratory symptoms occurred weekly; if symptoms were reported within 48 hours of onset, participants collected mid-nasal swabs and used a rapid home-based influenza immunoassay. An additional home-collected swab was returned to a laboratory for confirmatory influenza RT-PCR testing. Baloxavir antiviral treatment was prescribed and delivered to symptomatic and age-eligible participants, following a telehealth encounter.Results 124 households comprising 481 individuals self-monitored for respiratory symptoms, with 58 home tests administered. 12 home tests were positive for influenza, of which 8 were true positives confirmed by RT-PCR. The sensitivity and specificity of the home influenza test was 72.7% and 96.2%, respectively. There were 8 home deliveries of baloxavir, with 7 (87.5%) occurring within 3 hours of prescription, and all within 48 hours of symptom onset.Conclusions We demonstrate the feasibility of self-testing combined with rapid home delivery of influenza antiviral treatment. This approach may be an important control strategy for influenza epidemics and pandemics.Summary In this pilot study, 481 individuals self-monitored for respiratory symptoms. Of 58 home tests, 12 were influenza-positive. There were 8 baloxavir home deliveries within 48 hours of illness onset. A home-based approach to influenza diagnosis and treatment could be feasible.Competing Interest StatementH.Y.C. has received research support from GlaxoSmithKline, Novavax, and Sanofi Pasteur; J.A.E. has received research support from AstraZeneca, GlaxoSmithKine, Merck, and Pfizer and served as a consultant for Sanofi Pasteur and Meissa Vaccines. M.L.J. has received research support from Sanofi Pasteur. M.B. receives research support and serves as a consultant for Ansun Biopharma, Gilead Sciences, Janssen, and Vir Biotechnology; and serves as a consultant to GlaxoSmithKline, ReViral, ADMA, Pulmocdie and ModernaClinical TrialNCT04141930Funding StatementThe Seattle Flu Study is funded by Gates Ventures. The funder was not involved in the design of the study, does not have any ownership over the management and conduct of the study, the data, or the rights to publish.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:University of Washington Institutional Review Board (STUDY00008200)All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData and code used for analyses may be available upon request. |
The Seattle Flu Study: a multi-arm community-based prospective study protocol for assessing influenza prevalence, transmission, and genomic epidemiology (preprint)
Chu HY , Boeckh M , Englund JA , Famulare M , Lutz B , Nickerson DA , Rieder M , Starita LM , Shendure J , Bedford T , Adler A , Brandstetter E , Frazer CD , Han PD , Gulati RK , Hadfield J , Jackson M , Kiavand A , Kimball LE , Lacombe K , Logue JK , Lyon VR , Newman KL , Sibley TR , Zigman Suchsland M , Wolf C . medRxiv 2020 2020.03.02.20029595 Introduction Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterize, and potentially contain new and emerging influenza strains at a population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population.Methods and Analysis Starting in the 2018-19 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses, and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modeling platforms are in development to characterize the regional spread of influenza and other respiratory pathogens.Ethics and Dissemination The study was approved by the University of Washington’s Institutional Review Board. Results will be disseminated through talks at conferences, peer-reviewed publications, and on the study website (www.seattleflu.org).Strengths and limitations of this study- Large-scale multiple-arm study of respiratory illness characterization with collection of samples from individuals in the community as well as in ambulatory care and hospital settings- Integration of sociodemographic, clinical, and geospatial data on a regional level- Multiplex molecular testing for multiple viral and bacterial pathogens and whole genome sequencing of influenza for detailed molecular epidemiologic characterization and transmission mapping- Geographically and socioeconomically diverse sampling of community-based acute respiratory illnessesCompeting Interest StatementAmanda Adler, Elisabeth Brandstetter, Michael Famulare, Chris D. Frazar, Peter D. Han, Reena K. Gulati, James Hadfield, Michael L. Jackson, Anahita Kiavand, Louise E. Kimball, Kirsten Lacombe, Jennifer Logue, Victoria Lyon, Kira L. Newman, Thomas R. Sibley, Jay Shendure, Lea Starita, Monica L. Zigman Suchsland, and Caitlin Wolf declare no competing interests. Helen Y Chu receives research support from Sanofi, Cepheid, and Genentech/Roche and is a consultant for Merck. Janet Englund receives research support to her institution from Astrazeneca, GlaxoSmithKline, Merck, and Novavax and is a consultant for Sanofi Pasteur and Meissa Vaccines.Funding StatementThe Seattle Flu Study is funded through the Brotman Baty Institute. The funder was not involved in the design of the study, does not have any ownership over the management and conduct of the study, the data, or the rights to publishAuthor DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable YesThe data will be accessed only by authorized individuals on the study team. Access to deidentified, aggregated data and analysis code will be publicly available on the study web page (www.seattleflu.org). http://www.seattleflu.org |
Seroprevalence of SARS-CoV-2 Antibodies in Seattle, Washington—October 2019–April 2020 (preprint)
McCulloch DJ , Jackson ML , Hughes JP , Lester S , Mills L , Freeman B , Rasheed MAU , Thornburg NJ , Chu HY . medRxiv 2020 2020.12.07.20244103 Estimating prevalence of SARS-CoV-2 antibodies is important to determine disease burden. We tested residual samples from 763 Seattle-area adults for SARS-CoV-2 antibodies. Prevalence rose from 0% to 1.2% between October 2019–April 2020, suggesting a small percentage of this metropolitan-area cohort had been infected with SARS-CoV-2 at that time.Competing Interest StatementHelen Y. Chu receives research support from Cepheid and is a consultant for Merck, Pfizer, the Bill and Melinda Gates Foundation, and Ellume. Michael L. Jackson receives research funding from Sanofi Pasteur. Denise J. McCulloch, James P. Hughes, Sandra Lester, Lisa Mills, Brandi Freeman, Mohammad Ata Ut Rasheed, and Natalie J. Thornburg, declare no competing interests.Funding StatementThis work was supported by the University of Washington Department of Medicine Scholars Award to Helen Chu.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:University of Washington IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data analyzed during the current study are available from the corresponding author on reasonable request. |
Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study (preprint)
Rogers JH , Cox SN , Link AC , Nwanne G , Han PD , Pfau B , Chow EJ , Wolf CR , Boeckh M , Hughes JP , Halloran ME , Uyeki TM , Shim MM , Duchin J , Englund JA , Mosites E , Rolfes MA , Starita LA , Chu HY . medRxiv 2023 30 Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1/1/2020 -5/31/2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged >=3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00 - 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12 - 5.91; staff: 3.86, 95% CI 2.43 - 5.79). Most infections were asymptomatic at time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study
Rogers JH , Cox SN , Link AC , Nwanne G , Han PD , Pfau B , Chow EJ , Wolf CR , Boeckh M , Hughes JP , Halloran ME , Uyeki TM , Shim MM , Duchin J , Englund JA , Mosites E , Rolfes MA , Starita LA , Chu HY . Epidemiol Infect 2023 151 1-48 Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, | 34 SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or | 35 outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 | 36 homeless shelters in King County, Washington to estimate the occurrence of laboratory37 confirmed SARS-CoV-2 infection and risk factors during 1/1/2020 -5/31/2021. Symptom surveys | 38 and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 | 39 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified | 40 4.74 (95% CI 4.00 – 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI | 41 4.12 – 5.91; staff: 3.86, 95% CI 2.43 – 5.79). Most infections were asymptomatic at time of | 42 detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher | 43 test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, | 44 residents were less likely to report symptoms than staff. Participants who were vaccinated | 45 against seasonal influenza and were current smokers had lower odds of having an infection | 46 detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in | 47 ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate | 48 settings. |
CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design
Babu TM , Feldstein LR , Saydah S , Acker Z , Boisvert CL , Briggs-Hagen M , Carone M , Casto A , Cox SN , Ehmen B , Englund JA , Fortmann SP , Frivold CJ , Groom H , Han PD , Kuntz JL , Lockwood T , Midgley CM , Mularski RA , Ogilvie T , Reich SL , Schmidt MA , Smith N , Starita L , Stone J , Vandermeer M , Weil AA , Wolf CR , Chu HY , Naleway AL . BMJ Open 2023 13 (7) e071446 INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media. |
Streptococcus pneumoniae nasal carriage patterns with and without common respiratory virus detections in households in Seattle, WA, USA before and during the COVID-19 pandemic
Bennett JC , Emanuels A , Heimonen J , O'Hanlon J , Hughes JP , Han PD , Chow EJ , Ogokeh CE , Rolfes MA , Lockwood CM , Pfau B , Uyeki TM , Shendure J , Hoag S , Fay K , Lee J , Sibley TR , Rogers JH , Starita LM , Englund JA , Chu HY . Front Pediatr 2023 11 1198278 BACKGROUND: Respiratory viruses might influence Streptococcus pneumoniae nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative S. pneumoniae nasal carriage density in a household setting before and during the COVID-19 pandemic. METHODS: From November 2019-June 2021, we enrolled participants in a remote household surveillance study of respiratory pathogens. Participants submitted weekly reports of acute respiratory illness (ARI) symptoms. Mid-turbinate or anterior nasal swabs were self-collected at enrollment, when ARI occurred, and, in the second year of the study only, from household contacts after SARS-CoV-2 was detected in a household member. Specimens were tested using multiplex reverse-transcription PCR for respiratory pathogens, including S. pneumoniae, rhinovirus, adenovirus, common human coronavirus, influenza A/B virus, respiratory syncytial virus (RSV) A/B, human metapneumovirus, enterovirus, and human parainfluenza virus. We estimated differences in semiquantitative S. pneumoniae nasal carriage density, estimated by the inverse of S. pneumoniae relative cycle threshold (Crt) values, with and without viral detection for any virus and for specific respiratory viruses using linear generalized estimating equations of S. pneumoniae Crt values on virus detection adjusted for age and swab type and accounting for clustering of swabs within households. RESULTS: We collected 346 swabs from 239 individuals in 151 households that tested positive for S. pneumoniae (n = 157 with and 189 without ≥1 viruses co-detected). Difficulty breathing, cough, and runny nose were more commonly reported among individuals with specimens with viral co-detection compared to without (15%, 80% and 93% vs. 8%, 57%, and 51%, respectively) and ear pain and headache were less commonly reported (3% and 26% vs. 16% and 41%, respectively). For specific viruses among all ages, semiquantitative S. pneumoniae nasal carriage density was greater with viral co-detection for enterovirus, RSV A/B, adenovirus, rhinovirus, and common human coronavirus (P < 0.01 for each). When stratified by age, semiquantitative S. pneumoniae nasal carriage density was significantly greater with viral co-detection among children aged <5 (P = 0.002) and 5-17 years (P = 0.005), but not among adults aged 18-64 years (P = 0.29). CONCLUSION: Detection of common respiratory viruses was associated with greater concurrent S. pneumoniae semiquantitative nasal carriage density in a household setting among children, but not adults. |
Previous health care experiences' influence on health care perceptions among residents of six homeless shelters in Seattle, Washington, July-October 2021
Meehan AA , Cox SN , Thuo NB , Rogers JH , Link AC , Martinez MA , Lo NK , Manns BJ , Rolfes MA , Chow EJ , Chu HY , Mosites E , Al Achkar M . J Patient Cent Res Rev 2023 10 (3) 111-120 PURPOSE: The study purpose was to learn and describe 1) where homeless shelter residents receive health care, 2) what contributes to positive or negative health care experiences among shelter residents, and 3) shelter resident perceptions toward health care. METHODS: Semi-structured interviews (SSIs) utilizing purposive sampling and focus group discussions (FGDs) utilizing convenience sampling were conducted at 6 homeless shelters in Seattle-King County, Washington, during July-October 2021. All residents (age ≥18) were eligible to participate. SSIs were conducted with 25 residents, and 8 FGDs were held. Thematic analysis was conducted using Dedoose. RESULTS: Participants received health care in settings ranging from no regular care to primary care providers. Four elements emerged as contributing positively and negatively to health care experiences: 1) ability to access health care financially, physically, and technologically; 2) clarity of communication from providers and staff about appointment logistics, diagnoses, and treatment options; 3) ease of securing timely follow-up services; and 4) respect versus stigma and discrimination from providers and staff. Participants who felt positively toward health care found low- or no-cost care to be widely available and encouraged others to seek care. However, some participants described health care in the United States as greedy, classist, discriminatory, and untrustworthy. Participants reported delaying care and self-medicating in anticipation of discrimination. CONCLUSIONS: Findings demonstrate that while people experiencing homelessness can have positive experiences with health care, many have faced negative interactions with health systems. Improving the patient experience for those experiencing homelessness can increase engagement and improve health outcomes. |
Risk of Adverse Maternal and Fetal Outcomes Associated with COVID-19 Variants of Concern: A Sequential Prospective Meta-Analysis (preprint)
Farooq F , Oakley E , Kerchner D , Hee Kim JY , Akelo V , Tippett Barr BA , Bevilacqua E , Bracero N , del Mar Gil M , Delgado-Lopez C , Favre G , Buhigas IF , Hillary Leung HY , Longo VL , Panchaud A , Poon LC , Martinez-Portilla RJ , Valencia-Prado M , Tielsch JM , Smith ER , Omore R , Ouma G , Onyango C , Otieno K , Were ZA , Were J , Maisonneuve E , Poncelet C , de Tejada BM , Quibel T , Monod C , Yu FNY , Kong CW , Lo TK , So PL , Leung WC , Meli F , Bonanni G , Romanzi F , Torcia E , di Ilio C , Aquise A , Rayo MN , Santacruz B , Gonzalez-Gea L , Laiseca S , Ferrer LN , Huertas MM , Rosario GM , Ramos NA , Gonzalez SV . medRxiv 2023 04 Introduction The main objective of this study is to conduct an individual patient data meta-analysis with collaborators from various countries to identify SARS-CoV-2 variants of concern associated with adverse maternal and neonatal outcomes. Methods Eligible studies included registries and single- or multi-site cohort studies that recruited pregnant and recently postpartum women with confirmed COVID-19. Studies must have enrolled at least 25 women within a defined catchment area. Studies also had to have data that overlapped more than a single COVID-19 variant time period. We invited principal investigators already participating in an ongoing sequential, prospective meta-analysis of perinatal COVID-19. Investigators shared individual patient data (IPD) with the technical team for review and analysis. We examined 31 outcomes related to: i) COVID-19 severity (n=5); ii) maternal morbidities including adverse birth outcomes (n=14); iii) fetal and neonatal morbidity and mortality (n=5) and iv) adverse birth outcomes (n=8). SARS-CoV-2 strains that have been identified as variants of concern (VOC) by the WHO were analyzed using the publicly available strain frequency data by Nextstrain.org and strains were classified as dominant when they were more than half of sequences in a given geographic area. We applied a 2-stage IPD meta-analytic framework to generate pooled relative risks, with 95% CI for each dominant variant and outcome pair when there were one or more studies with available data. Results Our data show that the Delta wave, compared to Omicron, was associated with a higher risk of all adverse COVID-19 severity outcomes in pregnancy including risk of hospitalization [RR 4.02 (95% CI 1.10, 14.69), n=1 study], risk of ICU admissions [RR 2.59 (95% CI 1.26, 5.30, n=3 studies], risk of critical care admission [RR 2.52 (95% CI 1.25, 5.08, n=3 studies], risk of needing ventilation [RR 3.96 (95% CI 1.47, 10.71), n=3 studies] and risk of pneumonia [RR 6.73 (95% CI 2.17, 20.90), n=3 studies]. The majority of maternal morbidity and mortality indicators were not at increased risk during any of the COVID-19 variant waves except hemorrhage, any Cesarean section, intrapartum Cesarean section and maternal composite outcome, although data was limited. Risk of fetal and neonatal morbidity and mortality did not show significant increases in risks during any of the COVID-19 waves except stillbirth and perinatal death during the Delta wave ([RR 4.84 (95% CI 1.37, 17.05, n=3 studies], [RR 6.03 (95%CI 1.63, 22.34), n=3 studies], respectively) when compared to the Pre-alpha wave. Adverse birth outcomes including very low birthweight and very preterm birth also showed increased risks during the Delta wave compared to the Pre-alpha wave. Discussion During periods of Delta strain predominance, all COVID-19 severity outcomes were more severe among pregnant women, compared to periods when other COVID-19 strains predominated. In addition, there are limited data comparing the impact of different variants on pregnancy outcomes. This highlights the importance of ongoing genomic surveillance among special populations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
CASCADIA: A prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults utilizing a remote nasal swab collection and web-based survey design (preprint)
Babu TM , Feldstein LR , Saydah S , Acker Z , Boisvert CL , Briggs-Hagen M , Carone M , Casto A , Cox SN , Ehmen B , Englund JA , Fortmann SP , Frivold CJ , Groom H , Han P , Kuntz JL , Lockwood T , Midgley CM , Mularski RA , Ogilvie T , Reich S , Schmidt MA , Smith N , Starita L , Stone J , Vandermeer M , Weil AA , Wolf CR , Chu HY , Naleway AL . medRxiv 2023 07 Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Method(s): CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. Ethics and dissemination: All study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage (preprint)
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . medRxiv 2020 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA. |
Respiratory syncytial virus and other respiratory virus infections in residents of homeless shelters - King County, Washington, 2019-2021
McCulloch DJ , Rogers JH , Wang Y , Chow EJ , Link AC , Wolf CR , Uyeki TM , Rolfes MA , Mosites E , Sereewit J , Duchin JS , Sugg NK , Greninger AL , Boeckh MJ , Englund JA , Shendure J , Hughes JP , Starita LM , Roychoudhury P , Chu HY . Influenza Other Respir Viruses 2023 17 (6) e13166 Respiratory syncytial virus (RSV) causes disproportionate morbidity and mortality in vulnerable populations. We tested residents of homeless shelters in Seattle, Washington for RSV in a repeated cross-sectional study as part of community surveillance for respiratory viruses. Of 15 364 specimens tested, 35 had RSV detected, compared to 77 with influenza. The most common symptoms for both RSV and influenza were cough and rhinorrhea. Many individuals with RSV (39%) and influenza (58%) reported that their illness significantly impacted their ability to perform their regular activities. RSV and influenza demonstrated similar clinical presentations and burden of illness in vulnerable populations living in congregate settings. |
Six months survival and risk factors for attrition for patients detected with cryptococcal antigenemia through screening in Malawi
Chisale MRO , Jordan A , Kamudumuli PS , Mvula B , Odo M , Maida A , Kandulu J , Chilima B , Sinyiza FW , Katundu P , Lee HY , Mtegha R , Wu TJ , Bitirinyo J , Nyirenda R , Kalua T , Greene G , Chiller T . PLoS One 2023 18 (5) e0284367 MAIN OBJECTIVE: A cohort of adult Malawian people living with HIV (PLHIV) testing positive for cryptococcal antigenemia was observed and followed to determine the outcomes and risk factors for attrition. METHODS CONCEPT: Eligible PLHIV were enrolled at 5 health facilities in Malawi, representing different levels of health care. ART naïve patients, ART defaulters returning to care, and patients with suspected or confirmed ART treatment failure with CD4 <200 cells/μL or clinical stage 3 or 4 were enrolled and received CrAg tests on whole blood specimens from August 2018 to August 2019. Hospitalized PLHIV were enrolled and tested for CrAg from January 2019 to August 2019, regardless of CD4 or clinical stage. Patients with cryptococcal antigenemia were managed per Malawian clinical guidelines and were followed up for six months. Survival and risk factors for attrition at six months were assessed. RESULTS: A total of 2146 patients were screened and 112 (5.2%) had cryptococcal antigenemia. Prevalence ranged from 3.8% (Mzuzu Central Hospital) to 25.8% (Jenda Rural Hospital). Of the 112 patients with antigenemia, 33 (29.5%) were diagnosed with concurrent CM at the time of enrollment. Six-month crude survival of all patients with antigenemia (regardless of CM status) ranged from 52.3% (assuming lost-to-follow-up (LTFU) patients died) to 64.9% (if LTFU survived). Patients who were diagnosed with concurrent CM by CSF test had poor survival (27.3-39.4%). Patients with antigenemia who were not diagnosed with concurrent CM had 71.4% (if LTFU died)- 89.8% (if LTFU survived) survival at six months. In adjusted analyses, patients with cryptococcal antigenemia detected after admission to inpatient care (aHR: 2.56, 1.07-6.15) and patients with concurrent CM at the time of positive antigenemia result (aHR: 2.48, 1.04-5.92) had significantly higher hazard of attrition at six months. CONCLUSIONS: Overall, our findings indicate a need for routine access to CrAg screening and pre-emptive fluconazole treatment as a way to detect cryptococcal antigenemia and prevent CM in outpatient and inpatient settings. Rapid access to diagnosis and treatment for cryptococcal meningitis (CM) with gold-standard antifungals is needed to improve survival of patients with advanced HIV in Malawi. |
Remdesivir for the Treatment of Covid-19 - Final Report
Beigel JH , Tomashek KM , Dodd LE , Mehta AK , Zingman BS , Kalil AC , Hohmann E , Chu HY , Luetkemeyer A , Kline S , Lopez de Castilla D , Finberg RW , Dierberg K , Tapson V , Hsieh L , Patterson TF , Paredes R , Sweeney DA , Short WR , Touloumi G , Lye DC , Ohmagari N , Oh MD , Ruiz-Palacios GM , Benfield T , Fätkenheuer G , Kortepeter MG , Atmar RL , Creech CB , Lundgren J , Babiker AG , Pett S , Neaton JD , Burgess TH , Bonnett T , Green M , Makowski M , Osinusi A , Nayak S , Lane HC , ACTT-1 Study Group Members , Uyeki Timothy . N Engl J Med 2020 383 (19) 1813-1826 BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.). |
Cryptic transmission of SARS-CoV-2 in Washington State.
Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Huang ML , Nalla A , Pepper G , Reinhardt A , Xie H , Shrestha L , Nguyen TN , Adler A , Brandstetter E , Cho S , Giroux D , Han PD , Fay K , Frazar CD , Ilcisin M , Lacombe K , Lee J , Kiavand A , Richardson M , Sibley TR , Truong M , Wolf CR , Nickerson DA , Rieder MJ , Englund JA , Hadfield J , Hodcroft EB , Huddleston J , Moncla LH , Müller NF , Neher RA , Deng X , Gu W , Federman S , Chiu C , Duchin J , Gautom R , Melly G , Hiatt B , Dykema P , Lindquist S , Queen K , Tao Y , Uehara A , Tong S , MacCannell D , Armstrong GL , Baird GS , Chu HY , Shendure J , Jerome KR . medRxiv 2020 Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding. |
Programmatic implications of national recent HIV infection surveillance in Cambodia
Suthar AB , Ouk V , Samreth S , Ngauv B , Bain R , Eng B , Hy C , Ernst A , Rutherford GW , Yang C , Ly V , Albalak R . J Infect Dis 2023 228 (10) 1347-1351 We compared characteristics of HIV diagnosis and recent HIV infection (i.e., likely acquired within the last year) in Cambodia. We included individuals ≥ 15 years old accessing HIV testing. From August/2020-August/2022, 53,031 people were tested for HIV, 6,868 were newly diagnosed, and 192 were recently infected. We found differences in geographical burden and risk behaviors with diagnosis and recency (e.g., men who have sex with men, transgender women, and entertainment workers had a nearly two-fold increased odds of testing recent compared to being diagnosed with HIV). Recent infection surveillance may provide unique insights into ongoing HIV acquisition to inform programs. |
Results from a test-and-treat study for influenza among residents of homeless shelters in King County, WA: A stepped-wedge cluster-randomized trial.
Rogers JH , Casto AM , Nwanne G , Link AC , Martinez MA , Nackviseth C , Wolf CR , Hughes JP , Englund JA , Sugg N , Uyeki TM , Han PD , Pfau B , Shendure J , Chu HY . Influenza Other Respir Viruses 2023 17 (1) e13092 BACKGROUND: Persons experiencing homelessness face increased risk of influenza as overcrowding in congregate shelters can facilitate influenza virus spread. Data regarding on-site influenza testing and antiviral treatment within homeless shelters remain limited. METHODS: We conducted a cluster-randomized stepped-wedge trial of point-of-care molecular influenza testing coupled with antiviral treatment with baloxavir or oseltamivir in residents of 14 homeless shelters in Seattle, WA, USA. Residents ≥3 months with cough or ≥2 acute respiratory illness (ARI) symptoms and onset <7 days were eligible. In control periods, mid-nasal swabs were tested for influenza by reverse transcription polymerase chain reaction (RT-PCR). The intervention period included on-site rapid molecular influenza testing and antiviral treatment for influenza-positives if symptom onset was <48 h. The primary endpoint was monthly influenza virus infections in the control versus intervention periods. Influenza whole genome sequencing was performed to assess transmission and antiviral resistance. RESULTS: During 11/15/2019-4/30/2020 and 11/2/2020-4/30/2021, 1283 ARI encounters from 668 participants were observed. Influenza virus was detected in 51 (4%) specimens using RT-PCR (A = 14; B = 37); 21 influenza virus infections were detected from 269 (8%) intervention-eligible encounters by rapid molecular testing and received antiviral treatment. Thirty-seven percent of ARI-participant encounters reported symptom onset < 48 h. The intervention had no effect on influenza virus transmission (adjusted relative risk 1.73, 95% confidence interval [CI] 0.50-6.00). Of 23 influenza genomes, 86% of A(H1N1)pdm09 and 81% of B/Victoria sequences were closely related. CONCLUSION: Our findings suggest feasibility of influenza test-and-treat strategies in shelters. Additional studies would help discern an intervention effect during periods of increased influenza activity. |
Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA.
Chow EJ , Casto AM , Sampoleo R , Mills MG , Han PD , Xie H , Pfau B , Nguyen TV , Sereewit J , Rogers JH , Cox SN , Rolfes MA , Ogokeh C , Mosites E , Uyeki TM , Greninger AL , Hughes JP , Shim MM , Sugg N , Duchin JS , Starita LM , Englund JA , Roychoudhury P , Chu HY . Emerg Infect Dis 2022 28 (11) 2343-2347 To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections. |
Trends and factors associated with change in COVID-19 vaccination intent among residents and staff in six Seattle homeless shelters, March 2020 to August 2021.
Cox SN , Rogers JH , Thuo NB , Meehan A , Link AC , Lo NK , Manns BJ , Chow EJ , Al Achkar M , Hughes JP , Rolfes MA , Mosites E , Chu HY . Vaccine X 2022 12 100232 INTRODUCTION: Achieving high COVID-19 vaccination coverage in homeless shelters is critical in preventing morbidity, mortality, and outbreaks, however, vaccination coverage remains lower among people experiencing homelessness (PEH) than the general population. METHODS: We conducted a cross-sectional study to retrospectively describe attitudes and identify factors associated with change in COVID-19 vaccination intent among shelter residents and staff during March 2020 - August 2021. To identify factors associated with change in COVID-19 vaccine intent becoming more positive overall compared to other attitudes, we utilized a Poisson model to calculate Risk Ratios with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori. RESULTS: From July 12 - August 2, 2021, 97 residents and 20 staff participated in surveys across six shelters in Seattle King County, Washington. Intent to be vaccinated against COVID-19 increased from 45.3% (n=53) when recalling attitudes in March 2020 to 74.4% (n=87) as of August 2021, and was similar among residents and staff. Many participants (43.6%, n=51) indicated feeling increasingly accepting about receiving a COVID-19 vaccine since March 2020, while 13.7% (n=16) changed back and forth, 10.3% (n=12) became more hesitant, and 32.5% (n=38) had no change in intent. In the model examining the relationship between becoming more positive about receiving a COVID-19 vaccine compared to all other attitudes (n=116), we found a 57.2% increase in vaccine acceptability (RR 1.57; 95% CI: 1.01, 2.45) among those who reported worsening mental health since the start of the pandemic. CONCLUSIONS: Findings highlight opportunities to improve communication with residents and staff about COVID-19 vaccination and support a need for continued dialogue and a person-centered approach to understanding the sociocultural complexities and dynamism of vaccine attitudes at shelters.Clinical Trial Registry Number: NCT04141917. |
The effects of the COVID-19 pandemic on community respiratory virus activity.
Chow EJ , Uyeki TM , Chu HY . Nat Rev Microbiol 2022 21 (3) 195-210 The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused substantial global morbidity and deaths, leading governments to turn to non-pharmaceutical interventions to slow down the spread of infection and lessen the burden on health care systems. These policies have evolved over the course of the COVID-19 pandemic, including after the availability of COVID-19 vaccines, with regional and country-level differences in their ongoing use. The COVID-19 pandemic has been associated with changes in respiratory virus infections worldwide, which have differed between virus types. Reductions in respiratory virus infections, including by influenza virus and respiratory syncytial virus, were most notable at the onset of the COVID-19 pandemic and continued in varying degrees through subsequent waves of SARS-CoV-2 infections. The decreases in community infection burden have resulted in reduced hospitalizations and deaths associated with non-SARS-CoV-2 respiratory infections. Respiratory virus evolution relies on the maintaining of a diverse genetic pool, but evidence of genetic bottlenecking brought on by case reduction during the COVID-19 pandemic has resulted in reduced genetic diversity of some respiratory viruses, including influenza virus. By describing the differences in these changes between viral species across different geographies over the course of the COVID-19 pandemic, we may better understand the complex factors involved in community co-circulation of respiratory viruses. |
SARS-CoV-2 Screening Testing in Schools: A Comparison of School- vs Home-Based Collection Methods.
Chung E , Magedson A , Emanuels A , Luiten K , Pfau B , Truong M , Chow EJ , Hughes JP , Uyeki TM , Englund JA , Nickerson DA , Lockwood CM , Shendure J , Starita LM , Chu HY . J Pediatric Infect Dis Soc 2022 11 (11) 522-524 We implemented a voluntary SARS-CoV-2 screening testing study for kindergarten-2nd grade students in a Washington School district. Weekly SARS-CoV-2 testing participation was higher for students with staff-collected nasal swabs at school than for students with parent-collected swabs at home. |
The clinical and genomic epidemiology of seasonal human coronaviruses in congregate homeless shelter settings: A repeated cross-sectional study.
Chow EJ , Casto AM , Rogers JH , Roychoudhury P , Han PD , Xie H , Mills MG , Nguyen TV , Pfau B , Cox SN , Wolf CR , Hughes JP , Uyeki TM , Rolfes MA , Mosites E , Shim MM , Duchin JS , Sugg N , Starita LA , Englund JA , Chu HY . Lancet Reg Health Am 2022 15 100348 BACKGROUND: The circulation of respiratory viruses poses a significant health risk among those residing in congregate settings. Data are limited on seasonal human coronavirus (HCoV) infections in homeless shelter settings. METHODS: We analysed data from a clinical trial and SARS-CoV-2 surveillance study at 23 homeless shelter sites in King County, Washington between October 2019-May 2021. Eligible participants were shelter residents aged 3 months with acute respiratory illness. We collected enrolment data and nasal samples for respiratory virus testing using multiplex RT-PCR platform including HCoV. Beginning April 1, 2020, eligibility expanded to shelter residents and staff regardless of symptoms. HCoV species was determined by RT-PCR with species-specific primers, OpenArray assay or genomic sequencing for samples with an OpenArray relative cycle threshold <22. FINDINGS: Of the 14,464 samples from 3281 participants between October 2019-May 2021, 107 were positive for HCoV from 90 participants (median age 40 years, range: 09-81 years, 38% female). HCoV-HKU1 was the most common species identified before and after community-wide mitigation. No HCoV-positive samples were identified between May 2020-December 2020. Adults aged 50 years had the highest detection of HCoV (11%) among virus-positive samples among all age-groups. Species and sequence data showed diversity between and within HCoV species over the study period. INTERPRETATION: HCoV infections occurred in all congregate homeless shelter site age-groups with the greatest proportion among those aged 50 years. Species and sequencing data highlight the complexity of HCoV epidemiology within and between shelters sites. FUNDING: Gates Ventures, Centers for Disease Control and Prevention, National Institute of Health. |
The Clinical and Genomic Epidemiology of Rhinovirus in Homeless Shelters-King County, Washington.
Chow EJ , Casto AM , Roychoudhury P , Han PD , Xie H , Pfau B , Nguyen TV , Sereewit J , Rogers JH , Cox SN , Wolf CR , Rolfes MA , Mosites E , Uyeki TM , Greninger AL , Hughes JP , Shim MM , Sugg N , Duchin JS , Starita LM , Englund JA , Chu HY . J Infect Dis 2022 226 S304-S314 BACKGROUND: Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. METHODS: We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019-May 2021. Shelter residents or guardians aged 3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After April 1, 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. RESULTS: There were 1,066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the COVID-19 pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for 4 months. CONCLUSIONS: RV infections persisted through community mitigation measures and was most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. |
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