Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 216 Records) |
Query Trace: Uyeki TM[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. |
Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP)
Fiore AE , Fry A , Shay D , Gubareva L , Bresee JS , Uyeki TM . MMWR Recomm Rep 2011 60 (1) 1-24 This report updates previous recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of antiviral agents for the prevention and treatment of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2008;57[No. RR-7]).This report contains information on treatment and chemoprophylaxis of influenza virus infection and provides a summary of the effectiveness and safety of antiviral treatment medications. Highlights include recommendations for use of 1) early antiviral treatment of suspected or confirmed influenza among persons with severe influenza (e.g., those who have severe, complicated, or progressive illness or who require hospitalization); 2) early antiviral treatment of suspected or confirmed influenza among persons at higher risk for influenza complications; and 3) either oseltamivir or zanamivir for persons with influenza caused by 2009 H1N1 virus, influenza A (H3N2) virus, or influenza B virus or when the influenza virus type or influenza A virus subtype is unknown; 4) antiviral medications among children aged <1 year; 5) local influenza testing and influenza surveillance data, when available, to help guide treatment decisions; and 6) consideration of antiviral treatment for outpatients with confirmed or suspected influenza who do not have known risk factors for severe illness, if treatment can be initiated within 48 hours of illness onset. Additional information is available from CDC's influenza website at http://www.cdc.gov/flu, including any updates or supplements to these recommendations that might be required during the 2010-11 influenza season. Health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information. Recommendations related to the use of vaccines for the prevention of influenza during the 2010-11 influenza season have been published previously (CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices [ACIP], 2010. MMWR 2010;59[No. RR-8]). |
Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010
Fiore AE , Uyeki TM , Broder K , Finelli L , Euler GL , Singleton JA , Iskander JK , Wortley PM , Shay DK , Bresee JS , Cox NJ . MMWR Recomm Rep 2010 59 1-62 This report updates the 2009 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8] and CDC. Use of influenza A (H1N1) 2009 monovalent vaccine---recommendations of the Advisory Committee on Immunization Practices [ACIP], 2009. MMWR 2009;58:[No. RR-10]). The 2010 influenza recommendations include new and updated information. Highlights of the 2010 recommendations include 1) a recommendation that annual vaccination be administered to all persons aged >or=6 months for the 2010-11 influenza season; 2) a recommendation that children aged 6 months--8 years whose vaccination status is unknown or who have never received seasonal influenza vaccine before (or who received seasonal vaccine for the first time in 2009-10 but received only 1 dose in their first year of vaccination) as well as children who did not receive at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine regardless of previous influenza vaccine history should receive 2 doses of a 2010-11 seasonal influenza vaccine (minimum interval: 4 weeks) during the 2010--11 season; 3) a recommendation that vaccines containing the 2010-11 trivalent vaccine virus strains A/California/7/2009 (H1N1)-like (the same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; 4) information about Fluzone High-Dose, a newly approved vaccine for persons aged >or=65 years; and 5) information about other standard-dose newly approved influenza vaccines and previously approved vaccines with expanded age indications. Vaccination efforts should begin as soon as the 2010-11 seasonal influenza vaccine is available and continue through the influenza season. These recommendations also include a summary of safety data for U.S.-licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2010-11 influenza season also will be available at this website. Recommendations for influenza diagnosis and antiviral use will be published before the start of the 2010-11 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information. |
Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009
Fiore AE , Shay DK , Broder K , Iskander JK , Uyeki TM , Mootrey G , Bresee JS , Cox NJ . MMWR Recomm Rep 2009 58 1-52 This report updates the 2008 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2008;57[No. RR-7]). Information on vaccination issues related to the recently identified novel influenza A H1N1 virus will be published later in 2009. The 2009 seasonal influenza recommendations include new and updated information. Highlights of the 2009 recommendations include 1) a recommendation that annual vaccination be administered to all children aged 6 months-18 years for the 2009-10 influenza season; 2) a recommendation that vaccines containing the 2009-10 trivalent vaccine virus strains A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; and 3) a notice that recommendations for influenza diagnosis and antiviral use will be published before the start of the 2009-10 influenza season. Vaccination efforts should begin as soon as vaccine is available and continue through the influenza season. Approximately 83% of the United States population is specifically recommended for annual vaccination against seasonal influenza; however, <40% of the U.S. population received the 2008-09 influenza vaccine. These recommendations also include a summary of safety data for U.S. licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2009-10 influenza season also can be found at this website. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information. |
Oseltamivir may or may not reduce hospitalizations
Uyeki TM , Hui DSC , Lee N . JAMA Intern Med 2023 184 (1) 116 Hanula et al1 reported findings of a systematic review and meta-analysis that included 15 randomized clinical trials (RCTs) of oseltamivir treatment for outpatients with influenza (age ≥12 years). The authors found no association between oseltamivir treatment of laboratory-confirmed influenza and risk of hospitalization among 6295 total participants or in subanalyses of older participants (mean age, ≥65 years; relative risk [RR], 0.99; 95% CI, 0.19-5.13) or participants with high-risk comorbidities (RR, 0.90; 95% CI, 0.37-2.17). | | These study findings did not definitively determine whether oseltamivir treatment of outpatients with influenza reduces their risk of progression to severe disease.1 The included RCTs studied mild end points (eg, time to alleviation of symptoms, duration of uncomplicated influenza illness). Moreover, none of the RCTs were designed nor sufficiently powered to assess the end point of hospitalization and most were conducted among patients without increased risk for severe influenza complications. |
Influenza antiviral shortages reported by state and territorial public health officials, 2022-2023
Kojima N , Peterson L , Hawkins R , Allen M , Flannery B , Uyeki TM . JAMA 2023 330 (18) 1793-1795 This study provides survey results from state and territorial public health preparedness directors regarding antiviral shortages during the 2022-2023 respiratory viral season. | eng |
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. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Tsay JJ , Wu BG , Yeung ST , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal SA , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman DH , Weiden M , Hegu A , Evans L , Uyeki TM , Clemente JC , De Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst CV , Koide S , Stapleford KA , Khanna KM , Ghedin E , Segal LN . medRxiv 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
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. |
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. |
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. |
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. |
Estimated Incubation Period and Serial Interval for Human-to-Human Influenza A(H7N9) Virus Transmission
Zhou L , Li Q , Uyeki TM . Emerg Infect Dis 2019 25 (10) 1982-1983 We estimated the incubation period and serial interval for human-to-human-transmitted avian influenza A(H7N9) virus infection using case-patient clusters from epidemics in China during 2013-2017. The median incubation period was 4 days and serial interval 9 days. China's 10-day monitoring period for close contacts of case-patients should detect most secondary infections. |
First Case of Covid-19 in the United States. Reply.
Uyeki TM , Holshue ML , Diaz G . N Engl J Med 2020 382 (21) e53 The authors reply: Weng et al. question the clinical benefit of remdesivir treatment. In our article, we noted that the decision to administer remdesivir for compassionate use was based on the patient’s worsening clinical status. No inferences are possible from the uncontrolled treatment of one patient, and we stated, “randomized, controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.” | | Tsung notes that an increase in lymphocyte counts and subsequent clinical improvement are consistent with activation of the adaptive immune response and resolution of SARS-CoV-2 infection. IgM and IgA antibodies may be detectable early in the clinical course, and IgG antibodies can be detected a median of 14 days after the onset of illness.1 We agree that the adaptive immune response contributes to clinical recovery and clearance of SARS-CoV-2, although one study showed that seroconversion was not correlated with a rapid decline in the SARS-CoV-2 load.2 In another study that showed a good correlation between IgG and neutralizing antibody titers, an increase in IgG antibody levels was correlated with a decrease in the viral load between 1 and 3 weeks after the onset of illness, but SARS-CoV-2 RNA was still detectable for prolonged periods.3 | | Zhang inquires about detection of SARS-CoV-2 in stool and urine specimens after remdesivir treatment. In our patient, although a stool specimen collected on day 7 of illness was positive with high cycle threshold values (36 to 38) that were consistent with detection of viral RNA and probably not infectious virus, a stool specimen obtained from the patient on day 14 of illness was negative. SARS-CoV-2 RNA was not detected in urine specimens; these findings are consistent with those in a larger study.4 | | Wen et al. and Link and Hold raise the issue of fecal–oral transmission of SARS-CoV-2. Diarrhea has been reported to occur in patients with Covid-19, and it can precede the development of respiratory symptoms and progression to pneumonia. SARS-CoV-2 RNA has been detected in stool specimens, and recovery of live infectious virus from stool has been reported.4 Further studies are needed to understand the implications of SARS-CoV-2 detected in stool for transmission of the virus. | | Ren et al. argue that high-resolution low-dose chest CT should be performed instead of chest radiography in persons with fever and suspected Covid-19. The Centers for Disease Control and Prevention recommends collection of nasopharyngeal swab specimens and lower respiratory specimens, if available, for SARS-CoV-2 testing and prioritizes testing of hospitalized patients and symptomatic health care workers. Furthermore, the American College of Radiology has noted concerns regarding prevention and control of SARS-CoV-2 transmission in health care facilities, including transmission that may occur with the use of CT scanners, and has recommended that CT should not be used to screen for or diagnose Covid-19.5 |
Influenza.
Uyeki TM , Hui DS , Zambon M , Wentworth DE , Monto AS . Lancet 2022 400 (10353) 693-706 Annual seasonal influenza epidemics of variable severity caused by influenza A and B virus infections result in substantial disease burden worldwide. Seasonal influenza virus circulation declined markedly in 2020-21 after SARS-CoV-2 emerged but increased in 2021-22. Most people with influenza have abrupt onset of respiratory symptoms and myalgia with or without fever and recover within 1 week, but some can experience severe or fatal complications. Prevention is primarily by annual influenza vaccination, with efforts underway to develop new vaccines with improved effectiveness. Sporadic zoonotic infections with novel influenza A viruses of avian or swine origin continue to pose pandemic threats. In this Seminar, we discuss updates of key influenza issues for clinicians, in particular epidemiology, virology, and pathogenesis, diagnostic testing including multiplex assays that detect influenza viruses and SARS-CoV-2, complications, antiviral treatment, influenza vaccines, infection prevention, and non-pharmaceutical interventions, and highlight gaps in clinical management and priorities for clinical research. |
Use of severe acute respiratory syndrome coronavirus 2 antibody tests by US infectious disease physicians: Results of an emerging infections network survey, March 2022
Gundlapalli AV , Beekmann SE , Jones JM , Thornburg NJ , Clarke KEN , Uyeki TM , Satheshkumar PS , Carroll DS , Plumb ID , Briggs-Hagen M , Santibañez S , David-Ferdon C , Polgreen PM , McDonald LC . Open Forum Infect Dis 2023 10 (3) ofad091 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. METHODS: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. RESULTS: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. CONCLUSIONS: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance. |
Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.
Anesi GL , Andrews A , Bai HJ , Bhatraju PK , Brett-Major DM , Broadhurst MJ , Campbell ES , Cobb JP , Gonzalez M , Homami S , Hypes CD , Irwin A , Kratochvil CJ , Krolikowski K , Kumar VK , Landsittel DP , Lee RA , Liebler JM , Lutrick K , Marts LT , Mosier JM , Mukherjee V , Postelnicu R , Rodina V , Segal LN , Sevransky JE , Spainhour C , Srivastava A , Uyeki TM , Wurfel MM , Wyles D , Evans L . Crit Care Med 2023 51 (4) 445-459 OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% (sd, 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked. |
Leveraging International Influenza Surveillance Systems and programs during the COVID-19 pandemic
Marcenac P , McCarron M , Davis W , Igboh LS , Mott JA , Lafond KE , Zhou W , Sorrells M , Charles MD , Gould P , Arriola CS , Veguilla V , Guthrie E , Dugan VG , Kondor R , Gogstad E , Uyeki TM , Olsen SJ , Emukule GO , Saha S , Greene C , Bresee JS , Barnes J , Wentworth DE , Fry AM , Jernigan DB , Azziz-Baumgartner E . Emerg Infect Dis 2022 28 (13) S26-s33 A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential. |
Probable vertical transmission of Alpha variant of concern (B.1.1.7) with evidence of SARS-CoV-2 infection in the syncytiotrophoblast, a case report.
Bullock HA , Fuchs E , Martines RB , Lush M , Bollweg B , Rutan A , Nelson A , Brisso M , Owusu-Ansah A , Sitzman C , Ketterl L , Timmons T , Lopez P , Mitchell E , McCutchen E , Figliomeni J , Iwen P , Uyeki TM , Reagan-Steiner S , Donahue M . Front Med (Lausanne) 2022 9 1099408 INTRODUCTION: Definitive vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been rarely reported. We present a case of a third trimester pregnancy with fetal distress necessitating cesarean section that demonstrated maternal, placental, and infant infection with the SARS-CoV-2 Alpha variant/B.1.1.7. METHODS: CDC's Influenza SARS-CoV-2 Multiplex RT-PCR Assay was used to test for SARS-CoV-2 in a maternal NP swab, maternal plasma, infant NP swab, and formalin-fixed paraffin-embedded (FFPE) placental tissue specimens. Whole genome sequencing (WGS) was performed on maternal plasma, infant, and placental specimens to determine the SARS-CoV-2 genotype. Histopathological evaluation, SARS-CoV-2 immunohistochemistry testing (IHC), and electron microscopy (EM) analysis were performed on placenta, umbilical cord, and membrane FFPE blocks. RESULTS: All specimens tested positive for SARS-CoV-2 by RT-PCR. WGS further revealed identical SARS-CoV-2 sequences from clade 20I/501Y.V1 (lineage Alpha/B.1.1.7) in maternal plasma, infant, and placental specimens. Histopathologic evaluation of the placenta showed histiocytic and neutrophilic intervillositis with fibrin deposition and trophoblast necrosis with positive SARS-CoV-2 immunostaining in the syncytiotrophoblast and electron microscopy evidence of coronavirus. DISCUSSION: These findings suggest vertical transmission of SARS-CoV-2, supported by clinical course timing, identical SARS-CoV-2 genotypes from maternal, placental, and infant samples, and IHC and EM evidence of placental infection. However, determination of the timing or distinction between prepartum and peripartum SARS-CoV-2 transmission remains unclear. |
Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.
Bhatraju PK , Morrell ED , Stanaway IB , Sathe NA , Srivastava A , Postelnicu R , Green R , Andrews A , Gonzalez M , Kratochvil CJ , Kumar VK , Hsiang TY , Gale M Jr , Anesi GL , Wyles D , Broadhurst MJ , Brett-Major D , Mukherjee V , Sevransky JE , Landsittel D , Hung C , Altemeier WA , Gharib SA , Uyeki TM , Cobb JP , Liebler JM , Crosslin DR , Jarvik GP , Segal LN , Evans L , Mikacenic C , Wurfel MM . Crit Care Explor 2023 5 (1) e0827 Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log(2) increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10(-5)). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients. |
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. |
Influenza-associated neurologic disease in children: Greater efforts are needed to prevent and reduce these severe complications (invited commentary)
Uyeki TM . J Pediatric Infect Dis Soc 2022 11 (12) 541-542 Influenza virus infection of the upper respiratory tract causes acute respiratory illness in most symptomatic children but can precipitate a wide range of moderate-to-severe complications. Neurologic complications such as acute encephalopathy and encephalitis in children with influenza have been recognized in Japan since the 1980s [1–3] and have also been reported worldwide. Both influenza A and B virus infections are associated with encephalopathy and encephalitis [4]. Other acute neurologic complications associated with influenza include exacerbation of chronic neurologic conditions, transient altered mental status, febrile seizures, status epilepticus, Reye syndrome (with or without salicylate exposure), cerebrovascular accident, and while less frequent, delayed onset of some complications have been reported such as post-infectious encephalopathy, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and transverse myelitis. |
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. |
Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections.
Postelnicu R , Srivastava A , Bhatraju PK , Wurfelc MM , Anesi GL , Gonzalez M , Andrews A , Lutrick K , Kumar VK , Uyeki TM , Cobb PJ , Segal LN , Brett-Major D , Liebler JM , Kratochvil CJ , Mukherjee V , Broadhurst MJ , Lee R , Wyles D , Sevransky JE , Evans L , Landsittel D . Crit Care Explor 2022 4 (10) e0773 Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI. |
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. |
Low quality antibody responses in critically ill patients hospitalized with pandemic influenza A(H1N1)pdm09 virus infection
Lu X , Guo Z , Li ZN , Holiday C , Liu F , Jefferson S , Gross FL , Tzeng WP , Kumar A , York IA , Uyeki TM , Tumpey T , Stevens J , Levine MZ . Sci Rep 2022 12 (1) 14971 Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17-65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009-2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract. |
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