Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 290 Records) |
Query Trace: Reed C[original query] |
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Responding to the return of influenza in the United States by applying Centers for Disease Control and Prevention surveillance, analysis, and modeling to inform understanding of seasonal influenza
Borchering RK , Biggerstaff M , Brammer L , Budd A , Garg S , Fry AM , Iuliano AD , Reed C . JMIR Public Health Surveill 2024 10 e54340 We reviewed the tools that have been developed to characterize and communicate seasonal influenza activity in the United States. Here we focus on systematic surveillance and applied analytics, including seasonal burden and disease severity estimation, short-term forecasting, and longer-term modeling efforts. For each set of activities, we describe the challenges and opportunities that have arisen because of the COVID-19 pandemic. In conclusion, we highlight how collaboration and communication have been and will continue to be key components of reliable and actionable influenza monitoring, forecasting, and modeling activities. |
Implementing a needs assessment to advance health equity in overdose prevention and surveillance initiatives
Winston TR , Reed M , Roberts M , Panjwani A , Farfalla J , Pless V , Miles A , Rooks-Peck C , Underwood NL . Public Health Rep 2024 333549241239905 OBJECTIVES: State, local, and federal agencies have expanded efforts to address the root causes of overdoses, including health inequity and related social determinants of health. As an Overdose Data to Action (OD2A) technical assistance provider, the Association of State and Territorial Health Officials (ASTHO) conducted the first national needs assessment to understand capacity and technical assistance needs of OD2A jurisdictions in advancing health equity. METHODS: ASTHO designed and disseminated the OD2A Recipient Health Equity Needs Assessment (RHENA) to 66 OD2A-funded jurisdictions from February to March 2022. OD2A principal investigators and staff were contacted via email and asked to complete the needs assessment within 6 weeks. One coder manually coded open-ended responses, conducted a thematic analysis on the qualitative data, and performed a simple frequency analysis on the quantitative data. RESULTS: Fifty-two jurisdictions (78.8%) responded, including 36 states, 12 cities/counties, and 2 territories. Most jurisdictions (n = 46; 88.5%) reported having a formal or informal health equity lead in place. Common barriers included a lack of access to data sources (n = 37; 71.2%), lack of partnerships (n = 20; 38.5%), and lack of funding (n = 14; 26.9%). Respondents reported needing more information sharing among jurisdictions and partner organizations, coaching on best practices, and routine discussions such as peer-to-peer learning sessions. CONCLUSION: Findings suggest that gaps remain in programmatic policies and principles to address inequities in overdose prevention. Results are being used to identify additional technical assistance opportunities, jurisdictional capacity, and approaches to advance health equity. |
Interim estimates of 2023-24 seasonal influenza vaccine effectiveness - United States
Frutos AM , Price AM , Harker E , Reeves EL , Ahmad HM , Murugan V , Martin ET , House S , Saade EA , Zimmerman RK , Gaglani M , Wernli KJ , Walter EB , Michaels MG , Staat MA , Weinberg GA , Selvarangan R , Boom JA , Klein EJ , Halasa NB , Ginde AA , Gibbs KW , Zhu Y , Self WH , Tartof SY , Klein NP , Dascomb K , DeSilva MB , Weber ZA , Yang DH , Ball SW , Surie D , DeCuir J , Dawood FS , Moline HL , Toepfer AP , Clopper BR , Link-Gelles R , Payne AB , Chung JR , Flannery B , Lewis NM , Olson SM , Adams K , Tenforde MW , Garg S , Grohskopf LA , Reed C , Ellington S . MMWR Morb Mortal Wkly Rep 2024 73 (8) 168-174 In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally. |
Age-disparate and intergenerational sex partnerships and HIV: the role of gender norms among adolescent girls and young women in Malawi
Reed DM . BMC Public Health 2024 24 (1) 575 BACKGROUND: Age-mixing (age-disparate [5-9 years difference] and intergenerational [≥ 10 years difference]) partnerships are hypothesized drivers of HIV in adolescent girls and young women (AGYW; 15-24 years). These partnerships are often associated with increased gender inequities which undermine women's agency and assertiveness. We assessed whether age-mixing partnerships were associated with HIV in Malawi and if endorsement of inequitable gender norms modifies this relationship. METHODS: We analyzed data from the Malawi Population-based HIV Impact Assessment, a nationally representative household survey conducted in 2015-2016. Participants underwent HIV testing and completed questionnaires related to actively endorsed gender norms and sexual risk behavior. We used multivariate logistic regression and multiplicative interaction to assess associations among AGYW who reported the age of their primary sex partner from the last year. RESULTS: The analysis included 1,958 AGYW (mean age = 19.9 years, SD = 0.1), 459 (23.4%) and 131 (6.7%) of whom reported age-disparate and intergenerational partnerships, respectively. AGYW in age-mixing partnerships accounted for 13% of all AGYW and were older, more likely to reside in urban areas, to be married or cohabitating with a partner, and to have engaged in riskier sexual behavior compared with AGYW in age-concordant partnerships (p < 0.05). HIV prevalence among AGYW in age-disparate and intergenerational partnerships was 6.1% and 11.9%, respectively, compared with 3.2% in age-concordant partnerships (p < 0.001). After adjusting for residence, age, education, employment, wealth quintile, and ever been married or cohabitated as married, AGYW in age-disparate and intergenerational partnerships had 1.9 (95% CI: 1.1-3.5) and 3.4 (95% CI: 1.6-7.2) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. Among the 614 (31% of the study group) who endorsed inequitable gender norms, AGYW in age-disparate and intergenerational partnerships had 3.5 (95% CI: 1.1-11.8) and 6.4 (95% CI: 1.5-27.8) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. CONCLUSIONS: In this Malawi general population survey, age-mixing partnerships were associated with increased odds of HIV among AGYW. These findings highlight inequitable gender norms as a potential focus for HIV prevention and could inform interventions targeting structural, cultural, and social constraints of this key group. |
Marburgvirus resurgence in Kitaka Mine bat population after extermination attempts, Uganda.
Amman BR , Nyakarahuka L , McElroy AK , Dodd KA , Sealy TK , Schuh AJ , Shoemaker TR , Balinandi S , Atimnedi P , Kaboyo W , Nichol ST , Towner JS . Emerg Infect Dis 2014 20 (10) 1761-4 Marburg virus (MARV) and Ravn virus (RAVV), collectively called marburgviruses, cause Marburg hemorrhagic fever (MHF) in humans. In July 2007, 4 cases of MHF (1 fatal) occurred in miners at Kitaka Mine in southern Uganda. Later, MHF occurred in 2 tourists who visited Python Cave, ≈50 km from Kitaka Mine. One of the tourists was from the United States (December 2007) and 1 was from the Netherlands (July 2008); 1 case was fatal (1,2,3). The cave and the mine each contained 40,000–100,000 Rousettus aegyptiacus bats (Egyptian fruit bats). | | Longitudinal investigations of the outbreaks at both locations were initiated by the Viral Special Pathogens Branch of the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA, and Entebbe, Uganda) in collaboration with the Uganda Wildlife Authority (UWA) and the Uganda Virus Research Institute (UVRI). During these studies, genetically diverse MARVs and RAVVs were isolated directly from bat tissues, and infection levels of the 2 viruses were found to increase in juvenile bats on a predictable bi-annual basis (4,5). However, investigations at Kitaka Mine were stopped when the miners exterminated the bat colony by restricting egress from the cave with papyrus reed barriers and then entangling the bats in fishing nets draped over the exits. The trapping continued for weeks, and the entrances were then sealed with sticks and plastic. These depopulation efforts were documented by researchers from UVRI, the CDC, the National Institute of Communicable Diseases (Sandringham, South Africa), and UWA during site visits to Kitaka Mine (Technical Appendix Figure). In August 2008, thousands of dead bats were found piled in the forest, and by November 2008, there was no evidence of bats living in the mine; whether 100% extermination was achieved is unknown. CDC, UVRI, and UWA recommended against extermination, believing that any results would be temporary and that such efforts could exacerbate the problem if bat exclusion methods were not complete and permanent (6,7). |
CIC2022: An informatics-driven strategy for improving immunization healthcare data quality using 2D barcoding and barcode scanning practices
Reza F , Jones C , Reed JH . Appl Clin Inform 2024 Manual data entry is time-consuming, inefficient, and error prone. In contrast, leveraging two-dimensional (2D) barcodes and barcode scanning tools is a rapid, efficient, and effective practice for automatically entering data accurately and completely during vaccine inventorying and administration. CDC pilots in a variety of healthcare settings documented the clinical and public health impact of 2D barcode scanning practices on data quality and completeness, time savings, workflow efficiencies, and staff experience. A sample of 50 million emergency use authorization (EUA) COVID-19 vaccine records were analyzed for accuracy and completeness across three data fields: lot number, expiration date, and National Drug Code (NDC). These vaccines did not include a 2D barcode containing these data fields, thus necessitating manual entry of vaccine data at administration. During a CDC pilot with clinic sites, comparison was made between automatically scanned and manually entered data for routine vaccines for accuracy and completeness across these data fields. Analysis of 50 million manually entered EUA vaccine administration records indicated significant gaps in data accuracy and completeness across three data fields observed. Over half of the 50 million EUA vaccine NDCs (53%) and one-third of the expiration dates (35%) analyzed had missing or inaccurate data recorded. Pilot data also showed many errors when manually entered. However, when 67,951 (out of 72,979) vaccines were scanned during the pilot, nearly all entries were complete and accurate across all three data fields (ranging from 99.7% to 99.999% accurate). Vaccine 2D barcode scanning practices increased data accuracy and completeness (up to 99.999% accurate) across data fields assessed. When used consistently, vaccine 2D barcode scanning can resolve the issues demonstrated in manually entered data. To realize these benefits, the immunization community should widely adopt scanning practices. To increase use, CDC has developed a Vaccine 2D Barcode National Adoption Strategy and resources to guide implementation. |
Respirable coal mine dust in the vicinity of a roof bolter: an inter-laboratory study to compare wet versus dry dust collection systems
Animah F , Greth A , Afrouz S , Keles C , Akinseye T , Pan L , Reed WR , Sarver E . Min Metall Explor null [Epub ahead of print] Among underground coal miners, roof bolter operators are generally considered to have some of the highest risks for hazardous respirable dust exposure. This is because bolting requires drilling into roof strata that can often be a source of silica and silicate dust, which are associated with occupational lung diseases. However, little is known about the variability of dust characteristics (e.g., mineralogy constituents, particle size) in the vicinity of the bolter-or when specific dust controls are applied. As part of a prior NIOSH study, respirable dust samples were collected during several different events in standardized locations around an active roof bolter, and personal samples were also collected from the operator during the cleanout of the bolter's dust collection system when it was equipped with a novel wet dust box versus a traditional dry box. Those samples were made available for follow-up analysis by scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), as well as direct-on-filter Fourier transform infrared spectroscopy (FTIR). Results showed variability in dust constituents and particle sizes at locations around the roof bolter, and indicated some event-to-event differences in dust sources. Additionally, compared to the dry dust box, the wet dust box appeared to reduce (by 41-82%) the relative silica and silicate content in the respirable dust to which the operator was exposed during cleanout. Furthermore, an inter-laboratory comparison demonstrated the reproducibility of a standardized direct-on-filter FTIR method for estimating quartz mass (i.e., the predominant form of crystalline silica) in respirable coal mine dust samples. However, for constituent analysis by SEM-EDX, differences observed between results from two independent labs indicate that standardization of the analytical protocol is necessary to enable comparability of results. |
Sex differences in COVID-19 symptom severity and trajectories among ambulatory adults
Massion SP , Howa AC , Zhu Y , Kim A , Halasa N , Chappell J , McGonigle T , Mellis AM , Deyoe JE , Reed C , Rolfes MA , Talbot HK , Grijalva CG . Influenza Other Respir Viruses 2023 17 (12) e13235 BACKGROUND: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood. METHODS: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model. RESULTS: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males (p < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed. CONCLUSIONS: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males. |
The role of asymptomatic infections in influenza transmission: what do we really know
Montgomery MP , Morris SE , Rolfes MA , Kittikraisak W , Samuels AM , Biggerstaff M , Davis WW , Reed C , Olsen SJ . Lancet Infect Dis 2023 Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps. |
Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018
Doyle JD , Garg S , O'Halloran AC , Grant L , Anderson EJ , Openo KP , Alden NB , Herlihy R , Meek J , Yousey-Hindes K , Monroe ML , Kim S , Lynfield R , McMahon M , Muse A , Spina N , Irizarry L , Torres S , Bennett NM , Gaitan MA , Hill M , Cummings CN , Reed C , Schaffner W , Talbot HK , Self WH , Williams D . Influenza Other Respir Viruses 2023 17 (12) e13228 BACKGROUND: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. METHODS: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. RESULTS: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. CONCLUSIONS: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making. |
Barriers and facilitators to HIV service access among Hispanic/Latino gay, bisexual, and other men who have sex with men in metropolitan Atlanta-a qualitative analysis
Hassan R , Saldana CS , Garlow EW , Gutierrez M , Hershow RB , Elimam D , Adame JF , Andía JF , Padilla M , Gonzalez Jimenez N , Freeman D , Johnson EN , Reed K , Holland DP , Orozco H , Pedraza G , Hayes C , Philpott DC , Curran KG , Wortley P , Agnew-Brune C , Gettings JR . J Urban Health 2023 100 (6) 1193-1201 Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population. |
Communicating the value of influenza vaccines to patients: Translating vaccine effectiveness to acceptance
Tenforde MW , Dawood FS , Ellington SR , Grohskopf LA , Flannery B , Garg S , Reed C . Ann Intern Med 2023 176 (12) 1670-1671 Influenza vaccines have been routinely recommended in the United States for some groups since 1960 and for everyone 6 months of age or older for more than a decade. Yet, annual influenza vaccination coverage has rarely exceeded 50% in children and younger adults or 70% in adults aged 65 years or older (1). Long-standing barriers to influenza vaccine uptake include beliefs that influenza illness is mild or inconsequential and vaccines are not effective, concerns about safety and adverse effects, and distrust of the medical system and disparities in access to vaccines (1, 2). | | During the COVID-19 pandemic, influenza vaccination coverage rates remained low overall and declined in some groups (1, 3). Although the first year of the COVID-19 pandemic temporarily interrupted circulation of seasonal respiratory viruses, the United States experienced high levels of influenza virus, SARS-CoV-2, and respiratory syncytial virus co-circulation during the 2022 to 2023 influenza season, putting a strain on health care resources. As the 2023 to 2024 season begins, internal medicine physicians and other health care professionals play an important role in communicating the benefits of vaccinations against influenza and other respiratory viruses. A health care professional’s recommendation and offer of or referral for vaccination have been shown over many seasons to be one of the strongest factors associated with willingness to get vaccinated (2). |
In situ hybridization (RNAscope) detection of bluetongue virus serotypes 10 and 17 in experimentally co-infected culicoides sonorensis
Carpenter M , Benavides Obon A , Kopanke J , Lee J , Reed K , Sherman T , Rodgers C , Stenglein M , McDermott E , Mayo C . Pathogens 2023 12 (10) Bluetongue virus (BTV) is a segmented, double-stranded RNA virus transmitted by Culicoides biting midges. Infection of domestic and wild ruminants with BTV can result in a devastating disease and significant economic losses. As a virus with a segmented genome, reassortment among the BTV serotypes that have co-infected a host may increase genetic diversity, which can alter BTV transmission dynamics and generate epizootic events. The objective of this study was to determine the extent of dissemination and characterize the tropism of BTV serotypes 10 and 17 in co-infected Culicoides sonorensis. Midges were exposed to both BTV serotypes via blood meal and processed for histologic slides 10 days after infection. An in situ hybridization approach was employed using the RNAscope platform to detect the nucleic acid segment 2 of both serotypes. Observations of the mosaic patterns in which serotypes did not often overlap suggest that co-infection at the cellular level may not be abundant with these two serotypes in C. sonorensis. This could be a consequence of superinfection exclusion. Understanding BTV co-infection and its biological consequences will add an important dimension to the modeling of viral evolution and emergence. |
High influenza incidence and disease severity among children and adolescents aged <18 years - United States, 2022-23 season
White EB , O'Halloran A , Sundaresan D , Gilmer M , Threlkel R , Colón A , Tastad K , Chai SJ , Alden NB , Yousey-Hindes K , Openo KP , Ryan PA , Kim S , Lynfield R , Spina N , Tesini BL , Martinez M , Schmidt Z , Sutton M , Talbot HK , Hill M , Biggerstaff M , Budd A , Garg S , Reed C , Iuliano AD , Bozio CH . MMWR Morb Mortal Wkly Rep 2023 72 (41) 1108-1114 During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October. |
Database derived from an electronic medical record-based surveillance network of US emergency department patients with acute respiratory illness
Kline JA , Reed B , Frost A , Alanis N , Barshay M , Melzer A , Galbraith JW , Budd A , Winn A , Pun E , Camargo CA Jr . BMC Med Inform Decis Mak 2023 23 (1) 224 BACKGROUND: For surveillance of episodic illness, the emergency department (ED) represents one of the largest interfaces for generalizable data about segments of the US public experiencing a need for unscheduled care. This protocol manuscript describes the development and operation of a national network linking symptom, clinical, laboratory and disposition data that provides a public database dedicated to the surveillance of acute respiratory infections (ARIs) in EDs. METHODS: The Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) network includes 26 academic investigators, from 24 sites, with 91 hospitals, and the Centers for Disease Control and Prevention (CDC) to survey viral infections. All data originate from electronic medical records (EMRs) accessed by structured query language (SQL) coding. Each Tuesday, data are imported into the standard data form for ARI visits that occurred the prior week (termed the index file); outcomes at 30 days and ED volume are also recorded. Up to 325 data fields can be populated for each case. Data are transferred from sites into an encrypted Google Cloud Platform, then programmatically checked for compliance, parsed, and aggregated into a central database housed on a second cloud platform prior to transfer to CDC. RESULTS: As of August, 2023, the network has reported data on over 870,000 ARI cases selected from approximately 5.2 million ED encounters. Post-contracting challenges to network execution have included local shifts in testing policies and platforms, delays in ICD-10 coding to detect ARI cases, and site-level personnel turnover. The network is addressing these challenges and is poised to begin streaming weekly data for dissemination. CONCLUSIONS: The RESP-LENS network provides a weekly updated database that is a public health resource to survey the epidemiology, viral causes, and outcomes of ED patients with acute respiratory infections. |
Severity of influenza-associated hospitalisations by influenza virus type and subtype in the USA, 2010-19: a repeated cross-sectional study
Sumner KM , Masalovich S , O'Halloran A , Holstein R , Reingold A , Kirley PD , Alden NB , Herlihy RK , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Monroe ML , Leegwater L , Henderson J , Lynfield R , McMahon M , McMullen C , Angeles KM , Spina NL , Engesser K , Bennett NM , Felsen CB , Lung K , Shiltz E , Thomas A , Talbot HK , Schaffner W , Swain A , George A , Rolfes MA , Reed C , Garg S . Lancet Microbe 2023 4 (11) e903-e912 BACKGROUND: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons. METHODS: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season. FINDINGS: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death. INTERPRETATION: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating. FUNDING: The US Centers for Disease Control and Prevention. |
Methods for Estimation of SARS-CoV-2 Seroprevalence and Reported COVID-19 Cases in U.S. Children, August 2020—May 2021 (preprint)
Couture A , Lyons BC , Mehrotra ML , Sosa L , Ezike N , Ahmed FS , Brown CM , Yendell S , Azzam IA , Katić BJ , Cope A , Dickerson K , Stone J , Traxler LB , Dunn JR , Davis LB , Reed C , Clarke KEN , Flannery B , Charles MD . medRxiv 2021 2021.09.26.21263756 Background and Objectives Case-based surveillance of pediatric COVID-19 cases underestimates the prevalence of SARS-CoV-2 infections among children and adolescents. Our objectives were to: 1) estimate monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years and 2) calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 14 U.S. states.Methods Using data from commercial laboratory seroprevalence surveys, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. Seroprevalence estimates were based on SARS-CoV-2 anti-nucleocapsid immunoassays from February to May 2021. We compared estimated numbers of children infected with SARS-CoV-2 by May 2021 to cumulative incidence of confirmed and probable COVID-19 cases from case-based surveillance, and calculated infection: case ratios by state and type of anti-SARS-CoV-2 nucleocapsid immunoassay used for seroprevalence testing.Results Analyses included 67,321 serum specimens tested for SARS-CoV-2 antibodies among children in 14 U.S. states. Estimated ratios of SARS-CoV-2 infections to reported confirmed and probable COVID-19 cases among children and adolescents varied by state and type of immunoassay, ranging from 0.8-13.3 in May 2021.Conclusions Through May 2021, the majority of children in selected states did not have detectable SARS-CoV-2 nucleocapsid antibodies. Case-based surveillance underestimated the number of children infected with SARS-CoV-2, however the predicted extent of the underestimate varied by state, immunoassay, and over time. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding for this work was supported by CDC (Atlanta, Georgia).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:This activity was reviewed by Centers for Disease Control and Prevention and determined to be consistent with non human participant research activity. Informed consent was waived, as data were deidentified. 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).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.YesDeidentified individual participant data will not be made available.CDCCenters of Disease Control and PreventionMIS-CMultisystem inflammatory syndrome in childrenEUAEmergency Use AuthorizationFDAU.S. Food and Drug AdministrationACIPAdvisory Committee on Immunizations PracticesNNucleocapsidSSpikeIgImmunoglobulinCIConfidence intervals |
Modeling effectiveness of testing strategies to prevent COVID-19 in nursing homes —United States, 2020 (preprint)
See I , Paul P , Slayton RB , Steele MK , Stuckey MJ , Duca L , Srinivasan A , Stone N , Jernigan JA , Reddy SC . medRxiv 2021 2020.12.18.20248255 Background SARS-CoV-2 outbreaks in nursing homes can be large with high case fatality. Identifying asymptomatic individuals early through serial testing is recommended to control COVID-19 in nursing homes, both in response to an outbreak (“outbreak testing” of residents and healthcare personnel) and in facilities without outbreaks (“non-outbreak testing” of healthcare personnel). The effectiveness of outbreak testing and isolation with or without non-outbreak testing was evaluated.Methods Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., “effectiveness”) through either outbreak testing alone or outbreak plus non-outbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated.Results Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak testing were mostly negated if accompanied by decreases in infection control practice.Conclusions When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.Summary Mathematical modeling evaluated the effectiveness of serially testing asymptomatic persons in a nursing home in response to a SARS-CoV-2 outbreak with or without serial testing of asymptomatic staff in the absence of known SARS-CoV-2 infections.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received. All work was conducted as part of government duties.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:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (see e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C 552a; 44 U.S.C. 351 et seq.).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).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.YesData provided in supplemental materials or publicly available through links in the manuscript. https://github.com/cdcepi/Nursing-home-SARS-CoV-2-testing-model/ |
Prevention and Attenuation of COVID-19 by BNT162b2 and mRNA-1273 Vaccines (preprint)
Thompson MG , Burgess JL , Naleway AL , Tyner H , Yoon SK , Meece J , Olsho LEW , Caban-Martinez AJ , Fowlkes AL , Lutrick K , Groom HC , Dunnigan K , Odean MJ , Hegmann K , Stefanski E , Edwards LJ , Schaefer-Solle N , Grant L , Ellingson K , Kuntz JL , Zunie T , Thiese MS , Ivacic L , Wesley MG , Mayo Lamberte J , Sun X , Smith ME , Phillips AL , Groover KD , Yoo YM , Gerald J , Brown RT , Herring MK , Joseph G , Beitel S , Morrill TC , Mak J , Rivers P , Poe BP , Lynch B , Zhou Y , Zhang J , Kelleher A , Li Y , Dickerson M , Hanson E , Guenther K , Tong S , Bateman A , Reisdorf E , Barnes J , Azziz-Baumgartner E , Hunt DR , Arvay ML , Kutty P , Fry AM , Gaglani M . medRxiv 2021 2021.06.01.21257987 BACKGROUND Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions.METHODS Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020—April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription–polymerase-chain-reaction (RT-PCR). VE was calculated as 100%×(1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation.RESULTS SARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post-dose-1 to 13 days after dose-2) or fully (≥14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%–97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants.CONCLUSIONS Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.Competing Interest StatementAllison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work. Kurt T. Hegmann serves at the Editor of the American College of Occupational and Environmental Medicine evidence-based practice guidelines. Matthew S. These reported grants and personal fees from Reed Group and the American College of Occupational and Environmental Medicine, outside the submitted work. Other authors have reported no conflicts of interest.Funding StatementFunding provided in whole or in part by federal funds from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention under contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Laboratory, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc.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:This study was reviewed and approved by the University of Arizona IRB as the single IRB for this studyAll 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.YesSummary data will be available once all study objectives are met. |
Estimating COVID-19 Hospitalizations in the United States with surveillance data using a Bayesian Hierarchical model (preprint)
Couture A , Iuliano D , Chang H , Patel N , Gilmer M , Steele M , Havers F , Whitaker M , Reed C . medRxiv 2021 2021.10.14.21264992 Introduction In the United States, COVID-19 is a nationally notifiable disease, cases and hospitalizations are reported to the CDC by states. Identifying and reporting every case from every facility in the United States may not be feasible in the long term. Creating sustainable methods for estimating burden of COVID-19 from established sentinel surveillance systems is becoming more important. We aimed to provide a method leveraging surveillance data to create a long-term solution to estimate monthly rates of hospitalizations for COVID-19.Methods We estimated monthly hospitalization rates for COVID-19 from May 2020 through April 2021 for the 50 states using surveillance data from COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) and a Bayesian hierarchical model for extrapolation. We created a model for six age groups (0-17, 18-49, 50-64, 65-74, 75-84, and ≥85 years), separately. We identified covariates from multiple data sources that varied by age, state, and/or month, and performed covariate selection for each age group based on two methods, Least Absolute Shrinkage and Selection Operator (LASSO) and Spike and Slab selection methods. We validated our method by checking sensitivity of model estimates to covariate selection and model extrapolation as well as comparing our results to external data.Results We estimated 3,569,500 (90% Credible Interval:3,238,000 – 3,934,700) hospitalizations for a cumulative incidence of 1,089.8 (988.6 – 1,201.3) hospitalizations per 100,000 population with COVID-19 in the United States from May 2020 through April 2021. Cumulative incidence varied from 352 – 1,821per 100,000 between states. The age group with the highest cumulative incidence was aged ≥85 years (5,583.1; 5,061.0 – 6,157.5). The monthly hospitalization rate was highest in December (183.8; 154.5 – 218.0). Our monthly estimates by state showed variations in magnitudes of peak rates, number of peaks and timing of peaks between states.Conclusions Our novel approach to estimate COVID-19 hospitalizations has potential to provide sustainable estimates for monitoring COVID-19 burden, as well as a flexible framework leveraging surveillance data.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding for this work was supported by CDC (Atlanta, Georgia). The authors received no financial support for the research, authorship, or publication of these data.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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.YesData will not be made available online.BRFSSBehavioral Risk Factor Surveillance SystemCDCCenters for Disease Control and PreventionCKDchronic kidney diseaseCOPDchronic obstructive pulmonary diseaseCOVID-19Coronavirus Disease 2019COVID-NETCoronavirus Disease 2019-Associated Hospitalization Surveillance NetworkCrICredible IntervalFluSurv-NETInfluenza Hospitalization Surveillance NetworkHHSDepartment of Health and Human ServicesICUintensive care unitLASSO east Absolute Shrinkage and Selection OperatorMCMCMarkov chain Monte CarloNCHSNational Center for Health StatisticsNNDSSNational Notifiable Disease Surveillance SystemNVSSNational Vital Statistics SystemSARS-CoV-2Severe Acute Respiratory Syndrome Coronavirus 2 |
Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020 (preprint)
Havers FP , Reed C , Lim T , Montgomery JM , Klena JD , Hall AJ , Fry AM , Cannon DL , Chiang CF , Gibbons A , Krapiunaya I , Morales-Betoulle M , Roguski K , Rasheed MAU , Freeman B , Lester S , Mills L , Carroll DS , Owen SM , Johnson JA , Semenova V , Schiffer J , Thornburg NJ , Blackmore C , Blog D , Dunn A , Lindquist S , Pritchard S , Sosa L , Turabelidze G , Wiesman J , Williams RW . medRxiv 2020 2020.06.25.20140384 Importance Reported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected.Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States.Design Serologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies.Setting Connecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington State’s (WA) Puget Sound region.Participants Persons of all ages with serum collected during intervals from March 23 through May 3, 2020.Exposure SARS-CoV-2 virus infection.Main outcomes and measures We estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date.Results We tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site.Conclusions and relevance Our seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures.Question What proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020?Findings We tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data.Meaning For most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by the Centers for Disease Control and Prevention.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:This protocol underwent review by CDC human subjects research officials, who determined that the testing represented non-research activity in the setting of a public health response to the COVID-19 pandemic.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 su h 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.YesA limited dataset will be made publicly available at a later time. |
A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex (preprint)
Muller-Schiffmann A , Michon M , Lingappa AF , Yu SF , Du L , Deiter F , Broce S , Mallesh S , Crabtree J , Lingappa UF , Macieik A , Muller L , Ostermann PN , Andree M , Adams O , Schaal H , Hogan RJ , Tripp RA , Appaiah U , Anand SK , Campi TW , Ford MJ , Reed JC , Lin J , Akintunde O , Copeland K , Nichols C , Petrouski E , Moreira AR , Jiang IT , DeYarman N , Brown I , Lau S , Segal I , Goldsmith D , Hong S , Asundi V , Briggs EM , Phyo NS , Froehlich M , Onisko B , Matlack K , Dey D , Lingappa JR , Prasad MD , Kitaygorodskyy A , Solas D , Boushey H , Greenland J , Pillai S , Lo MK , Montgomery JM , Spiropoulou CF , Korth C , Selvarajah S , Paulvannan K , Lingappa VR . bioRxiv 2021 18 We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Changes in Transmission and Symptoms of SARS-CoV-2 in United States Households, April 2020-September 2022 (preprint)
Mellis AM , Lauring AS , Talbot HK , McLean HQ , Morrissey KG , Stockwell MS , Bowman NM , Maldonado Y , Ellingson KD , Rao S , Biddle JE , Johnson S , Ogokeh C , Salvatore PP , Reed C , Smith-Jeffcoat SE , Meece JK , Hanson KE , Belongia EA , Bendall EE , Gilbert J , Olivo V , Merrill LS , McLaren SH , Sano E , Vargas CY , Saiman L , Silverio Francisco RA , Bullock A , Lin J , Govindarajan P , Goodman SH , Sarnquist CC , Lutrick K , Ledezma KI , Ramadan FA , Pryor K , Miiro FN , Asturias E , Dominguez S , Olson D , Izurieta HS , Chappell J , Lindsell C , Halasa N , Hart K , Zhu Y , Schmitz J , Rolfes MA , Grijalva CG . medRxiv 2023 19 Background: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Method(s): Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Finding(s): 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation(s): The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding(s): Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration. 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 distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C) (preprint)
Bodansky A , Sabatino JJ , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Asaki J , Pluvinage JV , Wilson MR , Loftis LL , Hobbs CV , Tarquinio KM , Kong M , Fitzgerald JC , Espinal PS , Walker TC , Schwartz SP , Crandall H , Irby K , Staat MA , Rowan CM , Schuster JE , Halasa NB , Gertz SJ , Mack EH , Maddux AB , Cvijanovich NZ , Zinter MS , Zambrano LD , Campbell AP , Randolph AG , Anderson MS , DeRisi JL , Kelley H , Murdock M , Colston C , Typpo KV , Sanders RC , Yates M , Smith C , Port E , Mansour R , Shankman S , Baig N , Zorensky F , Chatani B , McLaughlin G , Jones K , Coates BM , Newhams MM , Kucukak S , McNamara ER , Moon HK , Kobayashi T , Melo J , Jackson SR , Rosales MKE , Young C , Chen SR , Da Costa Aguiar R , Gutierrez-Arcelus M , Elkins M , Williams D , Williams L , Cheng L , Zhang Y , Crethers D , Morley D , Steltz S , Zakar K , Armant MA , Ciuculescu F , Flori HR , Dahmer MK , Levy ER , Behl S , Drapeau NM , Kietzman A , Hill S , Cullimore ML , McCulloh RJ , Nofziger RA , Rohlfs CC , Burnett R , Bush J , Reed N , Ampofo KK , Patel MM . medRxiv 2023 30 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. 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 4.0 International license. |
Design of different shapes of drill shroud to reduce dust deposit using computational fluid dynamics method
Zheng Y , Reed WR , Potts JD . CIM J 2023 11-20 Effective dust control using drill shroud air-blocking shelves was confirmed previously through laboratory tests, field studies, and computational fluid dynamics (CFD) simulations. However, when the drilling machine moves to different locations, deposits on these shelves can produce a large dust cloud. To minimize the dust exposure hazard, this study modified the drill shroud air-blocking shelves by using the concept of angle of repose to eliminate the deposits while at the same time, confining the dust inside the drill shroud. Two types of drill shroud inner shapes were evaluated using CFD models: U-shaped and V-shaped. In addition, a drill shroud with 45 blocking shelves was built to examine its dust control capacity. The angle of repose used to minimize dust problems during mast lowering was shown to be effective in reducing the dust problems during drilling. However, care must be taken to use a properly designed shroud because the V-shaped drill shroud can potentially exacerbate dust leakage. |
SARS-CoV-2 virus dynamics in recently infected people - data from a household transmission study (preprint)
Mellis AM , Meece JK , Halasa NB , Chappell JD , McLean HQ , Grijalva CG , Hanson KE , Zhu Y , Kim A , Deyoe J , Ivacic LC , Reed C , Talbot HK , Rolfes MA . medRxiv 2022 18 (10) 1699-1703 We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged >=50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms. 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. |
School-located influenza vaccination and community-wide indirect effects: Reconciling mathematical models to epidemiologic models (preprint)
Arinaminpathy N , Reed C , Biggerstaff M , Nguyen A , Athni TS , Arnold BF , Hubbard A , Colford JM , Reingold A , Benjamin-Chung J . medRxiv 2022 13 Background: Mathematical models and empirical epidemiologic studies (e.g., randomized and observational studies) are complementary tools but may produce conflicting results for a given research question. We used sensitivity analyses and bias analyses to explore such discrepancies in a study of the indirect effects of influenza vaccination. Method(s): We fit an age-structured, deterministic, compartmental model to estimate indirect effects of a school-based influenza vaccination program in California that was evaluated in a previous matched cohort study. To understand discrepancies in their results, we used 1) a model with constrained parameters such that projections matched the cohort study; and 2) probabilistic bias analyses to identify potential biases (e.g., outcome misclassification due to incomplete influenza testing) that, if corrected, would align the empirical results with the mathematical model. Result(s): The indirect effect estimate (% reduction in influenza hospitalization among older adults in intervention vs. control) was 22.3% (95% CI 7.6% - 37.1%) in the cohort study but only 1.6% (95% Bayesian credible intervals 0.4 - 4.4%) in the mathematical model. When constrained, mathematical models aligned with the cohort study when there was substantially lower pre-existing immunity among school-age children and older adults. Conversely, empirical estimates corrected for potential bias aligned with mathematical model estimates only if influenza testing rates were 15-23% lower in the intervention vs. comparison site. Conclusion(s): Sensitivity and bias analysis can shed light on why results of mathematical models and empirical epidemiologic studies differ for the same research question, and in turn, can improve study and model design. 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 4.0 International license. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities (preprint)
McLean HQ , Grijalva CG , Hanson KE , Zhu YG , Deyoe JE , Meece JK , Halasa NB , Chappell JD , Mellis A , Reed C , Belongia EA , Talbot HK , Rolfes MA . medRxiv 2021 OBJECTIVES: Examine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged ≥65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age. |
Multimodeling approach to evaluating the efficacy of layering pharmaceutical and nonpharmaceutical interventions for influenza pandemics
Prasad PV , Steele MK , Reed C , Meyers LA , Du Z , Pasco R , Alfaro-Murillo JA , Lewis B , Venkatramanan S , Schlitt J , Chen J , Orr M , Wilson ML , Eubank S , Wang L , Chinazzi M , Pastore YPiontti A , Davis JT , Halloran ME , Longini I , Vespignani A , Pei S , Galanti M , Kandula S , Shaman J , Haw DJ , Arinaminpathy N , Biggerstaff M . Proc Natl Acad Sci U S A 2023 120 (28) e2300590120 When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario. |
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