Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 46 Records) |
Query Trace: Lee JS[original query] |
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Literature review of pathogen agnostic molecular testing of clinical specimens from difficult-to-diagnose patients: Implications for public health
Downie DL , Rao P , David-Ferdon C , Courtney S , Lee JS , Kugley S , MacDonald PDM , Barnes K , Fisher S , Andreadis JL , Chaitram J , Mauldin MR , Salerno RM , Schiffer J , Gundlapalli AV . Health Secur 2024 To better identify emerging or reemerging pathogens in patients with difficult-to-diagnose infections, it is important to improve access to advanced molecular testing methods. This is particularly relevant for cases where conventional microbiologic testing has been unable to detect the pathogen and the patient's specimens test negative. To assess the availability and utility of such testing for human clinical specimens, a literature review of published biomedical literature was conducted. From a corpus of more than 4,000 articles, a set of 34 reports was reviewed in detail for data on where the testing was being performed, types of clinical specimens tested, pathogen agnostic techniques and methods used, and results in terms of potential pathogens identified. This review assessed the frequency of advanced molecular testing, such as metagenomic next generation sequencing that has been applied to clinical specimens for supporting clinicians in caring for difficult-to-diagnose patients. Specimen types tested were from cerebrospinal fluid, respiratory secretions, and other body tissues and fluids. Publications included case reports and series, and there were several that involved clinical trials, surveillance studies, research programs, or outbreak situations. Testing identified both known human pathogens (sometimes in new sites) and previously unknown human pathogens. During this review, there were no apparent coordinated efforts identified to develop regional or national reports on emerging or reemerging pathogens. Therefore, development of a coordinated sentinel surveillance system that applies advanced molecular methods to clinical specimens which are negative by conventional microbiological diagnostic testing would provide a foundation for systematic characterization of emerging and underdiagnosed pathogens and contribute to national biodefense strategy goals. |
Evaluation of crAssphages as a potential marker of human viral contamination in environmental water and fresh leafy greens
Suh SH , Lee JS , Kim SH , Vinjé J , Kim SH , Park GW . Front Microbiol 2024 15 1374568 CrAssphages are human gut bacteriophages with potential use as an indicator of human fecal contamination in water and other environmental systems. We determined the prevalence and abundance of crAssphages in water, food, and fecal samples and compared these estimates with the prevalence of norovirus. Samples were tested using two crAssphage-specific qPCR assays (CPQ056 and TN201-203) and for norovirus using TaqMan realtime RT-PCR. CrAssphage was detected in 40% of human fecal specimens, 61% of irrigation water samples, 58.5% of stream water samples, and 68.5% of fresh leafy greens samples. Interestingly, across all sample categories, crAssphage concentrations were 2-3 log10 higher than norovirus concentrations. The correlation of detection of crAssphage and norovirus was significant for the irrigation water samples (r = 0.74, p = 7.4e-06). Sequences obtained from crAssphage positive samples from human fecal and stream water samples phylogenetically clustered with genotype I crAssphages, whereas sequences derived from irrigation water samples clustered differently from other genotypes. Our data show that crAssphages were prevalent in norovirus-positive water samples and in fresh leafy green samples, there was a strong correlation between the presence of crAssphage and norovirus. CrAssphage genomic copies were consistently higher than norovirus copies in all sample types. Overall, our findings suggest that crAssphages could be used as reliable indicators to monitor fecal-borne virus contamination within the food safety chain. |
Surveillance for emerging and reemerging pathogens using pathogen agnostic metagenomic sequencing in the United States: A critical role for federal government agencies
Downie DL , Rao P , David-Ferdon C , Courtney S , Lee JS , Quiner C , MacDonald PDM , Barnes K , Fisher S , Andreadis JL , Chaitram J , Mauldin MR , Salerno RM , Schiffer J , Gundlapalli AV . Health Secur 2024 The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies. |
Telehealth use during the early COVID-19 public health emergency and subsequent health care costs and utilization
Lee JS . Health Aff Sch 2024 2 (1) Telehealth utilization increased during the COVID-19 pandemic, yet few studies have documented associations of telehealth use with subsequent medical costs and health care utilization. We examined associations of telehealth use during the early COVID-19 public health emergency (March-June 2020) with subsequent total medical costs and health care utilization among people with heart disease (HD). We created a longitudinal cohort of individuals with HD using MarketScan Commercial Claims data (2018-2022). We used difference-in-differences methodology adjusting for patients' characteristics, comorbidities, COVID-19 infection status, and number of in-person visits. We found that using telehealth during the stay-at-home order period was associated with a reduction in total medical costs (by -$1814 per person), number of emergency department visits (by -88.6 per 1000 persons), and number of inpatient admissions (by -32.4 per 1000 persons). Telehealth use increased per-person per-year pharmacy prescription claims (by 0.514) and average number of days' drug supply (by 0.773 days). These associated benefits of telehealth use can inform decision makers, insurance companies, and health care professionals, especially in the context of disrupted health care access. |
Association of economic policies with hypertension management and control: A systematic review
Zhang D , Lee JS , Pollack LM , Dong X , Taliano JM , Rajan A , Therrien NL , Jackson SL , Popoola A , Luo F . JAMA Health Forum 2024 5 (2) e235231 IMPORTANCE: Economic policies have the potential to impact management and control of hypertension. OBJECTIVES: To review the evidence on the association between economic policies and hypertension management and control among adults with hypertension in the US. EVIDENCE REVIEW: A search was carried out of PubMed/MEDLINE, Cochrane Library, Embase, PsycINFO, CINAHL, EconLit, Sociological Abstracts, and Scopus from January 1, 2000, through November 1, 2023. Included were randomized clinical trials, difference-in-differences, and interrupted time series studies that evaluated the association of economic policies with hypertension management. Economic policies were grouped into 3 categories: insurance coverage expansion such as Medicaid expansion, cost sharing in health care such as increased drug copayments, and financial incentives for quality such as pay-for-performance. Antihypertensive treatment was measured as taking antihypertensive medications or medication adherence among those who have a hypertension diagnosis; and hypertension control, measured as blood pressure (BP) lower than 140/90 mm Hg or a reduction in BP. Evidence was extracted and synthesized through dual review of titles, abstracts, full-text articles, study quality, and policy effects. FINDINGS: In total, 31 articles were included. None of the studies examined economic policies outside of the health care system. Of these, 16 (52%) assessed policies for insurance coverage expansion, 8 (26%) evaluated policies related to patient cost sharing for prescription drugs, and 7 (22%) evaluated financial incentive programs for improving health care quality. Of the 16 studies that evaluated coverage expansion policies, all but 1 found that policies such as Medicare Part D and Medicaid expansion were associated with significant improvement in antihypertensive treatment and BP control. Among the 8 studies that examined patient cost sharing, 4 found that measures such as prior authorization and increased copayments were associated with decreased adherence to antihypertensive medication. Finally, all 7 studies evaluating financial incentives aimed at improving quality found that they were associated with improved antihypertensive treatment and BP control. Overall, most studies had a moderate or low risk of bias in their policy evaluation. CONCLUSIONS AND RELEVANCE: The findings of this systematic review suggest that economic policies aimed at expanding insurance coverage or improving health care quality successfully improved medication use and BP control among US adults with hypertension. Future research is needed to investigate the potential effects of non-health care economic policies on hypertension control. |
Racial and ethnic differences in hypertension-related telehealth and in-person outpatient visits before and during the COVID-19 pandemic among Medicaid Beneficiaries
Lee JS , Bhatt A , Pollack LM , Jackson SL , Omeaku N , Lowe Beasley K , Wilson C , Luo F , Roy K . Telemed J E Health 2024 Background: Little is known about the trends and costs of hypertension management through telehealth among individuals enrolled in Medicaid. Methods: Using MarketScan(®) Medicaid database, we examined outpatient visits among people with hypertension aged 18-64 years. We presented the numbers of hypertension-related telehealth and in-person outpatient visits per 100 individuals and the proportion of hypertension-related telehealth outpatient visits to total outpatient visits by month, overall, and by race and ethnicity. For the cost analysis, we presented total and patient out-of-pocket (OOP) costs per visit for telehealth and in-person visits in 2021. Results: Of the 229,562 individuals, 114,445 (49.9%) were non-Hispanic White, 80,692 (35.2%) were non-Hispanic Black, 3,924 (1.71%) were Hispanic. From February to April 2020, the number of hypertension-related telehealth outpatient visits per 100 persons increased from 0.01 to 6.13, the number of hypertension-related in-person visits decreased from 61.88 to 52.63, and the proportion of hypertension-related telehealth outpatient visits increased from 0.01% to 10.44%. During that same time, the proportion increased from 0.02% to 13.9% for non-Hispanic White adults, from 0.00% to 7.58% for non-Hispanic Black adults, and from 0.12% to 19.82% for Hispanic adults. The average total and patient OOP costs per visit in 2021 were $83.82 (95% confidence interval [CI], 82.66-85.05) and $0.55 (95% CI, 0.42-0.68) for telehealth and $264.48 (95% CI, 258.87-269.51) and $0.72 (95% CI, 0.65-0.79) for in-person visits, respectively. Conclusions: Hypertension management via telehealth increased among Medicaid recipients regardless of race and ethnicity, during the COVID-19 pandemic. These findings may inform telehealth policymakers and health care practitioners. |
Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein
Keller MW , Keong LM , Rambo-Martin BL , Hassell N , Lacek KA , Wilson MM , Kirby MK , Liddell J , Owuor DC , Sheth M , Madden J , Lee JS , Kondor RJ , Wentworth DE , Barnes JR . Microbiol Spectr 2023 e0298223 The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection. |
A novel invasive Streptococcus pyogenes variant sublineage derived through recombinational replacement of the emm12 genomic region
Unoarumhi Y , Davis ML , Rowe LA , Mathis S , Li Z , Chochua S , Li Y , McGee L , Metcalf BJ , Lee JS , Beall B . Sci Rep 2023 13 (1) 21510 Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12. The 16 emm82/ST36 isolates were closely interrelated (pairwise SNP distance of 0-43), and shared the same emm82-containing recombinational fragment. emm82/ST36 isolates carried the sof12 structural gene, however the sof12 indel characteristic of emm12 strains was corrected to confer the SOF-positive phenotype. Five independent emm82/ST36 invasive case isolates comprised two sets of genetically indistinguishable strains. The emm82/ST36 isolates were primarily macrolide resistant (12/16 isolates), displayed at least 4 different core genomic arrangements, and carried 11 different combinations of virulence and resistance determinants. Phylogenetic analysis revealed that emm82/ST36 was within a minor (non-clade 1) portion of ST36 that featured almost all ST36 antibiotic resistance. This work documents emergence of a rapidly diversifying variant that is the first confirmed example of an emm pattern A strain switched to a pattern E strain. |
Trends in drug spending of oral anticoagulants for atrial fibrillation, 2014-2021
Lee JS , Han S , Therrien NL , Park C , Luo F , Essien UR . Am J Prev Med 2023 INTRODUCTION: This study documents cost trends in oral anticoagulants (OAC) in patients with newly diagnosed atrial fibrillation (AF). METHODS: Using MarketScan databases, the mean annual patients' out-of-pocket costs, insurance payments, and the proportion of patients initiating OAC within 90 days from AF diagnosis were calculated from July 2014 to June 2021. Costs of OACs (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) and the payments by three insurance types (commercial payers, Medicare, and Medicaid) were calculated. Patients' out-of-pocket costs and insurance payments were adjusted to 2021 prices. Joinpoint regression models were used to test trends of outcomes and average annual percent changes (AAPC) were reported. Data analyses were performed in 2022-2023. RESULTS: From July 2014 to June 2021, the mean annual out-of-pocket costs of any OAC increased for commercial insurance (AAPC 3.0%) and Medicare (AAPC 5.1%) but decreased for Medicaid (AAPC -3.3%). The mean annual insurance payments for any OAC significantly increased for all insurance groups (AAPC 13.1% [95% CI 11.3 to 15.0] for Medicare; AAPC 11.8% [95% CI 8.0 to 15.6] for commercial insurance; and AAPC 16.3% [95% CI 11.3 to 21.4] for Medicaid). The initiation of any OAC increased (AAPC 7.3% for commercial insurance; AAPC 10.2% for Medicare; AAPC 5.3% for Medicaid). CONCLUSIONS: There was a substantial increase in the overall cost burden of OACs and OAC initiation rates in patients with newly diagnosed AF in 2014-2021; these findings provide insights into the current and anticipated impact of rising drug prices on patients' and payers' financial burden. |
Social determinants of health-related Z codes and health care among patients with hypertension
Lee JS , MacLeod KE , Kuklina EV , Tong X , Jackson SL . AJPM Focus 2023 2 (2) 100089 INTRODUCTION: Tracking social needs can provide information on barriers to controlling hypertension and the need for wraparound services. No recent studies have examined ICD-10-CM social determinants of health-related Z codes (Z55-Z65) to indicate social needs with a focus on patients with hypertension. METHODS: Three cohorts were identified with a diagnosis of hypertension during 2016-2017 and continuously enrolled in fee-for-service insurance through June 2021: (1) commercial, age 18-64 years (n=1,024,012); (2) private insurance to supplement Medicare (Medicare Supplement), age ≥65 years (n=296,340); and (3) Medicaid, age ≥18 years (n=146,484). Both the proportion of patients and healthcare encounters or visits with social determinants of health-related Z code were summarized annually. Patient and visit characteristics were summarized for 2019. RESULTS: In 2020, the highest annual documentation of social determinants of health-related Z codes was among Medicaid beneficiaries (3.02%, 0.46% commercial, 0.42% Medicare Supplement); documentation was higher among inpatient than among outpatient visits for all insurance types. Z63 (related to primary support group) was more common among commercial and Medicare Supplement beneficiaries, and Z59 (housing and economic circumstances) was more common among Medicaid beneficiaries. The 2019 total unadjusted medical expenditures were 1.85, 1.78, and 1.61 times higher for those with social determinants of health-related Z code than for those without commercial, Medicare Supplement, and Medicaid, respectively. Patients with social determinants of health-related Z code also had higher proportions of diagnosed chronic conditions. Among Medicaid beneficiaries, differences in the presence of social determinants of health-related Z code by race or ethnicity were observed. CONCLUSIONS: Although currently underreported, social determinants of health-related Z codes provide an opportunity to integrate social and medical data and may help decision makers understand the need for additional services among individuals with hypertension. |
Rural and urban differences in hypertension management through telehealth before and during the COVID-19 pandemic among commercially insured patients
Lee JS , Bhatt A , Jackson SL , Pollack LM , Omeaku N , Lowe K , Wilson C , Luo F , Roy K . Am J Hypertens 2023 BACKGROUND: The COVID-19 pandemic prompted a rapid increase in telehealth use. However, limited evidence exists on how rural and urban residents used telehealth and in-person outpatient services to manage hypertension during the pandemic. METHODS: This longitudinal study analyzed 701,410 US adults (18-64 years) in the MarketScan Commercial Claims Database, who were continuously enrolled from January 2017 through March 2022. We documented monthly numbers of hypertension-related telehealth and in-person outpatient visits (per 100 individuals), and the proportion of telehealth visits among all hypertension-related outpatient visits, from January 2019 through March 2022. We used Welch's 2-tail t-test to differentiate monthly estimates by rural-urban status and month-to-month changes. RESULTS: From February through April 2020, the monthly number of hypertension-related telehealth visits per 100 individuals increased from 0.01 to 6.05 (P<0.001) for urban residents and from 0.01 to 4.56 (P<0.001) for rural residents. Hypertension-related in-person visits decreased from 20.12 to 8.30 (P<0.001) for urban residents and from 20.48 to 10.15 (P<0.001) for rural residents. The proportion of hypertension-related telehealth visits increased from 0.04% to 42.15% (P<0.001) for urban residents and from 0.06% to 30.98% (P<0.001) for rural residents. From March 2020 to March 2022, the monthly average of the proportions of hypertension-related telehealth visits was higher for urban residents than for rural residents (10.19% vs. 6.96%; P<0.001). CONCLUSIONS: Data show that rural residents were less likely to use telehealth for hypertension management. Understanding trends in hypertension-related telehealth utilization can highlight disparities in the sustained use of telehealth to advance accessible health care. |
Lab on a chip for detecting Clara cell protein 16 (CC16) for potential screening of the workers exposed to respirable silica aerosol
Ahn C , Lee T , Shin JH , Lee JS , Thiyagarajan Upaassana V , Ghosh S , Ku BK . Microfluid Nanofluidics 2023 27 (11) 1-10 Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625–20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R 2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. |
Trends in the longitudinal utilization of oral anticoagulants among newly diagnosed atrial fibrillation patients with commercial, Medicare, and Medicaid insurance
Lee JS , Han S , Therrien NL , Park C , Luo F , Essien UR . Am J Cardiol 2023 203 339-342 Long-term oral anticoagulation (OAC) is recommended for stroke prevention for most patients with atrial fibrillation (AF) and elevated stroke risk.1 While trends in initiation of OAC have been described,2,3 long-term trends in utilization of OAC in patients continuously followed for AF have not been adequately explored. Some healthcare systems adapted anticoagulation services to respond to disruptions during the COVID-19 pandemic.4 We thus investigated how OACs were utilized in patients with newly diagnosed AF from 2018 to 2021 across 3 insurance types: Medicare, Medicaid, and commercial. |
Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021 (preprint)
Dawson P , Worrell MC , Malone S , Fritz SA , McLaughlin HP , Montgomery BK , Boyle M , Gomel A , Hayes S , Maricque B , Lai AM , Neidich JA , Tinker SC , Lee JS , Tong S , Orscheln RC , Charney R , Rebmann T , Mooney J , Rains C , Yoon N , Petit M , Towns K , Goddard C , Schmidt S , Barrios LC , Neatherlin JC , Salzer JS , Newland JG . medRxiv 2022 21 Objective: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021. Method(s): We conducted a prospective cohort study of COVID-19 cases and exposures among students and staff (n=65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. An adjusted Cox regression model compared hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy. Result(s): From January-March 2021, a projected 23 (1%) school-based transmission events occurred among 1,636 school close contacts. There was no difference in the adjusted hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy (hazard ratio=1.00; 95% confidence interval: 0.97-1.03). Discussion(s): School-based SARS-CoV-2 transmission was rare in 103 K-12 schools implementing multiple COVID-19 prevention strategies. Modified student quarantine policies were not associated with increased school incidence of COVID-19. Modifications to student quarantine policies may be a useful strategy for K-12 schools to safely reduce disruptions to in-person education during times of increased COVID-19 community incidence. 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. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. 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. |
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA (preprint)
Gigante CM , Plumb M , Ruprecht A , Zhao H , Wicker V , Wilkins K , Matheny A , Khan T , Davidson W , Sheth M , Burgin A , Burroughs M , Padilla J , Lee JS , Batra D , Hetrick EE , Howard DT , Garfin J , Tate L , Hubsmith SJ , Mendoza RM , Stanek D , Gillani S , Lee M , Mangla A , Blythe D , SierraPatev S , Carpenter-Azevedo K , Huard RC , Gallagher G , Hall J , Ash S , Kovar L , Seabolt MH , Weigand MR , Damon I , Satheshkumar PS , McCollum AM , Hutson CL , Wang X , Li Y . bioRxiv 2022 17 Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3' terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv 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. |
Equipment-free detection of SARS-CoV-2 and Variants of Concern using Cas13 (preprint)
Arizti-Sanz J , Bradley AD , Zhang YB , Boehm CK , Freije CA , Grunberg ME , Kosoko-Thoroddsen TSF , Welch NL , Pillai PP , Mantena S , Kim G , Uwanibe JN , John OG , Eromon PE , Kocher G , Gross R , Lee JS , Hensley LE , Happi CT , Johnson J , Sabeti PC , Myhrvold C . medRxiv 2021 02 The COVID-19 pandemic, and the recent rise and widespread transmission of SARS-CoV-2 Variants of Concern (VOCs), have demonstrated the need for ubiquitous nucleic acid testing outside of centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes. SHINEv2 represents an important advance towards rapid nucleic acid tests that can be performed in any location. 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. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Genomic surveillance for SARS-CoV-2 variants: Circulation of Omicron lineages - United States, January 2022-May 2023
Ma KC , Shirk P , Lambrou AS , Hassell N , Zheng XY , Payne AB , Ali AR , Batra D , Caravas J , Chau R , Cook PW , Howard D , Kovacs NA , Lacek KA , Lee JS , MacCannell DR , Malapati L , Mathew S , Mittal N , Nagilla RR , Parikh R , Paul P , Rambo-Martin BL , Shepard SS , Sheth M , Wentworth DE , Winn A , Hall AJ , Silk BJ , Thornburg N , Kondor R , Scobie HM , Paden CR . MMWR Morb Mortal Wkly Rep 2023 72 (24) 651-656 CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics. |
Timing of outpatient postpartum care utilization among women with chronic hypertension and hypertensive disorders of pregnancy
Aqua JK , Ford ND , Pollack LM , Lee JS , Kuklina EV , Hayes DK , Vaughan AS , Coronado F . Am J Obstet Gynecol MFM 2023 5 (9) 101051 BACKGROUND: The postpartum period represents an opportunity to assess the cardiovascular health of women who experience chronic hypertension or hypertensive disorders of pregnancy. OBJECTIVES: To determine whether women with chronic hypertension or hypertensive disorders of pregnancy access outpatient postpartum care more quickly compared to women with no hypertension. STUDY DESIGN: We used data from the Merative MarketScan® Commercial Claims and Encounters Database. We included 275,937 commercially insured women aged 12-55 years who had a live birth or stillbirth delivery hospitalization between 2017-2018 and continuous insurance enrollment from 3 months before the estimated start of pregnancy to 6 months after delivery discharge. Using International Classification of Diseases 10th Revision Clinical Modification codes, we identified hypertensive disorders of pregnancy from inpatient or outpatient claims from 20 weeks gestation through delivery hospitalization and identified chronic hypertension from inpatient or outpatient claims from the beginning of the continuous enrollment period through delivery hospitalization. Distributions of time-to-event survival curves (time-to-first outpatient postpartum visit with a women's health, primary care, or cardiology provider) were compared between the hypertension types using Kaplan-Meier estimators and log rank tests. We used Cox proportional hazards models to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Time points of interest (3, 6, and 12 weeks) were evaluated per clinical postpartum care guidelines. RESULTS: Among commercially insured women, the prevalences of hypertensive disorders of pregnancy, chronic hypertension, and no documented hypertension were 11.7%, 3.4%, and 84.8%, respectively. The proportions of women with a visit within 3 weeks of delivery discharge were 28.5%, 26.4%, and 16.0% for hypertensive disorders of pregnancy, chronic, and no documented hypertension, respectively. By 12 weeks, the proportions increased to 62.4%, 64.5%, and 54.2%, respectively. Kaplan-Meier analyses indicated significant differences in utilization by hypertension type and interaction between hypertension type and time before and after 6 weeks. In adjusted Cox proportional hazards models, the utilization rate before 6 weeks among women with hypertensive disorders of pregnancy was 1.42 times the rate for women with no documented hypertension [aHR=1.42, 95% CI (1.39-1.45)]. Women with chronic hypertension also had higher utilization rates compared to women with no documented hypertension before 6 weeks [aHR=1.28, 95% CI: (1.24-1.33)]. Only chronic hypertension was significantly associated with utilization compared to the no documented hypertension group after 6 weeks [aHR=1.09, 95% CI: (1.03-1.14)]. CONCLUSIONS: In the 6 weeks following delivery discharge, women with hypertensive disorders of pregnancy and chronic hypertension attended outpatient postpartum care visits sooner than women with no documented hypertension. However, after 6 weeks this difference extended only to women with chronic hypertension. Overall, postpartum care utilization remained around 50-60% by 12 weeks in all groups. Addressing barriers to postpartum care attendance can ensure timely care for women at high risk for cardiovascular disease. |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
Trends and costs of US telehealth use among patients with cardiovascular disease before and during the COVID-19 pandemic
Lee JS , Lowe Beasley K , Schooley MW , Luo F . J Am Heart Assoc 2023 12 (4) e028713 Background The COVID-19 pandemic affected outpatient care delivery and patients' access to health care. However, no prior studies have documented telehealth use among patients with cardiovascular disease. Methods and Results We documented the number of telehealth and in-person outpatient encounters per 100 patients with cardiovascular disease and the percentage of telehealth encounters from January 2019 to June 2021, and the average payments per telehealth and in-person encounters across a 12-month period (July 2020-June 2021) using the MarketScan commercial database. From February 2020 to April 2020, the number of in-person encounters per 100 patients with cardiovascular disease decreased from 304.2 to 147.7, whereas that of telehealth encounters increased from 0.29 to 25.3. The number of in-person outpatient encounters then increased to 280.7 in June 2020, fluctuated between 268.1 and 346.4 afterward, and ended at 268.1 in June 2021, lower than the prepandemic levels. The number of telehealth encounters dropped to 16.8 in June 2020, fluctuated between 8.8 and 16.6 afterward, and ended at 8.8 in June 2021, higher than the prepandemic levels. Patients who were aged 18 to 35 years, women, and living in urban areas had higher percentages of telehealth encounters than those who were aged 35 to 64 years, men, and living in rural areas, respectively. The mean (95% CI) telehealth and in-person outpatient encounter costs per visit were $112.8 (95% CI, $112.4-$113.2) and $161.4 (95% CI, $160.4- $162.4), respectively. Conclusions There were large fluctuations in telehealth and in-person outpatient encounters during the pandemic. Our results provide insight into increased telehealth use among patients with cardiovascular disease after telehealth policy changes were implemented during the pandemic. |
Habitat connectivity and host relatedness influence virus spread across an urbanising landscape in a fragmentation-sensitive carnivore.
Kozakiewicz CP , Burridge CP , Lee JS , Kraberger SJ , Fountain-Jones NM , Fisher RN , Lyren LM , Jennings MK , Riley SPD , Serieys LEK , Craft ME , Funk WC , Crooks KR , VandeWoude S , Carver S . Virus Evol 2023 9 (1) veac122 Spatially heterogeneous landscape factors such as urbanisation can have substantial effects on the severity and spread of wildlife diseases. However, research linking patterns of pathogen transmission to landscape features remains rare. Using a combination of phylogeographic and machine learning approaches, we tested the influence of landscape and host factors on feline immunodeficiency virus (FIV(Lru)) genetic variation and spread among bobcats (Lynx rufus) sampled from coastal southern California. We found evidence for increased rates of FIV(Lru) lineage spread through areas of higher vegetation density. Furthermore, single-nucleotide polymorphism (SNP) variation among FIV(Lru) sequences was associated with host genetic distances and geographic location, with FIV(Lru) genetic discontinuities precisely correlating with known urban barriers to host dispersal. An effect of forest land cover on FIV(Lru) SNP variation was likely attributable to host population structure and differences in forest land cover between different populations. Taken together, these results suggest that the spread of FIV(Lru) is constrained by large-scale urban barriers to host movement. Although urbanisation at fine spatial scales did not appear to directly influence virus transmission or spread, we found evidence that viruses transmit and spread more quickly through areas containing higher proportions of natural habitat. These multiple lines of evidence demonstrate how urbanisation can change patterns of contact-dependent pathogen transmission and provide insights into how continued urban development may influence the incidence and management of wildlife disease. |
Comprehensive characterization of toxins during progression of inhalation anthrax in a non-human primate model
Boyer AE , Gallegos-Candela M , Lins RC , Solano MI , Woolfitt AR , Lee JS , Sanford DC , Knostman KAB , Quinn CP , Hoffmaster AR , Pirkle JL , Barr JR . PLoS Pathog 2022 18 (12) e1010735 Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late-fulminant. We report the comprehensive characterization of anthrax toxins, including total protective antigen (PA), total lethal factor (LF), total edema factor (EF), and their toxin complexes, lethal toxin and edema toxin in plasma, during the course of inhalation anthrax in 23 cynomolgus macaques. The toxin kinetics were predominantly triphasic with an early rise (phase-1), a plateau/decline (phase-2), and a final rapid rise (phase-3). Eleven animals had shorter survival times, meanstandard deviation of 58.77.6 hours (fast progression), 11 animals had longer survival times, 11334.4 hours (slow progression), and one animal survived. Median (lower-upper quartile) LF levels at the end-of-phase-1 were significantly higher in animals with fast progression [138 (54.9-326) ng/mL], than in those with slow progression [23.8 (15.6-26.3) ng/mL] (p = 0.0002), and the survivor (11.1 ng/mL). The differences were also observed for other toxins and bacteremia. Animals with slow progression had an extended phase-2 plateau, with low variability of LF levels across all time points and animals. Characterization of phase-2 toxin levels defined upper thresholds; critical levels for exiting phase-2 and entering the critical phase-3, 342 ng/mL (PA), 35.8 ng/mL (LF), and 1.10 ng/mL (EF). The thresholds were exceeded earlier in animals with fast progression (38.57.4 hours) and later in animals with slow progression (78.715.2 hours). Once the threshold was passed, toxin levels rose rapidly in both groups to the terminal stage. The time from threshold to terminal was rapid and similar; 20.87.4 hours for fast and 19.97.5 hours for slow progression. The three toxemic phases were aligned with the three clinical stages of anthrax for fast and slow progression which showed that anthrax progression is toxin- rather than time-dependent. This first comprehensive evaluation of anthrax toxins provides new insights into disease progression. |
Correction: Comparative outcomes for mature T and NK/T-cell lymphomas in people with and without HIV and to AIDS-defining lymphomas
Koh MJ , Merrill MH , Koh MJ , Stuver R , Alonso CD , Foss FM , Mayor AM , Gill J , Epeldegui M , Cachay E , Thorne JE , Silverberg MJ , Horberg MA , Atlhoff KN , Nijhawan AE , McGinnis KA , Lee JS , Rabkin CS , Napravnik S , Li J , Castilho JL , Shen C , Jain S . Blood Adv 2022 6 (15) 4436 An author's name was misspelled in the byline on page 1420. “Keri N. Atlhoff” should read “Keri N. Althoff.” The error has been corrected in the published article. |
Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021.
Dawson P , Worrell MC , Malone S , Fritz SA , McLaughlin HP , Montgomery BK , Boyle M , Gomel A , Hayes S , Maricque B , Lai AM , Neidich JA , Tinker SC , Lee JS , Tong S , Orscheln RC , Charney R , Rebmann T , Mooney J , Rains C , Yoon N , Petit M , Towns K , Goddard C , Schmidt S , Barrios LC , Neatherlin JC , Salzer JS , Newland JG . PLoS One 2022 17 (10) e0266292 OBJECTIVE: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021. METHODS: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a projected total. An adjusted Cox regression model compared hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy. RESULTS: From January-March 2021, a projected 23 (1%) school-based transmission events occurred among 1,636 school close contacts. There was no difference in the adjusted hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy (hazard ratio = 1.00; 95% confidence interval: 0.97-1.03). DISCUSSION: School-based SARS-CoV-2 transmission was rare in 103 K-12 schools implementing multiple COVID-19 prevention strategies. Modified student quarantine policies were not associated with increased school incidence of COVID-19. Modifications to student quarantine policies may be a useful strategy for K-12 schools to safely reduce disruptions to in-person education during times of increased COVID-19 community incidence. |
Assessment of Clinical and Virological Characteristics of SARS-CoV-2 Infection Among Children Aged 0 to 4 Years and Their Household Members.
Karron RA , Hetrich MK , Na YB , Knoll MD , Schappell E , Meece J , Hanson E , Tong S , Lee JS , Veguilla V , Dawood FS . JAMA Netw Open 2022 5 (8) e2227348 IMPORTANCE: Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies. OBJECTIVE: To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment andat approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies. MAIN OUTCOMES AND MEASURES: Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage. RESULTS: Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R=0.69; P<.001) but not children (ages 0-4 years: R=0.02; P=.91; ages 5-17 years: R=0.18; P=.58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P=.009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P=.006). CONCLUSIONS AND RELEVANCE: In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children. |
The evolution of medical countermeasures for Ebola virus disease: Lessons learned and next steps
Crozier I , Britson KA , Wolfe DN , Klena JD , Hensley LE , Lee JS , Wolfraim LA , Taylor KL , Higgs ES , Montgomery JM , Martins KA . Vaccines (Basel) 2022 10 (8) The Ebola virus disease outbreak that occurred in Western Africa from 2013-2016, and subsequent smaller but increasingly frequent outbreaks of Ebola virus disease in recent years, spurred an unprecedented effort to develop and deploy effective vaccines, therapeutics, and diagnostics. This effort led to the U.S. regulatory approval of a diagnostic test, two vaccines, and two therapeutics for Ebola virus disease indications. Moreover, the establishment of fieldable diagnostic tests improved the speed with which patients can be diagnosed and public health resources mobilized. The United States government has played and continues to play a key role in funding and coordinating these medical countermeasure efforts. Here, we describe the coordinated U.S. government response to develop medical countermeasures for Ebola virus disease and we identify lessons learned that may improve future efforts to develop and deploy effective countermeasures against other filoviruses, such as Sudan virus and Marburg virus. |
Impact of Age and Symptom Development on SARS-CoV-2 Transmission in Households With Children-Maryland, New York, and Utah, August 2020-October 2021.
Sumner KM , Karron RA , Stockwell MS , Dawood FS , Stanford JB , Mellis A , Hacker E , Thind P , Castro MJE , Harris JP , Deloria Knoll M , Schappell E , Hetrich MK , Duque J , Jeddy Z , Altunkaynak K , Poe B , Meece J , Stefanski E , Tong S , Lee JS , Dixon A , Veguilla V , Rolfes MA , Porucznik CA . Open Forum Infect Dis 2022 9 (8) ofac390 BACKGROUND: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. METHODS: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. RESULTS: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). CONCLUSIONS: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages. |
Effectiveness of two and three mRNA COVID-19 vaccine doses against Omicron- and Delta-Related outpatient illness among adults, October 2021-February 2022.
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Kiniry E , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Moehling Geffel K , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M . Influenza Other Respir Viruses 2022 16 (6) 975-985 Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 − adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: −6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. |
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