Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 548 Records) |
Query Trace: Wu R[original query] |
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Testing the shock protection performance of Type I construction helmets using impactors of different masses
Wu JZ , Pan CS , Ronaghi M , Wimer BM . Biomed Mater Eng 2024 BACKGROUND: Wearing protective helmets is an important prevention strategy to reduce work-related traumatic brain injuries. The existing standardized testing systems are used for quality control and do not provide a quantitative measure of the helmet performance. OBJECTIVE: To analyze the failure characterizations of Type I industrial helmets and develop a generalized approach to quantify the shock absorption performance of Type I industrial helmets based on the existing standardized setups. METHODS: A representative basic Type I construction helmet model was selected for the study. Top impact tests were performed on the helmets at different drop heights using two different impactor masses (3.6 and 5.0 kg). RESULTS: When the helmets were impacted with potential impact energies smaller than the critical potential impact energy values, there was a consistent relationship between the peak impact force and the potential impact energy. When the helmets were impacted under potential impact energies greater than the critical potential impact energy values, the peak impact forces increased steeply with increasing potential impact energy. CONCLUSION: A concept of safety margin for construction helmets based on potential impact energy was introduced to quantify the helmets' shock absorption performance. The proposed method will help helmet manufacturers improve their product quality. |
Durability of original monovalent mRNA vaccine effectiveness against COVID-19 Omicron-associated hospitalization in children and adolescents - United States, 2021-2023
Zambrano LD , Newhams MM , Simeone RM , Payne AB , Wu M , Orzel-Lockwood AO , Halasa NB , Calixte JM , Pannaraj PS , Mongkolrattanothai K , Boom JA , Sahni LC , Kamidani S , Chiotos K , Cameron MA , Maddux AB , Irby K , Schuster JE , Mack EH , Biggs A , Coates BM , Michelson KN , Bline KE , Nofziger RA , Crandall H , Hobbs CV , Gertz SJ , Heidemann SM , Bradford TT , Walker TC , Schwartz SP , Staat MA , Bhumbra SS , Hume JR , Kong M , Stockwell MS , Connors TJ , Cullimore ML , Flori HR , Levy ER , Cvijanovich NZ , Zinter MS , Maamari M , Bowens C , Zerr DM , Guzman-Cottrill JA , Gonzalez I , Campbell AP , Randolph AG . MMWR Morb Mortal Wkly Rep 2024 73 (15) 330-338 Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19. |
Notes from the field: Surveillance for multisystem inflammatory syndrome in children - United States, 2023
Yousaf AR , Lindsey KN , Wu MJ , Shah AB , Free RJ , Simeone RM , Zambrano LD , Campbell AP . MMWR Morb Mortal Wkly Rep 2024 73 (10) 225-228 |
Redefining pandemic preparedness: Multidisciplinary insights from the CERP modelling workshop in infectious diseases, workshop report
Nunes MC , Thommes E , Fröhlich H , Flahault A , Arino J , Baguelin M , Biggerstaff M , Bizel-Bizellot G , Borchering R , Cacciapaglia G , Cauchemez S , Barbier-Chebbah A , Claussen C , Choirat C , Cojocaru M , Commaille-Chapus C , Hon C , Kong J , Lambert N , Lauer KB , Lehr T , Mahe C , Marechal V , Mebarki A , Moghadas S , Niehus R , Opatowski L , Parino F , Pruvost G , Schuppert A , Thiébaut R , Thomas-Bachli A , Viboud C , Wu J , Crépey P , Coudeville L . Infect Dis Model 2024 9 (2) 501-518 In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop. The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness. Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness. |
A diverse group of small circular ssDNA viral genomes in human and non-human primate stools.
Ng TF , Zhang W , Sachsenröder J , Kondov NO , da Costa AC , Vega E , Holtz LR , Wu G , Wang D , Stine CO , Antonio M , Mulvaney US , Muench MO , Deng X , Ambert-Balay K , Pothier P , Vinjé J , Delwart E . Virus Evol 2015 1 (1) vev017 Viral metagenomics sequencing of fecal samples from outbreaks of acute gastroenteritis from the US revealed the presence of small circular ssDNA viral genomes encoding a replication initiator protein (Rep). Viral genomes were ∼2.5 kb in length, with bi-directionally oriented Rep and capsid (Cap) encoding genes and a stem loop structure downstream of Rep. Several genomes showed evidence of recombination. By digital screening of an in-house virome database (1.04 billion reads) using BLAST, we identified closely related sequences from cases of unexplained diarrhea in France. Deep sequencing and PCR detected such genomes in 7 of 25 US (28 percent) and 14 of 21 French outbreaks (67 percent). One of eighty-five sporadic diarrhea cases in the Gambia was positive by PCR. Twenty-two complete genomes were characterized showing that viruses from patients in the same outbreaks were closely related suggesting common origins. Similar genomes were also characterized from the stools of captive chimpanzees, a gorilla, a black howler monkey, and a lemur that were more diverse than the human stool-associated genomes. The name smacovirus is proposed for this monophyletic viral clade. Possible tropism include mammalian enteric cells or ingested food components such as infected plants. No evidence of viral amplification was found in immunodeficient mice orally inoculated with smacovirus-positive stool supernatants. A role for smacoviruses in diarrhea, if any, remains to be demonstrated. |
Tularemia clinical manifestations, antimicrobial treatment, and outcomes: An analysis of US surveillance data, 2006-2021
Wu HJ , Bostic TD , Horiuchi K , Kugeler KJ , Mead PS , Nelson CA . Clin Infect Dis 2024 78 S29-s37 BACKGROUND: Tularemia, a potentially fatal zoonosis caused by Francisella tularensis, has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. METHODS: Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006-2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. RESULTS: Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. CONCLUSIONS: Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia. |
Advanced child tax credit payments and national child abuse hotline contacts, 2019-2022
Merrill-Francis M , Chen MS , Dunphy C , Swedo EA , Zhang Kudon H , Metzler M , Mercy JA , Zhang X , Rogers TM , Wu Shortt J . Inj Prev 2024 BACKGROUND: Children in households experiencing poverty are disproportionately exposed to maltreatment. Income support policies have been associated with reductions in child abuse and neglect. The advance child tax credit (CTC) payments may reduce child maltreatment by improving the economic security of some families. No national studies have examined the association between advance CTC payments and child abuse and neglect. This study examines the association between the advance CTC payments and child abuse and neglect-related contacts to the Childhelp National Child Abuse Hotline. METHODS: A time series study of contacts to the Childhelp National Child Abuse Hotline between January 2019 and December 2022 was used to examine the association between the payments and hotline contacts. An interrupted time series (ITS) exploiting the variation in the advance CTC payments was estimated using fixed effects. RESULTS: The CTC advance payments were associated with an immediate 13.8% (95% CI -17.5% to -10.0%) decrease in contacts to the hotline in the ITS model. Following the expiration of the advance CTC payments, there was a significant and gradual 0.1% (95% CI +0.0% to +0.2%) daily increase in contacts. Sensitivity analyses found significant reductions in contacts following each payment, however, the reductions were associated with the last three of the six total payments. CONCLUSION: These findings suggest the advance CTC payments may reduce child abuse and neglect-related hotline contacts and continue to build the evidence base for associations between income-support policies and reductions in child abuse and neglect. |
Etiology of acute lower respiratory illness hospitalizations among infants in 4 countries
Kubale J , Kujawski S , Chen I , Wu Z , Khader IA , Hasibra I , Whitaker B , Gresh L , Simaku A , Simões EAF , Al-Gazo M , Rogers S , Gerber SI , Balmaseda A , Tallo VL , Al-Sanouri TM , Porter R , Bino S , Azziz-Baumgartner E , McMorrow M , Hunt D , Thompson M , Biggs HM , Gordon A . Open Forum Infect Dis 2023 10 (12) ofad580 BACKGROUND: Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear. METHODS: Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models. RESULTS: An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites-ranging from 65.2% (95% credible interval, 46.3%-79.6%) in Albania to 34.9% (95% credible interval, 20.0%-49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%-27.1%) and human metapneumovirus (range, 6.3%-12.0%) were the next-highest contributors to ALRI hospitalizations. CONCLUSIONS: We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide. |
Design and Implementation of a Federal Program to Engage Community Partners to Reduce Disparities in Adult COVID-19 Immunization Uptake, United States, 2021-2022
Ashenafi SG , Martinez GM , Jatlaoui TC , Koppaka R , Byrne-Zaaloff M , Falcón AP , Frank A , Keitt SH , Matus K , Moss S , Ruddock C , Sun T , Waterman MB , Wu TY . Public Health Rep 2023 333549231208642 Vaccination disparities are part of a larger system of health inequities among racial and ethnic groups in the United States. To increase vaccine equity of racial and ethnic populations, the Centers for Disease Control and Prevention (CDC) designed the Partnering for Vaccine Equity program in January 2021, which funded and supported national, state, local, and community organizations in 50 states-which include Indian Health Service Tribal Areas; Washington, DC; and Puerto Rico-to implement culturally tailored activities to improve access to, availability of, and confidence in COVID-19 and influenza vaccines. To increase vaccine uptake at the local level, CDC partnered with national organizations such as the National Urban League and Asian & Pacific Islander American Health Forum to engage community-based organizations to take action. Lessons learned from the program include the importance of directly supporting and engaging with the community, providing tailored messages and access to vaccines to reach communities where they are, training messengers who are trusted by those in the community, and providing support to funded partners through trainings on program design and implementation that can be institutionalized and sustained beyond the COVID-19 pandemic. Building on these lessons will ensure CDC and other public health partners can continue to advance vaccine equity, increase vaccine uptake, improve health outcomes, and build trust with communities as part of a comprehensive adult immunization infrastructure. |
Characteristics and clinical outcomes of vaccine-eligible US children under-5 years hospitalized for acute COVID-19 in a national network
Zambrano LD , Newhams MM , Simeone RM , Fleming-Dutra KE , Halasa N , Wu M , Orzel-Lockwood AO , Kamidani S , Pannaraj PS , Chiotos K , Cameron MA , Maddux AB , Schuster JE , Crandall H , Kong M , Nofziger RA , Staat MA , Bhumbra SS , Irby K , Boom JA , Sahni LC , Hume JR , Gertz SJ , Maamari M , Bowens C , Levy ER , Bradford TT , Walker TC , Schwartz SP , Mack EH , Guzman-Cottrill JA , Hobbs CV , Zinter MS , Cvijanovich NZ , Bline KE , Hymes SR , Campbell AP , Randolph AG . Pediatr Infect Dis J 2023 BACKGROUND AND OBJECTIVES: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. METHODS: We enrolled inpatients aged 8 months to <5 years with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. RESULTS: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. CONCLUSIONS: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization. |
Large-scale scientific study led by a professional organization during the COVID-19 pandemic: Operations, best practices, and lessons learned
Ondracek CR , Melanson SEF , Doan L , Schulz KM , Kleinman S , Zhao Z , Kumanovics A , Wu AHB , Wiencek J , Meng QH , Apple FS , Koch D , Vesper H , Pokuah F , Bryksin J , Myers GL , Christenson RH , Zhang YV . J Appl Lab Med 2023 In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor. |
The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano MA , Matentzoglu N , Coleman B , Addo-Lartey EB , Anagnostopoulos AV , Anderton J , Avillach P , Bagley AM , Bakštein E , Balhoff JP , Baynam G , Bello SM , Berk M , Bertram H , Bishop S , Blau H , Bodenstein DF , Botas P , Boztug K , Čady J , Callahan TJ , Cameron R , Carbon SJ , Castellanos F , Caufield JH , Chan LE , Chute CG , Cruz-Rojo J , Dahan-Oliel N , Davids JR , de Dieuleveult M , de Souza V , de Vries BBA , de Vries E , DePaulo JR , Derfalvi B , Dhombres F , Diaz-Byrd C , Dingemans AJM , Donadille B , Duyzend M , Elfeky R , Essaid S , Fabrizzi C , Fico G , Firth HV , Freudenberg-Hua Y , Fullerton JM , Gabriel DL , Gilmour K , Giordano J , Goes FS , Moses RG , Green I , Griese M , Groza T , Gu W , Guthrie J , Gyori B , Hamosh A , Hanauer M , Hanušová K , He YO , Hegde H , Helbig I , Holasová K , Hoyt CT , Huang S , Hurwitz E , Jacobsen JOB , Jiang X , Joseph L , Keramatian K , King B , Knoflach K , Koolen DA , Kraus ML , Kroll C , Kusters M , Ladewig MS , Lagorce D , Lai MC , Lapunzina P , Laraway B , Lewis-Smith D , Li X , Lucano C , Majd M , Marazita ML , Martinez-Glez V , McHenry TH , McInnis MG , McMurry JA , Mihulová M , Millett CE , Mitchell PB , Moslerová V , Narutomi K , Nematollahi S , Nevado J , Nierenberg AA , Čajbiková NN , Nurnberger JI Jr , Ogishima S , Olson D , Ortiz A , Pachajoa H , Perez de Nanclares G , Peters A , Putman T , Rapp CK , Rath A , Reese J , Rekerle L , Roberts AM , Roy S , Sanders SJ , Schuetz C , Schulte EC , Schulze TG , Schwarz M , Scott K , Seelow D , Seitz B , Shen Y , Similuk MN , Simon ES , Singh B , Smedley D , Smith CL , Smolinsky JT , Sperry S , Stafford E , Stefancsik R , Steinhaus R , Strawbridge R , Sundaramurthi JC , Talapova P , Tenorio Castano JA , Tesner P , Thomas RH , Thurm A , Turnovec M , van Gijn ME , Vasilevsky NA , Vlčková M , Walden A , Wang K , Wapner R , Ware JS , Wiafe AA , Wiafe SA , Wiggins LD , Williams AE , Wu C , Wyrwoll MJ , Xiong H , Yalin N , Yamamoto Y , Yatham LN , Yocum AK , Young AH , Yüksel Z , Zandi PP , Zankl A , Zarante I , Zvolský M , Toro S , Carmody LC , Harris NL , Munoz-Torres MC , Danis D , Mungall CJ , Köhler S , Haendel MA , Robinson PN . Nucleic Acids Res 2023 52 D1333-D1346 The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs. |
A finite element analysis of the effects of anchorage reaction forces and moments on structural stability of mast climbing work platforms
Wu JZ , Pan CS , Wimer BM , Warren CM , Villeneuve F , Dong RG . J Multiscale Modell null [Epub ahead of print] Mast climbing work platforms (MCWPs) have been increasingly used for construction projects, whereas their safety remains an important issue. As the mast in the Mast climbing work platform (MCWP) system is "slender" structurally, its anchorages must play an important role in maintaining its stability. Therefore, the anchorages and their attachments to a construction structure are likely among the most critical components for the MCWPs. This study developed finite element models of a representative MCWP and applied them to analyze the characteristics of the reaction forces at the anchorages when the work platform operates at different heights and under different loading conditions and to simulate the mast structure responses to the failure of one of the three anchorages. The results of this study indicate that the anchorage reaction forces are sensitive to the loading and operational conditions of the MCWP. The responses of the anchorage reaction forces may reflect the stability status or risk potential of the mast structure of the MCWP to collapse. The characteristics of the anchorage forces identified in this study can be used to help develop a structural safety monitoring system, to minimize the risk of catastrophic failures of MCWPs. The knowledge obtained in the study would help improve MCWP safety management at construction sites and help MCWP manufacturers to improve anchorage design and installation procedures to reduce the risk of the mast structure's instability or collapse. |
Effectiveness of maternal mRNA COVID-19 vaccination during pregnancy against COVID-19-associated hospitalizations in infants aged <6 months during SARS-cov-2 Omicron predominance - 20 states, March 9, 2022-May 31, 2023
Simeone RM , Zambrano LD , Halasa NB , Fleming-Dutra KE , Newhams MM , Wu MJ , Orzel-Lockwood AO , Kamidani S , Pannaraj PS , Irby K , Maddux AB , Hobbs CV , Cameron MA , Boom JA , Sahni LC , Kong M , Nofziger RA , Schuster JE , Crandall H , Hume JR , Staat MA , Mack EH , Bradford TT , Heidemann SM , Levy ER , Gertz SJ , Bhumbra SS , Walker TC , Bline KE , Michelson KN , Zinter MS , Flori HR , Campbell AP , Randolph AG . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1057-1064 Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19. |
Rotavirus genotypes in the post-vaccine era: A systematic review and meta-analysis of global, regional, and temporal trends in settings with and without rotavirus vaccine introduction
Amin AB , Cates JE , Liu Z , Wu J , Ali I , Rodriguez A , Panjwani J , Tate JE , Lopman BA , Parashar UD . J Infect Dis 2023 BACKGROUND: Even moderate differences in rotavirus vaccine effectiveness against non-vaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. METHODS: We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and non-introducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. RESULTS: Crude pooling of genotype data from 361 studies indicated higher G2P[4], a non-vaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to non-introducing settings, G2P[4] detections were more likely in settings with recent introduction (e.g. 1-2 years post-introduction aOR: 4.39 (95% CI: 2.87-6.72)) but were similarly likely in settings with more time elapsed since introduction, (e.g. 7 or more years aOR (1.62 95% CI: 0.49-5.37)). CONCLUSIONS: When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction. |
Multisystem inflammatory syndrome in children among persons who completed a two-dose COVID-19 vaccine primary series compared with those reporting no COVID-19 vaccination, US national MIS-C surveillance
Yousaf AR , Miller AD , Lindsey K , Shah AB , Wu MJ , Melgar M , Zambrano LD , Campbell AP . Pediatr Infect Dis J 2023 42 (12) e476-e478 We analyzed multisystem inflammatory syndrome in children cases by reported COVID-19 vaccination status (2-dose primary series vs. no vaccination). A total of 46% vaccinated versus 58% unvaccinated persons received intensive care unit-level care (P = 0.02); the risk of intensive care unit admission was 23% higher (adjusted relative risk: 1.23; 95% confidence interval: 1.03-1.48) among unvaccinated patients; 21 unvaccinated persons died. Multisystem inflammatory syndrome in children occurs after SARS-CoV-2 infection in vaccinated persons, but may be less severe. |
Public health research priorities for fungal diseases: A multidisciplinary approach to save lives
Smith DJ , Gold JAW , Benedict K , Wu K , Lyman M , Jordan A , Medina N , Lockhart SR , Sexton DJ , Chow NA , Jackson BR , Litvintseva AP , Toda M , Chiller T . J Fungi (Basel) 2023 9 (8) Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen. |
Fatal invasive mold infections after transplantation of organs recovered from drowned donors, United States, 2011-2021
Wu K , Annambhotla P , Free RJ , Ritter JM , Leitgeb B , Jackson BR , Toda M , Basavaraju SV , Gold JAW . Emerg Infect Dis 2023 29 (7) 1455-1458 Drowned organ donors can be exposed to environmental molds through the aspiration of water; transplantation of exposed organs can cause invasive mold infections in recipients. We describe 4 rapidly fatal cases of potentially donor-derived invasive mold infections in the United States, highlighting the importance of maintaining clinical suspicion for these infections in transplant recipients. |
Impact of the COVID-19 pandemic on inpatient antibiotic use in the United States, January 2019 through July 2022
O'Leary EN , Neuhauser MM , Srinivasan A , Dubendris H , Webb AK , Soe MM , Hicks LA , Wu H , Kabbani S , Edwards JR . Clin Infect Dis 2023 Antimicrobial use (AU) data reported to the National Healthcare Safety Network's Antimicrobial Use and Resistance Module between January 2019 and July 2022 were analyzed to assess the impact of the COVID-19 pandemic on inpatient antimicrobial use. |
Demographic disparities in mpox vaccination series completion, by route of vaccine administration - California, August 9, 2022-March 31, 2023
Salih T , Vance J , Quint J , Meza B , McNitt L , Lincoln WU , Schechter R . MMWR Morb Mortal Wkly Rep 2023 72 (30) 827-832 In August 2022, the Food and Drug Administration authorized JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic), a 2-dose series used for the prevention of Monkeypox virus infection, to be administered via a dose-sparing intradermal route, in addition to the previously authorized subcutaneous route. The California Department of Public Health investigated whether demographic disparities in vaccination series completion varied by route of administration of the recipient's first dose. Among California residents who received their first dose during August 9, 2022-March 31, 2023, a total of 59.8% received a second dose. Series completion was highest among non-Hispanic White persons (64.1%), persons aged ≥65 years (72.6%), and adults with male sex assignment at birth (62.1%); series completion was lowest among non-Hispanic Black or African American persons (51.3%), persons aged 18-24 years (42.9%), and adults assigned female sex at birth (42.8%). When the first dose was received by subcutaneous administration, overall series completion was 58.8% compared with 60.2% when the first dose was administered intradermally. Odds of series completion across all race and ethnicity groups, persons aged 18-64 years, community health conditions, and persons assigned male sex at birth were not greater when the first dose was administered subcutaneously compared with intradermally. Intradermal use of JYNNEOS vaccine did not lower overall 2-dose series completion rates. Continued efforts are needed to ensure persons at risk for Monkeypox virus infection receive both recommended doses. |
Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America
Erchick DJ , Subedi S , Verhulst A , Guillot M , Adair LS , Barros AJD , Chasekwa B , Christian P , da Silva BGC , Silveira MF , Hallal PC , Humphrey JH , Huybregts L , Kariuki S , Khatry SK , Lachat C , Matijasevich A , McElroy PD , Menezes AMB , Mullany LC , Perez TLL , Phillips-Howard PA , Roberfroid D , Santos IS , Ter Kuile FO , Ravilla TD , Tielsch JM , Wu LSF , Katz J . Popul Health Metr 2023 21 (1) 10 INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly. |
Surveillance of COVID-19 vaccination in US nursing homes, December 2020-April 2021 (preprint)
Geller AI , Budnitz DS , Dubendris H , Gharpure R , Soe M , Wu H , Kalayil EJ , Benin AL , Patel SA , Lindley MC , Link-Gelles R . medRxiv 2021 2021.05.14.21257224 Monitoring COVID-19 vaccination coverage among nursing home (NH) residents and staff is important to ensure high coverage and guide patient-safety policies. With the termination of the federal Pharmacy Partnership for Long-Term Care Program, another source of facility-based vaccination data is needed. We compared numbers of COVID-19 vaccinations administered to NH residents and staff reported by pharmacies participating in the temporary federal Pharmacy Partnership for Long-Term Care Program with those reported by NHs participating in new COVID-19 vaccination modules of CDC’s National Healthcare Safety Network (NHSN). Pearson correlation coefficients comparing the number vaccinated between the two approaches were 0.89, 0.96, and 0.97 for residents and 0.74, 0.90, and 0.90 for staff, in the weeks ending January 3, 10, and 17, respectively. Based on subsequent NHSN reporting, vaccination coverage with ≥1 vaccine dose reached 77% for residents and 50% for staff the week ending January 31 and plateaued through April 2021.Three-question summary boxWhat is the current understanding of the subject?Because of high risk of disease, nursing home residents and staff were prioritized for COVID-19 vaccination when doses were limited.What does this report add to the literature?National monitoring of nursing home residents and staff vaccination coverage through the CDC National Healthcare Safety Network (NHSN) correlated with vaccination administration reports from the federal Pharmacy Partnership for Long-Term Care Program in January 2021. NHSN-reported vaccination coverage rates plateaued from February through April 2021.What are the implications for public health practice?NHSN can track COVID-19 vaccination in nursing homes and help guide efforts to increase vaccine uptake in residents and staff.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors received no financial support for the research, authorship, and/or publication of this article.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. section 241(d); 5 U.S.C. section 552a; 44 U.S.C. section 3501 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 supporting the findings of the study are found in the manuscript and/or supplementary files. Any other data can be furnished upon request. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Koralov S , Wu B , Yeung S , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal S , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman D , Heguy A , Uyeki T , Clemente J , de Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst C , Koide S , Stapleford K , Khanna K , Ghedin E , Weiden M , Segal L . Res Sq 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Tsay JJ , Wu BG , Yeung ST , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal SA , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman DH , Weiden M , Hegu A , Evans L , Uyeki TM , Clemente JC , De Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst CV , Koide S , Stapleford KA , Khanna KM , Ghedin E , Segal LN . medRxiv 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
Imprinted anti-hemagglutinin and anti-neuraminidase antibody responses after childhood infections of A(H1N1) and A(H1N1)pdm09 influenza viruses (preprint)
Daulagala P , Mann BR , Leung K , Lau EHY , Yung L , Lei R , Nizami SIN , Wu JT , Chiu SS , Daniels RS , Wu NC , Wentworth D , Peiris M , Yen HL . bioRxiv 2023 2023.02.01.526741 Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralising anti-HA antibodies against HA antigenic variants. Here we systematically characterised the NA antigenic variants of seasonal A(H1N1) viruses from 1977 to 1991 and completed the antigenic profile of N1 NAs from 1977 to 2015. We identified that NA proteins of A/USSR/90/77, A/Singapore/06/86, and A/Texas/36/91 were antigenically distinct and mapped N386K as a key determinant of the NA antigenic change from A/USSR/90/77 to A/Singapore/06/86. With comprehensive panels of HA and NA antigenic variants of A(H1N1) and A(H1N1)pdm09 viruses, we determined hemagglutinin inhibition (HI) and neuraminidase inhibition (NI) antibodies from 130 subjects born between 1950-2015. Age-dependent imprinting was observed for both anti-HA and anti-NA antibodies, with the peak HI and NI titers predominantly detected from subjects at 4-12 years old during the year of initial virus isolation, except the age-independent anti-HA antibody response against A(H1N1)pdm09 viruses. More participants possessed antibodies that reacted to multiple antigenically distinct NA proteins than those with antibodies that reacted to multiple antigenically distinct HA proteins. Our results support the need to include NA proteins in seasonal influenza vaccine preparations.IMPORTANCE Seasonal influenza vaccines have aimed to generate neutralizing anti-HA antibodies for protection since licensure. More recently, anti-NA antibodies have been established as an additional correlate of protection. While HA and NA antigenic changes occurred discordantly, the anti-HA and anti-NA antibody profiles have rarely been analysed in parallel at the individual level, due to the limited knowledge on NA antigenic changes. By characterizing NA antigenic changes of A(H1N1) viruses, we determined the anti-HA and anti-NA antibody landscape against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses using sera of 130 subjects born between 1950-2015. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ≥1:40. With slower NA antigenic changes and cross-reactive anti-NA antibody responses, including NA protein in influenza vaccine preparation may enhance vaccine efficacy. (150 words) |
Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US (preprint)
Cramer EY , Ray EL , Lopez VK , Bracher J , Brennen A , Castro Rivadeneira AJ , Gerding A , Gneiting T , House KH , Huang Y , Jayawardena D , Kanji AH , Khandelwal A , Le K , Mühlemann A , Niemi J , Shah A , Stark A , Wang Y , Wattanachit N , Zorn MW , Gu Y , Jain S , Bannur N , Deva A , Kulkarni M , Merugu S , Raval A , Shingi S , Tiwari A , White J , Abernethy NF , Woody S , Dahan M , Fox S , Gaither K , Lachmann M , Meyers LA , Scott JG , Tec M , Srivastava A , George GE , Cegan JC , Dettwiller ID , England WP , Farthing MW , Hunter RH , Lafferty B , Linkov I , Mayo ML , Parno MD , Rowland MA , Trump BD , Zhang-James Y , Chen S , Faraone SV , Hess J , Morley CP , Salekin A , Wang D , Corsetti SM , Baer TM , Eisenberg MC , Falb K , Huang Y , Martin ET , McCauley E , Myers RL , Schwarz T , Sheldon D , Gibson GC , Yu R , Gao L , Ma Y , Wu D , Yan X , Jin X , Wang YX , Chen Y , Guo L , Zhao Y , Gu Q , Chen J , Wang L , Xu P , Zhang W , Zou D , Biegel H , Lega J , McConnell S , Nagraj VP , Guertin SL , Hulme-Lowe C , Turner SD , Shi Y , Ban X , Walraven R , Hong QJ , Kong S , van de Walle A , Turtle JA , Ben-Nun M , Riley S , Riley P , Koyluoglu U , DesRoches D , Forli P , Hamory B , Kyriakides C , Leis H , Milliken J , Moloney M , Morgan J , Nirgudkar N , Ozcan G , Piwonka N , Ravi M , Schrader C , Shakhnovich E , Siegel D , Spatz R , Stiefeling C , Wilkinson B , Wong A , Cavany S , España G , Moore S , Oidtman R , Perkins A , Kraus D , Kraus A , Gao Z , Bian J , Cao W , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Vespignani A , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Xiong X , Zheng A , Baek J , Farias V , Georgescu A , Levi R , Sinha D , Wilde J , Perakis G , Bennouna MA , Nze-Ndong D , Singhvi D , Spantidakis I , Thayaparan L , Tsiourvas A , Sarker A , Jadbabaie A , Shah D , Della Penna N , Celi LA , Sundar S , Wolfinger R , Osthus D , Castro L , Fairchild G , Michaud I , Karlen D , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Lee EC , Dent J , Grantz KH , Hill AL , Kaminsky J , Kaminsky K , Keegan LT , Lauer SA , Lemaitre JC , Lessler J , Meredith HR , Perez-Saez J , Shah S , Smith CP , Truelove SA , Wills J , Marshall M , Gardner L , Nixon K , Burant JC , Wang L , Gao L , Gu Z , Kim M , Li X , Wang G , Wang Y , Yu S , Reiner RC , Barber R , Gakidou E , Hay SI , Lim S , Murray C , Pigott D , Gurung HL , Baccam P , Stage SA , Suchoski BT , Prakash BA , Adhikari B , Cui J , Rodríguez A , Tabassum A , Xie J , Keskinocak P , Asplund J , Baxter A , Oruc BE , Serban N , Arik SO , Dusenberry M , Epshteyn A , Kanal E , Le LT , Li CL , Pfister T , Sava D , Sinha R , Tsai T , Yoder N , Yoon J , Zhang L , Abbott S , Bosse NI , Funk S , Hellewell J , Meakin SR , Sherratt K , Zhou M , Kalantari R , Yamana TK , Pei S , Shaman J , Li ML , Bertsimas D , Skali Lami O , Soni S , Tazi Bouardi H , Ayer T , Adee M , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller P , Xiao J , Wang Y , Wang Q , Xie S , Zeng D , Green A , Bien J , Brooks L , Hu AJ , Jahja M , McDonald D , Narasimhan B , Politsch C , Rajanala S , Rumack A , Simon N , Tibshirani RJ , Tibshirani R , Ventura V , Wasserman L , O'Dea EB , Drake JM , Pagano R , Tran QT , Ho LST , Huynh H , Walker JW , Slayton RB , Johansson MA , Biggerstaff M , Reich NG . medRxiv 2021 2021.02.03.21250974 Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information& Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. & Charlene Zalesky, and Claudia & Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill & Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, & Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.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:UMass-Amherst IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44 |
Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis (preprint)
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . bioRxiv 2019 666230 Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM. |
Mapping the Host-Pathogen Space to Link Longitudinal and Cross-sectional Biomarker Data: Leptospira Infection in California Sea Lions (Zalophus californianus) as a Case Study (preprint)
Prager KC , Buhnerkempe MG , Greig DJ , Orr AJ , Jensen ED , Gomez F , Galloway RL , Wu Q , Gulland FMD , Lloyd-Smith JO . bioRxiv 2019 819532 Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a bacterial infection (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve both our individual-level and population-level understanding of this host-pathogen system. We create a “host-pathogen space” by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to visualize and characterize changes in these values through time. We describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health. This mapping framework enables us to determine an individual’s location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure, including severe acute disease, chronic subclinical infection, and recovery. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and in certain cases we can impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space and using quantitative biomarker data provides more nuanced approaches for understanding and modeling disease dynamics in a system, yielding benefits for the clinician who needs to triage patients and prevent transmission, and for the disease ecologist or epidemiologist wishing to develop appropriate risk management strategies and assess health impacts on a population scale.Author Summary A pathogen can cause a range of disease severity across different host individuals, and these presentations change over the time-course from infection to recovery. These facts complicate the work of epidemiologists and disease ecologists seeking to understand the factors governing disease spread, often working with cross-sectional data. Recognizing these facts also highlights the shortcomings of classical approaches to modeling infectious disease, which typically rely on discrete and well-defined disease states. Here we show that by analyzing multiple biomarkers of health and infection simultaneously, treating these values as quantitative rather than binary indicators, and including a modest amount of longitudinal sampling of hosts, we can create a map of the host-pathogen interaction that shows the full spectrum of disease presentations and opens doors for new insights and predictions. By accounting for individual variation and capturing changes through time since infection, this mapping framework enables more robust interpretation of cross-sectional data; e.g., to detect predictive relationships between biomarkers and key outcomes such as survival, or to assess whether observed disease is associated with the pathogen of interest. This approach can help epidemiologists, ecologists and clinicians to better study and manage the many infectious diseases that exhibit complex relationships with their hosts. |
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus (preprint)
Shen WF , Galula JU , Liu JH , Liao MY , Huang CH , Wang YC , Wu HC , Liang JJ , Lin YL , Whitney MT , Chang GJ , Chen SR , Wu SR , Chao DY . bioRxiv 2018 351700 Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs. |
A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus (preprint)
Chao DY , Shen WF , Galula JU , Liu JH , Liao MY , Huang CH , Wang YC , Wu HC , Liang JJ , Lin YL , Whitney MT , Chang GJ , Chen SR , Wu SR . bioRxiv 2018 275685 Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP. |
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