Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 90 Records) |
Query Trace: McLaughlin M[original query] |
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Pre-existing immunocompromising conditions and outcomes of acute COVID-19 patients admitted for pediatric intensive care
Rowan CM , LaBere B , Young CC , Zambrano LD , Newhams MM , Kucukak S , McNamara ER , Mack EH , Fitzgerald JC , Irby K , Maddux AB , Schuster JE , Kong M , Dapul H , Schwartz SP , Bembea MM , Loftis LL , Kolmar AR , Babbitt CJ , Nofziger RA , Hall MW , Gertz SJ , Cvijanovich NZ , Zinter MS , Halasa NB , Bradford TT , McLaughlin GE , Singh AR , Hobbs CV , Wellnitz K , Staat MA , Coates BM , Crandall HR , Maamari M , Havlin KM , Schwarz AJ , Carroll CL , Levy ER , Moffitt KL , Campbell AP , Randolph AG , Chou J . Clin Infect Dis 2024 BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities. |
Using geographic disaggregation to compare tuberculosis epidemiology among American Indian and Alaska native persons-USA, 2010-2020
Springer YP , Kammerer JS , Felix D , Newell K , Tompkins ML , Allison J , Castrodale LJ , Chandler B , Helfrich K , Rothoff M , McLaughlin JB , Silk BJ . J Racial Ethn Health Disparities 2024 BACKGROUND: American Indian and Alaska Native (AIAN) populations are frequently associated with the highest rates of tuberculosis (TB) disease of any racial/ethnic group in the USA. We systematically investigated variation in patterns and potential drivers of TB epidemiology among geographically distinct AIAN subgroups. METHODS: Using data reported to the National Tuberculosis Surveillance System during 2010-2020, we applied a geographic method of data disaggregation to compare annual TB incidence and the frequency of TB patient characteristics among AIAN persons in Alaska with AIAN persons in other states. We used US Census data to compare the prevalence of substandard housing conditions in AIAN communities in these two geographic areas. RESULTS: The average annual age-adjusted TB incidence among AIAN persons in Alaska was 21 times higher than among AIAN persons in other states. Compared to AIAN TB patients in other states, AIAN TB patients in Alaska were associated with significantly higher frequencies of multiple epidemiologic TB risk factors (e.g., attribution of TB disease to recent transmission, previous diagnosis of TB disease) and significantly lower frequencies of multiple clinical risk factors for TB disease (e.g., diagnosis with diabetes mellitus, end-stage renal disease). Occupied housing units in AIAN communities in Alaska were associated with significantly higher frequencies of multiple measures of substandard housing conditions compared to AIAN communities in other states. CONCLUSIONS: Observed differences in patient characteristics and substandard housing conditions are consistent with contrasting syndromes of TB epidemiology in geographically distinct AIAN subgroups and suggest ways that associated public health interventions could be tailored to improve efficacy. |
STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE Statement.
Little J , Higgins JP , Ioannidis JP , Moher D , Gagnon F , von Elm E , Khoury MJ , Cohen B , Davey-Smith G , Grimshaw J , Scheet P , Gwinn M , Williamson RE , Zou GY , Hutchings K , Johnson CY , Tait V , Wiens M , Golding J , van Duijn C , McLaughlin J , Paterson A , Wells G , Fortier I , Freedman M , Zecevic M , King R , Infante-Rivard C , Stewart A , Birkett N . Ann Intern Med 2009 150 (3) 206-15 Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information into the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and issues of data volume that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. |
Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement.
Little J , Higgins JP , Ioannidis JP , Moher D , Gagnon F , von Elm E , Khoury MJ , Cohen B , Davey-Smith G , Grimshaw J , Scheet P , Gwinn M , Williamson RE , Zou GY , Hutchings K , Johnson CY , Tait V , Wiens M , Golding J , van Duijn C , McLaughlin J , Paterson A , Wells G , Fortier I , Freedman M , Zecevic M , King R , Infante-Rivard C , Stewart A , Birkett N . Hum Genet 2009 125 (2) 131-51 Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. |
STrengthening the REporting of Genetic Association Studies (STREGA): an extension of the STROBE statement.
Little J , Higgins JP , Ioannidis JP , Moher D , Gagnon F , von Elm E , Khoury MJ , Cohen B , Davey-Smith G , Grimshaw J , Scheet P , Gwinn M , Williamson RE , Zou GY , Hutchings K , Johnson CY , Tait V , Wiens M , Golding J , van Duijn C , McLaughlin J , Paterson A , Wells G , Fortier I , Freedman M , Zecevic M , King R , Infante-Rivard C , Stewart A , Birkett N . PLoS Med 2009 6 (2) e22 Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. |
Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement.
Little J , Higgins JP , Ioannidis JP , Moher D , Gagnon F , von Elm E , Khoury MJ , Cohen B , Davey-Smith G , Grimshaw J , Scheet P , Gwinn M , Williamson RE , Zou GY , Hutchings K , Johnson CY , Tait V , Wiens M , Golding J , van Duijn C , McLaughlin J , Paterson A , Wells G , Fortier I , Freedman M , Zecevic M , King R , Infante-Rivard C , Stewart A , Birkett N . Eur J Epidemiol 2009 24 (1) 37-55 Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. |
STrengthening the REporting of Genetic Association studies (STREGA)--an extension of the STROBE statement.
Little J , Higgins JP , Ioannidis JP , Moher D , Gagnon F , von Elm E , Khoury MJ , Cohen B , Davey-Smith G , Grimshaw J , Scheet P , Gwinn M , Williamson RE , Zou GY , Hutchings K , Johnson CY , Tait V , Wiens M , Golding J , van Duijn C , McLaughlin J , Paterson A , Wells G , Fortier I , Freedman M , Zecevic M , King R , Infante-Rivard C , Stewart A , Birkett N . Eur J Clin Invest 2009 39 (4) 247-66 Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct or analysis. |
Strengthening the reporting of genetic association studies (STREGA): an extension of the strengthening the reporting of observational studies in epidemiology (STROBE) statement.
Little J , Higgins JP , Ioannidis JP , Moher D , Gagnon F , von Elm E , Khoury MJ , Cohen B , Davey-Smith G , Grimshaw J , Scheet P , Gwinn M , Williamson RE , Zou GY , Hutchings K , Johnson CY , Tait V , Wiens M , Golding J , van Duijn C , McLaughlin J , Paterson A , Wells G , Fortier I , Freedman M , Zecevic M , King R , Infante-Rivard C , Stewart AF , Birkett N . J Clin Epidemiol 2009 62 (6) 597-608.e4 Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence, the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association (STREGA) studies initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. |
Temporally associated invasive pneumococcal disease and SARS-CoV-2 infection, Alaska, USA, 2020-2021
Newell K , Fischer M , Massey S , Orell L , Steinberg J , Tompkins M , Castrodale L , McLaughlin J . Emerg Infect Dis 2023 29 (9) 1765-1771 Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations. |
Sepsis program activities in acute care hospitals - National Healthcare Safety Network, United States, 2022
Dantes RB , Kaur H , Bouwkamp BA , Haass KA , Patel P , Dudeck MA , Srinivasan A , Magill SS , Wilson WW , Whitaker M , Gladden NM , McLaughlin ES , Horowitz JK , Posa PJ , Prescott HC . MMWR Morb Mortal Wkly Rep 2023 72 (34) 907-911 Sepsis, life-threatening organ dysfunction secondary to infection, contributes to at least 1.7 million adult hospitalizations and at least 350,000 deaths annually in the United States. Sepsis care is complex, requiring the coordination of multiple hospital departments and disciplines. Sepsis programs can coordinate these efforts to optimize patient outcomes. The 2022 National Healthcare Safety Network (NHSN) annual survey evaluated the prevalence and characteristics of sepsis programs in acute care hospitals. Among 5,221 hospitals, 3,787 (73%) reported having a committee that monitors and reviews sepsis care. Prevalence of these committees varied by hospital size, ranging from 53% among hospitals with 0-25 beds to 95% among hospitals with >500 beds. Fifty-five percent of all hospitals provided dedicated time (including assigned protected time or job description requirements) for leaders of these committees to manage a program and conduct daily activities, and 55% of committees reported involvement with antibiotic stewardship programs. These data highlight opportunities, particularly in smaller hospitals, to improve the care and outcomes of patients with sepsis in the United States by ensuring that all hospitals have sepsis programs with protected time for program leaders, engagement of medical specialists, and integration with antimicrobial stewardship programs. CDC's Hospital Sepsis Program Core Elements provides a guide to assist hospitals in developing and implementing effective sepsis programs that complement and facilitate the implementation of existing clinical guidelines and improve patient care. Future NHSN annual surveys will monitor uptake of these sepsis core elements. |
In silico analyses of penicillin binding proteins in Burkholderia pseudomallei uncovers SNPs with utility for phylogeography, species differentiation, and sequence typing (preprint)
Mclaughlin HP , Gulvik CA , Sue D . bioRxiv 2021 2021.10.08.463618 Background Burkholderia pseudomallei causes melioidosis. Sequence typing this pathogen can reveal geographical origin and uncover epidemiological associations. Here, we describe B. pseudomallei genes encoding putative penicillin binding proteins (PBPs) and investigate their utility for determining phylogeography and differentiating closely related species.Methodology & Principal Findings We performed in silico analysis to characterize 10 PBP homologs in B. pseudomallei 1026b. As PBP active site mutations can confer β-lactam resistance in Gram-negative bacteria, PBP sequences in two resistant B. pseudomallei strains were examined for similar alterations. Sequence alignments revealed single amino acid polymorphisms (SAAPs) unique to the multidrug resistant strain Bp1651 in the transpeptidase domains of two PBPs, but not directly within the active sites. Using BLASTn analyses of complete assembled genomes in the NCBI database, we determined genes encoding PBPs were conserved among B. pseudomallei (n=101) and Burkholderia mallei (n=26) strains. Within these genes, single nucleotide polymorphisms (SNPs) useful for predicting geographic origin of B. pseudomallei were uncovered. SNPs unique to B. mallei were also identified. Based on 11 SNPs identified in two genes encoding predicted PBP-3s, a dual-locus sequence typing (DLST) scheme was developed. The robustness of this typing scheme was assessed using 1,523 RefSeq genomes from B. pseudomallei (n=1,442) and B. mallei (n=81) strains, resulting in 32 sequence types (STs). Compared to multi-locus sequence typing (MLST), the DLST scheme demonstrated less resolution to support the continental separation of Australian B. pseudomallei strains. However, several STs were unique to strains originating from a specific country or region. The phylogeography of Western Hemisphere B. pseudomallei strains was more highly resolved by DLST compared to internal transcribed spacer (ITS) typing, and all B. mallei strains formed a single ST.Significance Conserved genes encoding PBPs in B. pseudomallei are useful for strain typing, can enhance predictions of geographic origin, and differentiate strains of closely related Burkholderia species.Author Summary Burkholderia pseudomallei causes the life-threatening disease melioidosis and is considered a biological threat and select agent by the United States government. This soil-dwelling bacterium is commonly found in regions of southeast Asia and northern Australia, but it is also detected in other tropical and sub-tropical areas around the world. With a predicted global burden of 165,000 annual cases and mortality rate that can exceed 40% without prompt and appropriate antibiotic treatment, understanding the epidemiology of melioidosis and mechanisms of antibiotic resistance in B. pseudomallei can benefit public health and safety. Recently, we identified ten conserved genes encoding putative penicillin binding proteins (PBPs) in B. pseudomallei. Here, we examined B. pseudomallei PBP sequences for amino acid mutations that may contribute to β-lactam resistance. We also uncovered nucleotide mutations with utility to predict the geographical origin of B. pseudomallei strains and to differentiate closely related Burkholderia species. Based on 11 informative single nucleotide polymorphisms in two genes each encoding a PBP-3, we developed a simple, targeted dual-locus typing approach.Competing Interest StatementThe authors have declared no competing interest. |
Optical microscopy reveals the dynamic nature of B. pseudomallei morphology during β-lactam antimicrobial susceptibility testing (preprint)
McLaughlin HP , Bugrysheva J , Sue D . bioRxiv 2020 2020.01.13.904995 Background In Gram-negative species, β-lactam antibiotics target penicillin binding proteins (PBPs) resulting in morphological alterations of bacterial cells. Observations of antibiotic-induced cell morphology changes can rapidly and accurately differentiate drug susceptible from resistant bacterial strains; however, resistant cells do not always remain unchanged. Burkholderia pseudomallei is a Gram-negative, biothreat pathogen and the causative agent of melioidosis, an often fatal infectious disease for humans.Results Here, we identified β-lactam targets in B. pseudomallei by in silico analysis. Ten genes encoding putative PBPs, including PBP-1, PBP-2, PBP-3 and PBP-6, were detected in the genomes of susceptible and resistant strains. Real-time, live-cell imaging of B. pseudomallei strains demonstrated dynamic morphological changes in broth containing clinically relevant β-lactam antibiotics. At sub-inhibitory concentrations of ceftazidime (CAZ), amoxicillin-clavulanic acid (AMC), and imipenem (IPM), filamentation, varying in length and proportion, was an initial response of the multidrug-resistant strain Bp1651 in exponential phase. However, a dominant morphotype reemerged during stationary phase that resembled cells unexposed to antibiotics. Similar morphology dynamics were observed for AMC-resistant strains, MSHR1655 and 724644, when exposed to sub-inhibitory concentrations of AMC. For all B. pseudomallei strains evaluated, increased exposure time and exposure to increased concentrations of AMC at and above minimal inhibitory concentrations (MICs) in broth resulted in cell morphology shifts from filaments to spheroplasts and/or cell lysis. B. pseudomallei morphology changes were more consistent in IPM. Spheroplast formation followed by cell lysis was observed for all strains in broth containing IPM at concentrations greater than or equal to MICs, however, the time to cell lysis was variable. Length of B. pseudomallei cells was strain-, drug- and drug concentration-dependent.Conclusions Both resistant and susceptible B. pseudomallei strains exhibited filamentation during early exposure to AMC and CAZ at concentrations used to interpret susceptibility (based on CLSI guidelines). While developing a rapid β-lactam antimicrobial susceptibility test based on cell-shape alone requires more extensive analyses, optical microscopy detected B. pseudomallei growth attributes that lend insight into antibiotic response and antibacterial mechanisms of action.(AST)Antimicrobial susceptibility test,(BMD)broth microdilution,(CLSI)Clinical and Laboratory Standards Institute,(IPM)imipenem,(CAZ)ceftazidime,(AMC)amoxicillin-clavulanic acid,(MDR)multidrug-resistant,(R)resistant,(I)intermediate,(S)susceptible,(SBA)Trypticase Soy Agar II with 5% sheep blood,(CAMHB)cation-adjusted Mueller Hinton broth,(MIC)minimal inhibitory concentrations,(TES)N-tris(hydroxymethyl) methyl-2-aminoethanesulfonic acid,(SESA)Segmentation and Extraction Surface Area,(SD)standard deviation,(PBPs)penicillin-binding proteins. |
Rapid Detection of Genetic Engineering, Structural Variation, and Antimicrobial Resistance Markers in Bacterial Biothreat Pathogens by Nanopore Sequencing (preprint)
Gargis AS , Cherney B , Conley AB , McLaughlin HP , Sue D . bioRxiv 2019 730093 Widespread release of Bacillus anthracis (anthrax) or Yersinia pestis (plague) would prompt a public health emergency. During an exposure event, high-quality whole genome sequencing (WGS) can identify genetic engineering, including the introduction of antimicrobial resistance (AMR) genes. Here, we developed rapid WGS laboratory and bioinformatics workflows using a long-read nanopore sequencer (MinION) for Y. pestis (6.5h) and B. anthracis (8.5h) and sequenced strains with different AMR profiles. Both salt-precipitation and silica-membrane extracted DNA were suitable for MinION WGS using both rapid and field library preparation methods. In replicate experiments, nanopore quality metrics were defined for genome assembly and mutation analysis. AMR markers were correctly detected and >99% coverage of chromosomes and plasmids was achieved using 100,000 raw sequencing reads. While chromosomes and large and small plasmids were accurately assembled, including novel multimeric forms of the Y. pestis virulence plasmid, pPCP1, MinION reads were error-prone, particularly in homopolymer regions. MinION sequencing holds promise as a practical, front-line strategy for on-site pathogen characterization to speed the public health response during a biothreat emergency. |
A distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C) (preprint)
Bodansky A , Sabatino JJ , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Asaki J , Pluvinage JV , Wilson MR , Loftis LL , Hobbs CV , Tarquinio KM , Kong M , Fitzgerald JC , Espinal PS , Walker TC , Schwartz SP , Crandall H , Irby K , Staat MA , Rowan CM , Schuster JE , Halasa NB , Gertz SJ , Mack EH , Maddux AB , Cvijanovich NZ , Zinter MS , Zambrano LD , Campbell AP , Randolph AG , Anderson MS , DeRisi JL , Kelley H , Murdock M , Colston C , Typpo KV , Sanders RC , Yates M , Smith C , Port E , Mansour R , Shankman S , Baig N , Zorensky F , Chatani B , McLaughlin G , Jones K , Coates BM , Newhams MM , Kucukak S , McNamara ER , Moon HK , Kobayashi T , Melo J , Jackson SR , Rosales MKE , Young C , Chen SR , Da Costa Aguiar R , Gutierrez-Arcelus M , Elkins M , Williams D , Williams L , Cheng L , Zhang Y , Crethers D , Morley D , Steltz S , Zakar K , Armant MA , Ciuculescu F , Flori HR , Dahmer MK , Levy ER , Behl S , Drapeau NM , Kietzman A , Hill S , Cullimore ML , McCulloh RJ , Nofziger RA , Rohlfs CC , Burnett R , Bush J , Reed N , Ampofo KK , Patel MM . medRxiv 2023 30 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
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. |
Multipathogen outbreak of bacillus cereus and clostridium perfringens among hospital workers in Alaska, August 2021
Newell K , Helfrich K , Isernhagen H , Jones M , Stickel G , McKeel H , Castrodale L , McLaughlin J . Public Health Rep 2023 333549231170220 OBJECTIVE: Clostridium perfringens and Bacillus cereus are common causes of reported foodborne illness. On August 6, 2021, the Alaska Division of Public Health identified a multipathogen gastrointestinal outbreak among hospital staff in Homer, Alaska. The objectives of this study were to identify the outbreak source and prevent future illness. METHODS: We conducted a retrospective cohort study of hospital staff who participated in luncheon events during August 5-7, 2021, and used an online survey to identify hospital staff with gastrointestinal illness. We defined case patients as people who reported new-onset gastrointestinal illness (diarrhea or abdominal cramping) after food consumption during the luncheon events. We calculated adjusted odds ratios of gastrointestinal illness associated with reported food exposures. We tested available food samples for C perfringens and B cereus and tested case patient stool specimens for C perfringens. We conducted an environmental investigation at the implicated vendor site. RESULTS: Of 202 survey responses, 66 (32.7%) people reported acute gastrointestinal illness: 64 (97.0%) reported diarrhea, 62 (94.9%) reported abdominal cramps, and none were hospitalized. Of 79 people who consumed ham and pulled pork sandwiches, 64 (81.0%) met the case definition; this food item was significantly associated with increased odds of gastrointestinal illness (adjusted odds ratio = 296.4; 95% CI, 76.7-2019.1). C perfringens and B cereus were isolated at confirmatory levels from sandwich samples. C perfringens enterotoxin was detected in all 5 stool specimens tested. Environmental investigators observed other food items at the sandwich vendor that were refrigerated outside the required temperature range (>41 °F); no clear handling deficiencies for the implicated food were identified. CONCLUSION: Quick notification and effective collaboration can help detect an outbreak, identify the responsible food vehicle, and mitigate further risk. |
Extracorporeal membrane oxygenation characteristics and outcomes in children and adolescents with COVID-19 or multisystem inflammatory syndrome admitted to U.S. ICUs
Bembea MM , Loftis LL , Thiagarajan RR , Young CC , McCadden TP , Newhams MM , Kucukak S , Mack EH , Fitzgerald JC , Rowan CM , Maddux AB , Kolmar AR , Irby K , Heidemann S , Schwartz SP , Kong M , Crandall H , Havlin KM , Singh AR , Schuster JE , Hall MW , Wellnitz KA , Maamari M , Gaspers MG , Nofziger RA , Lim PPC , Carroll RW , Coronado Munoz A , Bradford TT , Cullimore ML , Halasa NB , McLaughlin GE , Pannaraj PS , Cvijanovich NZ , Zinter MS , Coates BM , Horwitz SM , Hobbs CV , Dapul H , Graciano AL , Butler AD , Patel MM , Zambrano LD , Campbell AP , Randolph AG . Pediatr Crit Care Med 2023 24 (5) 356-71 OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C (n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 (n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge. |
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. |
Tachyarrhythmias During Hospitalization for COVID-19 or Multisystem Inflammatory Syndrome in Children and Adolescents.
Dionne A , Friedman KG , Young CC , Newhams MM , Kucukak S , Jackson AM , Fitzgerald JC , Smallcomb LS , Heidemann S , McLaughlin GE , Irby K , Bradford TT , Horwitz SM , Loftis LL , Soma VL , Rowan CM , Kong M , Halasa NB , Tarquinio KM , Schwarz AJ , Hume JR , Gertz SJ , Clouser KN , Carroll CL , Wellnitz K , Cullimore ML , Doymaz S , Levy ER , Typpo KV , Lansell AN , Butler AD , Kuebler JD , Zambrano LD , Campbell AP , Patel MM , Randolph AG , Newburger JW . J Am Heart Assoc 2022 11 (20) e025915 Background Cardiac complications related to COVID-19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID-19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID-19-related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID-19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4-17.4] versus 10.0 [range, 5.4-14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID-19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care. |
Systematic review of in vitro antimicrobial susceptibility testing for bacillus anthracis, 1947-2019
Maxson T , Kongphet-Tran T , Mongkolrattanothai T , Travis T , Hendricks K , Parker C , McLaughlin HP , Bugrysheva J , Ambrosio F , Michel P , Cherney B , Lascols C , Sue D . Clin Infect Dis 2022 75 S373-s378 Bacillus anthracis, the causative agent of anthrax, is a high-consequence bacterial pathogen that occurs naturally in many parts of the world and is considered an agent of biowarfare or bioterrorism. Understanding antimicrobial susceptibility profiles of B. anthracis isolates is foundational to treating naturally occurring outbreaks and to public health preparedness in the event of an intentional release. In this systematic review, we searched the peer-reviewed literature for all publications detailing antimicrobial susceptibility testing of B. anthracis. Within the set of discovered articles, we collated a subset of publications detailing susceptibility testing that followed standardized protocols for Food and Drug Administration-approved, commercially available antimicrobials. We analyzed the findings from the discovered articles, including the reported minimal inhibitory concentrations. Across the literature, most B. anthracis isolates were reported as susceptible to current first-line antimicrobials recommended for postexposure prophylaxis and treatment. The data presented for potential alternative antimicrobials will be of use if significant resistance to first-line antimicrobials arises, the strain is bioengineered, or first-line antimicrobials are not tolerated or available. |
Increased Mortality among Persons with Symptomatic COVID-19 During the Period of SARS-CoV-2 B.1.617.2 (Delta Variant) Predominance-Alaska, November 2020-October 2021.
Mooring EQ , Newell K , Castrodale L , Tompkins M , Frank M , McLaughlin J . Clin Infect Dis 2022 75 S298-S302 We compared the mortality risk in Alaska among persons with symptomatic COVID-19 during the period the Delta variant was dominant to those with symptomatic COVID-19 before Delta predominance. The Delta period was associated with 2.43-fold higher odds of death. Unvaccinated persons were 4.49 times more likely to die than fully vaccinated persons. |
Overcoming Barriers to Successful Climate and Health Adaptation Practice: Notes from the Field.
Mallen E , Joseph HA , McLaughlin M , English DQ , Olmedo C , Roach M , Tirdea C , Vargo J , Wolff M , York E . Int J Environ Res Public Health 2022 19 (12) State and local public health agencies are at the forefront of planning and responding to the health challenges of climate hazards but face substantial barriers to effective climate and health adaptation amidst concurrent environmental and public health crises. To ensure successful adaptation, it is necessary to understand and overcome these barriers. The U.S. Centers for Disease Control and Prevention Climate-Ready States and Cities Initiative (CRSCI) provides funding to state and local health departments to anticipate and respond to health impacts from climate change using the Building Resilience Against Climate Effects (BRACE) framework. This paper explores the barriers to and enablers of successful adaptation projects among BRACE West CRSCI grantees, including Arizona, California, Oregon, and the city and county of San Francisco. The barriers included competing demands such as the COVID-19 pandemic, dependence on partners with similar challenges, staff and leadership turnover, uncertain and complex impacts on at-risk populations, and inadequate resources. The enablers included effective partnerships, leadership support, dedicated and skilled internal staff, and policy windows enabling institutional change and reprioritization. These findings highlight effective strategies in the field that state and local health departments may use to anticipate potential barriers and establish their work in an environment conducive to successful adaptation. |
Life-Threatening Complications of Influenza versus COVID-19 in U.S. Children.
Halasa NB , Spieker AJ , Young CC , Olson SM , Newhams MM , Amarin JZ , Moffitt KL , Nakamura MM , Levy ER , Soma VL , Talj R , Weiss SL , Fitzgerald JC , Mack EH , Maddux AB , Schuster JE , Coates BM , Hall MW , Schwartz SP , Schwarz AJ , Kong M , Spinella PC , Loftis LL , McLaughlin GE , Hobbs CV , Rowan CM , Bembea MM , Nofziger RA , Babbitt CJ , Bowens C , Flori HR , Gertz SJ , Zinter MS , Giuliano JS , Hume JR , Cvijanovich NZ , Singh AR , Crandall HA , Thomas NJ , Cullimore ML , Patel MM , Randolph AG . Clin Infect Dis 2022 76 (3) e280-e290 BACKGROUND: Clinical differences between critical illness from influenza infection versus coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared U.S. children (8 months to 17 years) admitted to the intensive care or high acuity unit with influenza (17 hospitals, 12/19/2019-3/9/2020) or COVID-19 (52 hospitals, 3/15/2020-12/31/2020). We compared demographics, underlying conditions, clinical presentation, severity, and outcomes. Using mixed-effects models, we assessed the odds of death or requiring life-support for influenza versus COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median 5.2 vs. 13.8 years), less likely to be non-Hispanic black (14.5% vs. 27.6%) or Hispanic (24.0% vs. 36.2%), and less likely to have ≥1 underlying condition (66.4% vs. 78.5%) or be obese (21.4% vs. 42.2%). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life-support in children with influenza vs. COVID-19 were similar (adjusted odds ratio, 1.30 [95% CI: 0.78-2.15; P = 0.32]). Median duration of hospital stay was shorter for influenza than COVID-19 (5 versus 7 days). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19. |
In silico analyses of penicillin binding proteins in Burkholderia pseudomallei uncovers SNPs with utility for phylogeography, species differentiation, and sequence typing.
Mclaughlin HP , Gulvik CA , Sue D . PLoS Negl Trop Dis 2022 16 (4) e0009882 Burkholderia pseudomallei causes melioidosis. Sequence typing this pathogen can reveal geographical origin and uncover epidemiological associations. Here, we describe B. pseudomallei genes encoding putative penicillin binding proteins (PBPs) and investigate their utility for determining phylogeography and differentiating closely related species. We performed in silico analysis to characterize 10 PBP homologs in B. pseudomallei 1026b. As PBP active site mutations can confer β-lactam resistance in Gram-negative bacteria, PBP sequences in two resistant B. pseudomallei strains were examined for similar alterations. Sequence alignments revealed single amino acid polymorphisms (SAAPs) unique to the multidrug resistant strain Bp1651 in the transpeptidase domains of two PBPs, but not directly within the active sites. Using BLASTn analyses of complete assembled genomes in the NCBI database, we determined genes encoding PBPs were conserved among B. pseudomallei (n = 101) and Burkholderia mallei (n = 26) strains. Within these genes, single nucleotide polymorphisms (SNPs) useful for predicting geographic origin of B. pseudomallei were uncovered. SNPs unique to B. mallei were also identified. Based on 11 SNPs identified in two genes encoding predicted PBP-3s, a dual-locus sequence typing (DLST) scheme was developed. The robustness of this typing scheme was assessed using 1,523 RefSeq genomes from B. pseudomallei (n = 1,442) and B. mallei (n = 81) strains, resulting in 32 sequence types (STs). Compared to multi-locus sequence typing (MLST), the DLST scheme demonstrated less resolution to support the continental separation of Australian B. pseudomallei strains. However, several STs were unique to strains originating from a specific country or region. The phylogeography of Western Hemisphere B. pseudomallei strains was more highly resolved by DLST compared to internal transcribed spacer (ITS) typing, and all B. mallei strains formed a single ST. Conserved genes encoding PBPs in B. pseudomallei are useful for strain typing, can enhance predictions of geographic origin, and differentiate strains of closely related Burkholderia species. |
Acceptance of Saliva-Based Specimen Collection for SARS-CoV-2 Testing Among K-12 Students, Teachers, and Staff.
McLaughlin HP , Worrell MC , Malone S , Dawson P , Maricque B , Halpin JL , Lee S , Fritz SA , Tinker SC , Neidich JA , Towns K , Lee JS , Barrios LC , Neatherlin JC , Newland JG , Salzer JS . Public Health Rep 2022 137 (3) 333549221074395 OBJECTIVE: Saliva specimens collected in school populations may offer a more feasible, noninvasive alternative to nasal swabs for large-scale COVID-19 testing efforts in kindergarten through 12th grade (K-12) schools. We investigated acceptance of saliva-based COVID-19 testing among quarantined K-12 students and their parents, teachers, and staff members who recently experienced a SARS-CoV-2 exposure in school. METHODS: We surveyed 719 participants, in person or by telephone, who agreed to or declined a free saliva-based COVID-19 reverse-transcription polymerase chain reaction test as part of a surveillance investigation about whether they would have consented to testing if offered a nasal swab instead. We conducted this investigation in 6 school districts in Greene County (n = 3) and St. Louis County (n = 3), Missouri, from January 25 through March 23, 2021. RESULTS: More than one-third (160 of 446) of K-12 students (or their parents or guardians), teachers, and staff members who agreed to a saliva-based COVID-19 test indicated they would have declined testing if specimen collection were by nasal swab. When stratified by school level, 51% (67 of 132) of elementary school students or their parents or guardians would not have agreed to testing if a nasal swab was offered. CONCLUSIONS: Some students, especially those in elementary school, preferred saliva-based COVID-19 testing to nasal swab testing. Use of saliva-based testing might increase voluntary participation in screening efforts in K-12 schools to help prevent the spread of SARS-CoV-2. |
A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020.
Schuster JE , Halasa NB , Nakamura M , Levy ER , Fitzgerald JC , Young CC , Newhams MM , Bourgeois F , Staat MA , Hobbs CV , Dapul H , Feldstein LR , Jackson AM , Mack EH , Walker TC , Maddux AB , Spinella PC , Loftis LL , Kong M , Rowan CM , Bembea MM , McLaughlin GE , Hall MW , Babbitt CJ , Maamari M , Zinter MS , Cvijanovich NZ , Michelson KN , Gertz SJ , Carroll CL , Thomas NJ , Giuliano JS , Singh AR , Hymes SR , Schwarz AJ , McGuire JK , Nofziger RA , Flori HR , Clouser KN , Wellnitz K , Cullimore ML , Hume JR , Patel M , Randolph AG . J Pediatric Infect Dis Soc 2022 11 (5) 191-198 BACKGROUND: It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. METHODS: Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. RESULTS: Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). CONCLUSION: Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies. |
Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants.
Hobbs CV , Woodworth K , Young CC , Jackson AM , Newhams MM , Dapul H , Maamari M , Hall MW , Maddux AB , Singh AR , Schuster JE , Rowan CM , Fitzgerald JC , Irby K , Kong M , Mack EH , Staat MA , Cvijanovich NZ , Bembea MM , Coates BM , Halasa NB , Walker TC , McLaughlin GE , Babbitt CJ , Nofziger RA , Loftis LL , Bradford TT , Campbell AP , Patel MM , Randolph AG . Pediatr Infect Dis J 2021 41 (3) e81-e86 BACKGROUND: Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19. METHODS: Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients aged >7 days to <1 year hospitalized with symptomatic acute COVID-19. RESULTS: We report 232 infants aged >7 days to <1 year hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients aged >7 days to <18 years, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and <1% died. CONCLUSIONS: Infants accounted for over a fifth of children aged <18 years hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were <6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant. |
Distribution of SARS-CoV-2 Variants in a Large Integrated Health Care System - California, March-July 2021.
Malden DE , Bruxvoort KJ , Tseng HF , Ackerson B , Choi SK , Florea A , Tubert J , Takhar H , Aragones M , Hong V , Talarico CA , McLaughlin JM , Qian L , Tartof SY . MMWR Morb Mortal Wkly Rep 2021 70 (40) 1415-1419 Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.(†) Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States. |
Antimicrobial susceptibility of western hemisphere isolates of Burkholderia pseudomallei: Phenotypic and genomic analyses
Bugrysheva JV , Lascols C , McLaughlin HP , Gee JE , Elrod MG , Sue D . Microb Drug Resist 2021 27 (9) 1176-1185 Current antimicrobial treatment recommendations for melioidosis, the disease caused by Burkholderia pseudomallei, are largely based on studies of strains isolated from the Eastern Hemisphere (EH), where most human cases are identified and reported. In this study, we evaluated the antimicrobial susceptibility of 26 strains in the CDC (Centers for Diseases Control and Prevention) collection from the Western Hemisphere (WH) isolated from 1960 to 2015. Minimal inhibitory concentration (MIC) values were measured by standard broth microdilution for 16 antimicrobials following Clinical and Laboratory Standards Institute (CLSI) guidelines. Twenty-four of the 26 WH strains were susceptible to the six antimicrobials with CLSI-defined MIC susceptibility interpretive criteria for B. pseudomallei: amoxicillin/clavulanate, ceftazidime, imipenem, doxycycline, tetracycline, and trimethoprim/sulfamethoxazole. One WH strain demonstrated intermediate amoxicillin/clavulanate resistance and another strain had intermediate resistance to tetracycline. For all antimicrobials tested, the susceptibility profiles of WH isolates were comparable with previously reported MIC results of EH strains. The overall similarities suggest that the same antimicrobials are useful for melioidosis treatment in both the WH and EH. Using in silico analyses of WH genomes, we identified a novel amino acid substitution P258S in the beta-lactamase PenA, which may contribute to decreased susceptibility to amoxicillin/clavulanate in B. pseudomallei. |
Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents.
Geva A , Patel MM , Newhams MM , Young CC , Son MBF , Kong M , Maddux AB , Hall MW , Riggs BJ , Singh AR , Giuliano JS , Hobbs CV , Loftis LL , McLaughlin GE , Schwartz SP , Schuster JE , Babbitt CJ , Halasa NB , Gertz SJ , Doymaz S , Hume JR , Bradford TT , Irby K , Carroll CL , McGuire JK , Tarquinio KM , Rowan CM , Mack EH , Cvijanovich NZ , Fitzgerald JC , Spinella PC , Staat MA , Clouser KN , Soma VL , Dapul H , Maamari M , Bowens C , Havlin KM , Mourani PM , Heidemann SM , Horwitz SM , Feldstein LR , Tenforde MW , Newburger JW , Mandl KD , Randolph AG . EClinicalMedicine 2021 40 101112 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. METHODS: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. FINDINGS: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. INTERPRETATION: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C. |
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