Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
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Query Trace: Browning S [original query] |
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Global VAX: A U.S. contribution to global COVID-19 vaccination efforts, 2021-2023
Dahl BA , Tritter B , Butryn D , Dahlke M , Browning S , Gelting R , Fleming M , Ortiz N , Labrador J , Novak R , Fitter D , Bell E , McGuire M , Rosenbaum R , Pulwer R , Wun J , McCaffrey A , Chowdhury M , Parks N , Cunningham M , Mounts A , Curry D , Richardson D , Grant G . Vaccine 2024 In December 2021 the U.S. Government announced a new, whole-of-government $1.8 billion effort, the Initiative for Global Vaccine Access (Global VAX) in response to the global COVID-19 pandemic. Using the foundation of decades of U.S. government investments in global health and working in close partnership with local governments and key global and multilateral organizations, Global VAX enabled the rapid acceleration of the global COVID-19 vaccine rollout in selected countries, contributing to increased COVID-19 vaccine coverage in some of the world's most vulnerable communities. Through Global VAX, the U.S. Government has supported 125 countries to scale up COVID-19 vaccine delivery and administration while strengthening primary health care systems to respond to future health crises. The progress made by Global VAX has paved the way for a stronger global recovery and improved global health security. |
Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel
Lester SN , Stumpf M , Freeman BD , Mills L , Schiffer J , Semenova V , Jia T , Desai R , Browning P , Alston B , Ategbole M , Bolcen S , Chen A , David E , Manitis P , Tatum H , Qin Y , Zellner B , Drobeniuc J , Tejada-Strop A , Chatterjee P , Shrivastava-Ranjan P , Jenks MH , McMullan LK , Flint M , Spiropoulou CF , Niemeyer GP , Werner BJ , Bean CJ , Johnson JA , Hoffmaster AR , Satheshkumar PS , Schuh AJ , Owen SM , Thornburg NJ . Access Microbiol 2024 6 (2) Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies. |
Early detection and surveillance of the SARS-CoV-2 variant BA.2.86 - Worldwide, July-October 2023
Lambrou AS , South E , Ballou ES , Paden CR , Fuller JA , Bart SM , Butryn DM , Novak RT , Browning SD , Kirby AE , Welsh RM , Cornforth DM , MacCannell DR , Friedman CR , Thornburg NJ , Hall AJ , Hughes LJ , Mahon BE , Daskalakis DC , Shah ND , Jackson BR , Kirking HL . MMWR Morb Mortal Wkly Rep 2023 72 (43) 1162-1167 Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats. |
Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination (preprint)
Zhou ZH , Cortese MM , Fang JL , Wood R , Hummell DS , Risma KA , Norton AE , KuKuruga M , Kirshner S , Rabin RL , Agarabi C , Staat MA , Halasa N , Ware R , Stahl A , McMahon M , Browning P , Maniatis P , Bolcen S , Edwards KM , Su JR , Dharmarajan S , Forshee R , Broder KR , Anderson S , Kozlowski S . medRxiv 2023 12 (28) 4183-4189 Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to excipient polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. Method(s): Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020 - March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay. Anti-PEG IgG and IgM were measured using two different assays. Laboratorians were blinded to case/control status. Result(s): All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65%) were hospitalized and 7 (35%) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10%) case-patients vs 8 of 30 (27%) controls (p=0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0%) vs 1 of 30 (3%) controls (p>0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. Conclusion(s): Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination. 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. |
Evaluation of machine learning for predicting COVID-19 outcomes from a national electronic medical records database (preprint)
Browning S , Lee SH , Belay E , DeCuir J , Cato SG , Patel P , Schwartz N , Wong KK . medRxiv 2022 14 Objective: When novel diseases such as COVID-19 emerge, predictors of clinical outcomes might be unknown. Using data from electronic medical records (EMR) allows evaluation of potential predictors without selecting specific features a priori for a model. We evaluated different machine learning models for predicting outcomes among COVID-19 inpatients using raw EMR data. Material(s) and Method(s): In Premier Healthcare Data Special Release: COVID-19 Edition (PHD-SR COVID-19, release date March, 24 2021), we included patients admitted with COVID-19 during February 2020 through April 2021 and built time-ordered medical histories. Setting the prediction horizon at 24 hours into the first COVID-19 inpatient visit, we aimed to predict intensive care unit (ICU) admission, hyperinflammatory syndrome (HS), and death. We evaluated the following models: L2-penalized logistic regression, random forest, gradient boosting classifier, deep averaging network, and recurrent neural network with a long short-term memory cell. Result(s): There were 57,355 COVID-19 patients identified in PHD-SR COVID-19. ICU admission was the easiest outcome to predict (best AUC=79%), and HS was the hardest to predict (best AUC=70%). Models performed similarly within each outcome. Discussion(s): Although the models learned to attend to meaningful clinical information, they performed similarly, suggesting performance limitations are inherent to the data. Conclusion(s): Predictive models using raw EMR data are promising because they can use many observations and encompass a large feature space; however, traditional and deep learning models may perform similarly when few features are available at the individual patient level. 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. |
Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination
Zhou ZH , Cortese MM , Fang JL , Wood R , Hummell DS , Risma KA , Norton AE , KuKuruga M , Kirshner S , Rabin RL , Agarabi C , Staat MA , Halasa N , Ware RE , Stahl A , McMahon M , Browning P , Maniatis P , Bolcen S , Edwards KM , Su JR , Dharmarajan S , Forshee R , Broder KR , Anderson S , Kozlowski S . Vaccine 2023 BACKGROUND: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. METHODS: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. RESULTS: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. CONCLUSION: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination. |
IVIVE: Facilitating the use of in vitro toxicity data in risk assessment and decision making
Chang X , Tan YM , Allen DG , Bell S , Brown PC , Browning L , Ceger P , Gearhart J , Hakkinen PJ , Kabadi SV , Kleinstreuer NC , Lumen A , Matheson J , Paini A , Pangburn HA , Petersen EJ , Reinke EN , Ribeiro AJS , Sipes N , Sweeney LM , Wambaugh JF , Wange R , Wetmore BA , Mumtaz M . Toxics 2022 10 (5) During the past few decades, the science of toxicology has been undergoing a transformation from observational to predictive science. New approach methodologies (NAMs), including in vitro assays, in silico models, read-across, and in vitro to in vivo extrapolation (IVIVE), are being developed to reduce, refine, or replace whole animal testing, encouraging the judicious use of time and resources. Some of these methods have advanced past the exploratory research stage and are beginning to gain acceptance for the risk assessment of chemicals. A review of the recent literature reveals a burst of IVIVE publications over the past decade. In this review, we propose operational definitions for IVIVE, present literature examples for several common toxicity endpoints, and highlight their implications in decision-making processes across various federal agencies, as well as international organizations, including those in the European Union (EU). The current challenges and future needs are also summarized for IVIVE. In addition to refining and reducing the number of animals in traditional toxicity testing protocols and being used for prioritizing chemical testing, the goal to use IVIVE to facilitate the replacement of animal models can be achieved through their continued evolution and development, including a strategic plan to qualify IVIVE methods for regulatory acceptance. |
Donor-derived ehrlichiosis: Two clusters following solid organ transplantation
Saha A , Browning C , Dandamudi R , Barton K , Graepel K , Cullity M , Abusalah W , Christine D , Rossi C , Drexler N , Basavaraju S , Annambhotia P , Guillamet RV , Eid AJ , Maliakkal J , Miller A , Hugge C , Dharnidharka VR , Kandula P , Moritz MJ . Clin Infect Dis 2021 74 (5) 918-923 Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor derived clusters of ehrlichiosis are described here. During the summer of 2020, two cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis (HLH). Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All three were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization (OPO) and the OPTN for further investigation by public health authorities. |
Characteristics and Risk Factors of Hospitalized and Nonhospitalized COVID-19 Patients, Atlanta, Georgia, USA, March-April 2020.
Pettrone K , Burnett E , Link-Gelles R , Haight SC , Schrodt C , England L , Gomes DJ , Shamout M , O'Laughlin K , Kimball A , Blau EF , Ladva CN , Szablewski CM , Tobin-D'Angelo M , Oosmanally N , Drenzek C , Browning SD , Bruce BB , da Silva J , Gold JAW , Jackson BR , Morris SB , Natarajan P , Fanfair RN , Patel PR , Rogers-Brown J , Rossow J , Wong KK , Murphy DJ , Blum JM , Hollberg J , Lefkove B , Brown FW , Shimabukuro T , Midgley CM , Tate JE , Killerby ME . Emerg Infect Dis 2021 27 (4) 1164-1168 We compared the characteristics of hospitalized and nonhospitalized patients who had coronavirus disease in Atlanta, Georgia, USA. We found that risk for hospitalization increased with a patient's age and number of concurrent conditions. We also found a potential association between hospitalization and high hemoglobin A1c levels in persons with diabetes. |
Changes in SARS CoV-2 Seroprevalence Over Time in Ten Sites in the United States, March - August, 2020.
Lim T , Delorey M , Bestul N , Johannsen M , Reed C , Hall AJ , Fry AM , Edens C , Semenova V , Li H , Browning P , Desai R , Epperson M , Jia T , Thornburg NJ , Schiffer J , Havers FP . Clin Infect Dis 2021 73 (10) 1831-1839 BACKGROUND: Monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence can complement case reporting to inform more accurate estimates of SARS-CoV-2 infection burden, but few studies have undertaken repeated sampling over time on a broad geographic scale. METHODS: We performed serologic testing on a convenience sample of residual sera obtained from persons of all ages, at ten sites in the United States from March 23 through August 14, 2020, from routine clinical testing at commercial laboratories. We age-sex-standardized our seroprevalence rates using census population projections and adjusted for laboratory assay performance. Confidence intervals were generated with a two-stage bootstrap. We used Bayesian modeling to test whether seroprevalence changes over time were statistically significant. RESULTS: Seroprevalence remained below 10% at all sites except New York and Florida, where it reached 23.2% and 13.3%, respectively. Statistically significant increases in seroprevalence followed peaks in reported cases in New York, South Florida, Utah, Missouri and Louisiana. In the absence of such peaks, some significant decreases were observed over time in New York, Missouri, Utah, and Western Washington. The estimated cumulative number of infections with detectable antibody response continued to exceed reported cases in all sites. CONCLUSIONS: Estimated seroprevalence was low in most sites, indicating that most people in the U.S. have not been infected with SARS-CoV-2 as of July 2020. The majority of infections are likely not reported. Decreases in seroprevalence may be related to changes in healthcare-seeking behavior, or evidence of waning of detectable anti-SARS CoV-2 antibody levels at the population level. Thus, seroprevalence estimates may underestimate the cumulative incidence of infection. |
COVID-19 Clinical Phenotypes: Presentation and Temporal Progression of Disease in a Cohort of Hospitalized Adults in Georgia, United States.
da Silva JF , Hernandez-Romieu AC , Browning SD , Bruce BB , Natarajan P , Morris SB , Gold JAW , Neblett Fanfair R , Rogers-Brown J , Rossow J , Szablewski CM , Oosmanally N , D'Angelo MT , Drenzek C , Murphy DJ , Hollberg J , Blum JM , Jansen R , Wright DW , Sewell W , Owens J , Lefkove B , Brown FW , Burton DC , Uyeki TM , Patel PR , Jackson BR , Wong KK . Open Forum Infect Dis 2021 8 (1) ofaa596 BACKGROUND: The epidemiological features and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) have been described; however, the temporal progression and medical complications of disease among hospitalized patients require further study. Detailed descriptions of the natural history of COVID-19 among hospitalized patients are paramount to optimize health care resource utilization, and the detection of different clinical phenotypes may allow tailored clinical management strategies. METHODS: This was a retrospective cohort study of 305 adult patients hospitalized with COVID-19 in 8 academic and community hospitals. Patient characteristics included demographics, comorbidities, medication use, medical complications, intensive care utilization, and longitudinal vital sign and laboratory test values. We examined laboratory and vital sign trends by mortality status and length of stay. To identify clinical phenotypes, we calculated Gower's dissimilarity matrix between each patient's clinical characteristics and clustered similar patients using the partitioning around medoids algorithm. RESULTS: One phenotype of 6 identified was characterized by high mortality (49%), older age, male sex, elevated inflammatory markers, high prevalence of cardiovascular disease, and shock. Patients with this severe phenotype had significantly elevated peak C-reactive protein creatinine, D-dimer, and white blood cell count and lower minimum lymphocyte count compared with other phenotypes (P < .01, all comparisons). CONCLUSIONS: Among a cohort of hospitalized adults, we identified a severe phenotype of COVID-19 based on the characteristics of its clinical course and poor prognosis. These findings need to be validated in other cohorts, as improved understanding of clinical phenotypes and risk factors for their development could help inform prognosis and tailored clinical management for COVID-19. |
Comparison of Estimated SARS-CoV-2 Seroprevalence through Commercial Laboratory Residual Sera Testing and a Community Survey.
Bajema KL , Dahlgren FS , Lim TW , Bestul N , Biggs HM , Tate JE , Owusu C , Szablewski CM , Drenzek C , Drobeniuc J , Semenova V , Li H , Browning P , Desai R , Epperson M , Jia LT , Thornburg NJ , Edens C , Fry AM , Hall AJ , Schiffer J , Havers FP . Clin Infect Dis 2020 73 (9) e3120-e3123 We compared severe acute respiratory syndrome-related coronavirus-2 seroprevalence estimated from commercial laboratory residual sera and a community household survey in metropolitan Atlanta during April-May 2020 and found these two estimates to be similar (4.94% versus 3.18%). Compared with more representative surveys, commercial sera can provide an approximate measure of seroprevalence. |
Serologic testing of U.S. blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020.
Basavaraju SV , Patton ME , Grimm K , Rasheed MAU , Lester S , Mills L , Stumpf M , Freeman B , Tamin A , Harcourt J , Schiffer J , Semenova V , Li H , Alston B , Ategbole M , Bolcen S , Boulay D , Browning P , Cronin L , David E , Desai R , Epperson M , Gorantla Y , Jia T , Maniatis P , Moss K , Ortiz K , Park SH , Patel P , Qin Y , Steward-Clark E , Tatum H , Vogan A , Zellner B , Drobeniuc J , Sapiano MRP , Havers F , Reed C , Gerber S , Thornburg NJ , Stramer SL . Clin Infect Dis 2020 72 (12) e1004-e1009 BACKGROUND: SARS-CoV-2, the virus that causes COVID-19 disease, was first identified in Wuhan, China in December 2019, with subsequent worldwide spread. The first U.S. cases were identified in January 2020. METHODS: To determine if SARS-CoV-2 reactive antibodies were present in sera prior to the first identified case in the U.S. on January 19, 2020, residual archived samples from 7,389 routine blood donations collected by the American Red Cross from December 13, 2019 to January 17, 2020, from donors resident in nine states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at CDC for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan Ig) enzyme linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor binding domain / Ace2 blocking activity assay. RESULTS: Of the 7,389 samples, 106 were reactive by pan Ig. Of these 106 specimens, 90 were available for further testing. Eighty four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor binding domain / Ace2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all nine states. CONCLUSIONS: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to January 19, 2020. |
Antibody Responses after Classroom Exposure to Teacher with Coronavirus Disease, March 2020.
Brown NE , Bryant-Genevier J , Bandy U , Browning CA , Berns AL , Dott M , Gosciminski M , Lester SN , Link-Gelles R , Quilliam DN , Sejvar J , Thornburg NJ , Wolff BJ , Watson J . Emerg Infect Dis 2020 26 (9) 2263-5 After returning from Europe to the United States, on March 1, 2020, a symptomatic teacher received positive test results for severe acute respiratory syndrome coronavirus 2. Of the 21 students exposed to the teacher in the classroom, serologic results suggested past infection for 2. Classroom contact may result in virus transmission. |
Predictors at admission of mechanical ventilation and death in an observational cohort of adults hospitalized with COVID-19.
Jackson BR , Gold JAW , Natarajan P , Rossow J , Neblett Fanfair R , da Silva J , Wong KK , Browning SD , Bamrah Morris S , Rogers-Brown J , Hernandez-Romieu AC , Szablewski CM , Oosmanally N , Tobin-D'Angelo M , Drenzek C , Murphy DJ , Hollberg J , Blum JM , Jansen R , Wright DW , SeweSll WM , Owens JD , Lefkove B , Brown FW , Burton DC , Uyeki TM , Bialek SR , Patel PR , Bruce BB . Clin Infect Dis 2020 73 (11) e4141-e4151 BACKGROUND: Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. METHODS: We conducted a retrospective observational cohort investigation of 297 adults admitted to eight academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI) for predictors of invasive mechanical ventilation (IMV) and death. RESULTS: Compared with age <45 years, ages 65-74 years and ≥75 years were predictors of IMV (aOR 3.12, CI 1.47-6.60; aOR 2.79, CI 1.23-6.33) and the strongest predictors for death (aOR 12.92, CI 3.26-51.25; aOR 18.06, CI 4.43-73.63). Comorbidities associated with death (aORs from 2.4 to 3.8, p <0.05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Pre-hospital use vs. non-use of angiotensin receptor blockers (aOR 2.02, CI 1.03-3.96) and dihydropyridine calcium channel blockers (aOR 1.91, CI 1.03-3.55) were associated with death. CONCLUSIONS: After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death. |
Characteristics Associated with Hospitalization Among Patients with COVID-19 - Metropolitan Atlanta, Georgia, March-April 2020.
Killerby ME , Link-Gelles R , Haight SC , Schrodt CA , England L , Gomes DJ , Shamout M , Pettrone K , O'Laughlin K , Kimball A , Blau EF , Burnett E , Ladva CN , Szablewski CM , Tobin-D'Angelo M , Oosmanally N , Drenzek C , Murphy DJ , Blum JM , Hollberg J , Lefkove B , Brown FW , Shimabukuro T , Midgley CM , Tate JE , CDC COVID-19 Response Clinical Team , Browning Sean D , Bruce Beau B , da Silva Juliana , Gold Jeremy AW , Jackson Brendan R , Bamrah Morris Sapna , Natarajan Pavithra , Neblett Fanfair Robyn , Patel Priti R , Rogers-Brown Jessica , Rossow John , Wong Karen K . MMWR Morb Mortal Wkly Rep 2020 69 (25) 790-794 The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged >/=18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age >/=65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed. |
Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020.
Gold JAW , Wong KK , Szablewski CM , Patel PR , Rossow J , da Silva J , Natarajan P , Morris SB , Fanfair RN , Rogers-Brown J , Bruce BB , Browning SD , Hernandez-Romieu AC , Furukawa NW , Kang M , Evans ME , Oosmanally N , Tobin-D'Angelo M , Drenzek C , Murphy DJ , Hollberg J , Blum JM , Jansen R , Wright DW , Sewell WM3rd , Owens JD , Lefkove B , Brown FW , Burton DC , Uyeki TM , Bialek SR , Jackson BR . MMWR Morb Mortal Wkly Rep 2020 69 (18) 545-550 SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged >/=65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation(dagger) (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19. |
Development and validation of a robust multiplex serological assay to quantify antibodies specific to pertussis antigens
Rajam G , Carlone G , Kim E , Choi J , Paulos S , Park S , Jeyachandran A , Gorantla Y , Wong E , Sabnis A , Browning P , Desai R , Quinn CP , Schiffer J . Biologicals 2018 57 9-20 Despite wide spread vaccination, the public health burden of pertussis remains substantial. Current acellular pertussis vaccines comprise upto five Bordetella pertussis (Bp) antigens. Performing an ELISA to quantify antibody for each antigen is laborious and challenging to apply to pediatric samples where serum volume may be limited. We developed a microsphere based multiplex antibody capture assay (MMACA) to quantify antibodies to five pertussis antigens; pertussis toxin, pertactin, filamentous hemagglutinin and fimbrial antigens 2/3, and adenylate cyclase toxin in a single reaction (5-plex) with a calibrated reference standard, QC reagents and SAS((R)) based data analysis program. The goodness of fit (R(2)) of the standard curves for five analytes was >/=0.99, LLOQ 0.04-0.15 IU or AU/mL, accuracy 1.9%-23.8% (%E), dilutional linearity slopes 0.93-1.02 and regression coefficients r(2)=0.91-0.99. MMACA had acceptable precision within a median CV of 16.0%-22.8%. Critical reagents, antigen conjugated microsphere and reporter antibody exhibited acceptable (<12.3%) lot-lot variation. MMACA can be completed in <3h, requires low serum volume (5muL/multiplex assay) and has fast data turnaround time (<1min). MMACA has been successfully developed and validated as a sensitive, specific, robust and rugged method suitable for simultaneous quantification of anti-Bp antibodies in serum, plasma and DBS. |
A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis.
Nicol MP , Gnanashanmugam D , Browning R , Click ES , Cuevas LE , Detjen A , Graham SM , Levin M , Makhene M , Nahid P , Perez-Velez CM , Reither K , Song R , Spiegel HM , Worrell C , Zar HJ , Walzl G . Clin Infect Dis 2015 61Suppl 3 S164-72 Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area. |
Towards early inclusion of children in tuberculosis drugs trials: a consensus statement
Nachman S , Ahmed A , Amanullah F , Becerra MC , Botgros R , Brigden G , Browning R , Gardiner E , Hafner R , Hesseling A , How C , Jean-Philippe P , Lessem E , Makhene M , Mbelle N , Marais B , McIlleron H , McNeeley DF , Mendel C , Murray S , Navarro E , Anyalechi EG , Porcalla AR , Powell C , Powell M , Rigaud M , Rouzier V , Samson P , Schaaf HS , Shah S , Starke J , Swaminathan S , Wobudeya E , Worrell C . Lancet Infect Dis 2015 15 (6) 711-20 Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained. |
Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel
Graham SM , Ahmed T , Amanullah F , Browning R , Cardenas V , Casenghi M , Cuevas LE , Gale M , Gie RP , Grzemska M , Handelsman E , Hatherill M , Hesseling AC , Jean-Philippe P , Kampmann B , Kabra SK , Lienhardt C , Lighter-Fisher J , Madhi S , Makhene M , Marais BJ , McNeeley DF , Menzies H , Mitchell C , Modi S , Mofenson L , Musoke P , Nachman S , Powell C , Rigaud M , Rouzier V , Starke JR , Swaminathan S , Wingfield C . J Infect Dis 2012 205 Suppl 2 S199-208 There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis. |
Evaluation of tuberculosis diagnostics in children: 2. Methodological issues for conducting and reporting research evaluations of tuberculosis diagnostics for intrathoracic tuberculosis in children. Consensus from an expert panel
Cuevas LE , Browning R , Bossuyt P , Casenghi M , Cotton MF , Cruz AT , Dodd LE , Drobniewski F , Gale M , Graham SM , Grzemska M , Heinrich N , Hesseling AC , Huebner R , Jean-Philippe P , Kabra SK , Kampmann B , Lewinsohn D , Li M , Lienhardt C , Mandalakas AM , Marais BJ , Menzies HJ , Montepiedra G , Mwansambo C , Oberhelman R , Palumbo P , Russek-Cohen E , Shapiro DE , Smith B , Soto-Castellares G , Starke JR , Swaminathan S , Wingfield C , Worrell C . J Infect Dis 2012 205 Suppl 2 S209-15 Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children. In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children. |
Sensitivity and specificity of serologic assays for the detection of human infection with 2009 pandemic H1N1 virus in U.S. populations
Veguilla V , Hancock K , Schiffer J , Gargiullo P , Lu X , Aranio D , Branch A , Dong L , Holiday C , Liu F , Steward-Clark E , Sun H , Tsang B , Wang D , Whaley M , Bai Y , Cronin L , Browning P , Dababneh H , Noland H , Thomas L , Foster L , Quinn CP , Soroka SD , Katz JM . J Clin Microbiol 2011 49 (6) 2210-5 Swine origin 2009 H1N1 influenza virus has spread globally to cause the first influenza pandemic of the 21(st) century. Serological studies can improve our understanding of the extent of human infection and risk factors associated with transmission of this pandemic virus. The "gold standard" for serodiagnosis of human influenza infection is the detection of seroconversion between acute and convalescent stage samples. However, timing of seroepidemiologic investigations often precludes collection of truly acute phase sera, requiring development of serologic criteria for evaluating convalescent phase sera that optimize detection of true positives and true negatives. To guide seroepidemiologic investigations into the spread of the novel 2009 pandemic H1N1 virus, we characterized serum antibody responses to 2009 H1N1 virus in 87 individuals with confirmed viral infection and 227 non-exposed U.S. individuals using microneutralization (MN) and hemagglutination-inhibition (HI) assays. Sensitivity and specificity were determined for each assay alone, and in combination, for detection of 2009 H1N1-specific antibodies in convalescent sera. Although the HI assay was more specific for detecting antibody to 2009 H1N1, the MN was more sensitive, particularly for detecting low titer seroconversions. A combination of titers (MN ≥40 and HI ≥20) provided highest sensitivity (90%) and specificity (96%) for individuals aged < 60 years and 92% specificity for adults aged ≥60 years for detection of serologically confirmed 2009 H1N1 infections in U.S. populations during the first pandemic waves. These studies provide an approach to optimize timely serologic investigations for future pandemics or outbreaks of novel influenza viruses among humans. |
Legionella nagasakiensis sp. nov., isolated from water samples in Japan and Australia and from a patient with pneumonia in the United States
Yang PG , Benson RF , Ratcliff R , Brown EW , Steigerwalt AG , Thacker LW , Daneshvar M , Morey RE , Saito A , Fields BS . Int J Syst Evol Microbiol 2011 62 284-288 A novel Legionella species was identified based on 16S rRNA and mip (macrophage infectivity potentiator) gene sequencing analysis, cellular fatty acids, isoprenoid quinones, biochemical reactions, antigens, and quantitative DNA-DNA hybridization. The strain CDC-1796-JAP-E(T) was isolated from well water at the Nagassaki Municipal Medical Center, Japan. Two strains, CDC-3041-AUS-E and CDC-3558-AUS-E, were isolated from water samples during an outbreak of legionellosis in South Australia. The strain CDC-5427-OH-H was isolated from a 66-year-old female patient diagnosed with Legionnaires' disease in the U.S. The cells from these four strains were gram-negative, non-fluorescent, rod-shaped, and positive for alkaline phosphatase, esterase, leucine arylamidase, catalase, gelatinase, beta-lactamase, and tyrosine browning assay. Phylogenetic analysis of 16S rRNA and mip genes revealed that the four strains formed a distinct cluster within the genus Legionella. The bacteria contained branched-chain fatty acids and quinones that are typical of the genus Legionella. Slide agglutination tests demonstrated no cross-reaction with 52 previously described Legionellaceae. DNA hybridization studies indicated DNAs from the four strains were highly related (78-84%) but showed 29% relatedness to L. oakridgensis (ATCC 33761(T)) and less than 10% to other Legionella species tested. These characterizations suggest that the isolates represent a novel species, for which the name Legionella nagasakiensis sp. nov is proposed, for the type strain CDC-1796-JAP-E(T) (=ATCC BAA-1557(T)=JCM 15315(T)). |
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