Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
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Query Trace: Henning T[original query] |
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Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States (preprint)
Tenforde MW , Patel MM , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CT , Busse L , Lohuis CCT , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Gershengorn HB , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Self WH . medRxiv 2021 BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population. |
ICU Bed Utilization During the Coronavirus Disease 2019 Pandemic in a Multistate Analysis-March to June 2020
Douin DJ , Ward MJ , Lindsell CJ , Howell MP , Hough CL , Exline MC , Gong MN , Aboodi MS , Tenforde MW , Feldstein LR , Stubblefield WB , Steingrub JS , Prekker ME , Brown SM , Peltan ID , Khan A , Files DC , Gibbs KW , Rice TW , Casey JD , Hager DN , Qadir N , Henning DJ , Wilson JG , Patel MM , Self WH , Ginde AA . Crit Care Explor 2021 3 (3) e0361 OBJECTIVES: Given finite ICU bed capacity, knowledge of ICU bed utilization during the coronavirus disease 2019 pandemic is critical to ensure future strategies for resource allocation and utilization. We sought to examine ICU census trends in relation to ICU bed capacity during the rapid increase in severe coronavirus disease 2019 cases early during the pandemic. DESIGN: Observational cohort study. SETTING: Thirteen geographically dispersed academic medical centers in the United States. PATIENTS/SUBJECTS: We obtained daily ICU censuses from March 26 to June 30, 2020, as well as prepandemic ICU bed capacities. The primary outcome was daily census of ICU patients stratified by coronavirus disease 2019 and mechanical ventilation status in relation to ICU capacity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prepandemic overall ICU capacity ranged from 62 to 225 beds (median 109). During the study period, the median daily coronavirus disease 2019 ICU census per hospital ranged from 1 to 84 patients, and the daily ICU census exceeded overall ICU capacity for at least 1 day at five institutions. The number of critically ill patients exceeded ICU capacity for a median (interquartile range) of 17 (12-50) of 97 days at these five sites. All 13 institutions experienced decreases in their noncoronavirus disease ICU population, whereas local coronavirus disease 2019 cases increased. Coronavirus disease 2019 patients reached their greatest proportion of ICU capacity on April 12, 2020, when they accounted for 44% of ICU patients across all participating hospitals. Maximum ICU census ranged from 52% to 289% of overall ICU capacity, with three sites less than 80%, four sites 80-100%, five sites 100-128%, and one site 289%. CONCLUSIONS: From March to June 2020, the coronavirus disease 2019 pandemic led to ICU censuses greater than ICU bed capacity at fives of 13 institutions evaluated. These findings demonstrate the short-term adaptability of U.S. healthcare institutions in redirecting limited resources to accommodate a public health emergency. |
Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021.
Tenforde MW , Self WH , Naioti EA , Ginde AA , Douin DJ , Olson SM , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Patel MM , IVY Network Investigators . MMWR Morb Mortal Wkly Rep 2021 70 (34) 1156-1162 Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination. |
Lessons learned for public health workforce development: An evaluation of the Centers For Disease Control And Prevention's Laboratory Leadership Service Fellowship
McColloch C , Davis M , Araujo A , Theodore S , Barkley J , Paek M , Henning T . Eval Program Plann 2022 95 102147 The Centers for Disease Control and Prevention launched the Laboratory Leadership Service (LLS) Fellowship Program in July 2015 to develop public health laboratory (PHL) leaders who will improve PHL quality and safety. This article describes a retrospective, summative evaluation to determine the extent to which LLS has met its short-term goals for PHL workforce development. The evaluation relied on existing data from routine LLS data collection and reporting, supplemented with a new alumni survey. The purpose of the design was threefold: 1) to reduce data collection burden on program staff and participants, 2) to assess the value and limits of routine fellowship data for comprehensive public health workforce development program evaluation, and 3) to identify ways to improve LLS's routine data collections for program evaluation. We used descriptive statistics, qualitative analysis, and participatory methods (i.e., a data party) to analyze and interpret data. Results show LLS short-term outcome achievement and highlight opportunities for program improvement, particularly related to the design of certain training requirements and for future evaluations. Overall, the evaluation contributes to lessons learned for PHL workforce development efforts, including how routine data collections can contribute to comprehensive public health workforce development evaluations. |
Modeling clinical trajectory status of critically ill COVID-19 patients over time: A method for analyzing discrete longitudinal and ordinal outcomes.
Ward MJ , Douin DJ , Gong W , Ginde AA , Hough CL , Exline MC , Tenforde MW , Stubblefield WB , Steingrub JS , Prekker ME , Khan A , Files DC , Gibbs KW , Rice TW , Casey JD , Henning DJ , Wilson JG , Brown SM , Patel MM , Self WH , Lindsell CJ . J Clin Transl Sci 2022 6 (1) e61 Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross sectional timepoints, cumulative summary measures, or time-To-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate use of a multi-state transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients. © 2022 Cambridge University Press. All rights reserved. |
Identification of profiles and determinants of maternal pregnancy urinary biomarkers of phthalates and replacements in the Illinois Kids Development Study
Pacyga DC , Haggerty DK , Nicol M , Henning M , Calafat AM , Braun JM , Schantz SL , Strakovsky RS . Environ Int 2022 162 107150 BACKGROUND/OBJECTIVES: Pregnant women are exposed to multiple phthalates and their replacements, which are endocrine disrupting chemicals associated with adverse maternal and child health outcomes. Identifying maternal characteristics associated with phthalate/replacement exposure during pregnancy is important. METHODS: We evaluated 13 maternal sociodemographic and lifestyle factors, enrollment year, and conception season as determinants of exposure biomarkers of phthalates and their replacements in 482 pregnant women from the Illinois Kids Development Study (I-KIDS, enrolled 2013-2018). We quantified 19 phthalate/replacement metabolites in pools of five first-morning urines collected across pregnancy. K-means clustering identified women with distinct patterns of biomarker concentrations and principal component analysis (PCA) identified principal component (PC) profiles of biomarkers that exist together. We used multivariable regression models to evaluate associations of predictors with identified k-means clusters and PCs. RESULTS: K-means clustering identified two clusters of women: 1) low phthalate/di(2-ethylhexyl) terephthalate (∑DEHTP) and 2) high phthalate/∑DEHTP biomarker concentrations. PCA identified four PCs with loadings heaviest for biomarkers of plasticizer phthalates [di-isononyl, di-isodecyl, di-n-octyl phthalates] (PC1), of other phthalates [dibenzyl, di-n-butyl, di-iso-butyl phthalates] (PC2), of phthalate replacements [∑DEHTP, di(isononyl) cyclohexane-1,2-dicarboxylate (∑DiNCH)] (PC3), and of monoethyl phthalate [MEP] (PC4). Overall, age, marital status, income, parity, pre-pregnancy BMI, caffeine intake, enrollment year, and conception season were independently associated with k-means cluster membership and at least one PC. Additionally, race/ethnicity, education, employment, pregnancy intention, smoking status, alcohol intake, and diet were associated with at least one PC. For instance, women who conceived in the spring, summer, and/or fall months had lower odds of high phthalate/∑DEHTP cluster membership and had lower plasticizer phthalate, phthalate replacement, and MEP PC scores. CONCLUSIONS: Conception season, enrollment year, and several sociodemographic/lifestyle factors were predictive of phthalate/replacement biomarker profiles. Future studies should corroborate these findings, with a special focus on replacements to which pregnant women are becoming increasingly exposed. |
Effectiveness of mRNA vaccines in preventing COVID-19 hospitalization by age and burden of chronic medical conditions among immunocompetent US adults, March-August 2021.
Lewis NM , Naioti EA , Self WH , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , Ghamande SA , McNeal TA , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Hubel K , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Rhoads JP , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Schrag SJ , Kobayashi M , Verani JR , Patel MM , Tenforde MW . J Infect Dis 2021 225 (10) 1694-1700 In a multi-state network, vaccine effectiveness (VE) against COVID-19 hospitalizations was evaluated among immunocompetent adults (≥18-years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was higher at 96% (95% CI: 93-98%) among patients with no chronic medical conditions than patients with ≥3 categories of conditions (83% [95% CI: 76-88%]). VE was similar between those aged 18-64 years vs ≥65 years (p>0.05). Vaccine effectiveness against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing burden of comorbidities. |
Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity.
Tenforde MW , Self WH , Adams K , Gaglani M , Ginde AA , McNeal T , Ghamande S , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Rhoads JP , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Kobayashi M , Verani JR , Patel MM . JAMA 2021 326 (20) 2043-2054 IMPORTANCE: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. OBJECTIVE: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. DESIGN, SETTING, AND PARTICIPANTS: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. EXPOSURES: COVID-19 vaccination. MAIN OUTCOMES AND MEASURES: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. RESULTS: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). CONCLUSIONS AND RELEVANCE: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination. |
Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions - United States, March-August 2021.
Self WH , Tenforde MW , Rhoads JP , Gaglani M , Ginde AA , Douin DJ , Olson SM , Talbot HK , Casey JD , Mohr NM , Zepeski A , McNeal T , Ghamande S , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Mills L , Lester SN , Stumpf MM , Naioti EA , Kobayashi M , Verani JR , Thornburg NJ , Patel MM . MMWR Morb Mortal Wkly Rep 2021 70 (38) 1337-1343 Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization. |
Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel.
Pilishvili T , Gierke R , Fleming-Dutra KE , Farrar JL , Mohr NM , Talan DA , Krishnadasan A , Harland KK , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Krebs E , Steele MT , Beiser DG , Faine B , Haran JP , Nandi U , Schrading WA , Chinnock B , Henning DJ , Lovecchio F , Lee J , Barter D , Brackney M , Fridkin SK , Marceaux-Galli K , Lim S , Phipps EC , Dumyati G , Pierce R , Markus TM , Anderson DJ , Debes AK , Lin MY , Mayer J , Kwon JH , Safdar N , Fischer M , Singleton R , Chea N , Magill SS , Verani JR , Schrag SJ . N Engl J Med 2021 385 (25) e90 BACKGROUND: The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory disease coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting. METHODS: We conducted a test-negative case-control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19-like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose). RESULTS: The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer-BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely. CONCLUSIONS: The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic. (Funded by the Centers for Disease Control and Prevention.). |
Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States.
Tenforde MW , Patel MM , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CT , Busse L , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Gershengorn HB , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Self WH . Clin Infect Dis 2021 74 (9) 1515-1524 BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% CI: 80.7 to 91.3%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI: 79.3 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI: 20.8 to 82.6%) than without immunosuppression (91.3%; 95% CI: 85.6 to 94.8%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population. |
Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel - 33 U.S. Sites, January-March 2021.
Pilishvili T , Fleming-Dutra KE , Farrar JL , Gierke R , Mohr NM , Talan DA , Krishnadasan A , Harland KK , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Krebs E , Steele M , Beiser DG , Faine B , Haran JP , Nandi U , Schrading WA , Chinnock B , Henning DJ , LoVecchio F , Nadle J , Barter D , Brackney M , Britton A , Marceaux-Galli K , Lim S , Phipps EC , Dumyati G , Pierce R , Markus TM , Anderson DJ , Debes AK , Lin M , Mayer J , Babcock HM , Safdar N , Fischer M , Singleton R , Chea N , Magill SS , Verani J , Schrag S . MMWR Morb Mortal Wkly Rep 2021 70 (20) 753-758 Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection. |
Adults Hospitalized with COVID-19 -United States, March-June and October-December 2020: Implications for the Potential Effects of COVID-19 Tier-1 Vaccination on Future Hospitalizations and Outcomes.
Sami S , Tenforde MW , Talbot HK , Lindsell CJ , Steingrub JS , Shapiro NI , Ginde AA , Douin DJ , Prekker ME , Erickson HL , Brown SM , Peltan ID , Gong MN , Khan A , Exline MC , Files DC , Gibbs KW , Rice TW , Casey JD , Grijalva CG , Stubblefield WB , Womack KN , Hager DN , Qadir N , Chang SY , Henning DJ , Wilson JG , Self WH , Patel MM . Clin Infect Dis 2021 73 S32-S37 BACKGROUND: Because of the increased risk for severe coronavirus disease 2019 (COVID-19), the Advisory Committee on Immunization Practices (ACIP) initially prioritized COVID-19 vaccination for persons in long-term care facilities (LTCF), persons aged ≥65 years, and persons aged 16-64 years with high-risk medical conditions when there is limited vaccine supply. We compared characteristics and severe outcomes of hospitalized patients with COVID-19 in the United States between early and later in the pandemic categorized by groups at higher risk of severe COVID-19. METHODS: Observational study of sampled patients aged ≥18 years who tested positive for SARS-CoV-2 and admitted to one of 14 academic hospitals in the United States during March-June and October-December 2020. Demographic and clinical information were gathered from electronic health record data. RESULTS: Among 647 patients, 91% met ≥1 of the following risk factors for severe COVID-19 [91% March-June (n=434); 90% October-December (n=213)]; 19% were LTCF residents, 45% were aged ≥65-years, and 84% had ≥1 high-risk condition. The proportion of patients who resided in a LTCF declined significantly (25% vs. 6%) from early to later pandemic periods. Compared with patients at lower risk for severe COVID-19, in-hospital mortality was higher among patients at high risk for severe COVID-19 (20% vs. 7%); these differences were consistently observed between March-June and October-December. CONCLUSIONS: Most adults hospitalized with COVID-19 were those recommended to be prioritized for vaccination based on risk for developing severe COVID-19. These findings highlight the urgency to vaccinate patients at high risk for severe COVID-19 and monitor vaccination impact on hospitalizations and outcomes. |
Symptoms and recovery among adult outpatients with and without COVID-19 at 11 healthcare facilities-July 2020, United States.
Fisher KA , Olson SM , Tenforde MW , Self WH , Wu M , Lindsell CJ , Shapiro NI , Files DC , Gibbs KW , Erickson HL , Prekker ME , Steingrub JS , Exline MC , Henning DJ , Wilson JG , Brown SM , Peltan ID , Rice TW , Hager DN , Ginde AA , Talbot HK , Casey JD , Grijalva CG , Flannery B , Patel MM , Feldstein LR . Influenza Other Respir Viruses 2021 15 (3) 345-351 BACKGROUND: Symptoms of mild COVID-19 illness are non-specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID-19 are not well understood. METHODS: Adults aged ≥18 years with laboratory-confirmed COVID-19 and matched control patients who tested negative for SARS-CoV-2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health-related quality of life. Duration of symptoms, health-related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank-sum tests. Symptoms associated with COVID-19 case status were evaluated by multivariable logistic regression. RESULTS: Among 320 participants included, 157 were COVID-19 cases and 163 were SARS-CoV-2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID-19 in logistic regression models (adjusted odds ratio [aOR] = 32.4; 95% confidence interval [CI], 12.6-83.1). COVID-19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14 days after symptom onset (50% vs 32%, P < .001). Cases reported significantly more days of poor physical health during the past 14 days than controls (P < .01). CONCLUSIONS: Differentiating COVID-19 from other acute illnesses will require widespread diagnostic testing, especially during influenza seasons. Persistent COVID-19-related symptoms may negatively affect quality of life, even among those initially presenting with mild illness. |
Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Personnel in a Multistate Hospital Network - 12 States, April-August 2020.
Self WH , Tenforde MW , Stubblefield WB , Feldstein LR , Steingrub JS , Shapiro NI , Ginde AA , Prekker ME , Brown SM , Peltan ID , Gong MN , Aboodi MS , Khan A , Exline MC , Files DC , Gibbs KW , Lindsell CJ , Rice TW , Jones ID , Halasa N , Talbot HK , Grijalva CG , Casey JD , Hager DN , Qadir N , Henning DJ , Coughlin MM , Schiffer J , Semenova V , Li H , Thornburg NJ , Patel MM . MMWR Morb Mortal Wkly Rep 2020 69 (47) 1762-1766 Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection. |
Telework Before Illness Onset Among Symptomatic Adults Aged ≥18 Years With and Without COVID-19 in 11 Outpatient Health Care Facilities - United States, July 2020.
Fisher KA , Olson SM , Tenforde MW , Feldstein LR , Lindsell CJ , Shapiro NI , Files DC , Gibbs KW , Erickson HL , Prekker ME , Steingrub JS , Exline MC , Henning DJ , Wilson JG , Brown SM , Peltan ID , Rice TW , Hager DN , Ginde AA , Talbot HK , Casey JD , Grijalva CG , Flannery B , Patel MM , Self WH . MMWR Morb Mortal Wkly Rep 2020 69 (44) 1648-1653 Since March 2020, large-scale efforts to reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have continued. Mitigation measures to reduce workplace exposures have included work site policies to support flexible work site options, including telework, whereby employees work remotely without commuting to a central place of work.* Opportunities to telework have varied across industries among U.S. jobs where telework options are feasible (1). However, little is known about the impact of telework on risk for SARS-CoV-2 infection. A case-control investigation was conducted to compare telework between eligible symptomatic persons who received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results (case-patients, 153) and symptomatic persons with negative test results (control-participants, 161). Eligible participants were identified in outpatient health care facilities during July 2020. Among employed participants who reported on their telework status during the 2 weeks preceding illness onset (248), the percentage who were able to telework on a full- or part-time basis was lower among case-patients (35%; 42 of 120) than among control-participants (53%; 68 of 128) (p<0.01). Case-patients were more likely than were control-participants to have reported going exclusively to an office or school setting (adjusted odds ratio [aOR] = 1.8; 95% confidence interval [CI] = 1.2-2.7) in the 2 weeks before illness onset. The association was also observed when further restricting to the 175 participants who reported working in a profession outside the critical infrastructure(†) (aOR = 2.1; 95% CI = 1.3-3.6). Providing the option to work from home or telework when possible, is an important consideration for reducing the risk for SARS-CoV-2 infection. In industries where telework options are not available, worker safety measures should continue to be scaled up to reduce possible worksite exposures. |
Community and Close Contact Exposures Associated with COVID-19 Among Symptomatic Adults ≥18 Years in 11 Outpatient Health Care Facilities - United States, July 2020.
Fisher KA , Tenforde MW , Feldstein LR , Lindsell CJ , Shapiro NI , Files DC , Gibbs KW , Erickson HL , Prekker ME , Steingrub JS , Exline MC , Henning DJ , Wilson JG , Brown SM , Peltan ID , Rice TW , Hager DN , Ginde AA , Talbot HK , Casey JD , Grijalva CG , Flannery B , Patel MM , Self WH . MMWR Morb Mortal Wkly Rep 2020 69 (36) 1258-1264 Community and close contact exposures continue to drive the coronavirus disease 2019 (COVID-19) pandemic. CDC and other public health authorities recommend community mitigation strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). Characterization of community exposures can be difficult to assess when widespread transmission is occurring, especially from asymptomatic persons within inherently interconnected communities. Potential exposures, such as close contact with a person with confirmed COVID-19, have primarily been assessed among COVID-19 cases, without a non-COVID-19 comparison group (3,4). To assess community and close contact exposures associated with COVID-19, exposures reported by case-patients (154) were compared with exposures reported by control-participants (160). Case-patients were symptomatic adults (persons aged ≥18 years) with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing. Control-participants were symptomatic outpatient adults from the same health care facilities who had negative SARS-CoV-2 test results. Close contact with a person with known COVID-19 was more commonly reported among case-patients (42%) than among control-participants (14%). Case-patients were more likely to have reported dining at a restaurant (any area designated by the restaurant, including indoor, patio, and outdoor seating) in the 2 weeks preceding illness onset than were control-participants (adjusted odds ratio [aOR] = 2.4; 95% confidence interval [CI] = 1.5-3.8). Restricting the analysis to participants without known close contact with a person with confirmed COVID-19, case-patients were more likely to report dining at a restaurant (aOR = 2.8, 95% CI = 1.9-4.3) or going to a bar/coffee shop (aOR = 3.9, 95% CI = 1.5-10.1) than were control-participants. Exposures and activities where mask use and social distancing are difficult to maintain, including going to places that offer on-site eating or drinking, might be important risk factors for acquiring COVID-19. As communities reopen, efforts to reduce possible exposures at locations that offer on-site eating and drinking options should be considered to protect customers, employees, and communities. |
Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network - 13 Academic Medical Centers, April-June 2020.
Self WH , Tenforde MW , Stubblefield WB , Feldstein LR , Steingrub JS , Shapiro NI , Ginde AA , Prekker ME , Brown SM , Peltan ID , Gong MN , Aboodi MS , Khan A , Exline MC , Files DC , Gibbs KW , Lindsell CJ , Rice TW , Jones ID , Halasa N , Talbot HK , Grijalva CG , Casey JD , Hager DN , Qadir N , Henning DJ , Coughlin MM , Schiffer J , Semenova V , Li H , Thornburg NJ , Patel MM . MMWR Morb Mortal Wkly Rep 2020 69 (35) 1221-1226 Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission. |
Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020.
Tenforde MW , Kim SS , Lindsell CJ , Billig Rose E , Shapiro NI , Files DC , Gibbs KW , Erickson HL , Steingrub JS , Smithline HA , Gong MN , Aboodi MS , Exline MC , Henning DJ , Wilson JG , Khan A , Qadir N , Brown SM , Peltan ID , Rice TW , Hager DN , Ginde AA , Stubblefield WB , Patel MM , Self WH , Feldstein LR , IVY Network Investigators , CDC COVID-19 Response Team , Dorough Layne , Dzuris Nicole , Griggs Eric P , Kassem Ahmed M , Marcet Paula L , Ogokeh Constance E , Sciarratta Courtney N Siddula Akshita , Smith Emily R , Wu Michael J . MMWR Morb Mortal Wkly Rep 2020 69 (30) 993-998 Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2. |
Characteristics of Adult Outpatients and Inpatients with COVID-19 - 11 Academic Medical Centers, United States, March-May 2020.
Tenforde MW , Billig Rose E , Lindsell CJ , Shapiro NI , Files DC , Gibbs KW , Prekker ME , Steingrub JS , Smithline HA , Gong MN , Aboodi MS , Exline MC , Henning DJ , Wilson JG , Khan A , Qadir N , Stubblefield WB , Patel MM , Self WH , Feldstein LR , CDC COVID-19 Response Team , Kassem Ahmed M , Sciarratta Courtney N , Dzuris Nicole , Marcet Paula L , Siddula Akshita . MMWR Morb Mortal Wkly Rep 2020 69 (26) 841-846 Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged >/=18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3). |
Expanding US Laboratory Capacity for Neisseria gonorrhoeae Antimicrobial Susceptibility Testing and Whole Genome Sequencing through CDC's Antibiotic Resistance Laboratory Network.
Kersh EN , Pham CD , Papp JR , Myers R , Steece R , Kubin G , Gautom R , Nash EE , Sharpe S , Gernert KM , Schmerer M , Raphael BH , Henning T , Gaynor AM , Soge O , Schlanger K , Kirkcaldy RD , St Cyr SB , Torrone EA , Bernstein K , Weinstock H . J Clin Microbiol 2020 58 (4) US gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for Ng identification, capacity for culturing Ng in the US has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet, AST is critical for detecting and monitoring AR-Ng. In 2016, CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up national capacity for detecting several resistance threats including Ng. AR-Ng testing, a sub-activity of CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in MD, TN, TX, WA), and CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 Ng isolates, and CDC received 531 and 646 concerning isolates, and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported laboratory capacity for Ng-AST and associated genetic marker detection, expanding pre-existing notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention. |
In vitro activity of EDTA and TOL-463 against Neisseria gonorrhoeae
Nash EE , Henning TC , Pham CD , Pettus K , Sharpe S , Kersh EN . Diagn Microbiol Infect Dis 2018 93 (4) 369-371 Neisseria gonorrhoeae quickly develops drug resistance. Time-kill curves revealed that EDTA and TOL-463 inhibit growth similar to penicillin, ciprofloxacin, and azithromycin. Furthermore, synergistic and additive antimicrobial interactions occurred when EDTA and TOL-463 were combined with penicillin or azithromycin, respectively, suggesting that further investigations into these unconventional antimicrobials may be advantageous. |
Noncommunicable Disease Risk Factors in Developing Countries: Policy Perspectives
Kostova D , Chaloupka FJ , Frieden TR , Henning K , Paul J Jr , Osewe PL , Asma S . Prev Med 2017 105S S1-S3 Following advances in infectious disease control, noncommunicable diseases (NCDs) have overtaken other conditions as causes of premature death and disability in lower-income nations. The largest portion of the NCD burden in low- and middle-income countries (LMICs) is represented by cardiovascular diseases (CVD), followed by cancer, diabetes and chronic respiratory disease (World Health Organization, 2016). Although NCDs are often considered to be diseases of ageing, the NCD crisis in developing countries does not appear to be explained solely by longer life spans; the growth in NCD deaths and disability in these countries has occurred at a faster rate than the contemporaneous decline in communicable diseases (Stuckler, 2008). Specific circumstances that worsen NCD outcomes in LMICs relative to high-income countries are the timing of disease onset and the level of treatment after onset. NCDs in LMICs tend to occur earlier in life (WHO, 2016; (Institute for Health Metrics and Evaluation, 2013)), and may not receive adequate treatment once they occur (Cameron et al., 2011). Health systems in LMICs may not be equipped to address the needs of the chronically ill, and long-term treatment may not be accessible. This adverse combination of factors results in NCD outcomes that have broad societal, economic, and health security consequences in developing countries. Recognizing the role of NCDs as an impediment to international development, the 2030 Agenda for Sustainable Development has identified the reduction in premature NCD mortality among its primary targets (United Nations, 2015). |
Population attributable fraction of tubal factor infertility associated with chlamydia
Gorwitz RJ , Wiesenfeld HC , Chen PL , Hammond KR , Sereday KA , Haggerty CL , Johnson RE , Papp JR , Kissin DM , Henning TC , Hook EW 3rd , Steinkampf MP , Markowitz LE , Geisler WM . Am J Obstet Gynecol 2017 217 (3) 336 e1-336 e16 BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiologic studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared to white women, but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: To estimate the population attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (black, non-black), and assess how different definitions of C. trachomatis seropositivity and tubal factor infertility affect population attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL and Pittsburgh, PA during October 2012 - June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of one and three controls per case for black and non-black women, respectively. We assessed C. trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated C. trachomatis seropositivity and calculated C. trachomatis-TFI odds ratios and population attributable fraction, stratified by race. RESULTS: We enrolled 107 black women (47 cases, 60 controls) and 620 non-black women (140 cases, 480 controls). C. trachomatis seropositivity by either assay was 81% (95% confidence interval 73%, 89%) among black and 31% (95% confidence interval 28%, 35%) among non-black participants (P<0.001). Using the primary C. trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among blacks (odds ratio 1.22, 95% confidence interval 0.45, 3.28) or non-blacks (odds ratio 1.41, 95% confidence interval 0.95, 2.09), and the estimated population attributable fraction was 15% (95% confidence interval -97%, 68%) among blacks and 11% (95% confidence interval -3%, 23%) among non-blacks. Use of alternate serologic measures and tubal factor infertility definitions impacted the magnitude of the chlamydia-tubal factor infertility association, and resulted in a significant association among non-blacks. CONCLUSIONS: Low population attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background C. trachomatis seropositivity among controls, most striking among black participants, could have obscured an association with tubal factor infertility and resulted in a population attributable fraction that underestimates the true etiologic role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also impacts odds ratio and population attributable fraction estimates. |
Development of a rectal sexually transmitted infection (STI) model in Rhesus macaques using Chlamydia trachomatis serovars E and L2
Henning TR , Morris M , Ellis S , Kelley K , Phillips C , Ritter J , Jones T , Nachamkin E , Chen CY , Hong J , Kang J , Patton D , McNicholl J , Papp J , Kersh EN . J Med Primatol 2017 46 (5) 218-227 BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. RESULTS: Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies. |
Topical tenofovir protects against vaginal SHIV infection in macaques co-infected with chlamydia trachomatis and trichomonas vaginalis
Makarova N , Henning T , Taylor A , Dinh C , Lipscomb J , Aubert R , Hanson D , Phillips C , Papp J , Mitchell J , McNicholl J , Garcia-Lerma GJ , Heneine W , Kersh E , Dobard C . AIDS 2017 31 (6) 745-752 BACKGROUND: Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV), two prevalent sexual transmitted infections, are known to increase HIV risk in women and could potentially diminish pre-exposure prophylaxis (PrEP) efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether co-infection with CT/TV reduces protection by vaginal TFV gel. METHODS: Vaginal TFV gel dosing previously shown to provide 100% or 74% protection when applied either 30 minutes or 3 days before SHIV challenge was assessed in pigtailed macaques co-infected with CT/TV and challenged twice-weekly with SHIV162p3 for up to 10 weeks (2 menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 minutes or 3 days before each SHIV challenge. We additionally assessed TFV and TFV-diphosphate (TFV-DP) concentrations in plasma and vaginal tissues in CT/TV co-infected (n = 4) and uninfected (n = 4) macaques. RESULTS: CT/TV co-infections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV-infected after a median of 7 challenges (1 menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 minutes before SHIV challenge (p < 0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (p = 0.07). Plasma TFV and TFV-DP concentrations in tissues and vaginal lymphocytes were significantly higher in CT/TV co-infected compared to CT/TV uninfected macaques. CONCLUSIONS: Our findings in this model suggest that CT/TV co-infection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics. |
Increases in endogenous or exogenous progestins promote virus-target cell interactions within the non-human primate female reproductive tract
Carias AM , Allen SA , Fought AJ , Kotnik Halavaty K , Anderson MR , Jimenez ML , McRaven MD , Gioia CJ , Henning TR , Kersh EN , Smith JM , Pereira LE , Butler K , McNicholl SJ , Hendry RM , Kiser PF , Veazey RS , Hope TJ . PLoS Pathog 2016 12 (9) e1005885 Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels. |
Full House: a retrospective analysis of high sexually transmitted infection prevalence among adult film actors at a singular residence
Kendrick K , Brown V , Lords C , Matthias J , Henning I , Blackmore C , Likos A . Sex Transm Dis 2016 43 (9) 556-9 BACKGROUND: During a routine human immunodeficiency virus (HIV) investigation, Florida Department of Health staff identified a house (house A) in which over 150 individuals had resided at least briefly. Further investigation revealed that house A is used by the producer of a small adult film production company to board his actors. This report describes sexually transmitted infection (STI) prevalence among male actors in gay adult films residing in a common Florida residence. METHODS: LexisNexis Accurint was used to identify house A residents since October 2002 when the producer arrived. Information on STIs and interview data were obtained from Florida's STI surveillance system. An infection was considered to be associated with residence in house A if the date of diagnosis occurred 6 months before an individual's residence start date through 6 months after his residence end date. RESULTS: Excluding the producer, 150 men resided in house A starting from September 2003 to July 2015. Forty-six individuals had a reported case of HIV, syphilis, gonorrhea, and/or chlamydia with 92 infections total. Forty-two (46%) infections among 24 men were considered associated with residence in house A. CONCLUSIONS: LexisNexis Accurint was a useful tool for identifying house A residents, a highly mobile and highly sexually active population. There is a high prevalence of STIs among residents, but it is unclear where transmission is occurring. Settings like house A are good candidates for HIV pre-exposure prophylaxis and active STI screenings and may be an opportunity for public health officials to intervene in high-risk groups to reduce STI rates in the community. |
Recovery of Neisseria gonorrhoeae from 4 commercially available transport systems
Papp JR , Henning T , Khubbar M , Kalve V , Bhattacharyya S , Travanty E , Xavier K , Jones K , Rudrik JT , Gaynor A , Hagan C . Diagn Microbiol Infect Dis 2016 86 (2) 144-7 Four commercial transport systems for the recovery of Neisseria gonorrhoeae were evaluated in support of the need to obtain culture isolates for the detection of antimicrobial resistance. Bacterial recovery from the InTray GC system was superior with minimal loss of viability in contrast to non-nutritive transport systems. |
Combination emtricitabine and tenofovir disoproxil fumarate prevents vaginal SHIV infection in macaques harboring C. trachomatis and T. vaginalis
Radzio J , Henning T , Jenkins L , Ellis S , Farshy C , Phillips C , Holder A , Kuklenyik S , Dinh C , Hanson D , McNicholl J , Heneine W , Papp J , Kersh EN , Garcia-Lerma JG . J Infect Dis 2016 213 (10) 1541-5 Genital inflammation associated with STIs increases susceptibility to HIV but it is unclear if the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated if co-infection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral FTC/TDF. Macaques were exposed to SHIV vaginally each week for up to 16 weeks and received placebo or FTC/TDF peri-coitally. All placebos were infected with SHIV while 4/6 PrEP-treated animals remained uninfected (p=0.03). Oral FTC/TDF maintains efficacy in a macaque model of STI coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity. |
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