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Sulfonated polyether (ether) ketone, or sulfonated PEEK (sPEEK) membranes are one possible candidate for proton-transfer membranes in hydrogen fuel cells. Reaction with hydroxy radicals is expected to be a significant source of degradation of these membranes during fuel cell operation. In this work, the reactivity of the sPEEK polymer molecule with OH radicals is studied by M062X hybrid density functional calculations of the energetics of several reaction paths in a water environment as modeled by polarized continuum model (PCM) calculations. Reactants, products, encounter minima and transition states are optimized for a reaction pathway in which OH addition is followed by acid-catalyzed water elimination which cationizes the polymer, degradation is expected to follow this reaction as the unstable cation then undergoes bond-breaking or other reactions. Two pathways for this acid-catalyzed cationization, one in which a water molecule plays the role of an additional co-catalyst, are reported. Further calculations explore reaction pathways in which addition of OH to the polymer is followed by bond breaking reactions which would break the polymer chain or the bond between the polymer and sulfonyl groups. Examination of the free energy barriers to all these reactions, relative to reactants, suggest that these direct bond-breaking reactions may compete somewhat with acid-catalyzed water elimination following OH addition.

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2/BA.2.12.1 and BA.4/BA.5 subvariants have mutations associated with increased capacity to evade immunity when compared with prior variants. We evaluated mRNA monovalent booster dose effectiveness among persons ≥5 years old during BA.2/BA.2.12.1 and BA.4/BA.5 predominance. Methods A test-negative, case-control analysis included data from 12 148 pharmacy SARS-CoV-2 testing sites nationwide for persons aged ≥5 years with ≥1 coronavirus disease-2019 (COVID-19)-like symptoms and a SARS-CoV-2 nucleic acid amplification test from April 2 to August 31, 2022. Relative vaccine effectiveness (rVE) was estimated comparing 3 doses of COVID-19 mRNA monovalent vaccine to 2 doses; for tests among persons ≥50 years, rVE estimates also compared 4 doses to 3 doses (≥4 months since third dose). Results A total of 760 986 test-positive cases and 817 876 test-negative controls were included. Among individuals ≥12 years, rVE of 3 versus 2 doses ranged by age group from 45% to 74% at 1-month post vaccination and waned to 0% by 5–7 months post vaccination during the BA.4/BA.5 period. Adults aged ≥50 years (fourth dose eligible) who received 4 doses were less likely to have symptomatic SARS-CoV-2 infection compared with those with 3 doses; this rVE remained >0% through at least 3 months since last dose. For those aged ≥65 years, rVE of 4 versus 3 doses 1-month post vaccination was higher during BA.2/BA.2.12.1 (rVE = 49%; 95% confidence interval [CI], 43%–53%) than BA.4/BA.5 (rVE = 40%; 95% CI, 36%–44%). In 50- to 64-year-olds, rVE estimates were similar. Conclusions Monovalent mRNA booster doses provided additional protection against symptomatic SARS-CoV-2 infection during BA.2/BA.2.12.1 and BA.4/BA.5 subvariant circulation, but protection waned over time.

On September 1, 2022, bivalent COVID-19 mRNA vaccines, composed of components from the SARS-CoV-2 ancestral and Omicron BA.4/BA.5 strains, were recommended by the Advisory Committee on Immunization Practices (ACIP) to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance (1). Initial recommendations included persons aged ≥12 years (Pfizer-BioNTech) and ≥18 years (Moderna) who had completed at least a primary series of any Food and Drug Administration-authorized or -approved monovalent vaccine ≥2 months earlier (1). On October 12, 2022, the recommendation was expanded to include children aged 5-11 years. At the time of recommendation, immunogenicity data were available from clinical trials of bivalent vaccines composed of ancestral and Omicron BA.1 strains; however, no clinical efficacy data were available. In this study, effectiveness of the bivalent (Omicron BA.4/BA.5-containing) booster formulation against symptomatic SARS-CoV-2 infection was examined using data from the Increasing Community Access to Testing (ICATT) national SARS-CoV-2 testing program.* During September 14-November 11, 2022, a total of 360,626 nucleic acid amplification tests (NAATs) performed at 9,995 retail pharmacies for adults aged ≥18 years, who reported symptoms consistent with COVID-19 at the time of testing and no immunocompromising conditions, were included in the analysis. Relative vaccine effectiveness (rVE) of a bivalent booster dose compared with that of ≥2 monovalent vaccine doses among persons for whom 2-3 months and ≥8 months had elapsed since last monovalent dose was 30% and 56% among persons aged 18-49 years, 31% and 48% among persons aged 50-64 years, and 28% and 43% among persons aged ≥65 years, respectively. Bivalent mRNA booster doses provide additional protection against symptomatic SARS-CoV-2 in immunocompetent persons who previously received monovalent vaccine only, with relative benefits increasing with time since receipt of the most recent monovalent vaccine dose. Staying up to date with COVID-19 vaccination, including getting a bivalent booster dose when eligible, is critical to maximizing protection against COVID-19 (1).

The Centers for Medicare and Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1) assesses antibiotic administration, lactate measurement, and blood culture collection within 3 h of severe sepsis onset. The impact of the SEP-1 3-hour bundle among patients with severe sepsis is not extensively described. This investigation aimed to describe the impact of 3-hour bundle compliance on 28-day in-hospital mortality in patients with severe sepsis.This was a retrospective, propensity adjusted, nested case-control study assessing the impact of compliance with a 3-hour sepsis bundle among patients with severe sepsis.This study was conducted at a large, academic, tertiary care medical center in Detroit, Michigan from July 1, 2017 to December 31, 2019.Cases were defined as those suffering 28-day in-hospital mortality. Controls were defined as those surviving at or discharged by 28 days. Patients were separated based on 3-hour bundle compliance or noncompliance. Nested and overall cohorts were assessed. Severe sepsis time zero was manually validated. Patients with shock, requiring vasopressors within 8 h of time zero, or those not meeting SEP-1 inclusion criteria were excluded.The primary outcome was the propensity adjusted odds of 28-day in-hospital mortality among 3-hour bundle compliant versus noncompliant patients. Secondary outcomes included mortality for individual bundle element compliance, progression to septic shock, and predictors of mortality according to logistic regression.A total of 325 compliant and 325 noncompliant patients were included. The median Sequential Organ Failure Assessment (SOFA) score was three in each group. There was no difference in propensity adjusted odds of mortality among those compliant versus noncompliant with the 3-hour bundle (odds-ratio [OR] 1.039; 95% CI: 0.721-1.497; p = 0.838) or with individual bundle elements. SOFA score and female sex were predictors of mortality.Three-hour bundle compliance did not impact 28-day in-hospital mortality in patients with severe sepsis. Further research is needed to understand the impact of 3-hour bundle compliance on mortality in severe sepsis.

Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster.To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance.A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74 208 tests from children 5 to 11 years of age and 47 744 tests from adolescents 12 to 15 years of age with COVID-19-like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022.Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose).Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE = (1 - OR) × 100%.A total of 30 999 test-positive cases and 43 209 test-negative controls were included from children 5 to 11 years of age, as well as 22 273 test-positive cases and 25 471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.

IMPORTANCE: Monitoring COVID-19 vaccine performance over time since vaccination and against emerging variants informs control measures and vaccine policies. OBJECTIVE: To estimate the associations between symptomatic SARS-CoV-2 infection and receipt of BNT162b2, mRNA-1273, and Ad26.COV2.S by day since vaccination before and during Delta variant predominance (pre-Delta period: March 13-May 29, 2021; Delta period: July 18-October 17, 2021). DESIGN, SETTING, AND PARTICIPANTS: Test-negative, case-control design with data from 6884 US COVID-19 testing sites in the pharmacy-based Increasing Community Access to Testing platform. This study included 1 634 271 laboratory-based SARS-CoV-2 nucleic acid amplification tests (NAATs) from adults 20 years and older and 180 112 NAATs from adolescents 12 to 19 years old with COVID-19–like illness from March 13 to October 17, 2021. EXPOSURES: COVID-19 vaccination (1 Ad26.COV2.S dose or 2 mRNA doses) 14 or more days prior. MAIN OUTCOMES AND MEASURES: Association between symptomatic infection and prior vaccination measured using the odds ratio (OR) from spline-based multivariable logistic regression. RESULTS: The analysis included 390 762 test-positive cases (21.5%) and 1 423 621 test-negative controls (78.5%) (59.9% were 20-44 years old; 9.9% were 12-19 years old; 58.9% were female; 71.8% were White). Among adults 20 years and older, the BNT162b2 mean OR for days 14 to 60 after a second dose (initial OR) was lower during the pre-Delta period (0.10 [95% CI, 0.09-0.11]) than during the Delta period (0.16 [95% CI, 0.16-0.17]) and increased with time since vaccination (per-month change in OR, pre-Delta: 0.04 [95% CI, 0.02-0.05]; Delta: 0.03 [95% CI, 0.02-0.03]). The initial mRNA-1273 OR was 0.05 (95% CI, 0.04-0.05) during the pre-Delta period, 0.10 (95% CI, 0.10-0.11) during the Delta period, and increased with time (per-month change in OR, pre-Delta: 0.02 [95% CI, 0.005-0.03]; Delta: 0.03 [95% CI, 0.03-0.04]). The Ad26.COV2.S initial OR was 0.42 (95% CI, 0.37-0.47) during the pre-Delta period and 0.62 (95% CI, 0.58-0.65) during the Delta period and did not significantly increase with time since vaccination. Among adolescents, the BNT162b2 initial OR during the Delta period was 0.06 (95% CI, 0.05-0.06) among 12- to 15-year-olds, increasing by 0.02 (95% CI, 0.01-0.03) per month, and 0.10 (95% CI, 0.09-0.11) among 16- to 19-year-olds, increasing by 0.04 (95% CI, 0.03-0.06) per month. CONCLUSIONS AND RELEVANCE: Among adults, the OR for the association between symptomatic SARS-CoV-2 infection and COVID-19 vaccination (as an estimate of vaccine effectiveness) was higher during Delta variant predominance, suggesting lower protection. For mRNA vaccination, the steady increase in OR by month since vaccination was consistent with attenuation of estimated effectiveness over time; attenuation related to time was greater than that related to variant.

Assessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance.To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta).A test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states).Three doses of mRNA COVID-19 vaccine (third dose ≥14 days before test and ≥6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose).Association between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status.Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7245), 44.4% (n = 4570), and 41.6% (n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24).Among individuals seeking testing for COVID-like illness in the US in December 2021, receipt of 3 doses of mRNA COVID-19 vaccine (compared with unvaccinated and with receipt of 2 doses) was less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. These findings suggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.

Background The early administration of corticosteroids (CS) in patients with severe COVID-19 (hospitalized with need for supplemental oxygen) has been the only therapy to improve survival. However, the optimal dosing of CS remains unclear. Beginning March 2020 methylprednisolone (MP) in a dose of 40mg twice daily (high dose CS - HDC) was adopted at our institution. Based on emerging trials, this dose of MP was reduced to 16mg twice daily (moderate dose CS – MDC) in November 2020. The study aims to evaluate the outcome difference in patients receiving HDC versus MDC. Methods This pre-post quasi-experimental study was done at Henry Ford Hospital, an 877-bed tertiary care hospital in Detroit, Michigan. Consecutive patients in the HDC group from September 1, 2020 to November 15, 2020 were compared to the MDC group from November 30, 2020 to January 20, 2021. Only hospitalized patients with severe COVID-19 were included. The primary outcome was 28-day mortality. Secondary outcomes included progression to mechanical ventilation, length of hospital stay, discharge on supplemental oxygen and CS-associated adverse events. Patient demographics were evaluated using descriptive statistics. Bivariate and multivariable logistic regression analysis was planned to test the association between primary outcome and exposure. Results 470 patients were evaluated, 218 and 252 in the HDC and MDC groups respectively. Clinical characteristics and severity of illness on admission were comparable in both groups (Table 1). Among comorbidities - lung disease, cardiovascular disease and hypertension were higher in MDC. Antibiotic and tocilizumab use were lower in MDC. Significantly more patients in MDC group received oral CS. There was no difference in mortality between HDC and MDC through bivariate and multivariate analysis (14.7% and 13.5%, p < 0.712, adjusted OR 0.913 [0.514-1.619]) (Table 2,3). Median length of hospital stay was 5 and 6 days in HDC and MDC respectively (p < 0.001). There was no difference in CS-associated adverse events. Conclusion The survival in severe COVID-19 patients treated with MDC is comparable to HDC. Oral corticosteroids are an equally effective option. Disclosures Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Dexmedetomidine has revolutionized the field of critical care medicine, providing clinicians a short-acting, well-tolerated sedative. Cardiovascular adverse effects are well described with this agent (1). Less common adverse effects such as fever are increasingly being reported (2). Previous studies demonstrated no appreciable rate of dexmedetomidine-related fever (1, 3). Here we report a case of high-grade fever in the intensive care unit (ICU) after initiation of dexmedetomidine, with resolution after discontinuation. CASE PRESENTATION: A 34-year-old male with a past medical history of alcohol abuse and asthma was admitted to the general ward with Coronavirus disease 2019 (COVID-19) pneumonia. His course was complicated by severe hypoxia and subsequent pulseless electrical activity (PEA) arrest, requiring ICU transfer after achieving return of circulation and undergoing mechanical ventilation. On hospital day 7, after improvement in respiratory status with COVID-19 management including corticosteroids, as well as treatment with ceftriaxone and azithromycin given concern for superimposed bacterial pneumonia, he was transitioned to dexmedetomidine in preparation for a ventilator weaning trial. He developed fevers over the following 12 hours, initially to 39.4 C (102.9 F) prompting empiric sepsis management with intravenous fluids and broad-spectrum antibiotics (see figure-1). Despite this, he continued to have fevers to a maximum core temperature of 41.1 C (106 F). Blood, fungal, and respiratory cultures were unremarkable. With no clear infectious source or alternative explanation for severe hyperthermia, the decision was made to wean off dexmedetomidine given suspicion for drug-induced fever, upon which core temperature returned to 37.8 C (100.1 F). He remained afebrile, and eventually extubated and discharged in stable condition. DISCUSSION: We present a case of severe hyperthermia corresponding to, with a probable association using the Naranjo Adverse Drug Reaction Probability Scale, dexmedetomidine initiation, followed by resolution of fever after discontinuation. Antimicrobial therapy had no observable effect on the fever, and extensive infectious work-up was unremarkable. Completely attributing a febrile episode in the ICU setting to a medication is a difficult task. Furthermore, adequately powering studies to identify rare medication adverse effects in the ICU is a challenge, which may explain the absence of fever as a documented adverse effect of dexmedetomidine (1,2,4). In this case, no alternate diagnoses were evident, thus management was focused on discontinuing the presumed inciting agent. CONCLUSIONS: Recognizing dexmedetomidine as an etiology of severe hyperthermia in the ICU may help mitigate excessive therapies and improve outcomes. Further research is warranted to describe risk factors and proper recognition for when fevers occur with dexmedetomidine. REFERENCE #1: Hospira (2014) Precedex® (dexmedetomidine hydrochloride) [package insert]. Lake Forest, IL: Hospira, Inc. REFERENCE #2: Peterson J, Thomas W, Michaud C, et al. Incidence of Fever Associated With Dexmedetomidine in the Adult Intensive Care Unit. J Pharm Pract. 2021 Apr 5:8971900211004828. REFERENCE #3: Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine for Long-Term Sedation Investigators. JAMA. 2012 Mar 21;307(11):1151-60. DISCLOSURES: No relevant relationships by Raef Fadel, source=Web Response No relevant relationships by Sara Hegab, source=Web Response No relevant relationships by Michael Reaume, source=Web Response No relevant relationships by Zachary Smith, source=Web Response