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Fluoroquinolone resistance in Escherichia coli is principally caused by two kinds of mutations: those affecting the target proteins of the drugs, i.e. DNA gyrase and topoisomerase IV, and those affecting regulatory genes such as marA, soxS or robA. Recently, overexpression of the latter genes was linked to increased organic solvent tolerance in E. coli. Among 138 clinical fluoroquinolone-resistant and -susceptible clinical isolates of E. coli we found a high association between fluoroquinolone resistance and organic solvent tolerance. This finding suggests that E. coli may undergo an adaptive response to extrinsic substances other than quinolones while mutating to fluoroquinolone resistance. [ABSTRACT FROM PUBLISHER]

Background: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC)., Objective: To investigate clinical laboratory markers of SARS-CoV-2 and PASC., Design: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024)., Setting: 83 enrolling sites., Participants: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection., Measurements: Participants completed questionnaires and standard clinical laboratory tests., Results: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 10 9 cells/L [95% CI, 264.5 to 267.4 × 10 9 cells/L]) than participants without known prior infection (275.2 × 10 9 cells/L [CI, 268.5 to 282.0 × 10 9 cells/L]), as well as higher mean hemoglobin A 1c (HbA 1c ) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA 1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero., Limitation: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined., Conclusion: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0737.

Objective: This review aims to emphasize the role of pharmacists for optimization of evidence-based outcomes of finerenone in multidisciplinary kidney care teams during the early detection process of CKD patients. Data Sources: A PubMed literature search was performed using keywords pharmacists, chronic kidney disease (CKD), type 2 diabetes (T2D), and finerenone. Study Selection and Data Extraction: All English-language studies on the role of pharmacists in managing CKD patients or finerenone prescriptions were evaluated. Data Synthesis: CKD is a major health problem affecting millions worldwide, especially those with T2D. In recent years, new drugs have been added to the treatment options for patients with T2D and CKD, which have been shown to reduce the risk of cardiovascular and renal complications in large clinical trials. Conclusions: Pharmacists can help detect and treat CKD in patients with T2D. They may use indicators to identify potential candidates for appropriate finerenone therapy, such as stage of CKD, albuminuria level, serum potassium concentration, and use of RAAS inhibitors. Pharmacists can provide education on the benefits and usage of finerenone, monitor response to therapy, adjust the medications and doses, prevent drug interactions, help with adherence and tolerability issues, and coordinate with other healthcare providers., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hypoglycemia will inevitably occur. Being prepared and implementing a treatment plan should help to restore euglycemia and resolve hypoglycemia symptoms. The plan comprises fast-acting carbohydrates and, importantly, ready-to-use glucagon for self-administration when carbohydrates are not working or for third-party administration when the affected person is unwilling or unable to swallow (e.g., unconscious or in a coma)., Competing Interests: J.D.G. is a member of speakers bureaus for Abbott Diabetes, CeQur, Lilly, Novo Nordisk, Sanofi, and Xeris Pharmaceuticals. D.I. is a member of speakers bureaus for Abbott Diabetes, CeQur, Dexcom, Insulet, Lilly, Medtronic, and Novo Nordisk. No other potential conflicts of interest relevant to this article were reported., (© 2024 by the American Diabetes Association.)

In the United States, Doctor of Pharmacy (PharmD) programs are required to provide advanced pharmacy practice experiences (APPEs) in the core inpatient rotation areas of hospital/health system pharmacy and inpatient general medicine patient care. Colleges and Schools of Pharmacy (C/SOPs) nationwide are increasingly utilizing blended or longitudinal APPE models to offer experiential opportunities; however, there is a gap in the literature to support programs with delineating rotation-specific competencies when integrating two or more rotations together. Utilizing a survey instrument, PharmD students at two C/SOPs reported their onsite inpatient rotation sub-competency activities achieved within the four competency areas of Hospital/Health Pharmacy Systems, Medication Safety and Quality, Clinical Applications, and Professional Practice, which are listed in Appendix C of the 2016 Accreditation Council for Pharmacy Education Standards Guidance Document. Unpaired two-sample t -tests were performed to compare proportions of sub-competency activity occurrence in the two rotation settings. In total, 168 students reported inpatient activities related to the four competency areas, with 95-100% reporting their involvement in one or more sub-competency opportunities within each area. Of the 26 sub-competencies compared, 73% significantly facilitated the development of competency to a greater extent for one APPE inpatient rotation type over the other ( p < 0.05). The findings can be utilized by C/SOPs to support the delineation of rotation-specific competencies when blending inpatient experiential opportunities.

Within a multi-state viral genomic surveillance program, we evaluated whether proportions of SARS-CoV-2 infections attributed to the JN.1 variant and to XBB-lineage variants (including HV.1 and EG.5) differed between inpatient and outpatient care settings during periods of cocirculation. Both JN.1 and HV.1 were less likely than EG.5 to account for infections among inpatients versus outpatients (aOR=0.60 [95% CI: 0.43-0.84; p=0.003] and aOR=0.35 [95% CI: 0.21-0.58; p<0.001], respectively). JN.1 and HV.1 variants may be associated with a lower risk of severe illness. The severity of COVID-19 may have attenuated as predominant circulating SARS-CoV-2 lineages shifted from EG.5 to HV.1 to JN.1., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: People with diabetes who inject insulin with pen devices may reuse the pen needles (PNs), a practice that can cause PN tip deformity, breakage, and contamination, and that is associated with lipohypertrophy and injection-related pain., Objective: This retrospective study aimed to estimate the extent of PN reuse among people with diabetes in 2 insured populations in the United States., Methods: Using claims data for Commercial Fully Insured (CFI) and Medicare Advantage (MA) populations from 1-Oct-2018 to 31-Dec-2022, we identified adults with type 1 or type 2 diabetes (T1D/T2D) who had ≥ 1 claim for PNs and ≥ 2 claims for insulin from 1-Jan-2019 to 31-Dec-2021, with continuous medical/pharmacy eligibility for 3 months before first claim and 1 year after (follow-up). Those receiving hospice or palliative care or using mail order prescriptions were excluded. We compared actual annual fill rate of PNs with expected fill rate (assuming single use) according to prescribed insulin regimen. Whether the annual actual-to-expected ratio for PN numbers equaled 1 was evaluated using sign tests with 2-sided P values., Results: Median annual actual-to-expected ratios ranged from 0.41 (T1D basal+prandial cohort) to 0.82 (T2D basal cohort; all P < 0.001) in the CFI population (N = 10,854), and from 0.55 (TID basal + prandial) to 1.10 (T2D basal and basal + prandial; P = 0.382-< 0.001) in the MA population (N = 32,495); medians were 0.34 and 0.55 for 4 expected T2D basal + prandial injections/day in CFI and MA populations, respectively (P < 0.001). Annual actual-to-expected ratios were < 1 for 62% and 47% of CFI and MA populations, respectively. An estimated 2%-27% and 0%-17%, respectively, depending on insulin regimen, had inadequate supplies of PNs suggesting that PNs could have been used ≥ 5 times., Conclusion: These findings highlight the need for educating people with diabetes about reasons for avoiding PN reuse and the key role that pharmacists can play in providing this information and adequate supplies of PNs., Competing Interests: Disclosure Laura Lupton, Xiaowu Sun, Joaquim Fernandes, and Sudha Kishorekumar are employees of CVS Health (“CVS”), which received funding from embecta to support these analyses. Pasha Javadi, Ray Sieradzan, and Andrew Thach are employees and stockholders of embecta. Jennifer D. Goldman is on the speakers bureaus of NovoNordisk, Lilly, Abbott Diabetes, Xeris, and CeQur. Susan Cornell is on the advisory board for Novo Nordisk, Inc., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Few antiviral therapies have been studied in patients with COVID-19 and kidney impairment. Herein, efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-beta-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment., Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury (AKI), chronic kidney disease (CKD), or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on Day 1; 100 mg daily up to Day 5) or placebo (enrollment: March 2021-March 2022). The primary efficacy endpoint was the composite of all-cause mortality or invasive mechanical ventilation (IMV) through Day 29. Safety was evaluated through Day 60., Results: Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 (37.0%) participants had AKI (remdesivir, 60; placebo, 30), 64 (26.3%) had CKD (remdesivir, 44; placebo, 20), and 89 (36.6%) had kidney failure (remdesivir, 59; placebo, 30); 31 (12.8%) were COVID-19 vaccinated. Composite all-cause mortality or IMV through Day 29 was 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = 0.61). Treatment-emergent adverse events were reported in 80.4% versus 77.5% and serious adverse events in 50.3% versus 50.0% of participants who received remdesivir versus placebo, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function., Conclusions: Although underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in those with COVID-19 and severe kidney impairment. (EudraCT number: 2020-005416-22; Clinical Trials.gov number: NCT04745351)., Trial Registration: EudraCT number: 2020-005416-22; Clinical Trials.gov number: NCT04745351., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers., Competing Interests: Potential conflicts of interest. M. E. L., V. C., L. M. M., D. W., A. D. R., H. D., M. I., N. L. W., T. B., K. T., J. N., J. R., E. S., W. L., J. L., and S. L. are employees of Helix, Inc. M. E. L., M. I., and S. L. report contracted research from Pfizer. M. E. L., M. I., W. L., and S. L. report contracted research from the Centers for Disease Control and Prevention (CDC). M. I., M. E. L., J. L., D. W., and S. L. report support for attending meetings and/or travel from Helix. M. I., M. E. L., W. L., A. D. R., J. L., D. W., and N. L. W. report stock or stock options from Helix. M. E. L. reports contracted research and travel support from Novavax. E. B. is an employee of Janssen Pharmaceuticals and a prior employee of Helix, Inc. P. R. H. reports contracted research from Seegene USA and Helix, Inc. J. G. is employed by the University of Nevada, Reno, and Renown Health, and reports a professional relationship with the Desert Research Institute and research funding from Gilead Sciences and the National Institute of Environmental Health Sciences (NIEHS); reports consulting fees from Renown Health; and US Patent Application 63/467,250 “Dynamic risk management for breast cancer based on multi-factor genetic testing” with Dr. Alexandre Bolze. J. D. G. reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron; grants from Merck (BARDA) and Gilead; speaking honoraria and personal fees from Gilead Sciences, Inc, and Eli Lilly & Co; and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and LabCorp; and serving as a speaker or advisory board member for Gilead and Eli Lilly. J. G., M. I., N. L. W., and S. L. report patents pending or issued to Helix, Inc (M. I. and S. L.: US-11776694-B2 and US-20230178236-A1). P. A. P. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: J.D.G. is on the speakers’ bureau for Abbott Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Xeris. R.B. serves on advisory panels for AstraZeneca, Novo Nordisk, and Sanofi; has received research support for Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Ironwood, Janssen, Novo Nordisk, and Sanofi; and is on speakers’ bureaus for Amarin, Amgen, Boehringer Ingelheim, Kowa, Eli Lilly, Novo Nordisk, and Sanofi. E.M. has received consulting fees from Abbott Diabetes, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, and Sanofi and has been a speaker for Abbott Diabetes, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, it is developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of the coronavirus disease of 2019 (COVID-19). BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: The Pneumonia Score Index (PSI) was developed to estimate the risk of dying within 30 days of presentation for community-acquired pneumonia patients and is a strong predictor of 30-day mortality after COVID-19. However, three of its required 20 variables (skilled nursing home, altered mental status and pleural effusion) are not discreetly available in the electronic medical record (EMR), resulting in manual chart review for these 3 factors. The goal of this study is to compare a simplified 17-factor version (PSI-17) to the original (denoted PSI-20) in terms of prediction of 30-day mortality in COVID-19., Methods: In this retrospective cohort study, the hospitalized patients with confirmed SARS-CoV-2 infection between 2/28/20-5/28/20 were identified to compare the predictive performance between PSI-17 and PSI-20. Correlation was assessed between PSI-17 and PSI-20, and logistic regressions were performed for 30-day mortality. The predictive abilities were compared by discrimination, calibration, and overall performance., Results: Based on 1,138 COVID-19 patients, the correlation between PSI-17 and PSI-20 was 0.95. Univariate logistic regression showed that PSI-17 had performance similar to PSI-20, based on AUC, ICI and Brier Score. After adjusting for confounding variables by multivariable logistic regression, PSI-17 and PSI-20 had AUCs (95% CI) of 0.85 (0.83-0.88) and 0.86 (0.84-0.89), respectively, indicating no significant difference in AUC at significance level of 0.05., Conclusion: PSI-17 and PSI-20 are equally effective predictors of 30-day mortality in terms of several performance metrics. PSI-17 can be obtained without the manual chart review, which allows for automated risk calculations within an EMR. PSI-17 can be easily obtained and may be a comparable alternative to PSI-20., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: G.A.D reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, Edesa Biotech and NeuroBo Pharmaceuticals. J.D.G reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron, grants from Merck (BARDA) and Gilead, and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences and Labcorp; and serving as a consultant, speaker or advisory board member for Gilead, and Eli Lilly. All other authors have nothing to disclose., (Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Healthy dietary patterns rich in flavonoids may benefit cognitive performance over time. Among socioeconomically disadvantaged groups, the association between flavonoid intake and measures of cognition is unclear. This study sought to identify associations between flavonoid intake and cognitive performance among Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study participants (n = 1947) across three study visits. Flavonoid intakes were assessed via two 24-h dietary recalls. Cognitive performance was assessed via the Trail Making Test (TMT)-A and TMT-B, which provide measures of attention and executive function, respectively. Mixed effects linear regression was used to model TMT scores over three study visits against visit 1 (v1) flavonoid intake, time (years from v1), and the interaction between v1 flavonoid intake and time, capturing both the cross-sectional association between flavonoid intake and time at v1 as well as the longitudinal association between v1 flavonoid intake and the change in TMT scores over time. Prior to adjustment, inverse cross-sectional associations at v1 were observed between (1) anthocyanidin intake and TMT-A scores for the overall sample and (2) total flavonoid, anthocyanidin, flavan-3-ol, flavone, and flavonol intake and TMT-B scores for the overall sample and among White adults. Only the association between anthocyanidin intake and TMT-B at v1 among White adults persisted after adjustment (for demographic characteristics such as age). One possible explanation for the few significant associations is universally low flavonoid intakes resulting from the consumption of an unhealthy dietary pattern.

Infection, autoimmunity, and cancer are principal human health challenges of the 21 st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (T RM ) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A + immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A + CD8 + T cells correlate with reduced inflammation and increased humoral immunity and that they resemble T RM cells. Our results suggest NKG2A + biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer., Competing Interests: Declaration of interests J.R.H. is a consultant for Regeneron Pharmaceuticals. J.D.G. reports contracted research, a grant, and consulting fees from Gilead. K.M.C. reports being a shareholder in Geneoscopy LLC and has received consulting fees from Geneoscopy LLC, PACT Pharma, Tango Therapeutics, Flagship Labs 81 LLC, and the Rare Cancer Research Foundation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level., Competing Interests: Declaration of interests S.E.W., D.R.Z., J.M.-F., K. Sorg, and J.M.B. are employees of NanoString Technologies (NSTG). J.R.H. is on the scientific advisory board of NSTG., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis., Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms., Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options., Registration: NCT05172024., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Helen Chu reported consulting for Merck, GSK, Pfizer, Ellume, Janssen, Vindico CME, and the Bill and Melinda Gates Foundation, and receiving research support from Gates Ventures, Ellume, and Sanofi Pasteur. She also serves as a co-investigator on studies funded by Pfizer, Novavax, and GSK. Maged Costantine reported receiving grant support for work not related to RECOVER work/publications from Baxter International and Siemens Healthcare and personal consulting fees not related to this paper from Progenity, Quidel Ortho, and Siemens Healthcare. Kristine Erlandson reported research funding from Gilead Sciences and consulting payments from Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to the University of Colorado. Emily Gallagher reported consulting for Novartis, Flare Therapeutics and Seagen. Edward Gardner reported research support (clinical trials) from Gilead Sciences, ViiV Healthcare, and Cepheid. Jason Goldman reported research support from Gilead, Eli Lilly and Regeneron; grants from Gilead, Merck (BARDA); personal fees for consulting from Gilead, Eli Lilly; and non-financial support from Adaptive Biotechnologies and Labcorp/Monogram Biosciences outside the submitted work. Timothy Heinrich reported grant support from Merck Inc. and consulting fees from Roche. Rachel Hess reported serving as Data Safety Monitoring Board member for Astellas Pharmaceuticals unrelated to the current work. Leora Horwitz reported being a member of the National Academy of Medicine Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. Priscilla Hsue reported receiving honoraria from Gilead and Merck unrelated to study topic, receiving study drug from Regeneron unrelated to study topic, and receiving a research grant from Novartis. Judith James reported OMRF has licensed her IP to Progentec Biosciences, has received grant support from Progentec Biosciences, and serves on Advisory Committees to Glaxo Smith Klein, Merck and Novartis. Arthur Kim reports providing educational materials to Clinical Care Options and UpToDate and serving on a Data Safety Monitoring board for Kintor Pharmaceuticals, Ltd. Bruce Levy reported serving as a consultant for AstraZeneca, Entrinsic Biosciences, Gossamer Bio and Nocion Therapeutics and receiving research support from Amgen, Genentech, GlaxoSmithKline, Pieris Pharmaceuticals, SRA and Sanofi unrelated to the current work. Vincent Marconi reported receiving grants from NIH during the conduct of the study and grants from NIH, Veteran Affairs, and Centers for Disease Control and Prevention; grants, personal fees, nonfinancial support, and other from Lilly and Gilead; grants and personal fees from ViiV; and nonfinancial support from Bayer outside the submitted work. Grace McComsey reported serving as consultant for Merck, Gilead, ViiV, Janssen and have received research support from Pfizer, Vanda, Genentech, Roche, Redhill and Cognivue. Torri Metz reported being a site PI and a participant in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She also reported being a site PI for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Janet Mullington reported support for investigator-initiated research by "Open Medicine Foundation and the Patient-Led Research Collaborative" Princess Ogbogu reported research support from Astrazeneca, GSK, Blueprint medical; advisory board for Astrazeneca, GSK, Sanofi, Kalvista; and consulting for Astrazeneca, GSK Sairam Parthasarathy reported research funding to Institution from Sergey Brin foundation of COVID and Long-COVID research. Michael Peluso reported consulting fees from Gilead Sciences and AstraZeneca, and service on data safety monitoring board for American Gene Technologies. Sean Quigley reported service on speaker Board for Servier, Alnylam, Agios; service on advisory board for Recordati, Alexion. Franz Rischard reported research support from NIH/NHLBI, United Therapeutics, Acceleron/Merck, Janssen, Insmed, Aerovate, and Bayer; and consulting/advisory compensation from Acceleron and Bayer. Nadine Rouphael reported being a consultant for ICON and EMMES as a safety consultant for clinical trials; service on the advisory boards for Moderna; funds to institution from Sanofi, Lilly, Merck, Quidel and Pfizer. PJ Utz reported stock ownership of Gilead and PI of biomarker studies for Pfizer STOP-PASC paxlovid trial Juan Wisnivesky received receiving consulting honorarium from Sanofi, Banook, Prospero, PPD and Atea and research grants from Sanofi, Regeneron, Axella, and Arnold Consultants., (Copyright: © 2023 Horwitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals., Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections., Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling., Exposure: SARS-CoV-2 infection., Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds)., Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months., Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

The discovery and characterization of antigen-specific CD8 + T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then construct SCT libraries to capture SARS-CoV-2 specific CD8 + T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes is validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease., (© 2023. The Author(s).)

The human leukocyte antigen (HLA) locus plays a central role in adaptive immune function and has significant clinical implications for tissue transplant compatibility and allelic disease associations. Studies using bulk-cell RNA sequencing have demonstrated that HLA transcription may be regulated in an allele-specific manner and single-cell RNA sequencing (scRNA-seq) has the potential to better characterize these expression patterns. However, quantification of allele-specific expression (ASE) for HLA loci requires sample-specific reference genotyping due to extensive polymorphism. While genotype prediction from bulk RNA sequencing is well described, the feasibility of predicting HLA genotypes directly from single-cell data is unknown. Here we evaluate and expand upon several computational HLA genotyping tools by comparing predictions from human single-cell data to gold-standard, molecular genotyping. The highest 2-field accuracy averaged across all loci was 76% by arcasHLA and increased to 86% using a composite model of multiple genotyping tools. We also developed a highly accurate model (AUC 0.93) for predicting HLA-DRB345 copy number in order to improve genotyping accuracy of the HLA-DRB locus. Genotyping accuracy improved with read depth and was reproducible at repeat sampling. Using a metanalytic approach, we also show that HLA genotypes from PHLAT and OptiType can generate ASE ratios that are highly correlated (R 2 = 0.8 and 0.94, respectively) with those derived from gold-standard genotyping., Competing Interests: PK is a shareholder and a consultant to Inflammatix, Inc. JH is founder and board member of Isoplexis and PACT Pharma. JG declared contracted research with Gilead, Lilly, and Regeneron. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Solomon, Zheng, Dillon, Goldman, Hourigan, Heath and Khatri.)

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonilla, Peluso, Rodgers, Aberg, Patterson, Tamburro, Baizer, Goldman, Rouphael, Deitchman, Fine, Fontelo, Kim, Shaw, Stratford, Ceger, Costantine, Fisher, O’Brien, Maughan, Quigley, Gabbay, Mohandas, Williams and McComsey.)

Competing Interests: J.D.G. is on speakers bureaus for Abbott Diabetes, Amarin, Boehringer Ingelheim, CeQur Lilly, Novo Nordisk, and Xeris. N.S. has served on an advisory panel for Sanofi and, since article submission, has become an employee of AstraZeneca Pharmaceuticals.

Type 2 diabetes is a chronic, progressive disease, and its management results in a high emotional burden on patients. Eventually many patients require and can benefit from the use of insulin. This article reports results of a survey of patients and health care providers regarding their experiences of and challenges with the use of basal insulin. Health care providers can play a key role in helping people with type 2 diabetes overcome the challenges associated with the use of basal insulin, including connecting with their emotional needs and understanding the stressors associated with managing diabetes., Competing Interests: J.D.G. is a speaker for Abbot Diabetes, Lilly, Novo Nordisk, Sanofi, and Xeris. E.A.-S. is a consultant for Sanofi and a speaker for Novo Nordisk and Sanofi. C.P. and J.T. are employees of dQ&A. No other potential conflicts of interest relevant to this article were reported., (© 2023 by the American Diabetes Association.)

Background: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs., Methods: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee., Results: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval., Conclusions: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes., (© 2023 Wiley Periodicals LLC.)

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs <3%), and protein (27% vs <3%). FMF infants are more likely to have an early introduction (<12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Importance: SARS-CoV-2, which causes COVID-19, poses considerable morbidity and mortality risks. Studies using data collected during routine clinical practice can supplement randomized clinical trials to provide needed evidence, especially during a global pandemic, and can yield markedly larger sample sizes to assess outcomes for important patient subgroups., Objective: To evaluate the association of remdesivir treatment with inpatient mortality among patients with COVID-19 outside of the clinical trial setting., Design, Setting, and Participants: A retrospective cohort study in US hospitals using health insurance claims data linked to hospital chargemaster data from December 1, 2018, to May 3, 2021, was conducted among 24 856 adults hospitalized between May 1, 2020, and May 3, 2021, with newly diagnosed COVID-19 who received remdesivir and 24 856 propensity score-matched control patients., Exposure: Remdesivir treatment., Main Outcomes and Measures: All-cause inpatient mortality within 28 days of the start of remdesivir treatment for the remdesivir-exposed group or the matched index date for the control group., Results: A total of 24 856 remdesivir-exposed patients (12 596 men [50.7%]; mean [SD] age, 66.8 [15.4] years) and 24 856 propensity score-matched control patients (12 621 men [50.8%]; mean [SD] age, 66.8 [15.4] years) were included in the study. Median follow-up was 6 days (IQR, 4-11 days) in the remdesivir group and 5 days (IQR, 2-10 days) in the control group. There were 3557 mortality events (14.3%) in the remdesivir group and 3775 mortality events (15.2%) in the control group. The 28-day mortality rate was 0.5 per person-month in the remdesivir group and 0.6 per person-month in the control group. Remdesivir treatment was associated with a statistically significant 17% reduction in inpatient mortality among patients hospitalized with COVID-19 compared with propensity score-matched control patients (hazard ratio, 0.83 [95% CI, 0.79-0.87])., Conclusions and Relevance: In this retrospective cohort study using health insurance claims and hospital chargemaster data, remdesivir treatment was associated with a significantly reduced inpatient mortality overall among patients hospitalized with COVID-19. Results of this analysis using data collected during routine clinical practice and state-of-the-art methods complement results from randomized clinical trials. Future areas of research include assessing the association of remdesivir treatment with inpatient mortality during the circulation of different variants and relative to time from symptom onset.

Onsite and in-person experiential education has been well established to prepare practice-ready healthcare professionals, such as pharmacists. From COVID-19, the integration of remote educational delivery has occurred. As healthcare disciplines adjust to new experiential styles and innovate traditional methods, this paper highlights key areas for remote experiential education that can influence student experiences. Factors that are of importance to continuous quality improvement are described. A survey, utilizing the cloud-based software platform Qualtrics® headquartered in the United States, was developed to evaluate whether remote rotation delivery was comparable to traditional onsite experiential education, to assist with quality improvement for virtual experiential education, and to ensure the redesigned educational model meets accreditation standards for two schools of pharmacy. Numerous factors including work, time zone, Office of Experiential Education and preceptor responsiveness, and technology, were examined. Chi-Square test, t-test for proportions and odds ratios were utilized to evaluate results. Students with technology concerns throughout a remote rotation had a more than two-fold increase in identifying the virtual experience as worse than most/all other in-person rotations (p = 0.01). Preceptor responsiveness to questions and concerns significantly impact student perceptions of educational quality (p < 0.05). The majority of students perceived remote experiential education is equal to onsite experiences. Since continuous quality improvement is required by pharmacy accreditors and many other healthcare programs offering clinical opportunities, identifying factors is of importance to make future interventions in the remote experiential education delivery. This type of experiential learning became essential with COVID-19 impacting onsite clinical placements, and information can be used across health science disciplines at large.

Background: A person's daily nutrient intake and overall nutritional status are determined by a complex interplay of the types and amounts of foods ingested in combination with the timing and frequency of eating., Objectives: The aim was to summarize frequency of eating occasion data examined by the 2020 Dietary Guidelines Advisory Committee, the macronutrient contributions they provide, and meal frequency relative to dietary quality among the US population (≥2 y), with a focus on sex, age, race/Hispanic origin, and income., Methods: Demographic and 24-h recall data from the 2013-2016 NHANES were examined. An eating occasion was defined as "any ingestive event (e.g., solid food, beverage, water) that is either energy yielding or non-energy yielding"; all eating occasions were further divided into discrete meals and snacks. Frequency of meals and snacks was defined as "the number of daily EOs [eating occasions]," respectively. Diet quality was assessed via the Healthy Eating Index (HEI)-2015., Results: Most Americans consume 2 (28%) to 3 (64%) meals on a given day and >90% consume 2 to 3 snacks on that day. Adult, Hispanic, and non-Hispanic Black and lower-income (<131% family poverty-to-income ratio) Americans had a lower frequency of eating than children or adolescents, non-Hispanic White, and non-Hispanic Asian Americans and higher-income Americans, respectively. Americans who reported 3 meals on a given day consumed a diet higher in dietary quality than Americans who consumed 2 meals on a given day (HEI-2015: 61.0 vs. 55.0), regardless of population subgroup., Conclusions: The frequency of the types of eating occasions differs according to age, race and Hispanic origin, and income. Dietary quality is associated with the number of meals consumed. Healthy dietary patterns can be constructed in a variety of ways to suit different life stages, cultural practices, and income levels; improved diet quality and careful consideration of nutrient density when planning meals are warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19., Methods: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital., Results: A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31-.69) in the univariate model (P < .001) and 0.60 (.40-.90) in the risk-adjusted model (P = .01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39-1.00; P = .049)., Conclusion: Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Despite research that suggests flavonoids protect against metabolic syndrome (MetS) and evidence that intake of these compounds differs by race, knowledge about whether flavonoid-MetS associations vary among racial groups is limited. This study sought to estimate usual total flavonoid intake in African American and White adults and assess its sex- and sex/race-specific associations with MetS and its risk factors. Analysis of cross-sectional data from 1837 adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were analyzed. Usual total flavonoid intake was estimated using the NCI Method, and logistic regression measured its linkages with health outcomes. Among males overall and when stratified by race, odds of MetS and its risk factors low high-density lipoprotein cholesterol (HDL-C) and elevated glucose were lower at the 75th percentile of usual total flavonoid intake than at the 25th percentile (OR for MetS = 0.62; 95% CI = 0.53, 0.71). However, low HDL-C and elevated glucose were positively associated with usual flavonoid intake among females. The comparable associations by race within sex imply that the relationships between flavonoid and health outcomes may be evident across an array of intakes.

Background: Evening eating has been associated with higher energy intake and lower nutrient density. However, these qualities may not characterize all late evening (LE) eating patterns., Objective: We sought to characterize US adults' LE eating patterns on a given day and identify differences, if any, in pattern-specific associations with, and impact on, daily energy intake and total diet quality., Design: LE eating patterns, energy intakes, and Healthy Eating Index (HEI) scores were identified using Day-1 dietary recall data from the cross-sectional National Health and Nutrition Examination Survey 2013-2016., Participants/setting: The sample included adults aged ≥ 20 years (n = 9,861). LE reporters were respondents who consumed foods/beverages between 20:00 and 23:59 on the intake day., Main Outcome Measures: Energy intake and HEI-2015 scores by LE status/pattern and the impact of LE consumption on these measures., Statistical Analyses: Cluster analysis assigned individuals to LE eating patterns based on the LE energy contribution of food/beverage groups. Regression models estimated energy intake and HEI-2015 scores; estimates were compared between LE reporters and nonreporters. Similarly, LE's contribution to total energy and the difference in total HEI inclusive vs exclusive of LE consumption were estimated and compared among patterns., Results: Among US adults, 64.4% were LE reporters. Eleven LE patterns were identified; the six most prevalent patterns (representing 89% of LE reporters) were further analyzed. Daily energy intake in all prevalent patterns except the fruit pattern exceeded that of nonreporters by ≥ 268 kcal (unadjusted; P < 0.001), varying by pattern. Conversely, total HEI score did not differ from that of nonreporters (51.0) in any pattern except the fruit pattern, where it was higher (57.4, unadjusted; P < 0.001). Generally, LE consumption's impact on energy was high and its impact on HEI scores was low., Conclusions: Late evening food/beverage consumption is common among US adults, and LE patterns are not monolithic in their associations with, and impact on, total energy intake and dietary quality., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments. This retrospective study analyzed data from 6906 hospitalized adults with COVID-19 from a community health system across five states in the western United States. Risk models were developed to predict mechanical ventilation illness or death across one to 56 days of hospitalization, using clinical data available within the first hour after either admission with COVID-19 or a first positive SARS-CoV-2 test. For the seven-day interval, models for age ≥ 18 and < 50 years reached AUROC 0.81 (95% CI 0.71-0.91) and models for age ≥ 50 years reached AUROC 0.82 (95% CI 0.77-0.86). Models revealed differences in the statistical significance and relative predictive value of risk factors between older and younger patients including age, BMI, vital signs, and laboratory results. In addition, for hospitalized patients, sex and chronic comorbidities had lower predictive value than vital signs and laboratory results., (© 2022. The Author(s).)

Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunotherapy or other immunosuppressive cancer treatments, we summarize the evidence on outcomes from COVID-19; address the safety, immunogenicity, and efficacy of COVID-19 vaccination; and review COVID-19 antiviral therapeutics for the patient with cancer. Despite higher mortality for patients with cancer, treatment with immune checkpoint inhibitors does not seem to increase mortality risk based on observational evidence. Inhibitory therapies directed toward B-cell lineages, including monoclonal antibodies against CD20 and CAR T-cell therapies, are associated with poor outcomes in COVID-19; however, the data are sparse. Regarding vaccination in patients receiving immune checkpoint inhibitors, clinical efficacy comparable to that in the general population can be expected. In patients undergoing B-cell-depleting therapy, immunogenicity and clinical efficacy are curtailed, but vaccination is not futile, which is thought to be due to the cellular response. Vaccine reactogenicity and toxicity in all groups of patients with cancer are comparable to that of the general population. Preexposure prophylaxis with monoclonal antibodies directed against the viral spike may provide passive immunity for those not likely to mount an adequate vaccine response. If infected, prompt treatment with monoclonal antibodies or oral small molecule antivirals is beneficial, though with oral antiviral therapies, care must be taken to avoid drug interactions in patients with cancer.

Background: The oral, selective Janus kinase 1/2 inhibitor baricitinib has shown efficacy in studies of hospitalised adults with COVID-19. COV-BARRIER (NCT04421027) was a multinational, phase 3, randomised, double-blind, placebo-controlled trial of baricitinib in patients with confirmed SARS-CoV-2 infection. We aimed to evaluate the efficacy and safety of baricitinib plus standard of care in critically ill hospitalised adults with COVID-19 requiring invasive mechanical ventilation or extracorporeal membrane oxygenation., Methods: This exploratory trial followed the study design of COV-BARRIER in a critically ill cohort not included in the main phase 3 trial. The study was conducted across 18 hospitals in Argentina, Brazil, Mexico, and the USA. Participants (aged ≥18 years) hospitalised with laboratory-confirmed SARS-CoV-2 infection on baseline invasive mechanical ventilation or extracorporeal membrane oxygenation were randomly assigned (1:1) to baricitinib (4 mg) or placebo once daily for up to 14 days in combination with standard of care. Participants, study staff, and investigators were masked to study group assignment. Prespecified endpoints included all-cause mortality through days 28 and 60, number of ventilator-free days, duration of hospitalisation, and time to recovery through day 28. The efficacy analysis was done in the intention-to-treat population and the safety analysis was done in the safety population. This trial is registered with ClinicalTrials.gov, NCT04421027., Findings: Between Dec 23, 2020, and April 10, 2021, 101 participants were enrolled into the exploratory trial and assigned to baricitinib (n=51) or placebo (n=50) plus standard of care. Standard of care included baseline systemic corticosteroid use in 87 (86%) participants. Treatment with baricitinib significantly reduced 28-day all-cause mortality compared with placebo (20 [39%] of 51 participants died in the baricitinib group vs 29 [58%] of 50 in the placebo group; hazard ratio [HR] 0·54 [95% CI 0·31-0·96]; p=0·030; 46% relative reduction; absolute risk reduction 19%). A significant reduction in 60-day mortality was also observed in the baricitinib group compared with the placebo group (23 [45%] events vs 31 [62%]; HR 0·56 [95% CI 0·33-0·97]; p=0·027; 44% relative reduction; absolute risk reduction 17%). In every six baricitinib-treated participants, one additional death was prevented compared with placebo at days 28 and 60. The number of ventilator-free days did not differ significantly between treatment groups (mean 8·1 days [SD 10·2] in the baricitinib group vs 5·5 days [8·4] in the placebo group; p=0·21). The mean duration of hospitalisation in baricitinib-treated participants was not significantly shorter than in placebo-treated participants (23·7 days [SD 7·1] vs 26·1 days [3·9]; p=0·050). The rates of infections, blood clots, and adverse cardiovascular events were similar between treatment groups., Interpretation: In critically ill hospitalised patients with COVID-19 who were receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, treatment with baricitinib compared with placebo (in combination with standard of care, including corticosteroids) reduced mortality, which is consistent with the mortality reduction observed in less severely ill patients in the hospitalised primary COV-BARRIER study population. However, this was an exploratory trial with a relatively small sample size; therefore, further phase 3 trials are needed to confirm these findings., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests EWE reports research grants from the US Centers for Disease Control and Prevention (CDC), NIH, and Veterans Affairs; and has served as an unpaid consultant for Eli Lilly and Company. AVR reports research grants from Eli Lilly and Company; and has served as a speaker or consultant for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Roche, Sobi, and Union Chimique Belge. CEK, SdB, RL, MLBP, and SC are employees and shareholders of Eli Lilly and Company. JDG reports research support from Eli Lilly and Company, Regeneron Pharmaceuticals, and Gilead Sciences; grants from NIH, Biomedical Advanced Research and Development Authority (administered by Merck), and Eurofins Viracor; and has served as a speaker or consultant for Eli Lilly and Company, Gilead Sciences, and Mylan Pharmaceuticals. JFKS reports research grants from Eli Lilly and Company; and has served as a speaker or consultant for Eli Lilly and Company, Amgen, Novartis, Janssen, and NovoNordisk.​ VCM reports research grants from the CDC, Gilead Sciences, NIH, Veterans Affairs, and ViiV Healthcare; honoraria from Eli Lilly and Company; has served as an advisory board member for Eli Lilly and Company and Novartis; and has participated as a study section chair for the NIH., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 + T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies., Competing Interests: Declaration of interests J.R.H. and A.R. are founders and board members of PACT Pharma. J.R.H. is a board member of Isoplexis, and A.R. is the scientific advisor to Isoplexis. M.M.D. is a member of the Scientific Advisory Board of PACT Pharma. J.A.B. is a member of the Scientific Advisory Boards of Arcus, Solid, and VIR. J.A.B. is a member of the Board of Directors of Gilead and Provention. J.A.B. is the CEO of Sonoma Biotherapeutics. L.L.L. is on the scientific advisory boards of Alector, Atreca, Dragonfly, DrenBio, Nkarta, Obsidian Therapeutics, and SBI Biotech. R.G. has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, and Merck, has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and declares ownership in CellSpace Biosciences. P.D.G. is on the Scientific Advisory Board of Celsius, Earli, Elpiscience, Immunoscape, Rapt, and Nextech, was a scientific founder of Juno Therapeutics, and receives research support from Lonza. J.D.G. declared contracted research with Gilead, Lilly, and Regeneron. J.A.H. received consulting fees or honoraria from Gilead Sciences, Amplyx, Allovir, Allogene therapeutics, CRISPR therapeutics, CSL Behring, OptumHealth, Octapharma, and Takeda and research funding from Takeda, Allovir, Karius, and Gilead Sciences. Q.D., D.H.M., R.T., R.M.G., M.K., and T.M.S. have employment and equity ownership with Adaptive Biotechnologies. The remaining authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined., Methods: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90., Results: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]., Conclusions: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A better understanding of the metabolic alterations in immune cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may elucidate the wide diversity of clinical symptoms experienced by individuals with coronavirus disease 2019 (COVID-19). Here, we report the metabolic changes associated with the peripheral immune response of 198 individuals with COVID-19 through an integrated analysis of plasma metabolite and protein levels as well as single-cell multiomics analyses from serial blood draws collected during the first week after clinical diagnosis. We document the emergence of rare but metabolically dominant T cell subpopulations and find that increasing disease severity correlates with a bifurcation of monocytes into two metabolically distinct subsets. This integrated analysis reveals a robust interplay between plasma metabolites and cell-type-specific metabolic reprogramming networks that is associated with disease severity and could predict survival., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARB), the most commonly prescribed antihypertensive medications, counter renin-angiotensin-aldosterone system (RAAS) activation via induction of angiotensin-converting enzyme 2 (ACE2) expression. Considering that ACE2 is the functional receptor for SARS-CoV-2 entry into host cells, the association of ACEi and ARB with COVID-19 outcomes needs thorough evaluation., Methods: We conducted retrospective analyses using both unmatched and propensity score (PS)-matched cohorts on electronic health records (EHRs) to assess the impact of RAAS inhibitors on the risk of receiving invasive mechanical ventilation (IMV) and 30-day mortality among hospitalized COVID-19 patients. Additionally, we investigated the immune cell gene expression profiles of hospitalized COVID-19 patients with prior use of antihypertensive treatments from an observational prospective cohort., Results: The retrospective analysis revealed that there was no increased risk associated with either ACEi or ARB use. In fact, the use of ACEi showed decreased risk for mortality. Survival analyses using PS-matched cohorts suggested no significant relationship between RAAS inhibitors with a hospital stay and in-hospital mortality compared to non-RAAS medications and patients not on antihypertensive medications. From the analysis of gene expression profiles, we observed a noticeable up-regulation in the expression of 1L1R2 (an anti-inflammatory receptor) and RETN (an immunosuppressive marker) genes in monocytes among prior users of ACE inhibitors., Conclusion: Overall, the findings do not support the discontinuation of ACEi or ARB treatment and suggest that ACEi may moderate the COVID-19 hyperinflammatory response.

What Is Stop Oud?: The STOP OUD project is an observational study on the use of long-acting buprenorphine ( S ublocade) and a T amper resistant PICC clamp for O utpatient IV antibiotic administration in P atients with serious infections and O pioid U se D isorder (STOP OUD)., Background: The US opioid crisis is driving up serious infections related to intravenous drug use. These infections require prolonged courses of antibiotics, often resulting in lengthy hospital stays. Extended hospitalizations for monitored parenteral antibiotics for patients with opioid use disorder are challenging for patients, reduce bed capacity, and are associated with significant cost. This observational study reviews the administration of intravenous (IV) antibiotics in a monitored outpatient setting using long-acting injectable buprenorphine (Sublocade, Indivior Inc., North Chesterfield, VA) and a tamper resistant clamp in patients with opioid use disorder ., Methods: Long-acting buprenorphine and a tamper resistant clamp were used to treat patients with serious infections and opioid use disorder as outpatients., Results: Hospital days avoided were 30-days per STOP OUD project participant. Eleven of thirteen STOP OUD project participants completed their antibiotic courses as prescribed, there was no evidence of peripherally inserted central catheter (PICC) tampering, and they rated their care as a mean of 4.9/5 (SD 0.4). Institutional savings per STOP OUD patient was $33,000. Outpatient infusion costs were $9,300 for a net savings of $23,700 per STOP OUD project participant. Infections resolved in all participants., Conclusions: The STOP OUD project reduced hospital length of stay for patients with opioid use disorder and serious infections, and had a favorable financial impact., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

Background: Data on the characteristics of coronavirus disease 2019 (COVID-19) patients disaggregated by race/ethnicity remains limited. We evaluated the sociodemographic and clinical characteristics of patients across racial/ethnic groups and assessed their associations with COVID-19 outcomes., Methods: This retrospective cohort study examined 629 953 patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large health system spanning California, Oregon, and Washington between March 1 and December 31, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression., Results: A total of 570 298 patients with known race/ethnicity were tested for SARS-CoV-2, of whom 27.8% were non-White minorities: 54 645 individuals tested positive, with minorities representing 50.1%. Hispanics represented 34.3% of infections but only 13.4% of tests. Although generally younger than White patients, Hispanics had higher rates of diabetes but fewer other comorbidities. A total of 8536 patients were hospitalized and 1246 died, of whom 56.1% and 54.4% were non-White, respectively. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increased odds of testing positive and hospitalization were associated with all minority races/ethnicities. Hispanic patients also exhibited increased morbidity, and Hispanic race/ethnicity was associated with in-hospital mortality (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.14-1.70)., Conclusion: Major healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, required excess hospitalization and mechanical ventilation, and had higher odds of in-hospital mortality despite younger age. Targeted, culturally responsive interventions and equitable vaccine development and distribution are needed to address the increased risk of poorer COVID-19 outcomes among minority populations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described., Methods: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients., Results: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality., Conclusions: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)