Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Lung Protective Ventilation Adherence and Outcomes for Patients With COVID-19 Acute Respiratory Distress Syndrome Treated in an Intermediate Care Unit Repurposed to ICU Level of Care.

OBJECTIVE: During the COVID-19 pandemic, some centers converted intermediate care units (IMCUs) to COVID-19 ICUs (IMCU/ICUs). In this study, we compared adherence to lung protective ventilation (LPV) and outcomes for patients with COVID-19-related acute respiratory distress syndrome (ARDS) treated in an IMCU/ICU versus preexisting medical ICUs (MICUs). DESIGN: Retrospective observational study using electronic medical record data. SETTING: Two academic medical centers from March 2020 to September 2020 (period 1) and October 2020 to May 2021 (period 2), which capture the first two COVID-19 surges in this health system. PATIENTS: Adults with COVID-19 receiving invasive mechanical ventilation who met ARDS oxygenation criteria (Pao2/Fio2 ≤ 300 mm Hg or Spo2/Fio2 ≤ 315). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined LPV adherence as the percent of the first 48 hours of mechanical ventilation that met a restrictive definition of LPV of, tidal volume/predicted body weight (Vt/PBW) less than or equal to 6.5 mL/kg and plateau pressure (Pplat) less than or equal to 30 cm H2o. In an expanded definition, we added that if Pplat is greater than 30 cm H2o, Vt/PBW had to be less than 6.0 mL/kg. Using the restricted definition, period 1 adherence was lower among 133 IMCU/ICU versus 199 MICU patients (92% [95% CI, 50-100] vs. 100% [86-100], p = 0.05). Period 2 adherence was similar between groups (100% [75-100] vs. 95% CI [65-100], p = 0.68). A similar pattern was observed using the expanded definition. For the full study period, the adjusted hazard of death at 90 days was lower in IMCU/ICU versus MICU patients (hazard ratio [HR] 0.73 [95% CI, 0.55-0.99]), whereas ventilator liberation by day 28 was similar between groups (adjusted subdistribution HR 1.09 [95% CI, 0.85-1.39]). CONCLUSIONS: In patients with COVID-19 ARDS treated in an IMCU/ICU, LPV adherence was similar to, and observed survival better than those treated in preexisting MICUs. With adequate resources, protocols, and staffing, IMCUs provide an effective source of additional ICU capacity for patients with acute respiratory failure.

A very complicated UTI: malakoplakia following E. coli urinary tract infection.

Malakoplakia is a rare inflammatory disorder believed to result from a defect in macrophage phagocytic function triggering a granulomatous reaction. It can present with genitourinary, gastrointestinal, or cutaneous manifestations in immunocompromised or, less commonly, immunocompetent hosts. We describe a case of renal malakoplakia in a young, otherwise healthy patient presenting with nephromegaly and sepsis following an E. coli urinary tract infection. We discuss diagnosis and management, including antibiotic selection and the decision to pursue nephrectomy. This case highlights the potential for kidney recovery with prolonged antibiotic therapy in conjunction with adjunct immunomodulatory therapies and source control.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

Extended Versus Standard Proning Duration for COVID-19 Associated Acute Respiratory Distress Syndrome: A Target Trial Emulation Study.

RATIONALE: Prone positioning for > 16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. OBJECTIVE: To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe COVID-19 ARDS. METHODS: Data were extracted from a 5-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (> 24 hours) versus standard (16-24 hours) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended vs. standard proning on the primary outcome of 90-day mortality, and secondary outcomes of ventilator liberation and ICU discharge. Analytically we used inverse probability of treatment weighted (IPTW) Cox, or Fine and Gray regression models. RESULTS: 314 patients were included, 234 who received extended proning, and 80 who received standard duration. Extended proning patients were older, had greater comorbidity, were more often at an academic hospital, and had shorter time from admission to mechanical ventilation. After IPTW, characteristics were well balanced. Unadjusted 90-day mortality in the extended vs. standard proning groups was 39% vs 58%. In doubly-robust IPTW analyses, we found no significant effects of extended vs. standard proning duration on mortality (hazard ratio [95% CI] 0.95 [0.51-1.77]), ventilator liberation (sub-distribution hazard [sHR] 1.60, [0.97-2.64], or ICU discharge (sHR 1.31 [0.82-2.10]). CONCLUSION: Using target trial emulation, we found no significant effect of extended vs. standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Where the Postanesthesia Care Unit and Intensive Care Unit Meet.

The intensive care unit (ICU) was born from the postanesthesia care unit (PACU). In today's hospital systems, there remains a lot of overlap in the care missions of each location. The patient populations share many similarities and many of the same care, technology, and care protocols apply to patients in both units. As shown by the COVID-19 pandemic, there is immense value in maintaining protocols, processes, and staffing models for the safe care of ICU patients in the PACU when ICU demands exceed capacity.

The Role of Intermediate Care in Supporting Critically Ill Patients and Critical Care Infrastructure.

Intermediate care (IC) is used for patients who do not require the human and technological support of the intensive care unit (ICU) yet require more care and monitoring than can be provided on general wards. Though prevalent in many countries, there is marked variability in models of organization and staffing, as well as monitoring and interventions provided. In this article, the authors will discuss the historical background of IC, review the impact of IC on ICU and IC patient outcomes, and highlight where future studies can shed light on how to optimize IC organization and outcomes.

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Living with multimorbidity: A qualitative exploration of shared experiences of patients, family caregivers, and healthcare professionals in managing symptoms in the United States.

AIMS: To elicit experiences of patients, family caregivers, and healthcare professionals in intermediate care units (IMCUs) in an academic medical centre in Baltimore, MD related to the challenges and intricacies of multimorbidity management to inform development of a multimorbidity symptom management toolkit. DESIGN: Experience-based co-design. METHODS: Between July and October 2021, patients aged 55 years and older with multimorbidity admitted to IMCUs at an academic medical centre in Baltimore, Maryland, USA were recruited and interviewed in person. Interdisciplinary healthcare professionals working in the IMCU were interviewed virtually. Participants were asked questions about their role in recognizing and treating symptoms, factors affecting the quality of life, symptom burden and trajectory over time, and strategies that have and have not worked for managing symptoms. An inductive thematic analysis approach was used for analysis. RESULTS: Twenty-three interviews were conducted: 9 patients, 2 family caregivers, and 12 healthcare professionals. Patients' mean age was 67.5 (±6.5) years, over half (n = 5) were Black or Hispanic, and the average number of comorbidities was 3.67. Five major themes that affect symptom management emerged: (1) the patient-provider relationship; (2) open and honest communication; (3) accessibility of resources during hospitalization and at discharge; (4) caregiver support, training, and education; and (5) care coordination and follow-up care. CONCLUSION: Patients, caregivers, and healthcare professionals often have similar goals but different priorities for multimorbidity management. It is imperative to identify shared priorities and target holistic interventions that consider patient and caregiver experiences to improve outcomes. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE AND IMPACT: This paper addresses the paucity of research related to the shared experience of disease trajectory and symptom management for people living with multimorbidity. We found that patients, caregivers, and healthcare professionals often have similar goals but different care and communication priorities. Understanding differing priorities will help better design interventions to support symptom management so people with multimorbidity can have the best possible quality of life. REPORTING METHOD: We have adhered to the Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines in our reporting. PATIENT OR PUBLIC CONTRIBUTION: This study has been designed and implemented with patient and public involvement throughout the process, including community advisory board engagement in the project proposal phase and interview guide development, and member checking in the data collection and analysis phases. The method we chose, experience-based co-design, emphasizes the importance of engaging members of a community to act as experts in their own life challenges. In the coming phases of the study, the public will be involved in developing and testing a new intervention, informed by these qualitative interviews and co-design events, to support symptom management for people with multimorbidity.

Study protocol for Care cOORDInatioN And sympTom managEment (COORDINATE) programme: a feasibility study.

INTRODUCTION: Sustainable approaches to support care coordination and symptom management needs of critically ill adults living with multimorbidity are needed to combat the challenges and complexity that multimorbidity presents. The study aims to test the feasibility of the Care cOORDInatioN And sympTom managEment (COORDINATE) intervention to improve health outcomes of adults living with multimorbidity. METHODS AND ANALYSIS: A multicomponent nurse-driven intervention was developed using experience-based co-design and human-centred design. Inclusion criteria include (1) age 55 years and older, (2) admitted to an intermediate care unit, (3) presence of two or more chronic health conditions and (4) signed informed consent. Data collection will occur at baseline (time of recruitment predischarge) and 6 weeks and 3 months following hospital discharge. Outcome of interest from this feasibility study is to evaluate the financial, technical and logistic feasibility of a full-scale study including data collection and protocol adherence. Additionally, Cohen's d effect sizes for the change in outcomes over time will be computed to establish power calculations required for a full-scale study. The protocol was prepared in accordance with Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Institutional Review Board of Johns Hopkins Medical Institutions. Given the success of this feasibility study, the potential for the COORDINATE intervention to decrease the symptom burden and improve participant quality of life among critically ill people with multimorbidity will be tested in a full-scale study, and findings will be actively disseminated. TRIAL REGISTRATION NUMBER: NCT05985044.

Neuropathological findings in COVID-19 vs. non-COVID-19 acute respiratory distress syndrome-A case-control study.

Acute brain injury (ABI) and neuroinflammation is reported in COVID-19 and acute respiratory distress syndrome (ARDS). It remains unclear if COVID-19 plays an independent role in development of ABI compared to those with non-COVID-19 ARDS. We aimed to evaluate if COVID-19 ARDS is associated with higher risk and specific patterns of ABI compared to non-COVID-19 ARDS. We conducted an age and sex matched case-control autopsy study at a tertiary academic center. Ten patients with COVID-19 ARDS were matched to 20 non-COVID-19 ARDS patients. Baseline demographics were comparable between the two groups including severity of ARDS (p = 0.3). The frequency of overall ABI (70 vs. 60%), infratentorial ABI (40 vs. 25%), ischemic infarct (40 vs. 25%), intracranial hemorrhage (30 vs. 35%), and hypoxic-ischemic brain injury (30 vs. 35%) was similar between COVID-19 and non-COVID-19 ARDS patients, respectively (p > 0.05). Intracapillary megakaryocytes were exclusively seen in 30% of COVID-19 patients. Overall, frequency and pattern of ABI in COVID-19 ARDS was comparable to non-COVID-19.