Highly mutated monoclonal antibody 3F2 targets a conformational and strain-restricted epitope in human immunodeficiency virus gp41 with significant antibody-dependent cell cytotoxicity.

Identifying epitope targets by studying the native antibody (Ab) response can identify potential novel vaccine constructs. Studies suggest that long-term non-progressor (LTNP) subjects have inherent immune mechanisms that help to control viremia and disease progression. To explore a role for antibodies (Abs) in LTNP progression, our lab has previously characterized a number of highly mutated Abs that target conformational epitopes of the human immunodeficiency virus (HIV) envelope protein from a single LTNP subject (10076). One Ab clone, 10076-Q3-2C6, had significant cross-clade Ab-dependent cell cytotoxicity. To assess if other LTNP subjects produced similar Abs, we expressed another highly mutated Ab from another subject; subject 10002, clone 10002-Q1-3F2 (variable heavy chain, 63.2% amino acid sequence identity to predicted germline). After expression with its native light chain, the recombinant Ab 3F2 bound to the trimeric envelope protein of HIV (trimer), as well as to the ectodomain of gp41. 3F2 binding to gp41 peptide libraries was consistent with non-linear epitope binding and showed possible overlap with the epitope of 2C6. Ab competition assays suggested that 3F2 may bind near the immunodominant epitope 1 loop region (ID1) of gp41. 2C6 blocked the binding of ID1-loop-binding Abs and 3F2 to the trimer, but 3F2 failed to block 2C6 binding. Together, these results suggest that 3F2 binds to a non-linear conformational epitope primarily localized between the epitope of 2C6 and the ID1. Since they are targeted by functional Abs, a more complete understanding of these ID1 and near-ID1 epitopes may be exploited in future immunization strategies.

Should COVID-19 symptoms be used to cohort patients in the emergency department? A retrospective analysis.

OBJECTIVE: To determine how cohorting patients based on presenting complaints affects risk of nosocomial infection in crowded Emergency Departments (EDs) under conditions of high and low prevalence of COVID-19. METHODS: This was a retrospective analysis of presenting complaints and PCR tests collected during the COVID-19 epidemic from 4 EDs from a large hospital system in Bronx County, NY, from May 1, 2020 to April 30, 2021. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated for a symptom screen based on the CDC list of COVID-19 symptoms: fever/chills, shortness of breath/dyspnea, cough, muscle or body ache, fatigue, headache, loss of taste or smell, sore throat, nasal congestion/runny nose, nausea, vomiting, and diarrhea. PPV was calculated for varying values of prevalence. RESULTS: There were 80,078 visits with PCR tests. The sensitivity of the symptom screen was 64.7% (95% CI: 63.6, 65.8), specificity 65.4% (65.1, 65.8). PPV was 16.8% (16.5, 17.0) and NPV was 94.5% (94.4, 94.7) when the observed prevalence of COVID-19 in the ED over the year was 9.7%. The PPV of fever/chills, cough, body and muscle aches and nasal congestion/runny nose were each approximately 25% across the year, while diarrhea, nausea, vomiting and headache were less predictive, (PPV 4.7%-9.6%) The combinations of fever/chills, cough, muscle/body aches, and shortness of breath had PPVs of 40-50%. The PPV of the screen varied from 3.7% (3.6, 3.8) at 2% prevalence of COVID-19 to 44.3% (44.0, 44.7) at 30% prevalence. CONCLUSION: The proportion of patients with a chief complaint of COVID-19 symptoms and confirmed COVID-19 infection was exceeded by the proportion without actual infection. This was true when prevalence in the ED was as high as 30%. Cohorting of patients based on the CDC's list of COVID-19 symptoms will expose many patients who do not have COVID-19 to risk of nosocomially acquired COVID-19. EDs should not use the CDC list of COVID-19 symptoms as the only strategy to minimize exposure.

SARS-CoV-2 coinfection with additional respiratory virus does not predict severe disease: a retrospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) claimed over 4 million lives by July 2021 and continues to pose a serious public health threat. OBJECTIVES: Our retrospective study utilized respiratory pathogen panel (RPP) results in patients with SARS-CoV-2 to determine if coinfection (i.e. SARS-CoV-2 positivity with an additional respiratory virus) was associated with more severe presentation and outcomes. METHODS: All patients with negative influenza/respiratory syncytial virus testing who underwent RPP testing within 7 days of a positive SARS-CoV-2 test at a large, academic medical centre in New York were examined. Patients positive for SARS-CoV-2 with a negative RPP were compared with patients positive for SARS-CoV-2 and positive for a virus by RPP in terms of biomarkers, oxygen requirements and severe COVID-19 outcome, as defined by mechanical ventilation or death within 30 days. RESULTS: Of the 306 SARS-CoV-2-positive patients with RPP testing, 14 (4.6%) were positive for a non-influenza virus (coinfected). Compared with the coinfected group, patients positive for SARS-CoV-2 with a negative RPP had higher inflammatory markers and were significantly more likely to be admitted (P = 0.01). Severe COVID-19 outcome occurred in 111 (36.3%) patients in the SARS-CoV-2-only group and 3 (21.4%) patients in the coinfected group (P = 0.24). CONCLUSIONS: Patients infected with SARS-CoV-2 along with a non-influenza respiratory virus had less severe disease on presentation and were more likely to be admitted-but did not have more severe outcomes-than those infected with SARS-CoV-2 alone.

ABO blood type association with SARS-CoV-2 infection mortality: A single-center population in New York City.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a variable clinical course with significant mortality. Early reports suggested higher rates of SARS-CoV-2 infection in patients with type A blood and enrichment of type A individuals among COVID-19 mortalities. STUDY DESIGN AND METHODS: The study includes all patients hospitalized or with an emergency department (ED) visit who were tested for SARS-CoV-2 between March 10, 2020 and June 8, 2020 and had a positive test result by nucleic acid test (NAT) performed on a nasopharyngeal swab specimen. A total of 4968 patients met the study inclusion criteria, with a subsequent 23.1% (n = 1146/4968) all-cause mortality rate in the study cohort. To estimate overall risk by ABO type and account for the competing risks of in-hospital mortality and discharge, we calculated the cumulative incidence function (CIF) for each event. Cause-specific hazard ratios (csHRs) for in-hospital mortality and discharge were analyzed using multivariable Cox proportional hazards models. RESULTS: Type A blood was associated with the increased cause-specific hazard of death among COVID-19 patients compared to type O (HR = 1.17, 1.02-1.33, p = .02) and type B (HR = 1.32,1.10-1.58, p = .003). CONCLUSIONS: Our study shows that ABO histo-blood group type is associated with the risk of in-hospital death in COVID-19 patients, warranting additional inquiry. Elucidating the mechanism behind this association may reveal insights into the susceptibility and/or immunity to SARS-CoV-2.

Monoclonal Antibody 2C6 Targets a Cross-Clade Conformational Epitope in gp41 with Highly Active Antibody-Dependent Cell Cytotoxicity.

Previous studies in our laboratory characterized a panel of highly mutated HIV-specific conformational epitope-targeting antibodies (Abs) from a panel of HIV-infected long-term nonprogressors (LTNPs). Despite binding HIV envelope protein and having a high number of somatic amino acid mutations, these Abs had poor neutralizing activity. Because of the evidence of antigen-driven selection and the long CDR3 region (21 amino acids [aa]), we further characterized the epitope targeting of monoclonal Ab (MAb) 76-Q3-2C6 (2C6). We confirmed that 2C6 binds preferentially to trimeric envelope and recognizes the clades A, B, and C SOSIP trimers. 2C6 binds gp140 constructs of clades A, B, C, and D, suggesting a conserved binding site that we localized to the ectodomain of gp41. Ab competition with MAb 50-69 suggested this epitope localizes near aa 579 to 613 (referenced to HXB2 gp160). Peptide library scanning showed consistent binding in this region but to only a single peptide. Lack of overlapping peptide binding supported a nonlinear epitope structure. The significance of this site is supported by 2C6 having Ab-dependent cell cytotoxicity (ADCC) against envelope proteins from two clades. Using 2C6 and variants, alanine scanning mutagenesis identified three amino acids (aa 592, 595, and 596) in the overlapping region of the previously identified peptide. Additional amino acids at sites 524 and 579 were also identified, helping explain its conformational requirement. The fact that different amino acids were included in the epitope depending on the targeted protein supports the conclusion that 2C6 targets a native conformational epitope. When we mapped these amino acids on the trimerized structure, they spanned across oligomers, supporting the notion that the epitope targeted by 2C6 lies in a recessed pocket between two gp41 oligomers. A complete understanding of the epitope specificity of ADCC-mediating Abs is essential for developing effective immunization strategies that optimize protection by these Abs.IMPORTANCE This paper further defines the function and area of the HIV trimeric envelope protein targeted by the monoclonal antibody 2C6. 2C6 binding is influenced by amino acid mutations across two separate gp41 sections of the envelope trimer. This epitope is recognized on multiple clades (variant groups of circulating viruses) of gp41, gp140 trimers, and SOSIP trimers. For the clades tested, 2C6 has robust ADCC. As the target of 2C6 is available in the major clades of HIV and has robust ADCC activity, further definition and appreciation of targeting of antibodies similar to 2C6 during vaccine development should be considered.

Identification of a mimotope of a complex gp41 Human Immunodeficiency VIrus epitope related to a non-structural protein of Hepacivirus previously implicated in Kawasaki disease.

Background: We have previously isolated a highly mutated VH1-02 antibody termed group C 76-Q13-6F5 (6F5) that targets a conformational epitope on gp41. 6F5 has the capacity to mediate Ab dependent cell cytotoxicity (ADCC). When the VH1-02 group C 76 antibodies variable chain sequence was reverted to germline (76Canc), this still retained ADCC activity. Due to this ability for the 76Canc germline antibody to functionally target this epitope, we sought to identify a protein target for vaccine development. Methods: Initially, we interrogated peptide targeting by screening a microarray containing 29,127 linear peptides. Western blot and ELISAs were used to confirm binding and explore human serum targeting. Autoimmune targeting was further interrogated on a yeast-displayed human protein microarray. Results: 76Canc specifically recognized a number of acidic peptides. Meme analysis identified a peptide sequence similar to a non-structural protein of Hepacivirus previously implicated in Kawasaki disease (KD). Binding was confirmed to top peptides, including the Hepacivirus-related and KD-related peptide. On serum competitions studies using samples from children with KD compared to controls, targeting of this epitope showed no specific correlation to having KD. Human protein autoantigen screening was also reassuring. Conclusions: This study identifies a peptide that can mimic the gp41 epitope targeted by 76C group antibodies (i.e. a mimotope). We show little risk of autoimmune targeting including any inflammation similar to KD, implying non-specific targeting of this peptide during KD. Development of such peptides as the basis for vaccination should proceed cautiously.

Improving Resident Hospital Discharge Communication by Changing Electronic Health Record Templates to Enhance Primary Care Provider Satisfaction.

BACKGROUND AND OBJECTIVES: Despite use of standardized electronic health record templates, the structure of discharge summaries may hinder communication from inpatient settings to primary care providers (PCPs). We developed an enhanced electronic discharge summary template to improve PCP satisfaction with written discharge summaries targeting diagnoses, medication reconciliation, laboratory test results, specialist follow-up, and recommendations. METHODS: Resident template usage was measured using statistical process control charts. PCP reviewers' discharge summary satisfaction was surveyed using 5-point Likert scales analyzed using the Mann-Whitney U test. Residents were surveyed for satisfaction. RESULTS: Resident template usage increased from 61% initially to 72% of discharge summaries at 6 months. The PCP reviewers reported increased satisfaction for summaries using the template compared with those without (4.3 vs 3.9, P = .003). Surveyed residents desired template inclusion in the default electronic discharge summary (93%). CONCLUSIONS: This system-level resident-initiated quality improvement initiative created a novel discharge summary template that achieved widespread usage among residents and significantly increased outpatient PCP satisfaction.

Presence of coronary aneurysms during Kawasaki Disease (KD) correlates with lower levels of autoantibodies to both full form and spliced variant of immune regulator Del-1.

Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium. Del-1 has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against DEL-1 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not overall higher in children with KD. Elevation in Post-IVIG samples in comparison to pre-IVIG and convalescent samples supports the commonality of anti-Del-1 antibodies. Autoantibodies were notably lower in children with KD who had coronary Z score elevations in comparison to those who did not.

Hospitalist perspective on pandemic related clinical and administrative changes: a cross sectional survey study.

OBJECTIVE: Hospitalists have played a leading role in caring for hospitalized COVID-19 patients. Many clinical and administrative changes occurred in hospitals to meet the varied pandemic needs. We surveyed hospitalists to understand their perspective on pandemic-related changes in technology, models of care, administration and leadership, impact on personal lives, and which of these changes should be continued versus reverting to pre-pandemic practices. METHODS: A 30-question survey was distributed to hospitalists working across the United States between 6 April 2022 to 16 May 2022. Baseline demographics were measured, and post-pandemic perspectives related to changes were analyzed. Perspectives were measured using a 5-point Likert scale and responses were categorized into 'agree' and 'did not agree' for analysis. Variation was assessed using Chi-square or Fisher exact tests. Open-ended questions were reported following qualitative content analysis organized into themes and reported as frequency. RESULTS: 177 respondents (39%) completed the survey. Nearly three-fourths favored hybrid meetings, and two-thirds preferred to continue new models of care. Nearly 90% desired more family and leisure time, continued wellness, and support services, and resumption of social gatherings. No major differences in perspectives were noted between hospitalists at teaching facilities and non-teaching facilities except for resuming protected time for non-clinical activities in those from teaching facilities (83.0% vs 62.5%). Respondents less than age 50 were more likely to prefer virtual meetings (59.0% vs 31.3%). Content analysis of open-ended questions resulted in different themes for each question. Respondents favored more work-life balance and less administrative and logistical work burden. CONCLUSIONS: Hospitalists preferred to continue the use of technology and new models of care even in the post-pandemic period and express a desire for more work-life balance and less administrative and logistical work burden.

Pharmacy-driven performance improvement initiative to increase compliance with intravenous smart pump drug error reduction systems at a large urban academic medical center.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Smart pump dose error reduction systems (DERS) reduce errors for intravenous (IV) administration medications by warning users of order, calculation, and programming errors. The purpose of this performance improvement initiative was to increase IV smart pump DERS usage from 77% to 95% at a large, urban academic medical center. METHODS: A pharmacy-led team with nurses, physicians, and quality improvement specialists executed interventions from July 2020 through April 2022 to increase DERS compliance. A discovery phase (phase I) was followed by 6 Plan-Do-Study-Act (PDSA) cycles created to address barriers to DERS utilization. Phase I revealed that problems involving the DERS library and bedside nurse training were the major drivers of noncompliance. Phase II consisted of 3 system-level PDSA cycles, and phase III included 3 focused group PDSA cycles. Data were collected monthly from the smart pump reporting software by the informatics pharmacist and analyzed by the team to assess compliance rates in response to the corresponding interventions. RESULTS: The median DERS compliance increased from 77% to 83% over the 2-year period, which correlates with approximately 109,000 additional infusions run on DERS each year within our institution. The implementation of a DERS problem reporting tool accessed through the medication administration record resulted in the most pronounced improvement. CONCLUSION: DERS compliance improved following system-level sustainable interventions, although further PDSA cycles are needed to meet the goal DERS utilization rate of 95%. The results of this study may help other institutions attempting to improve DERS utilization create targeted interventions.

Robust humoral immune response after boosting in children with Multisystem Inflammatory Syndrome in Children.

The exact pathogenesis of Multisystem Inflammatory Syndrome in Children (MIS-C) is unknown. Reports on response to vaccination in children who had MIS-C are lacking. Using prospectively enrolled children, we report on humoral immune responses prior to and after SARS-CoV-2 immune rechallenge. Recurrent auricular chondritis was also noted in one child.

Clonal expansion and markers of directed mutation of IGHV4-34 B cells in plasmablasts during Kawasaki disease.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The cause remains unknown; however, epidemiologic and demographic data support a single preceding infectious agent may lead to KD. A variety of pathophysiologic responses have been proposed, including direct invasion of the coronary arteries, a superantigen response, and a post-infectious autoimmune phenomenon. A role for B cell responses during KD are supported by numerous findings including B cell specific markers identified in genome wide association studies. We have recently published data showing children with KD have similar plasmablast (PB) responses to children with infections. Since during other infections, cells expressing antibodies against the preceding infection are enriched in PBs, we sought to explore the specific antibodies encoded by PBs during KD. In one child we see a massive expansion in IGHV4-34 utilizing antibodies, which has been associated with autoimmunity in the past. We further explored this expansion of IGHV4-34 utilization during the peripheral PB rise with next generation sequencing (NGS) analysis and utilizing newer techniques of chromium chip single cell separation (10x Genomics®). We also utilized peptide array screening to attempt to identify an antigen to the most prolific clones.

Humoral cross-coronavirus responses against the S2 region in children with Kawasaki disease.

Multisystem Inflammatory Syndrome in Children (MIS-C), a post infectious complication of SARS CoV-2 infection, shares enough features with Kawasaki Disease (KD) that some have hypothesized cross-coronavirus (CoV) immunity may explain the shared pathology. Recent studies have shown that humoral cross-reactivity of the CoVs, particularly of OC43, is focused on the S2 region of the Spike protein. Due to efforts utilizing CoV S2 regions to produce a cross-CoV vaccine, we wished to assess SARS-CoV-2 S2 reactivity in children with KD and assess if cardiac involvement in KD correlated with S2 CoV antibody targeting. The presence of cross-reactivity does not distinguish KD from febrile controls and does not correlate with cardiac involvement in KD. These findings support that, in relation to cardiac vascular inflammation, vaccines targeting the S2 region appear to be a safe approach, but there is disparity in the ability of CoV species to raise cross-reactive S2 targeted antibodies.

Antibody dependent cell cytotoxicity is maintained by the unmutated common ancestor of 6F5, a Gp41 conformational epitope targeting antibody that utilizes heavy chain VH1-2.

In studies on monoclonal IgG antibodies (mAbs) from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated Abs against a complex conformational epitope with contributions from both gp41 the N terminal and C terminal heptad repeat helices. Despite using the VH1-2 gene segment, known to contribute to some of the broadest neutralizing Abs against HIV, members of these Abs, termed group 76C Abs, did not exhibit broad neutralization. Because of the high number of mutations and use of VH1-2, our goal was to characterize the non-neutralizing functions of Abs of group 76C, to assess if targeting of the epitope correlates with LTNP, and to assess the maturation of these Abs by comparison to their predicted common ancestor. Serum competition assays showed group 76C Abs were enriched in LTNPs, in comparison to VRC-01. Specific group 76C clones 6F5 and 6F11, expressed as recombinant Abs, both have robust ADCC activity, despite their sequence disparity. Sequence analysis predicted the common ancestor of this clonal group would utilize the germline non-mutated variable gene. We produced a recombinant ancestor Ab (76Canc) with a heavy chain utilizing the germline variable gene sequence paired to the 6F5 light chain. Competition with group 76C recombinant Ab 6F5 confirms 76Canc binds HIV envelope constructs near the original group C epitope. 76Canc demonstrates comparable ADCC to 6F5 and 6F11 when using gp41 constructs of both clade B and clade C. The functional capability of Abs utilizing germline VH1-2 has implications for disease control and vaccine development.

Early treatment with thiamine and mortality among patients with alcohol use disorder who are hospitalized for pneumonia.

BACKGROUND: The paucity of research linking thiamine treatment with improved outcomes may be driving its underutilization among patients at risk for Wernicke encephalopathy. OBJECTIVE: To assess relationships of thiamine usage to outcomes of patients hospitalized with alcohol use disorder and pneumonia. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective cohort study of adult patients hospitalized with pneumonia who also have alcohol use disorder and were treated with benzodiazepines during the initial two hospital days, between 2010 and 2015 at hospitals participating in the Premier Healthcare Database. EXPOSURE: Any thiamine treatment, and, among those treated, high-dose thiamine treatment, during the initial two hospital days. MAIN OUTCOME AND MEASURES: Death on days 3-14 of hospitalization (primary); discharge home; transfer to intensive care unit; length of stay (LOS). We used propensity-weighted models to estimate treatment effects. RESULTS: Among 36,732 patients from 625 hospitals, 26,520 (72.2%) patients received thiamine, with mortality of 6.5% and 8.1% among recipients and nonrecipients, respectively. With propensity score adjustment, thiamine was associated with reduced mortality (odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.75-0.85) and more frequent discharges to home (OR: 1.10, 95% CI: 1.06-1.14). Other outcomes were similar. Relative to low-dose thiamine, high-dose thiamine was not associated with mortality (adjusted OR: 0.99, 95% CI: 0.89-1.10), but LOS was longer (ratio of means: 1.06, 95% CI: 1.04-1.08), and discharges to home were less frequent (OR: 0.92, 95% CI: 0.87-0.97). CONCLUSION: Thiamine is not reliably given to patients with pneumonia and alcohol use disorder receiving benzodiazepines. Improving thiamine administration may represent an opportunity to save lives in this high-risk group of inpatients.

Creation of a medical ward from non-clinical space amidst the Covid-19 pandemic.

INTRODUCTION: Hospitals were mandated to dramatically increase capacity during the Covid-19 crisis in New York City. Conversion of non-clinical space into medical units designated for Covid-19 patients became necessary to accommodate this mandate. METHODS: Non-clinical space was converted into medical units at multiple campuses of a large academic hospital system over 1 week. The conversion required construction to deliver basic care including oxygen supplementation. Creation of provider workspaces, handwashing areas, and colour-coded infection control zones was prioritized. Selection criteria were created with a workflow to determine appropriate patients for transfer into converted space. Staffing of converted space shifted as hospitalizations surged. RESULTS: The unit was open for 18 days and accommodated 170 unique patients. Five patients (2.9%) required transfer to a higher level of care. There were no respiratory arrests, cardiac arrests, or deaths in the new unit. CONCLUSION: Converting non-clinical space to a medical unit was accomplished quickly with staffing, workflow for appropriate patients, few patients who returned to a higher level of care, and no respiratory or cardiac arrests or deaths on the unit.

Early and Significant Reduction in C-Reactive Protein Levels After Corticosteroid Therapy Is Associated With Reduced Mortality in Patients With COVID-19.

BACKGROUND: Corticosteroids may be beneficial in a subset of patients with coronavirus disease 2019 (COVID-19), but predictors of therapeutic response remain unknown. C-reactive protein (CRP) is a routinely measured biomarker, and reduction in its levels after initiation of therapy may predict inpatient mortality. METHODS: In this retrospective cohort study, the charts of patients who were admitted to Montefiore Medical Center between March 10, 2020, and May 2, 2020 for the management of COVID-19 were examined. Of all patients who met inclusion criteria, patients who received corticosteroid treatment were categorized as CRP responders (≥50% CRP level reduction) and CRP nonresponders (<50% CRP level reduction) based on change in CRP within 72 hours of corticosteroid treatment initiation. The outcomes of interest were two-fold: (1) CRP response after treatment with corticosteroid, and (2) differences in mortality among patients with CRP response compared those without. RESULTS: Of 2,707 patients admitted during the study period, 324 received corticosteroid treatment. Of patients who received corticosteroid treatment, CRP responders had reduced risk of death compared with risk among CRP nonresponders (25.2% vs 47.8%; unadjusted odds ratio [OR], 0.37; 95% CI, 0.21-0.65; P <.001). This effect remained strong and significant after adjustment for potential confounders (adjusted OR, 0.27; 95% CI, 0.14-0.54; P <.001). CONCLUSION: Reduction in CRP by 50% or more within 72 hours of initiating corticosteroid therapy potentially predicts inpatient mortality. This may serve as an early biomarker of response to corticosteroid therapy in patients with COVID-19.

Serum Responses of Children With Kawasaki Disease Against Severe Acute Respiratory Syndrome Coronavirus 2 Proteins.

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.

Reducing peripherally inserted central catheters and midline catheters by training nurses in ultrasound-guided peripheral intravenous catheter placement.

BACKGROUND: Training nurses in ultrasound-guided peripheral intravenous catheter placement might reduce the use of more invasive venous access devices (peripherally inserted central catheters (PICC) and midline catheters). METHODS: We implemented an abbreviated training in ultrasound-guided peripheral intravenous catheter placement for nurses on an inpatient medical unit and provided a portable ultrasound device for 10 months. RESULTS: Nurses on this unit placed 99 ultrasound-guided peripheral intravenous catheters with a high level of success. During the implementation period, PICC and midline catheter placement decreased from a mean 4.8 to 2.5 per month, meeting criteria for special cause variation. In the postimplementation period, the average catheter use reverted to 4.3 per month on the intervention unit. A comparison inpatient medical unit without training or access to a portable ultrasound device experienced no significant change in PICC and midline catheter use throughout the study period (mean of 6.0 per month). CONCLUSIONS: These results suggest that an abbreviated training in ultrasound-guided peripheral intravenous catheter placement for nurses on an inpatient medical unit is sufficient to reduce PICC and midline catheters.

Screening of Clostridioides difficile carriers in an urban academic medical center: Understanding implications of disease.

OBJECTIVE: Efforts to reduce Clostridioides difficile infection (CDI) have targeted transmission from patients with symptomatic C. difficile. However, many patients with the C. difficile organism are carriers without symptoms who may serve as reservoirs for spread of infection and may be at risk for progression to symptomatic C. difficile. To estimate the prevalence of C. difficile carriage and determine the risk and speed of progression to symptomatic C. difficile among carriers, we established a pilot screening program in a large urban hospital. DESIGN: Prospective cohort study. SETTING: An 800-bed, tertiary-care, academic medical center in the Bronx, New York. PARTICIPANTS: A sample of admitted adults without diarrhea, with oversampling of nursing facility patients. METHODS: Perirectal swabs were tested by polymerase chain reaction for C. difficile within 24 hours of admission, and patients were followed for progression to symptomatic C. difficile. Development of symptomatic C. difficile was compared among C. difficile carriers and noncarriers using a Cox proportional hazards model. RESULTS: Of the 220 subjects, 21 (9.6%) were C. difficile carriers, including 10.2% of the nursing facility residents and 7.7% of the community residents (P = .60). Among the 21 C. difficile carriers, 8 (38.1%) progressed to symptomatic C. difficile, but only 4 (2.0%) of the 199 noncarriers progressed to symptomatic C. difficile (hazard ratio, 23.9; 95% CI, 7.2-79.6; P < .0001). CONCLUSIONS: Asymptomatic carriage of C. difficile is prevalent among admitted patients and confers a significant risk of progression to symptomatic CDI. Screening for asymptomatic carriers may represent an opportunity to reduce CDI.