Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Real world effectiveness of tixagevimab/cilgavimab (Evusheld) in the Omicron era.

BACKGROUND: Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases. METHODS: Through retrospective electronic medical record chart review, we identified patients who received T/C between January 1 -July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups. RESULTS: Of 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10-0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17-0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03-0.94; p = 0.04). CONCLUSION: We identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

4th Generation HIV screening in the emergency department: net profit or loss for hospitals?

ABSTRACTThe objective of this study was to determine hospital costs and revenue of universal opt-out HIV ED screening. An electronic medical record (EMR)-directed, automated ED screening program was instituted at an academic medical center in San Diego, California. A base model calculated net income in US dollars for the hospital by comparing annual testing costs with reimbursements using payor mixes and cost variables. To account for differences in payor mixes, testing costs, and reimbursement rates across hospitals in the US, we performed a probabilistic sensitivity analysis. The base model included a total of 12,513 annual 4th generation HIV tests with the following payor mix: 18% Medicare, 9% MediCal, 28% commercial and 8% self-payers, with the remainder being capitated contracts. The base model resulted in a net profit for the hospital. In the probabilistic sensitivity analysis, universal 4th generation HIV screening resulted in a net profit for the hospital in 81.9% of simulations. Universal 4th generation opt-out HIV screening in EDs resulted in a net profit to an academic hospital. Sensitivity analysis indicated that ED HIV screening results in a net-profit for the majority of simulations, with higher proportions of self-payers being the major predictor of a net loss.

Deep Dive into the Long Haul: Analysis of Symptom Clusters and Risk Factors for Post-Acute Sequelae of COVID-19 to Inform Clinical Care.

Long COVID is a chronic condition characterized by symptoms such as fatigue, dyspnea, and cognitive impairment that persist or relapse months after an acute infection with the SARS-CoV-2 virus. Many distinct symptoms have been attributed to Long COVID; however, little is known about the potential clustering of these symptoms and risk factors that may predispose patients to certain clusters. In this study, an electronic survey was sent to patients in the UC San Diego Health (UCSDH) system who tested positive for COVID-19, querying if patients were experiencing symptoms consistent with Long COVID. Based on survey results, along with patient demographics reported in the electronic health record (EHR), linear and logistic regression models were used to examine putative risk factors, and exploratory factor analysis was performed to determine symptom clusters. Among 999 survey respondents, increased odds of Long COVID (n = 421; 42%) and greater Long COVID symptom burden were associated with female sex (OR = 1.73, 99% CI: 1.16-2.58; ß = 0.48, 0.22-0.75), COVID-19 hospitalization (OR = 4.51, 2.50-8.43; ß = 0.48, 0.17-0.78), and poorer pre-COVID self-rated health (OR = 0.75, 0.57-0.97; ß = -0.19, -0.32--0.07). Over one-fifth of Long COVID patients screened positive for depression and/or anxiety, the latter of which was associated with younger age (OR = 0.96, 0.94-0.99). Factor analysis of 16 self-reported symptoms suggested five symptom clusters-gastrointestinal (GI), musculoskeletal (MSK), neurocognitive (NC), airway (AW), and cardiopulmonary (CP), with older age (ß = 0.21, 0.11-0.30) and mixed race (ß = 0.27, 0.04-0.51) being associated with greater MSK symptom burden. Greater NC symptom burden was associated with increased odds of depression (OR = 5.86, 2.71-13.8) and anxiety (OR = 2.83, 1.36-6.14). These results can inform clinicians in identifying patients at increased risk for Long COVID-related medical issues, particularly neurocognitive symptoms and symptom clusters, as well as informing health systems to manage operational expectations on a population-health level.

Population-Based Evaluation of Postacute Coronavirus Disease-2019 (COVID-19) Chronic Sequelae in Patients Who Tested Positive for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

The true incidence and comprehensive characteristics of Long Coronavirus Disease-19 (COVID-19) are currently unknown. This is the first population-based outreach study of Long COVID within an entire health system, conducted to determine operational needs to care for patients with Long COVID.

Microbial Metabolite 3-Indolepropionic Acid Mediates Immunosuppression.

The microbial-derived metabolite, 3-indolepropionic acid (3-IPA), has been intensely studied since its origins were discovered in 2009; however, 3-IPA's role in immunosuppression has had limited attention. Untargeted metabolomic analyses of T-cell exhaustion and immunosuppression, represented by dysfunctional under-responsive CD8+ T cells, reveal a potential role of 3-IPA in these responses. T-cell exhaustion was examined via infection of two genetically related mouse strains, DBA/1J and DBA/2J, with lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl13). The different mouse strains produced disparate outcomes driven by their T-cell responses. Infected DBA/2J presented with exhausted T cells and persistent infection, and DBA/1J mice died one week after infection from cytotoxic T lymphocytes (CTLs)-mediated pulmonary failure. Metabolomics revealed over 70 metabolites were altered between the DBA/1J and DBA/2J models over the course of the infection, most of them in mice with a fatal outcome. Cognitive-driven prioritization combined with statistical significance and fold change were used to prioritize the metabolites. 3-IPA, a tryptophan-derived metabolite, was identified as a high-priority candidate for testing. To test its activity 3-IPA was added to the drinking water of the mouse models during LCMV Cl13 infection, with the results showing that 3-IPA allowed the mice to survive longer. This negative immune-modulation effect might be of interest for the modulation of CTL responses in events such as autoimmune diseases, type I diabetes or even COVID-19. Moreover, 3-IPA's bacterial origin raises the possibility of targeting the microbiome to enhance CTL responses in diseases such as cancer and chronic infection.

Prevalence of SARS-CoV-2 infection in Baja California, Mexico: Findings from a community-based survey in February 2021 in the Mexico-United States border.

Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estimate the seroprevalence and real time polymerase chain reaction (RT-PCR) prevalence of SARS-CoV-2 infection in the three most populous cities of Baja California prior to scale-up of a national COVID-19 vaccination campaign. Probabilistic three-stage clustered sampling was used to conduct a population-based household survey of residents five years and older in the three cities. RT-PCR testing was performed on nasopharyngeal swabs and SARS-CoV-2 seropositivity was determined by IgG antibody testing using fingerstick blood samples. An interviewer-administered questionnaire assessed participants' knowledge, attitudes, and preventive practices regarding COVID-19. In total, 1,126 individuals (unweighted sample) were surveyed across the three cities. Overall prevalence of SARS-CoV-2 infection by RT-PCR was 7.8% (95% CI 5.5-11.0) and IgG seroprevalence was 21.1% (95% CI 17.4-25.2). There was no association between border crossing in the past 6 months and SARS-CoV-2 prevalence (unadjusted OR 0.40, 95%CI 0.12-1.30). While face mask use and frequent hand washing were common among participants, quarantine or social isolation at home to prevent infection was not. Regarding vaccination willingness, 30.4% (95% CI 24.4-3 7.1) of participants said they were very unlikely to get vaccinated. Given the high prevalence of active SARS-CoV-2 infection in Baja California at the end of the first year of the pandemic, combined with its low seroprevalence and the considerable proportion of vaccine hesitancy, this important area along the Mexico-United States border faces major challenges in terms of health literacy and vaccine uptake, which need to be further explored, along with its implications for border restrictions in future epidemics.

Designing a critical care solution using in-person and telemedicine approaches in the US-Mexico border area during COVID-19.

BACKGROUND: UC San Diego Health System (UCSDHS) is the largest academic medical center and integrated care network in US-Mexico border area of California contiguous to the Northern Baja region of Mexico. The COVID-19 pandemic compelled several UCSDHS and local communities to create awareness around best methods to promote regional health in this economically, socially, and politically important border area. PURPOSE: To improve understanding of optimal strategies to execute critical care collaborative programs between academic and community health centers facing public health emergencies during the COVID-19 pandemic, based on the experience of UCSDHS and several community hospitals (one US, two Mexican) in the US-Mexico border region. METHODS: After taking several preparatory steps, we developed a two-phase program that included 1) in-person activities to perform needs assessments, hands-on training and education, and morale building and 2) creation of a telemedicine-based (Tele-ICU) service for direct patient management and/or educational coaching experiences.Findings.A clinical and educational program between academic and community border hospitals was feasible, effective, and well received. CONCLUSION: We offer several policy-oriented recommendations steps for academic and community healthcare programs to build educational, collaborative partnerships to address COVID-19 and other cross-cultural, international public health emergencies.

The Development and Implementation of Preventive Medicine Resident Rotations in a Shelter Serving Asylum-Seekers at the US-Mexico Border.

Asylum-seekers present to the US-Mexico border with a variety of acute health needs. In December 2018, the County of San Diego Health and Human Services Agency partnered with the University of California, San Diego to provide health screenings to asylum-seekers at a humanitarian shelter administered by Jewish Family Services. The assessments screened for communicable diseases and acute conditions. Preventive medicine residents in the HRSA-funded UCSD-SDSU (University of California, San Diego-San Diego State University) Residency were trained to become an integral part of the program. Training included cultural competency, public health interface, protocol development and implementation, interdisciplinary teamwork, and quality improvement. Over 18 months, nearly 20000 asylum-seekers were screened, which allowed for the detection of an imported influenza outbreak and prevented any major public health incidents or medical errors. This health screening program for asylum-seekers provided an important experience for preventive medicine trainees. In turn, preventive medicine and other trainees were valuable contributors to the program.

An In-Person and Telemedicine "Hybrid" System to Improve Cross-Border Critical Care in COVID-19.

Background: UC San Diego Health System (UCSDHS) is an academic medical center and integrated care network in the US-Mexico border area of California contiguous to the Mexican Northern Baja region. The COVID-19 pandemic deeply influenced UCSDHS activities as new public health challenges increasingly related to high population density, cross-border traffic, economic disparities, and interconnectedness between cross-border communities, which accelerated development of clinical collaborations between UCSDHS and several border community hospitals - one in the US, two in Mexico - as high volumes of severely ill patients overwhelmed hospitals. Objective: We describe the development, implementation, feasibility, and acceptance of a novel critical care support program in three community hospitals along the US-Mexico border. Methods: We created and instituted a hybrid critical care program involving: 1) in-person activities to perform needs assessments of equipment and supplies and hands-on training and education, and 2) creation of a telemedicine-based (Tele-ICU) service for direct patient management and/or consultative, education-based experiences. We collected performance metrics surrounding adherence to evidence-based practices and staff perceptions of critical care delivery. Findings: In-person intervention phase identified and filled gaps in equipment and supplies, and Tele-ICU program promoted adherence to evidence-based practices and improved staff confidence in caring for critically ill COVID-19 patients at each hospital. Conclusion: A collaborative, hybrid critical care program across academic and community centers is feasible and effective to address cross-cultural public health emergencies.

Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever.

Lassa fever (LF) causes multisystem disease and has a fatality rate <70%. Severe cases exhibit abnormal coagulation, endothelial barrier disruption, and dysfunctional platelet aggregation but the underlying mechanisms remain poorly understood. In Sierra Leone during 2015-2018, we assessed LF patients' day-of-admission plasma samples for levels of proteins necessary for coagulation, fibrinolysis, and platelet function. P-selectin, soluble endothelial protein C receptor, soluble thrombomodulin, plasminogen activator inhibitor 1, ADAMTS-13, von Willebrand factor, tissue factor, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were more elevated in LF patients than in controls. Endothelial protein C receptor, thrombomodulin, intercellular adhesion molecule 1, plasminogen activator inhibitor 1, D-dimer, and hepatocyte growth factor were higher in fatal than nonfatal LF cases. Platelet disaggregation occurred only in samples from fatal LF cases. The impaired homeostasis and platelet dysfunction implicate alterations in the protein C pathway, which might contribute to the loss of endothelial barrier function in fatal infections.

Universal HIV and Birth Cohort HCV Screening in San Diego Emergency Departments.

Universal HIV and HCV screening in emergency departments (ED) can reach populations who are less likely to get tested otherwise. The objective of this analysis was to evaluate universal opt-out HIV and HCV screening in two EDs in San Diego. HIV screening for persons aged 13-64 years (excluding persons known to be HIV+ or reporting HIV testing within last 12 months) was implemented using a 4th generation HIV antigen/antibody assay; HCV screening was offered to persons born between 1945 and 1965. Over a period of 16 months, 12,575 individuals were tested for HIV, resulting in 33 (0.26%) new HIV diagnoses, of whom 30 (90%) were successfully linked to care. Universal screening also identified 74 out-of-care for >12-months HIV+ individuals of whom 50 (68%) were successfully relinked to care. Over a one-month period, HCV antibody tests were conducted in 905 individuals with a seropositivity rate of 9.9% (90/905); 61 seropositives who were newly identified or never treated for HCV had HCV RNA testing, of which 31 (51%) resulted positive (3.4% of all participants, including 18 newly identified RNA positives representing 2% of all participants), and 13/31 individuals (42%) were linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by >7-fold, underlining the importance of HCV screening in EDs.

Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics.

Understanding of T cell exhaustion and successful therapy to restore T cell function was first described using Clone (Cl) 13 variant selected from the lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) 53b parental strain. T cell exhaustion plays a pivotal role in both persistent infections and cancers of mice and humans. C57BL/6, BALB, SWR/J, A/J, 129, C3H, and all but one collaborative cross (CC) mouse strain following Cl 13 infection have immunosuppressed T cell responses, high PD-1, and viral titers leading to persistent infection and normal life spans. In contrast, the profile of FVB/N, NZB, PL/J, SL/J, and CC NZO mice challenged with Cl 13 is a robust T cell response, high titers of virus, PD-1, and Lag3 markers on T cells. These mice all die 7 to 9 d after Cl 13 infection. Death is due to enhanced pulmonary endothelial vascular permeability, pulmonary edema, collapse of alveolar air spaces, and respiratory failure. Pathogenesis involves abundant levels of Cl 13 receptor alpha-dystroglycan on endothelial cells, with high viral replication in such cells leading to immunopathologic injury. Death is aborted by blockade of interferon-1 (IFN-1) signaling or deletion of CD8 T cells.

Actinotignum schaalii Infection: A Clandestine Cause of Sterile Pyuria?

Actinotignum schaalii is an underappreciated cause of urinary tract infections (UTIs) in older adults. The diagnosis may be missed due to difficulty isolating and identifying the organism. Complications can result because the organism is intrinsically resistant to 2 commonly used drugs to treat UTI, as illustrated by this case.

Rethinking Antimicrobial Prophylaxis in the Transplant Patient in the World of Emerging Resistant Organisms-Where Are We Today?

PURPOSE OF REVIEW: The use of prophylactic antibiotics during the neutropenic period in hematopoietic stem cell transplantation has been the standard of care at most institutions for the past 20 years. We sought to review the benefits and risks of this practice. RECENT FINDINGS: Emerging data has highlighted the potential costs of antibacterial prophylaxis, from selecting for antibiotic resistance to perturbing the microbiome and contributing to increase risk for Clostridium difficile and perhaps graft-versus-host-disease, conditions which may lead to poorer outcomes. Though in many studies prophylactic antibiotics improved morbidity and mortality outcomes, the potential harms including antibiotic resistance, Clostridium difficile infection, and alterations of the gut microbiome should be considered. Future studies aimed to better risk-stratify patients and limit the use of broad-spectrum antibiotics are warranted.