Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults - United States, December 2020-March 2023.

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test-positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test-negative participants). Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test-positive and COVID test-negative participants = 18.3% and 16.1%, respectively; p>0.05). Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID-like conditions.

Association of Ketamine Dosing with Intubation and Other Adverse Events in Patients with Behavioral Emergencies.

OBJECTIVE: Varying rates of complications have been reported for prehospital sedation with ketamine, and the relationship to dosing has not been studied on a large scale. We evaluated the association between prehospital ketamine dosing and rates of intubations and other adverse events in patients with behavioral emergencies. METHODS: Using the 2018/2019 ESO public-use research datasets, we included all non-traumatic, adult behavioral and drug-related EMS encounters with ketamine administration. Based on consensus guidelines, we stratified patients into "above" and "at/below" the maximum dosing for sedation (2 mg/kg IV/IO or 5 mg/kg IM) using the highest single dose of ketamine given. We created propensity scores for matched subjects using 1:1 propensity score matching. Using logistic regression, we compared rates of intubation and other airway interventions, antipsychotic coadministration, improvement reported by EMS, hypoxia, hypotension, and cardiac arrest between the two groups. RESULTS: We included 2383 patients: 478 in the above and 1905 in the at/below dose group. Above-dose ketamine was associated with a higher rate of intubation or supraglottic airway placement (6.4% v 3.3%, OR 2.0, 95% CI 1.00-3.90). Other airway interventions were similar (40.0% v 40.0%, OR 1, 95% CI 0.80-1.30). The above-dose group also showed a higher rate of improvement noted by EMS clinicians (92.5% v 88.7%, OR 1.6, 95% CI 1.01-2.40). The rates of antipsychotic coadministration, hypoxia, hypotension, and cardiac arrest were similar between the cohorts. CONCLUSIONS: Patients given ketamine doses above consensus recommendations for sedation appeared more likely to receive prehospital intubation but not more likely to experience other adverse events.

Mathematical model predicts anti-adhesion-antibiotic-debridement combination therapies can clear an antibiotic resistant infection.

As antimicrobial resistance increases, it is crucial to develop new treatment strategies to counter the emerging threat. In this paper, we consider combination therapies involving conventional antibiotics and debridement, coupled with a novel anti-adhesion therapy, and their use in the treatment of antimicrobial resistant burn wound infections. Our models predict that anti-adhesion-antibiotic-debridement combination therapies can eliminate a bacterial infection in cases where each treatment in isolation would fail. Antibiotics are assumed to have a bactericidal mode of action, killing bacteria, while debridement involves physically cleaning a wound (e.g. with a cloth); removing free bacteria. Anti-adhesion therapy can take a number of forms. Here we consider adhesion inhibitors consisting of polystyrene microbeads chemically coupled to a protein known as multivalent adhesion molecule 7, an adhesin which mediates the initial stages of attachment of many bacterial species to host cells. Adhesion inhibitors competitively inhibit bacteria from binding to host cells, thus rendering them susceptible to removal through debridement. An ordinary differential equation model is developed and the antibiotic-related parameters are fitted against new in vitro data gathered for the present study. The model is used to predict treatment outcomes and to suggest optimal treatment strategies. Our model predicts that anti-adhesion and antibiotic therapies will combine synergistically, producing a combined effect which is often greater than the sum of their individual effects, and that anti-adhesion-antibiotic-debridement combination therapy will be more effective than any of the treatment strategies used in isolation. Further, the use of inhibitors significantly reduces the minimum dose of antibiotics required to eliminate an infection, reducing the chances that bacteria will develop increased resistance. Lastly, we use our model to suggest treatment regimens capable of eliminating bacterial infections within clinically relevant timescales.

Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds.

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model.

T and B cell subsets differentially correlate with amyloid deposition and neurocognitive function in patients with amnestic mild cognitive impairment after one year of physical activity.

Individuals with amnestic mild cognitive impairment (aMCI) experience cognitive declines in learning and memory greater than expected for normal aging, and are at a high risk of dementia. We previously reported that sedentary aMCI patients exhibited neuroinflammation that correlated with brain amyloid beta (Aß) burden, as determined by 18F-florbetapir positron emission tomography (PET). These aMCI patients enrolled in a one-year randomized control trial (AETMCI, NCT01146717) to test the beneficial effects of 12 months of moderate-to-high intensity aerobic exercise training (AET) or stretching/toning (ST) control intervention on neurocognitive function. A subset of aMCI participants had PET imaging, cognitive testing, and immunophenotyping of cerebrospinal fluid (CSF) and peripheral blood after AET or ST interventions. As adaptive immune responses were similar between AET and ST groups, we combined AET/ST into a general 'physical activity' (PA) group and compared Aß burden, cognitive function, and adaptive immune cell subsets to sedentary lifestyle before intervention. We found that PAinduced immunomodulation of CD4+ and CD8+ T cells in CSF correlated with changes in Aß burden in brain regions associated with executive function. Furthermore, after PA, cognitive scores on tests of memory, processing speed, attention, verbal fluency, and executive function were associated with increased percent representation of circulating naïve B + T cells. We review the literature on aMCI-related cognition and immune changes as they relate to exercise, and highlight how our preliminary data suggest a complex interplay between the adaptive immune system, physical activity, cognition, and Aß burden in aMCI.

Adaptive lymphocyte profiles correlate to brain Aß burden in patients with mild cognitive impairment.

BACKGROUND: We previously found that subjects with amnestic mild cognitive impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid similar to multiple sclerosis, a central nervous system autoimmune disease. We therefore hypothesized that early neuroinflammation would reflect increases in brain amyloid burden during amnestic mild cognitive impairment. METHODS: Cerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitive impairment (12 men, 12 women; 66 ± 6 years; 0.5 Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal fluid and blood included immune profiling by multi-parameter flow cytometry, genotyping for apolipoprotein (APO)ε, and quantification of cytokine and immunoglobin levels. Amyloid (A)ß deposition was determined by 18F-florbetapir positron emission tomography. Spearman rank order correlations were performed to assess simple linear correlation for parameters including amyloid imaging, central and peripheral immune cell populations, and protein cytokine levels. RESULTS: Soluble Aß42 in the cerebrospinal fluid declined as Aß deposition increased overall and in the precuneous and posterior cingulate cortices. Lymphocyte profiling revealed a significant decline in T cell populations in the cerebrospinal fluid, specifically CD4+ T cells, as Aß deposition in the posterior cingulate cortex increased. In contrast, increased Aß burden correlated positively with increased memory B cells in the cerebrospinal fluid, which was exacerbated in APOε4 carriers. For peripheral circulating lymphocytes, only B cell populations decreased with Aß deposition in the precuneous cortex, as peripheral T cell populations did not correlate with changes in brain amyloid burden. CONCLUSIONS: Elevations in brain Aß burden associate with a shift from T cells to memory B cells in the cerebrospinal fluid of subjects with amnestic mild cognitive impairment in this exploratory cohort. These data suggest the presence of cellular adaptive immune responses during Aß accumulation, but further study needs to determine whether lymphocyte populations contribute to, or result from, Aß dysregulation during memory decline on a larger cohort collected at multiple centers. TRIAL REGISTRATION: AETMCI NCT01146717.

Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022.

Background: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. Results: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). Conclusions: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. Trial registration: NCT04610515.

Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms.

Background: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. Methods: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. Results: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. Conclusions: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.

Ethnic and racial differences in self-reported symptoms, health status, activity level, and missed work at 3 and 6 months following SARS-CoV-2 infection.

Introduction: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. Methods: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. Results: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). Discussion: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

Branched-Chain Amino Acids Are Linked with Alzheimer's Disease-Related Pathology and Cognitive Deficits.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with a complex pathophysiology. Type 2 diabetes (T2D) is a strong risk factor for AD that shares similar abnormal features including metabolic dysregulation and brain pathology such as amyloid and/or Tau deposits. Emerging evidence suggests that circulating branched-chain amino acids (BCAAs) are associated with T2D. While excess BCAAs are shown to be harmful to neurons, its connection to AD is poorly understood. Here we show that individuals with AD have elevated circulating BCAAs and their metabolites compared to healthy individuals, and that a BCAA metabolite is correlated with the severity of dementia. APPSwe mouse model of AD also displayed higher plasma BCAAs compared to controls. In pursuit of understanding a potential causality, BCAA supplementation to HT-22 neurons was found to reduce genes critical for neuronal health while increasing phosphorylated Tau. Moreover, restricting BCAAs from diet delayed cognitive decline and lowered AD-related pathology in the cortex and hippocampus in APP/PS1 mice. BCAA restriction for two months was sufficient to correct glycemic control and increased/restored dopamine that were severely reduced in APP/PS1 controls. Treating 5xFAD mice that show early brain pathology with a BCAA-lowering compound recapitulated the beneficial effects of BCAA restriction on brain pathology and neurotransmitters including norepinephrine and serotonin. Collectively, this study reveals a positive association between circulating BCAAs and AD. Our findings suggest that BCAAs impair neuronal functions whereas BCAA-lowering alleviates AD-related pathology and cognitive decline, thus establishing a potential causal link between BCAAs and AD progression.

Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection.

BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODS: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTS: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONS: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

Importance: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. Objective: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. Exposures: SARS-CoV-2 status (positive or negative test result) at enrollment. Main Outcomes and Measures: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. Results: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (ß = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: ß = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: ß = 4.16; 95% CI, 2.12-6.20; P < .001). Conclusions and Relevance: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Survey-based Evaluation of Resident and Attending Financial Literacy.

INTRODUCTION: Physician finances are linked to wellness and burnout. However, few physicians receive financial management education. We sought to determine the financial literacy and educational need of attending and resident physician at an academic emergency medicine (EM) residency. METHODS: We performed a cross-sectional, survey study at an academic EM residency. We devised a 49-question survey with four major domains: demographics (16 questions); Likert-scale questions evaluating value placed on personal finances (3 questions); Likert-scale questions evaluating perceived financial literacy (11 questions); and a financial literacy test based on previously developed and widely used financial literacy questions (19 questions). We administered the survey to EM attendings and residents. We analyzed the data using descriptive statistics and compared attending and resident test question responses. RESULTS: A total of 44 residents and 24 attendings responded to the survey. Few (9.0% of residents, 12.5% of attendings) reported prior formal financial education. However, most respondents (70.5% of residents and 79.2% of attendings) participated in financial self-learning. On a five-point Likert scale (not at all important: very important), respondents felt that financial independence (4.7 ± 0.8) and their finances (4.7±0.8) were important for their well-being. Additionally, they valued being prepared for retirement (4.7±0.9). Regarding perceived financial literacy (very uncomfortable: very comfortable), respondents had the lowest comfort level with investing in the stock market (2.7±1.5), applying for a mortgage (2.8±1.6), and managing their retirement (3.0±1.4). Residents scored significantly lower than attendings on the financial literacy test (70.8% vs 79.6%, P<0.01), and residents scored lower on questions pertaining to investment (78.8% v 88.9%, P<0.01) and insurance and taxes (47.0% v 70.8%, P<0.01). Overall, respondents scored lower on questions about retirement (58.8%, P<0.01) and insurance and taxes (54.7%, P<0.01). CONCLUSION: Emergency physicians' value of financial literacy exceeded confidence in financial literacy, and residents reported poorer confidence than attendings. We identified deficiencies in emergency physicians' financial literacy for retirement, insurance, and taxes.

Outcomes of end-stage renal disease patients in the PROCESS trial.

OBJECTIVE: Intravenous fluid administration is a main component of sepsis therapy, but physicians are cautious about giving fluids to end-stage renal disease (ESRD) patients out of concern for causing volume overload. We compared the outcomes of septic shock patients with and without ESRD and evaluated the association between early intravenous fluid administration and outcomes. METHODS: We analyzed patients enrolled in the Protocolized Care for Early Septic Shock (PROCESS) trial, which studied different resuscitation strategies for early septic shock. Stratifying for ESRD, we compared patient characteristics, course of care, and outcomes between ESRD and non-ESRD. Using multivariable logistic regression, we determined the association between 6-hour total fluid volume (> = 30 mL/kg vs < 30 mL/kg) from preenrollment and outcomes. RESULTS: There were 84 ESRD and 1257 non-ESRD patients. ESRD patients had a higher median Charlson Comorbidity score (5 vs 2, P < .001), higher median acute physiology and chronic health evaluation (APACHE) II score (26.5 vs 20.0, P < .001), and lower 6-hour intravenous fluid administration (54.7 vs 68.3 mL/kg, P < .001). Ninety-day mortality (33.3% vs 29.3%, P = .43) and intubation rate (31.0% vs 33.4%, P = .64) did not differ between groups. Fewer ESRD received > = 30 mL/kg (66.6% vs 86.7% P < .001). For ESRD, receipt of > = 30 mL/kg intravenous fluid did not alter any outcome. For non-ESRD patients, receiving   ≥30 mL/kg of intravenous fluid was associated with increased 90-day mortality (adjusted odds ratio = 1.64; 95% confidence interval, 1.03-2.61). CONCLUSIONS: In the PROCESS trial, ESRD patients had similar outcomes to non-ESRD patients. Although ESRD patients received less intravenous fluid administration, most received over 30 mL/kg in the first 6 hours. In contrast to non-ESRD patients, receiving  ≥30 mL/kg of intravenous fluid was not associated with worse outcomes in ESRD.

Video laryngoscopy for out of hospital cardiac arrest.

INTRODUCTION: Endotracheal intubation is an import component of out-of-hospital cardiac arrest (OHCA) resuscitation. In this analysis, we evaluate the association of video laryngoscopy (VL) with first pass success and return of spontaneous circulation (ROSC) using a national OHCA cohort. METHODS: We analyzed 2018 data from ESO Inc. (Austin, TX), a national prehospital electronic health record. We included all adult, non-traumatic cardiac arrests undergoing endotracheal intubation. We defined VL and direct laryngoscopy (DL) based on paramedic recorded intubation device. The primary outcomes were first pass success, ROSC, and sustained ROSC. Using multivariable, mixed models, we determined the association between VL and first pass success rate, ROSC, and sustained ROSC (survival to ED or ROSC in the field for greater than 20 min), fitting agency as a random intercept and adjusting for confounders. RESULTS: We included 22,132 patients cared for by 914 EMS agencies, including 5702 (25.7%) VL and 16,430 (74.2%) DL. Compared to DL, VL had a lower rate of bystander CPR, but other characteristics were similar between the groups. VL exhibited higher first pass success than DL (75.1% v 69.5%, p < .001). On mixed model analysis, VL was associated with a higher first pass success (OR 1.5, CI 1.3-1.6) but not ROSC (OR 1.1, CI 0.97-1.2) or sustained ROSC (OR 1.1, CI 0.9-1.2). CONCLUSION: While associated with higher FPS, VL was not associated with increased rate of ROSC. The role of VL in OHCA remains unclear.

Airway strategy and chest compression quality in the Pragmatic Airway Resuscitation Trial.

BACKGROUND: Chest compression (CC) quality is associated with improved out-of-hospital cardiopulmonary arrest (OHCA) outcomes. Airway management efforts may adversely influence CC quality. We sought to compare the effects of initial laryngeal tube (LT) and initial endotracheal intubation (ETI) airway management strategies upon chest compression fraction (CCF), rate and interruptions in the Pragmatic Airway Resuscitation Trial (PART). METHODS: We analyzed CPR process files collected from adult OHCA enrolled in PART. We used automated signal processing techniques and a graphical user interface to calculate CC quality measures and defined interruptions as pauses in chest compressions longer than 3 s. We determined CC fraction, rate and interruptions (number and total duration) for the entire resuscitation and compared differences between LT and ETI using t-tests. We repeated the analysis stratified by time before, during and after airway insertion as well as by successive 3-min time segments. We also compared CC quality between single vs. multiple airway insertion attempts, as well as between bag-valve-mask (BVM-only) vs. ETI or LT. RESULTS: Of 3004 patients enrolled in PART, CPR process data were available for 1996 (1001 LT, 995 ETI). Mean CPR analysis duration were: LT 22.6 ±â€¯10.8 min vs. ETI 25.3 ±â€¯11.3 min (p < 0.001). Mean CC fraction (LT 88% vs. ETI 87%, p = 0.05) and rate (LT 114 vs. ETI 114 compressions per minute (cpm), p = 0.59) were similar between LT and ETI. Median number of CC interruptions were: LT 11 vs. ETI 12 (p = 0.001). Total CC interruption duration was lower for LT than ETI (LT 160 vs. ETI 181 s, p = 0.002); this difference was larger before airway insertion (LT 56 vs. ETI 78 s, p < 0.001). There were no differences in CC quality when stratified by 3-min time epochs. CONCLUSION: In the PART trial, compared with ETI, LT was associated with shorter total CC interruption duration but not other CC quality measures. CC quality may be associated with OHCA airway management.

IL-10 polymorphism associated with decreased risk for mortality after burn injury.

OBJECTIVE: Evaluation of single nucleotide polymorphisms (SNPs) in the interleukin-10 promoter (-592 and -819) on risk for death after burn injury. METHODS: Association between the IL-10 SNPs and outcome after burn injury was evaluated in a cohort of 265 patients from Parkland Hospital, Dallas, TX with ≥ 15% TBSA burns without non-burn trauma (ISS ≤ 16), traumatic or anoxic brain injury or spinal cord injury, who survived >48 h under an IRB-approved protocol. Clinical data were collected prospectively and genotyping was conducted by TaqMan assay. Whole blood from 31 healthy volunteers was stimulated with LPS (100 ng/mL) to determine the level of IL-10 expression for each allele by enzyme-linked immunosorbent assay (ELISA). RESULTS: After adjustment for percent total body surface area (TBSA) burned, inhalation injury, age, gender, and race/ethnicity, carriage of ­592A and/or ­819T was significantly associated (P = 0.014) with a decreased risk for death (adjusted odds ratio: 0.404; 95% CI: 0.197-0.829). As the candidate SNPs were in complete linkage disequilibrium, it was not possible to distinguish which allele was associated with decreased mortality risk. Age, inhalation injury, and full-thickness burn size were significantly associated with increased risk for death. In the LPS stimulated blood of healthy controls, carriage of the -592A and/or -819T allele demonstrated a trend for decreased levels of IL-10 (P = 0.079). CONCLUSION: Carriage of the ­592A and/or ­819T allele in the IL-10 promoter appears to reduce the risk for death after burn injury.

Clinical characteristics and course of out-of-hospital shock in a national emergency medical services cohort.

BACKGROUND: Shock from medical and traumatic conditions can result in organ injury and death. Limited data describe out-of-hospital treatment of shock. We sought to characterize adult out-of-hospital shock care in a national emergency medical services (EMS) cohort. METHODS: This cross-sectional study used 2018 data from ESO, Inc. (Austin, TX), a national EMS electronic health record system, containing data from 1289 EMS agencies in the United States. We included adult (age ≥18 years) non-cardiac arrest patients with shock, defined as initial systolic blood pressure ≤80 mm Hg. We compared patient demographics, clinical characteristics, and response (defined as systolic blood pressure increase) between medical and traumatic shock patients, looking at systolic blood pressure trends over the first 90 minutes of care. RESULTS: Among 6,156,895 adult 911 responses, shock was present in 62,867 (1.02%; 95% confidence interval [CI] = 1.01%-1.03%); 54,239 (86.3%) medical and 5978 (9.5%) traumatic, and 2650 unknown. Medical was more common than traumatic shock in women and older patients. The most common injuries associated with traumatic shock were falls (37.6%) and motor vehicle crashes (18.7%). Mean initial and final medical systolic blood pressure were 71 ± 10 mm Hg and 99 ± 24 mm Hg. Systolic blood pressure increased in 88.8% and decreased or did not change in 11.0%. Mean initial and final trauma systolic blood pressure were 71 ± 13 mm Hg and 105 ± 28 mm Hg; systolic blood pressure increased in 90.4% and decreased/did not change in 9.6%. On fractional polynomial modeling, systolic blood pressure changes were greater and faster for trauma than medical shock. CONCLUSIONS: In this national series, 1 of every 100 EMS encounters involved shock. These findings highlight the current course and care of shock in the out-of-hospital setting.