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Summary: Post-COVID-19 conditions (long COVID) has impacted many individuals, yet risk factors for this condition are poorly understood. This retrospective analysis of 88,943 COVID-19 patients at a multi-state US health system compares phenotypes, laboratory tests, medication orders, and outcomes for 1,086 long-COVID patients and their matched controls. We found that history of chronic pulmonary disease (CPD) (odds ratio: 1.9, 95% CI: [1.5, 2.6]), migraine (OR: 2.2, [1.6, 3.1]), and fibromyalgia (OR: 2.3, [1.3, 3.8]) were more common for long-COVID patients. During the acute infection phase long COVID patients exhibited high triglycerides, low HDL cholesterol, and a high neutrophil-lymphocyte ratio; and were more likely hospitalized (5% vs. 1%). Our findings suggest severity of acute infection and history of CPD, migraine, chronic fatigue syndrome (CFS), or fibromyalgia as risk factors for long COVID. These results suggest that suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.

Abstract The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma. We identified 144 adults treated at Mayo clinic sites who had received anti-CD20 therapies within a median of 5.9 months prior to the COVID-19 index date. About one-third (34.7%) were hospitalized within 14 days and nearly half (47.9%) within 90 days. COVID-19 directed therapy included anti-spike monoclonal antibodies (n = 30, 20.8%), and, among those hospitalized within 14 days (n = 50), remdesivir (n = 45, 90.0%), glucocorticoids (n = 36, 72.0%) and convalescent plasma (n = 24, 48.0%). The duration from receipt of last dose of anti-CD20 therapy did not correlate with outcomes. The overall 90-day mortality rate was 14.7%. Administration of convalescent plasma within 14 days of the COVID-19 diagnosis was not significantly associated with any study outcome. Further study of COVID-19 in CD20-depleted individuals is needed focusing on the early administration of new and potentially combination antiviral agents, associated or not with vaccine-boosted convalescent plasma.

Abstract Purpose Continuous kidney replacement therapy (CKRT) is an increasingly common intervention for critically ill patients with kidney failure. Because CKRT affects body temperature, detecting infections in patients on CKRT is challenging. Understanding the relation between CKRT and body temperature may facilitate earlier detection of infection. Methods We retrospectively reviewed adult patients (≥ 18 years) admitted to the intensive care unit at Mayo Clinic in Rochester, Minnesota, from December 1, 2006, through November 31, 2015, who required CKRT. We summarized central body temperatures for these patients according to the presence or absence of infection. Results We identified 587 patients who underwent CKRT during the study period, of whom 365 had infections, and 222 did not have infections. We observed no statistically significant differences in minimum (P = .70), maximum (P = .22), or mean (P = .55) central body temperature for patients on CKRT with infection vs. those without infection. While not on CKRT (before CKRT initiation and after cessation), all three body temperature measurements were significantly higher in patients with infection than in those without infection (all P

BackgroundTo describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes.MethodsThis observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts.ResultsWe included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001).ConclusionsThere was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020 and 2022 and used Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest calculated introduction into Minnesota was to Hennepin County from a domestic source around 22 January 2020; 6 weeks before the first confirmed case in the state. This led to the virus spreading to Northern Minnesota and, eventually, the rest of the state. International introductions were most abundant in Hennepin (home to the Minneapolis/St. Paul International Airport) totaling 45 (out of 107) over the 2-year period. Southern Minnesota counties were most common for domestic introductions, with 19 (out of 64), potentially driven by bordering states such as Iowa and Wisconsin as well as Illinois, which is nearby. Hennepin also was, by far, the most dominant source of in-state transmissions to other Minnesota locations (n = 772) over the 2-year period. We also analyzed the diversity of the location source of SARS-CoV-2 viruses in each county and noted the timing of state-wide policies as well as trends in clinical cases. Neither the number of clinical cases nor the major policy decisions, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, appeared to have an impact on virus diversity across each individual county.IMPORTANCEWe analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission “sinks.” In addition, major policies, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, did not appear to have an impact on virus diversity across individual counties.

Abstract The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 14.19, 95% CI 6.15–32.75, p value = 3.41 × 10–10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85–90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.

We report an imported case of myositis caused by a rare parasite, Haycocknema perplexum, in Australia in a 37-year-old man who had progressive facial, axial, and limb weakness, dysphagia, dysphonia, increased levels of creatine kinase and hepatic aminotransferases, and peripheral eosinophilia for 8 years. He was given extended, high-dose albendazole.

Objective: To examine the clinical characteristics, risk of hospitalization, and mortality of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Patients and Methods: We retrospectively reviewed all patients with SARS-CoV-2 reinfection at all Mayo Clinic sites between May 23, 2020, and June 30, 2021 (the period before the emergence of the Delta variant in the United States). The reinfection was defined as a positive SARS-CoV-2 test more than or equal to 90 days after initial infection or 45-89 days after with symptomatic second episode. Vaccination status was classified as fully vaccinated, first dose, and unvaccinated. Comparative analysis of baseline characteristics and comorbidities was performed by hospitalization and vaccination status. The survival analysis of the hospitalized patients was performed using Cox proportional hazard regression. Results: Among the 554 patients reinfected with SARS-CoV-2, 59 (10.6%) were pediatric, and 495 (89.4%) were adults. The median age was 13.9 years (interquartile range, 8.5-16.5 years) for the pediatric and 50.2 years (interquartile range, 28.4-65.6 years) for the adult population. Among the adult patients, the majority were unvaccinated (83.4%, n=413), and the duration to reinfection from initial infection was the longest in the fully vaccinated group (P

Summary: Background: The emergency use authorisation of BNT162b2 (tozinameran; Comirnaty, Pfizer–BioNTech) for children aged 5–17 years has resulted in rapid vaccination in the paediatric population. However, there are few studies of adverse events associated with vaccination in children. The aim of this study was to systematically assess the adverse events of two-dose BNT162b2 vaccination in the paediatric population. Methods: We conducted a retrospective analysis of patient electronic health records (EHRs) of children aged 5–17 years who received the primary two-dose series of the BNT162b2 vaccine between Jan 5, 2021, and Aug 5, 2022, at the Mayo Clinic Health System (MN, FL, AZ, IA, and WI), USA. Using natural language processing, we automatically curated adverse events reported by physicians in EHR clinical notes before and after vaccination. To determine significant adverse events after BNT162b2 vaccination, we calculated risk differences, which was defined as the percentage difference between the rate of children with an adverse event after a vaccine dose and the baseline rate of children with an adverse event before vaccination. 95% CIs and p values were calculated using the Miettinen and Nurminen score method. Findings: 56 436 individuals aged 5–17 years (20 227 aged 5–11 years and 36 209 aged 12–17 years) with EHRs in the Mayo Clinic Health Systems were included in the study. Overall, the reporting of adverse events remained low in passive surveillance. Serious adverse events were rare after the first and second doses of BNT162b2, with rates of anaphylaxis (six [0·01%] of 56 436), myocarditis (five [0·01%]), and pericarditis (three [0·01%]) consistent with previous studies. Among the 20 227 5–11-year-olds, there were increased risks of fatigue (58 after second dose vs 41 before first dose; risk difference [RD]dose2 0·08% [95% CI –0·01 to 0·18], p=0·044) and fever (104 after second dose vs 77 before first dose; RDdose2 0·13% [0·00 to 0·27], p=0·022) after the second dose. Among the 36 209 12–17-year-olds, there were increased risks of arthralgia (69 after second dose vs 48 before first dose; RDdose2 0·06% [–0·00 to 0·12], p=0·026), chills (58 after second dose vs 40 before first dose; RDdose2 0·05% [–0·00 to 0·11], p=0·034), and myalgia (96 after second dose vs 73 before first dose; RDdose2 0·06% [–0·01 to 0·14], p=0·038) after the second dose. Although the overall incidence was low, there was an increased risk of myocarditis in males aged 12–17 years after the second dose (five after second dose vs zero before first dose; RDdose2 0·03% [0·01 to 0·07], p=0·013), with median age being 15 years (IQR 14 to 16). Interpretation: Overall, this data suggests that vaccination with BNT162b2 in the paediatric population is generally safe and well-tolerated. Further research is warranted to investigate the basis for the increased risk of myocarditis in adolescent males. Additionally, further studies are needed to confirm whether the findings in our study population apply to the whole vaccinated paediatric population. Funding: nference.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Objectives: Differences in management and outcomes of brain abscesses due to gram-positive (GPB) versus gram-negative bacteria (GNB) are not well defined. Methods: A retrospective review of adult patients with brain abscesses due to monomicrobial infection from 2009 through 2020 was performed. Results: A total 177 patients had a monomicrobial brain abscess; 143 (80.8%) caused by GPB and 34 (19.2%) by GNB. Patients with GNB had more history of head/neck surgery than those with GPB (58.8% vs 36.4%; P = 0.02). Pathogens in the GNB group included Pseudomonas aeruginosa (29.4%), Klebsiella spp (20.6%), and Enterobacter spp (20.6%). Pathogens in the GPB group included Staphylococcus aureus (32.2%) and Streptococcus spp (31.5%). Most patients had combined medical/surgical management (64.7% GNB vs 63.6% GPB). The median duration of antibiotic therapy was 42 days, and there was no significant difference in infection relapse or 3-month survival rate. Patients with GNB were more likely to have therapeutic failure than those with GPB (44.1% vs 22.4%; P = 0.01). Conclusions: Compared with brain abscesses caused by GPB, those due to GNB were more likely to occur in patients who had undergone prior head and neck surgery . No statistically significant difference in outcomes was observed between the groups; however, patients with GNB had a higher therapeutic failure rate than those with GPB.

Background: Pyogenic brain abscess poses a significant management challenge to clinicians, hence early diagnosis and interventions are critical. Our objective was to assess predictors of failure of therapy among patients with pyogenic brain abscesses according to surgical versus medical treatment. Methods: Retrospectively reviewed adults with pyogenic brain abscesses at our institution between 2009 and 2020. Treatment was classified as early surgical intervention and no early surgical treatment (medical therapy). Propensity score (PS) adjustment and multivariable regression were used to assess risk of treatment failure from surgical intervention and baseline covariates. Results: A total of 224 patients had pyogenic brain abscess, of whom 106 (47.3%) had early surgical treatment and 118 (52.7%) had medical treatment only. Significant predictors of surgical (vs. medical) treatment included essential hypertension (odds ratio [OR] 95% confidence interval [95% CI] = 2.06 [1.01–4.18]), abscesses number (single vs. multiple, OR [95% CI] =4.81 [1.64–14.08]), midline shift (OR [95% CI] = 3.09 [1.22–7.82]). At 6 months, treatment failure cumulative incidence was 27.1% in the medical group (n = 31) and 21.3% in early surgical group (n = 22). PS-adjusted analysis showed beneficial effect of early surgical treatment (hazard ratio [HR] [95% CI] = 0.55 [0.31–0.98]). Multivariable regression showed similar but statistically nonsignificant estimate of surgical benefit (HR [95% CI] =0.59 [0.34–1.01]; P = 0.056), and significant associations of Charlson Comorbidity Index (CCI) (P = 0.019) and pre-existing central nervous system hardware (P = 0.034) with increased risk of treatment failure. Conclusions: Higher CCI and pre-existing CNS hardware were significant risk factors associated with treatment failure. In propensity-adjusted analysis, early surgery was associated with a 45% reduction in risk of 6-month treatment failure.

Abstract Understanding the relationships between pre-existing conditions and complications of COVID-19 infection is critical to identifying which patients will develop severe disease. Here, we leverage ~1.1 million clinical notes from 1803 hospitalized COVID-19 patients and deep neural network models to characterize associations between 21 pre-existing conditions and the development of 20 complications (e.g. respiratory, cardiovascular, renal, and hematologic) of COVID-19 infection throughout the course of infection (i.e. 0–30 days, 31–60 days, and 61–90 days). Pleural effusion was the most frequent complication of early COVID-19 infection (89/1803 patients, 4.9%) followed by cardiac arrhythmia (45/1803 patients, 2.5%). Notably, hypertension was the most significant risk factor associated with 10 different complications including acute respiratory distress syndrome, cardiac arrhythmia, and anemia. The onset of new complications after 30 days is rare and most commonly involves pleural effusion (31–60 days: 11 patients, 61–90 days: 9 patients). Lastly, comparing the rates of complications with a propensity-matched COVID-negative hospitalized population confirmed the importance of hypertension as a risk factor for early-onset complications. Overall, the associations between pre-COVID conditions and COVID-associated complications presented here may form the basis for the development of risk assessment scores to guide clinical care pathways.

Objective: To determine the association between chronic statin use and mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). Patients and Methods: We identified a retrospective cohort of patients requiring admission at the Mayo Clinic using our enterprise-wide COVID-19 registry from March 1, 2020, through September 30, 2020. Available information included age, sex, use of statins, medical comorbidities, and 30-day mortality. We estimated the association of statins with 30-day mortality using odds ratios and 95% CIs from logistic regression modeling. Results: Patients (N=1295) between the ages of 30 and 80 years tested positive for COVID-19 and required admission during the study period, of whom 500 (38.6%) were taking statins at admission. Patients taking statins were older and more likely to have diabetes mellitus or congestive heart failure. Within 30 days of diagnosis, 59 (4.6%) died. In multivariable analysis, statin users did not have statistically different odds of death within 30 days with an odds ratio of 1.14 (95% CI, 0.64 to 2.03; P=.67) compared to nonusers. Conclusion: Patients with COVID-19 taking statins had similar 30-day mortality to those not taking statins after adjusting for relevant covariates. Although this is partly influenced by a higher prevalence of risk factors for more severe COVID-19 presentation not entirely adjusted for by the Charlson comorbidity index, these data would not support statins as a likely therapeutic intervention for COVID-19 in the hospital setting.

Abstract Background Beta-lactams (i.e., penicillins, cephalosporins, carbapenems, monobactams) are the most widely used class of antibiotics in critically ill patients. There is substantial interpatient variability in beta-lactam pharmacokinetics which renders their effectiveness and safety largely unpredictable. One strategy to ensure achievement of therapeutic concentrations is drug level testing (“therapeutic drug monitoring”; TDM). While studies have suggested promise with beta-lactam TDM, it is not yet widely available or implemented. This protocol presents a mixed-methods study designed to examine healthcare practitioners’ perspectives on the use and implementation of beta-lactam TDM in the critically ill. Methods An explanatory sequential mixed-methods design will be used [QUANT → qual]. First, quantitative data will be collected through a web-based questionnaire directed at clinicians at three academic medical centers at different phases of beta-lactam TDM implementation (not yet implemented, partially implemented, fully implemented). The sampling frame will include providers from a variety of disciplines that interact with drug level testing and interpretation in the critical care environment including pharmacists, intensivists, infectious diseases experts, medical/surgical trainees, and advanced practice providers. Second, approximately 30 individuals will be purposively sampled from survey respondents to conduct in-depth qualitative interviews to explain and expand upon the results from the quantitative strand. Normalization Process Theory and the Consolidated Framework for Implementation Science will be used to guide data analysis. Discussion These data will be used to answer two specific questions: “What are ICU practitioners’ perspectives on implementing beta-lactam TDM?” and “What factors contribute to the success of beta-lactam TDM program implementation?” Results of this study will be used to design future implementation strategies for beta-lactam TDM programs in the critically ill. Trial registration NCT04755777 .

This study aimed to determine if the crossing point of the initial positive SARS-CoV-2 PCR test correlated with patient demographics, subsequent hospitalization, or duration of positivity. Seventy-three patients with two or more positive PCR tests had a median time of 23 days to two consecutive negative results.

Objective: To describe the design, implementation, and utilization of electronic health record (EHR)–based digital health surveillance strategies used to manage the coronavirus disease 2019 (COVID-19) pandemic and to ensure delivery of high-quality clinical care, such as case identification, remote monitoring, telemedicine services, and recruitment to clinical trials at Mayo Clinic. Methods: The design and implementation work described in this report was performed at Mayo Clinic, a large multistate integrated health care system with more than 1.5 million annual patient visits that uses the Epic EHR system. Rule-based live registries were designed in the EHR system to classify patients who currently test positive for COVID-19, patients who test positive but have recovered from COVID-19, patients who are thought to have COVID-19 but do not yet meet clinical diagnostic criteria, patients who test negative for COVID-19, and patients who exceed a risk score for serious complications from COVID-19. Results: By use of registries, custom dashboards and operational reports were developed to provide a daily high-level summary for clinical practice use and up-to-date information to manage individual patients affected by COVID-19, including support of case identification, contact isolation, and other care management tasks. Conclusion: We developed and implemented a systematic approach to the use of EHR patient registries to manage the COVID-19 pandemic that proved feasible and useful in a large multistate group clinical practice. The key to harnessing the potential of digital surveillance tools to promote patient-centered care during the COVID-19 pandemic was to use the registry data, reports, and dashboards as informatics tools to inform decision-making.

Abstract Clinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Haemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), Varicella, pneumococcal conjugate (PCV13), Geriatric Flu, and hepatitis A/hepatitis B (HepA–HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI (0.32, 0.64), p-value: 6.9e−05). Overall, this study identifies existing approved vaccines which can be promising candidates for pre-clinical research and Randomized Clinical Trials towards combating COVID-19.

OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Objective: To compare the predictive performance of Epic Systems Corporation’s proprietary intensive care unit (ICU) mortality risk model (IMRM) with that of the Acute Physiology and Chronic Health Evaluation (APACHE) IV score. Methods: This is a retrospective cohort study of patients treated from January 1, 2008, through January 1, 2018. This single-center study was performed at Mayo Clinic (Rochester, MN), a tertiary care teaching and referral center. The primary outcome was death in the ICU. Discrimination of each risk model for hospital mortality was assessed by comparing area under the receiver operating characteristic curve (AUROC). Results: The cohort mostly comprised older patients (median age, 64 years) and men (56.7%). The mortality rate of the cohort was 3.5% (2251 of 63,775 patients). The AUROC for mortality prediction was 89.7% (95% CI, 89.5% to 89.9%) for the IMRM, which was significantly greater than the AUROC of 88.2% (95% CI, 87.9% to 88.4%) for APACHE IV (P

OBJECTIVES:. To describe hospital variation in use of “guideline-based care” for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN:. Retrospective, observational study. SETTING:. The Society of Critical Care Medicine’s Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS:. Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS:. Hospital-level use of “guideline-based care” for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS:. Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in “guideline-based care.” A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1–3.4) for receipt of “guideline-based care” compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47–62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use “guideline-based care” quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3–1.9; p = 0.49). CONCLUSIONS:. During the first year of the COVID-19 pandemic, only half of patients received “guideline-based care” for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Abstract Objective: Despite evidence favoring perioperative antibiotic prophylaxis (ABP) use in patients undergoing craniotomy to reduce rates of surgical site infections (SSIs), standardized protocols are lacking. We describe demographic characteristics, risk factors, and ABP choice in patients with craniotomy complicated with SSI. Design: Retrospective case series from January 1, 2017, through December 31, 2020. Setting: Tertiary-care referral center. Patients: Adults who underwent craniotomy and were diagnosed with an SSI. Methods: Logistic regression to estimate odds ratios and 95% confidence intervals to identify factors associated with SSIs. Results: In total, 5,328 patients undergoing craniotomy were identified during the study period; 59 (1.1%) suffered an SSI. Compared with non-SSI cases, patients with SSI had a significantly higher frequency of emergency procedures: 13.5% versus 5.8% (P = .02; odds ratio [OR], 2.52; 95% confidene interval [CI], 1.10–5.06; P = .031). Patients with SSI had a higher rate of a dirty (5.1% vs 0.9%) and lower rate of clean-contaminated (3.3% vs 14.5%) wound class than those without infection (P = .002). Nearly all patients received ABP before craniotomy (98.3% in the SSI group vs 99.6% in the non-SSI group; P = .10). Combination of vancomycin and cefazolin as dual therapy was more prevalent in the group of patients without infection (n = 1,761, 34.1%) than those with SSI (n = 4, 6.8%) (P < .001), associated with decreased odds for SSI (OR, 0.17; 95% CI, 0.005–0.42; P ≤ .001). Conclusions: SSI are frequently seen after an emergent neurosurgical procedure and a dirty wound classification. Combination of prophylactic cefazolin and vancomycin is associated with decreased risk for SSI.

Objective: To evaluate the performance of an Electronic Health Record (EHR) integrated risk score for COVID-19 positive outpatients to predict 30-day risk of hospitalization. Patients and Methods: A retrospective observational study of 67 470 patients with COVID-19 confirmed by polymerase chain reaction (PCR) test between March 12, 2020 and February 8, 2021. Risk scores were calculated based on data in the chart at the time of the incident infection. Results: The Mayo Clinic COVID-19 risk score consisted of 13 components included age, sex, chronic lung disease, congenital heart disease, congestive heart failure, coronary artery disease, diabetes mellitus, end stage liver disease, end stage renal disease, hypertension, immune compromised, nursing home resident, and pregnant. Univariate analysis showed all components, except pregnancy, have significant ( P

IMPORTANCE:. At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES:. To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES:. Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS:. Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE:. Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

BackgroundCOVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. ObjectiveHere, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. MethodsWe retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient’s first positive COVID-19 nucleic acid test result. ResultsThe GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P

IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Summary: Patients with COVID-19 can experience symptoms and complications after viral clearance. It is important to identify clinical features of patients who are likely to experience these prolonged effects. We conducted a retrospective study to compare longitudinal laboratory test measurements (hemoglobin, hematocrit, estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen) in patients rehospitalized after PCR-confirmed SARS-CoV-2 clearance (n = 104) versus patients not rehospitalized after viral clearance (n = 278). Rehospitalized patients had lower median hemoglobin levels in the year prior to COVID-19 diagnosis (Cohen's D = −0.50; p = 1.2 × 10−3) and during their active SARS-CoV-2 infection (Cohen's D = −0.71; p = 4.6 × 10−8). Rehospitalized patients were also more likely to be diagnosed with moderate or severe anemia during their active infection (Odds Ratio = 4.07; p = 4.99 × 10−9). These findings suggest that anemia-related laboratory tests should be considered in risk stratification algorithms for patients with COVID-19.

Introduction Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the USA, having high incidence in intensive care units (ICU). Antibiotic use increases risk of CDI, with fluoroquinolones (FQs) particularly implicated. In healthcare settings, antibiotic stewardship (AS) and infection control interventions are effective in CDI control, but there is little evidence regarding the most effective AS interventions. Preprescription authorisation (PPA) restricting FQs is a potentially promising AS intervention to reduce CDI. The FQ Restriction for the Prevention of CDI (FIRST) trial will evaluate the effectiveness of an FQ PPA intervention in reducing CDI rates in adult ICUs compared with preintervention care, and evaluate implementation effectiveness using a human-factors and systems engineering model.Methods and analysis This is a multisite, stepped-wedge, cluster, effectiveness-implementation clinical trial. The trial will take place in 12 adult medical-surgical ICUs with ≥10 beds, using Epic as electronic health record (EHR) and pre-existing AS programmes. Sites will receive facilitated implementation support over the 15-month trial period, succeeded by 9 months of follow-up. The intervention comprises a clinical decision support system for FQ PPA, integrated into the site EHRs. Each ICU will be considered a single site and all ICU admissions included in the analysis. Clinical data will be extracted from EHRs throughout the trial and compared with the corresponding pretrial period, which will constitute the baseline for statistical analysis. Outcomes will include ICU-onset CDI rates, FQ days of therapy (DOT), alternative antibiotic DOT, average length of stay and hospital mortality. The study team will also collect implementation data to assess implementation effectiveness using the Systems Engineering Initiative for Patient Safety model.Ethics and dissemination The trial was approved by the Institutional Review Board at the University of Wisconsin-Madison (2018-0852-CP015). Results will be made available to participating sites, funders, infectious disease societies, critical care societies and other researchers.Trial registration number NCT03848689.

Abstract Background Chlorhexidine gluconate (CHG) bathing of hospitalized patients may have benefit in reducing hospital-acquired bloodstream infections (HABSIs). However, the magnitude of effect, implementation fidelity, and patient-centered outcomes are unclear. In this meta-analysis, we examined the effect of CHG bathing on prevention of HABSIs and assessed fidelity to implementation of this behavioral intervention. Methods We undertook a meta-analysis by searching Medline, EMBASE, CINAHL, Scopus, and Cochrane’s CENTRAL registry from database inception through January 4, 2019 without language restrictions. We included randomized controlled trials, cluster randomized trials and quasi-experimental studies that evaluated the effect of CHG bathing versus a non-CHG comparator for prevention of HABSIs in any adult healthcare setting. Studies of pediatric patients, of pre-surgical CHG use, or without a non-CHG comparison arm were excluded. Outcomes of this study were HABSIs, patient-centered outcomes, such as patient comfort during the bath, and implementation fidelity assessed through five elements: adherence, exposure or dose, quality of the delivery, participant responsiveness, and program differentiation. Three authors independently extracted data and assessed study quality; a random-effects model was used. Results We included 26 studies with 861,546 patient-days and 5259 HABSIs. CHG bathing markedly reduced the risk of HABSIs (IRR = 0.59, 95% confidence interval [CI]: 0.52–0.68). The effect of CHG bathing was consistent within subgroups: randomized (0.67, 95% CI: 0.53–0.85) vs. non-randomized studies (0.54, 95% CI: 0.44–0.65), bundled (0.66, 95% CI: 0.62–0.70) vs. non-bundled interventions (0.51, 95% CI: 0.39–0.68), CHG impregnated wipes (0.63, 95% CI: 0.55–0.73) vs. CHG solution (0.41, 95% CI: 0.26–0.64), and intensive care unit (ICU) (0.58, 95% CI: 0.49–0.68) vs. non-ICU settings (0.56, 95% CI: 0.38–0.83). Only three studies reported all five measures of fidelity, and ten studies did not report any patient-centered outcomes. Conclusions Patient bathing with CHG significantly reduced the incidence of HABSIs in both ICU and non-ICU settings. Many studies did not report fidelity to the intervention or patient-centered outcomes. For sustainability and replicability essential for effective implementation, fidelity assessment that goes beyond whether a patient received an intervention or not should be standard practice particularly for complex behavioral interventions such as CHG bathing. Trial registration Study registration with PROSPERO CRD42015032523.

Purpose The purpose of the present study was to investigate body mass index, multi-morbidity, and COVID-19 Risk Score as predictors of severe COVID-19 outcomes. Patients Patients from this study are from a well-characterized patient cohort collected at Mayo Clinic between January 1, 2020 and May 23, 2020; with confirmed COVID-19 diagnosis defined as a positive result on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays from nasopharyngeal swab specimens. Measures Demographic and clinical data were extracted from the electronic medical record. The data included: date of birth, gender, ethnicity, race, marital status, medications (active COVID-19 agents), weight and height (from which the Body Mass Index (BMI) was calculated, history of smoking, and comorbid conditions to calculate the Charlson Comorbidity Index (CCI) and the U.S Department of Health and Human Services (DHHS) multi-morbidity score. An additional COVID-19 Risk Score was also included. Outcomes included hospital admission, ICU admission, and death. Results Cox proportional hazards models were used to determine the impact on mortality or hospital admission. Age, sex, and race (white/Latino, white/non-Latino, other, did not disclose) were adjusted for in the model. Patients with higher COVID-19 Risk Scores had a significantly higher likelihood of being at least admitted to the hospital (HR = 1.80; 95% CI = 1.30, 2.50; P

Objective To describe the process and outcome of creating a patient cohort in the early stages of the COVID-19 pandemic in order to better understand the process of and predict the outcomes of COVID-19. Patients and Methods A total of 1169 adults aged 18 years of age or older who tested positive in Mayo Clinic Rochester or the Mayo Clinic Midwest Health System between January 1 and May 23 of 2020. Results Patients were on average 43.9 years of age and 50.7% were female. Most patients were white (69.0%), and Blacks (23.4%) and Asians (5.8%) were also represented in larger numbers. Hispanics represented 16.3% of the sample. Just under half of patients were married (48.4%). Common comorbid conditions included: cardiovascular diseases (25.1%), dyslipidemia (16.0%), diabetes mellitus (11.2%), chronic obstructive pulmonary disease (6.6%), asthma (7.5%), and cancer (5.1%). All other comorbid conditions were less the 5% in prevalence. Data on 3 comorbidity indices are also available including the: DHHS multi-morbidity score, Charlson Comorbidity Index, and Mayo Clinic COVID-19 Risk Factor Score. Conclusion In addition to managing the ever raging pandemic and growing death rates, it is equally important that we develop adequate resources for the investigation and understanding of COVID-19-related predictors and outcomes.

Background: Consecutive negative SARS-CoV-2 PCR test results are being considered to estimate viral clearance in COVID-19 patients. However, there are anecdotal reports of hospitalization from protracted COVID-19 complications despite such confirmed viral clearance, presenting a clinical conundrum. Methods: We conducted a retrospective analysis of 222 hospitalized COVID-19 patients to compare those that were readmitted post-viral clearance (hospitalized post-clearance cohort, n = 49) with those that were not re-admitted post-viral clearance (non-hospitalized post-clearance cohort, n = 173) between February and October 2020. In order to differentiate these two cohorts, we used neural network models for the ‘augmented curation’ of comorbidities and complications with positive sentiment in the Electronic Hosptial Records physician notes. Findings: In the year preceding COVID-19 onset, anemia (n = 13 [26.5%], p-value: 0.007), cardiac arrhythmias (n = 14 [28.6%], p-value: 0.015), and acute kidney injury (n = 7 [14.3%], p-value: 0.030) were significantly enriched in the physician notes of the hospitalized post-clearance cohort. Interpretation: Overall, this retrospective study highlights specific pre-existing conditions that are associated with higher hospitalization rates in COVID-19 patients despite viral clearance and motivates follow-up prospective research into the associated risk factors. Funding: This work was supported by Nference, inc.

Background: Coagulopathies are a major class among COVID-19 associated complications. Although anticoagulants such as unfractionated Heparin and Enoxaparin are both being used for therapeutic mitigation of COVID associated coagulopathy (CAC), differences in their clinical outcomes remain to be investigated. Methods: We analyzed records of 1,113 patients in the Mayo Clinic Electronic Health Record (EHR) database who were admitted to the hospital for COVID-19 between April 4, 2020 and August 31, 2020, including 19 different Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Among this patient population, we compared cohorts of patients who received different types of anticoagulants, including 441 patients who received unfractionated Heparin and 166 patients who received Enoxaparin. Clinical outcomes at 28 days were compared, and propensity score matching was used to control for potential confounding variables including: demographics, comorbidities, ICU status, chronic kidney disease stage, and oxygenation status. Patients with a history of acute kidney injury and patients who received multiple types of anticoagulants were excluded from the study. Findings: We find that COVID-19 patients administered unfractionated Heparin but not Enoxaparin have higher rates of 28-day mortality (risk ratio: 4.3; 95% Confidence Interval [C.I.].: [1.8, 10.2]; p-value: 8.5e−4, Benjamini Hochberg [BH] adjusted p-value: 2.1e−3), after controlling for potential confounding factors. Interpretation: This study emphasizes the need for mechanistically investigating differential modulation of the COVID-associated coagulation cascades by Enoxaparin versus unfractionated Heparin. Funding: This work was supported by Nference, inc.

Importance/Background: During current public health emergency of COVID-19 pandemic, repurposing of existing antiviral drugs may be an efficient strategy since there is no proven effective treatment. Published literature shows Remdesivir has broad-spectrum antiviral activity against numerous RNA viruses and has been recently recognized as a promising therapy against SARS-CoV-2.Methods: A systematic search was conducted for full length manuscripts published between inception and July 19th, 2020 focussing on efficacy and safety of Remdesivir in COVID-19. The primary outcomes were defined as mortality rate and median days to recovery based on the available pooled data. The secondary outcome was adverse events rate and drug discontinuation rate.Statistical Analysis: All outcomes were performed using Comprehensive Meta-Analysis software package (Bio stat, Englewood, NJ, USA).Results: A total of 1,895 patients from 9 studies were included in this qualitative synthesis. In patients treated with Remdesivir, the mean recovery time was 15.84 days (95% CI 11.68–20, SE 2.12; I2 = 97.24) and the pooled mortality rate was 11.3% (95% CI 7.9–16%; I2 = 74.85). However, treatment with Remdesivir was associated with adverse effects (55.3%, 95% CI 31.5–76.9%; I2 = 97.66) eventually warranting the discontinuation of the drug (17.8%, 95% CI 8.6–33.1%; I2 = 95.64). The meta-analysis of three clinical trials indicated that administration of Remdesivir significantly reduces the mortality compared to the placebo (OR 0.70, 95% CI 0.58–0.84, p ≤ 0.001; I2 = 16.6).Conclusions and Relevance: The result of contemporary meta-analysis suggests mortality benefit with Remdesivir in COVID-19 and median recovery time was over 2 weeks. The pooled mortality with Remdesivir was found to be very low, and this analysis can shed light on this potential treatment for COVID-19 patients.

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVIDpos; n = 2,317) versus COVID-19-negative (COVIDneg; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVIDpos over COVIDneg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVIDpos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

Abstract Background Inefficient processes of care delivery during acute resuscitation can compromise the “Golden Hour,” the time when quick interventions can rapidly determine the course of the patient’s outcome. Checklists have been shown to be an effective tool for standardizing care models. We developed a novel electronic tool, the Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN) to facilitate standardized evaluation and treatment approach for acutely decompensating patients. The checklist was enforced by the use of a “prompter,” a team member separate from the leader who records and reviews pertinent CERTAIN algorithms and verbalizes these to the team. Our hypothesis was that the CERTAIN model, with the use of the tool and a prompter, can improve clinician performance and satisfaction in the evaluation of acute decompensating patients in a simulated environment. Methods Volunteer clinicians with valid adult cardiac life support (ACLS) certification were invited to test the CERTAIN model in a high-fidelity simulation center. The first session was used to establish a baseline evaluation in a standard clinical resuscitation scenario. Each subject then underwent online training before returning to a simulation center for a live didactic lecture, software knowledge assessment, and practice scenarios. Each subject was then evaluated on a scenario with a similar content to the baseline. All subjects took a post-experience satisfaction survey. Video recordings of the pre-and post-test sessions were evaluated using a validated method by two blinded reviewers. Results Eighteen clinicians completed baseline and post-education sessions. CERTAIN prompting was associated with reduced omissions of critical tasks (46 to 32%, p

Background: Blastomycosis can cause severe disease with progressive respiratory failure and dissemination even in immunocompetent individuals. We sought to evaluate risk factors for severe disease and mortality using clinical and laboratory data within a large health system in an endemic area. Methods: We performed a retrospective cohort study of patients diagnosed with blastomycosis at all Mayo Clinic sites from 1 January 2004 through 31 March 2020. Diagnosis was established by culture, histopathology/cytopathology, serology, antigen testing, or PCR. Disease was categorized as mild for patients treated in the outpatient setting, moderate for hospitalized patients who did not require intensive care, and severe for patients admitted to the intensive care unit. Logistic regression was used to evaluate risk factors for severe disease. A Cox proportional hazards model was constructed to evaluate mortality. Findings: We identified 210 patients diagnosed with blastomycosis. Mean age was 51 years (range, 6–84). Most subjects were male (71.0%). Extrapulmonary disease was confirmed in 24.8%. In this cohort, 40.5% of patients had mild disease, 37.6% had moderate disease, and 21.9% had severe disease. Independent risk factors for severe disease were neutrophilia (odds ratio (OR) 3.35 (95% CI 1.53–7.35), p = 0.002) and lymphopenia (OR 3.34 (95% CI 1.59–7.03), p = 0.001). Mortality at 90 days was 11.9%. Median time from diagnosis to death was 23 days (interquartile range 8–31 days). Independent risk factors for mortality were age (OR 1.04 (95% CI 1.01–1.08), p = 0.009), neutrophilia (OR 2.84 (95% CI 1.04–7.76), p = 0.041), and lymphopenia (OR 4.50 (95% CI 1.67–12.11), p = 0.003). Blastomyces immunodiffusion had an overall sensitivity of 39.6% (95% CI 30.1–49.8). Sensitivity was higher among those who were tested 4 weeks or longer after the onset of symptoms. Urine Blastomyces antigen had a significantly higher sensitivity of 80.8% (95% CI 68.1–89.2) compared to serology. There was a trend towards higher antigen concentration in patients with severe disease. The sensitivity of PCR from respiratory specimens was 67.6% (95% CI 50.1–85.5). Conclusion: In this cohort, we did not find an association between pharmacologic immunosuppression and disease severity. Lymphopenia at diagnosis was an independent risk factor for mortality. This simple marker may aid clinicians in determining disease prognosis.