Pathological autoantibody internalisation in myositis.

OBJECTIVES: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption. METHODS: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing. RESULTS: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets. CONCLUSIONS: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.

A phantom study investigating effective strategies for reducing fetal dose in pregnant patients with head and neck cancer.

PURPOSE: To measure the out-of-field doses for various treatment planning techniques and assess the impact on fetal dose with and without the use of custom shielding. MATERIALS AND METHODS: A total of six treatment plans were generated with different treatment techniques such as 3-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT), utilizing both 6 MV flattened beams and flattening filter-free (FFF) beams. The measurements were carried out both out-of-field at the surface and at depth to assess the dose reduction achieved by removing the flattening filter and incorporating shielding. RESULTS: The custom-made frame shielding can effectively reduce the surface dose with a maximum reduction of 15.2% observed in VMAT plans and achieve a maximum reduction of 100% for cone beam computed tomography (CBCT) imaging. Out-of-field dose measurements conducted at depth, positioned 58 cm inferior to the target isocenter, reveal that the shielding effectiveness consistently remains the greatest for 3DCRT technique. A maximum reduction of 21% is observed when utilizing a flattening filter-free beam. CONCLUSION: The results of this study indicate that the 3DCRT technique exhibits the least amount of scatter radiation both near and far from the treatment isocenter, which is the most suitable approach for radiation therapy of pregnant patients. In cases where meeting dose constraints for critical organs becomes challenging, VMAT technique emerges as the most suitable treatment technique for reducing out-of-field doses. Additionally, a flattening filter-free beam significantly reduces out-of-field doses due to lower contributions from head scatter.

Nailfold capillaroscopy findings of a multicentric multi-ethnic cohort of patients with idiopathic inflammatory myopathies.

OBJECTIVES: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test. RESULTS: Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number. CONCLUSIONS: NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.

Reducing Vocal Fatigue While Preserving Realism During Video Game Voice-Overs Using the Vocal Combat Technique: A Randomized Controlled Trial.

OBJECTIVE: Vocal Combat Technique (VCT) teaches indirect and direct behavioral voice techniques to voice-over artists performing in violent video games. Although previous work on VCT has shown promise for mitigating dysphonia symptoms, a randomized clinical trial has yet to be undertaken. Therefore, we completed a randomized, controlled trial between a group of experienced video game voice-over actors receiving VCT and a control group comparison. METHODS: A total of 24 video game voice-over actors completed this study. Participants were randomly assigned to receive VCT or indirect vocal hygiene training prior to completing an intensive 1-hour video game voice recording session. The primary outcome was a change in Voice Handicap Index-10 (VHI-10) preperformance/postperformance. Secondary measures included a modified version of the Evaluation of the Ability to Sing Easily (m-EASE), the Vocal Tract Discomfort Scale (VTDS), and questions regarding return to work. Participants were also rated on the realism of their vocal performance by a blinded video game director. RESULTS: The VCT group showed a significantly smaller change in VHI-10 and m-EASE scores postperformance, and a higher increased likelihood to return to work compared to the control group. There were no group differences for VTDS or realism ratings. Four participants from the control group exhibited outlier behavior with more pronounced phonotraumatic symptoms following performance than all other participants. CONCLUSIONS: VCT shows evidence of mitigating symptoms of dysphonia while preserving the realism of the vocal performance. More work is needed to understand performers at risk for more severe vocal symptoms following extreme voice-over work, so as to target them for preventative techniques and voice preservation.

Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.

OBJECTIVES: Myositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients. METHODS: RNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies. RESULTS: A set of 135 genes, including SCRT1 and MADCAM1, was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei. CONCLUSIONS: Based on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study.

Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis.

OBJECTIVES: Inflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis. METHODS: Bulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM). RESULTS: Unsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway. CONCLUSIONS: We identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis.

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.

OBJECTIVES: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies. METHODS: Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies. RESULTS: Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer. CONCLUSIONS: Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

Analysis of Lumbar Fusion and Lumbar Arthroplasty Videos on YouTube.

BACKGROUND: Patients often use the internet for information on their spinal surgeries. The goal of this study was to assess and compare the quality of lumbar fusion and arthroplasty videos on YouTube and to identify predictors of video quality. STUDY DESIGN: Cross-sectional. METHODS: YouTube was searched utilizing 3 search terms for both lumbar fusion and lumbar arthroplasty. Fifty videos from each search were categorized and analyzed. Videos were analyzed using 3 scoring systems: JAMA, informative, and clinical scores. The JAMA score rates online information based on 4 factors: authorship, attribution, disclosure, and currency. The informative score previously devised by Zhang et al was also applied to each video. Finally, 2 surgery-specific scores were created for lumbar fusion and lumbar arthroplasty based on peer-reviewed information. These were modeled on the informed consent procedure. Data analysis was conducted using the Jamovi 1.1.9.0. RESULTS: Eighty-four unique lumbar fusion videos and 82 lumbar arthroplasty videos were analyzed. Educational videos were the most common in fusion (78%) and arthroplasty (47%) groups; however, arthroplasty videos were more likely to be commercial (17%, P = 0.01). Fusion videos were more viewed (P < 0.001); however, arthroplasty videos had higher positivity ratings (P < 0.01). Overall, quality was poor for videos in both categories. Mean JAMA scores were 1.57 and 1.70 for fusion and arthroplasty, respectively, and did not differ significantly (P = 0.32). Fusion videos had higher informative scores (1.57 vs 1.23, P = 0.02) and higher clinical scores (21.8% vs 15.9%, P = 0.06). CONCLUSION: Information on YouTube for lumbar fusion and arthroplasty is poor. However, information on fusion is better than arthroplasty. Metadata can be used to help patients pick higher quality videos. CLINICAL RELEVANCE: This paper provides clinicians with an oversight of what their patients may accessing on the internet. Patients may have incorrect information regarding the surgical proceedure they are being offered. These misconceptions must be resovled in order to gain true informed consent from the patient and avoid damage to the surgeon-patient relationship.

Clinical and immunological signatures of severe COVID-19 in previously healthy patients with clonal hematopoiesis

Identifying additional risk factors for COVID-19 severity in numerous previously healthy patients without canonical clinical risk factors remains challenging. In this study, we investigate whether clonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes various inflammatory responses, may exert COVID-19 severity. We examine the clinical impact of CHIP in 143 laboratory-confirmed COVID-19 patients. Both stratified analyses and logistic regression including the interaction between canonical risk factors and CHIP show that CHIP is an independent risk factor for severe COVID-19, especially in previously healthy patients. Analyses of 60,310 single-cell immune transcriptome profiles identify distinct immunological signatures for CHIP (+) severe COVID-19 patients, particularly in classical monocytes, with a marked increase in pro-inflammatory cytokine responses and potent IFN-{gamma} mediated hyperinflammation signature. We further demonstrate that the enhanced expression of CHIP (+) specific IFN-{gamma} response genes is attributed to the CHIP mutation-dependent epigenetic reprogramming of poised or bivalent cis-regulatory elements. Our results highlight a unique immunopathogenic mechanism of CHIP in the progression of severe COVID-19, which could be extended to elucidate how CHIP contributes to a variety of human infectious diseases.

Views of stakeholders on factors influencing shared decision-making in the Eastern Mediterranean Region: a systematic review

Background: Shared decision-making is advocated as a key component of patient-centred care and associated with many benefits that improve patient outcomes. However, shared decision-making is not yet embedded in clinical practice and confronts many barriers that hinder its implementation especially in countries of the World Health Organization (WHO) Eastern Mediterranean Region. Aims: We conducted a systematic review to identify and understand factors influencing shared decision-making in the Region. Methods: We searched PsycINFO, CINAHL, PubMed, Medline, Scopus and Saudi Digital Library for articles published between January 1997 and February 2019. Studies conducted in the Region that reported barriers, facilitators, experiences, expectations and attitudes to shared decision-making were included. The MixedMethods Appraisal Tool (MMAT) was used to assess the methodological quality of the studies in this review. Results: Of the 1813 initial articles retrieved, 19 eligible articles were identified. The main factors that emerged were grouped under three broad themes: participant factors (patients/families and physicians); consultation factors (relation- ship between participants, engaging patients, evaluating preferences, introducing options, providing information, and decision making); and healthcare system factors (organizational characteristics, time constraints, continuity of care, and healthcare resources). Conclusions: There is growing interest in shared decision-making in several countries in the Region. However, there are many existing barriers that hinder the implementation of shared decision-making. These need to be addressed before shared decision-making can be fully adopted in these countries.

A rotary mechanism for allostery in bacterial hybrid malic enzymes.

Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux. Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA, a molecular indicator of the metabolic state of the cell. Here we solve the structure of a MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA) domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic enzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scale rearrangement that rotates the catalytic subunits 70° between the two states, identifying MaeB as a new model enzyme for the study of ligand-induced conformational change. Our work provides the mechanistic basis for metabolic control of hybrid malic enzymes, and identifies inhibition-insensitive variants that may find utility in synthetic biology.

Derivation and validation of a triage tool for acutely ill adults with suspected COVID-19: The PRIEST observational cohort study

ObjectivesWe aimed to derive and validate a triage tool, based on clinical assessment alone, for predicting adverse outcome in acutely ill adults with suspected COVID-19 infection. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. The primary outcome was death or organ support (respiratory, cardiovascular, or renal) by record review at 30 days. We split the cohort into derivation and validation sets, developed a clinical score based on the coefficients from multivariable analysis using the derivation set, and the estimated discriminant performance using the validation set. ResultsWe analysed 11773 derivation and 9118 validation cases. Multivariable analysis identified that age, sex, respiratory rate, systolic blood pressure, oxygen saturation/inspired oxygen ratio, performance status, consciousness, history of renal impairment, and respiratory distress were retained in analyses restricted to the ten or fewer predictors. We used findings from multivariable analysis and clinical judgement to develop a score based on the NEWS2 score, age, sex, and performance status. This had a c-statistic of 0.80 (95% confidence interval 0.79-0.81) in the validation cohort and predicted adverse outcome with sensitivity 0.98 (0.97-0.98) and specificity 0.34 (0.34-0.35) for scores above four points. ConclusionA clinical score based on NEWS2, age, sex, and performance status predicts adverse outcome with good discrimination in adults with suspected COVID-19 and can be used to support decision-making in emergency care. RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533

Prognostic accuracy of emergency department triage tools for adults with suspected COVID-19: The PRIEST observational cohort study

ObjectivesThe World Health Organisation (WHO) and National Institute for Health and Care Excellence (NICE) recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to estimate the accuracy of triage tools for predicting severe illness in adults presenting to the emergency department (ED) with suspected COVID-19 infection. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the United Kingdom (UK). We collected data from people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020, and used presenting data to determine the results of assessment with the following triage tools: the WHO algorithm, NEWS2, CURB-65, CRB-65, PMEWS and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome. ResultsWe analysed data from 20892 adults, of whom 4672 (22.4%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2614 (12.5%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point) 0.70; SFAHP (7-point) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.96 and 0.95 respectively), at the expense of specificity (0.31 and 0.27 respectively). NEWS2 showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used. ConclusionCURB-65, PMEWS and NEWS2 provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity. RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533

Prognostic accuracy of emergency department triage tools for children with suspected COVID-19: The PRIEST observational cohort study

ObjectivesEmergency department clinicians can use triage tools to predict adverse outcome and support management decisions for children presenting with suspected COVID-19. We aimed to estimate the accuracy of triage tools for predicting severe illness in children presenting to the emergency department (ED) with suspected COVID-19 infection. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 44 EDs across the United Kingdom (UK). We collected data from children attending with suspected COVID-19 between 26 March 2020 and 28 May 2020, and used presenting data to determine the results of assessment using the WHO algorithm, swine flu hospital pathway for children (SFHPC), Paediatric Observation Priority Score (POPS) and Childrens Observation and Severity Tool (COAST). We recorded 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome. ResultsWe collected data from 1530 children, including 26 (1.7%) with an adverse outcome. C-statistics were 0.80 (95% confidence interval 0.73-0.87) for the WHO algorithm, 0.80 (0.71-0.90) for POPS, 0.76 (0.67-0.85) for COAST, and 0.71 (0.59-0.82) for SFHPC. Using pre-specified thresholds, the WHO algorithm had the highest sensitivity (0.85) and lowest specificity (0.75), but POPS and COAST could optimise sensitivity (0.96 and 0.92 respectively) at the expense of specificity (0.25 and 0.38 respectively) by using a threshold of any score above zero instead of the pre-specified threshold. ConclusionExisting triage tools have good but not excellent prediction for adverse outcome in children with suspected COVID-19. POPS and COAST could achieve an appropriate balance of sensitivity and specificity for supporting decisions to discharge home by considering any score above zero to be positive. RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533

Characterisation of 22446 patients attending UK emergency departments with suspected COVID-19 infection: Observational cohort study

BackgroundHospital emergency departments play a crucial role in the Initial management of suspected COVID-19 infection. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results. MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22446 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. ResultsAdults were acutely unwell (median NEWS2 score 4) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.9%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Adult men and women presented in similar numbers (10210 versus 10506), but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.7% v 13.3%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to be admitted (60.8%, 57.3%, 69.6%) or die (11.9%, 11.2%, 16.8%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with confirmed COVID-19 had similar age and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.7% v 15.9%). ConclusionsImportant differences exist between patient groups presenting to the emergency department with suspected COVID-19. People with confirmed COVID-19 have a poor prognosis, compared with similar emergency admissions without confirmed COVID-19. RegistrationISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533

Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: Observational cohort study

BackgroundMeasurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19. MethodsWe undertook an observational cohort study across 70 emergency departments during first wave of the COVID-19 pandemic in the United Kingdom. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. ResultsWe analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% confidence interval 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were respectively 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019). ConclusionsPost-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19. RegistrationISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533 Key messagesWhat is already known on this subject? O_LIPost exertional decrease in oxygen saturation can be used to predict prognosis in chronic lung diseases C_LIO_LIPost exertional desaturation has been proposed as a way of predicting adverse outcome in people with suspected COVID-19 C_LI What this study adds: O_LIPost-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19 C_LI