key: cord-0714775-2csmifiz
authors: O'Reilly, Gerard M; Mitchell, Rob D; Mitra, Biswadev; Akhlaghi, Hamed; Tran, Viet; Furyk, Jeremy S; Buntine, Paul; Wong, Anselm; Gangathimmaiah, Vinay; Knott, Jonathan; Moore, Allison; Ahn, Jung Ro; Chan, Quillan; Wang, Andrew; Goh, Han; Loughman, Ashley; Lowry, Nicole; Hackett, Liam; Sri‐Ganeshan, Muhuntha; Chapman, Nicole; Raos, Maximilian; Noonan, Michael P; Smit, De Villiers; Cameron, Peter A
title: Outcomes for emergency department patients with suspected and confirmed COVID‐19: An analysis of the Australian experience in 2020 (COVED‐5)
date: 2021-08-13
journal: Emerg Med Australas
DOI: 10.1111/1742-6723.13837
sha: d9bbc87964980b4484f94ba0c734b23bc2dbe7e6
doc_id: 714775
cord_uid: 2csmifiz

OBJECTIVE: The aim of the present study was to describe the characteristics and outcomes of patients presenting to Australian EDs with suspected and confirmed COVID‐19 during 2020, and to determine the predictors of in‐hospital death for SARS‐CoV‐2 positive patients. METHODS: This analysis from the COVED Project presents data from 12 sites across four Australian states for the period from 1 April to 30 November 2020. All adult patients who met local criteria for suspected COVID‐19 and underwent testing for SARS‐CoV‐2 in the ED were eligible for inclusion. Study outcomes were mechanical ventilation and in‐hospital mortality. RESULTS: Among 24 405 eligible ED presentations over the whole study period, 423 tested positive for SARS‐CoV‐2. During the ‘second wave’ from 1 July to 30 September 2020, 26 (6%) of 406 SARS‐CoV‐2 patients received invasive mechanical ventilation, compared to 175 (2%) of the 9024 SARS‐CoV‐2 negative patients (odds ratio [OR] 3.5; 95% confidence interval [CI] 2.3–5.2, P < 0.001), and 41 (10%) SARS‐CoV‐2 positive patients died in hospital compared to 312 (3%) SARS‐CoV‐2 negative patients (OR 3.2; 95% CI 2.2–4.4, P = 0.001). For SARS‐CoV‐2 positive patients, the strongest independent predictors of hospital death were age (OR 1.1; 95% CI 1.1–1.1, P < 0.001), higher triage category (OR 3.5; 95% CI 1.3–9.4, P = 0.012), obesity (OR 4.2; 95% CI 1.2–14.3, P = 0.024) and receiving immunosuppressive treatment (OR 8.2; 95% CI 1.8–36.7, P = 0.006). CONCLUSIONS: ED patients who tested positive for SARS‐CoV‐2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.

• For this report from the COVED Project, data was available for 24 405 eligible patients (tested for SARS-CoV-2 in the ED) from 12 sites across four Australian states for the period from 1 April to 30 November 2020, of which 423 were SARS-CoV-2 positive. • ED patients who tested positive for SARS-CoV-2 had higher odds of mechanical ventilation and death in hospital. • The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.

presenting to Australian EDs with suspected and confirmed COVID-19 during 2020, and to determine the predictors of in-hospital death for SARS-CoV-2 positive patients.

Methods: This analysis from the COVED Project presents data from 12 sites across four Australian states for the period from 1 April to 30 November 2020. All adult patients who met local criteria for suspected COVID-19 and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes were mechanical ventilation and in-hospital mortality. Conclusions: ED patients who tested positive for SARS-CoV-2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.

The COVID-19 pandemic continues to have a global impact. Increasingly, 'variants of concern' are precipitating further waves of infection, leading to significant morbidity and mortality. [1] [2] [3] While Australia has been relatively successful in containing the spread of the virus, sporadic outbreaks continue to place pressure on the healthcare system. [4] [5] [6] For Australian EDs, the cycle of intermittent regional surges has necessitated the ongoing use of rigorous infection prevention and control (IPC) precautions. This continues to impact the delivery of emergency care, particularly for patients who meet case definition criteria for COVID-19 and require SARS-CoV-2 testing and isolation in the ED. [6] [7] [8] [9] In this context, there is a persisting need for data regarding the epidemiology and outcomes of patients with suspected and confirmed COVID-19. Understanding the clinical predictors of severe disease can help inform clinical care and disposition decisions. 10 The COVID-19 ED (COVED) Quality Improvement Project was initiated in April 2020 to inform clinical decision making and system reforms in Australian EDs. 11 COVED-1 and COVED-2, which coincided with Australia's 'first wave', demonstrated a low positive test rate, with no SARS-CoV-2 positive patients receiving mechanical ventilation or dying in the ED of the single participating site. 12, 13 These studies also identified a high number of patients meeting case definition criteria and requiring isolation. 12, 13 COVED-3 reported data across eight EDs during July 2020, and revealed no difference in the rates of mechanical ventilation and in-hospital death between SARS-CoV-2 positive and negative patients. The main clinical predictors of a COVID-19 diagnosis were subjective fever, bilateral infiltrates on chest X-ray (CXR), non-smoking status and absence of leucocytosis. 14 COVED-4 reported data from 12 EDs in four Australian states across July and August 2020. 6 While the casepositivity rate remained relatively low, COVED-4 established that patients who were SARS-CoV-2 positive on ED testing were more likely than SARS-CoV-2 negative patients to require mechanical ventilation and/or die in hospital. Similar to COVED-3, strong clinical predictors of a positive SARS-CoV-2 test result were self-reported fever, bilateral infiltrates on CXR, absence of leucocytosis and sore throat. 6 The aim of the present study was to describe the ED experience of COVID-19 in Australia during 2020. Specifically, COVED-5 reports the epidemiology and outcomes of patients presenting to Australian EDs with suspected COVID-19, and, for the first time, establishes the predictors of in-hospital death among patients who return a positive SARS-CoV-2 test result.

The COVED Project is a prospective cohort study that commenced on 1 April 2020. The research protocol has been published previously. 11 The study includes adult patients who had a SARS-CoV-2 polymerase chain reaction (PCR) test requested in the ED and were managed with IPC precautions for 'suspected COVID-19'. Testing criteria were guided by the various health jurisdictions, and have evolved throughout the Project. These have been summarised in previous COVED publications. 6, 14 This analysis (COVED-5) describes study findings for eligible patients who presented to the 12 participating EDs (The Alfred Hospital, St Vincent's Hospital Melbourne, Austin Hospital, Box Hill Hospital, The Royal Melbourne Hospital, University Hospital Geelong, Royal Hobart Hospital, Launceston General Hospital, North-West Regional Hospital, Mersey Community Hospital, Sutherland Hospital Sydney and Townsville University Hospital) over the 8-month period from 1 April to 30 November 2020. The Project's study sites represent a mixture of urban and regional EDs across Victoria, Tasmania, New South Wales and Queensland, and commenced participation in the COVED Project at different stages during 2020 (Table 1 ). In all of these locations, alternative non-ED testing sites (e.g. screening clinics) were in operation for those with minor symptoms who did not require emergency care. Patients who presented to these clinics and were not assessed in the ED were excluded from the present study.

The present study (COVED-5) analysed the demographic and ED arrival data for the period 1 April to 30 November 2020. It then compared the outcomes of mechanical ventilation and death between SARS-CoV-2 positive and negative patients (based on ED testing) during Australia's second wave, defined as 1 July to 30 September 2020. These dates were selected on the basis of a markedly increased frequency of SARS-CoV-2 positive test results during this period. For those patients who were SARS-CoV-2 positive on ED testing, COVED-5 then investigated the associations between in-hospital death and a range of ED-relevant clinical variables, as listed in the COVED protocol. 11 Finally, the study identified variables to be included in a model predicting death for patients who tested positive for SARS-CoV-2 in the ED. All variables for which a univariable association with in-hospital death was demonstrated were candidates for model inclusion.

Stepwise multivariable logistic regression was performed to arrive at the final prediction model.

Administrative and clinical data for study participants were collected from hospital electronic medical record (EMR) systems. Some variables were automatically extracted from data warehouses, however all sites relied on some degree of manual record review. Data have been entered into a novel COVED Registry utilising Research Electronic Data Capture (REDCap) tools, hosted and managed by Helix (Monash University). 15, 16 Symmetrical numerical data have been summarised using the mean and standard deviation; skewed and ordinal data have been summarised using the median and interquartile range; and categorical data have been summarised using frequency and percentage. Data were analysed using Stata statistical software (version 15.1; StataCorp, College Station, TX, USA). A P-value of <0.05 was defined to be statistically significant. Ethics approval was obtained from the Alfred Human Research Ethics Committee (Project No: 188/20).

During the study period, there were 24 405 patient presentations to the participating EDs that met inclusion criteria and were available for analysis. Of these, 423 patients returned a positive SARS-CoV-2 test result and 23 982 were negative. The dates and case numbers for the data submitted from each site are summarised in Table 1 . Table 2 summarises the baseline demographic and ED arrival characteristics of included patients for both the overall study period (1 April to 30 November 2020) and the 'second wave' study period (1 July to 30 September 2020). There were no statistically significant differences in the distribution of age, sex, mode of arrival or triage category between SARS-CoV-2 positive and negative patients.

Patient outcomes for the period 1 July to 30 September 2020, representing Australia's second wave, are summarised in Table 3 Table 4 describes the ED-relevant clinical features of the patients who were subsequently confirmed as SARS-CoV-2 positive on ED testing, comparing those who died in hospital to those who survived to hospital discharge. This analysis was conducted over the whole study period of 1 April to 30 November 2020. There was a statistically significant univariable association between hospital death and age (OR 1.1; 95% CI 1.1-1.1, P < 0.001). The strength of this association is further illustrated in Figure 1 ; specifically, there were no deaths among patients less than 50 years of age testing positive to SARS-CoV-2 in the ED. SARS-CoV-2 ED patients who were assigned a triage category of 1 or 2 (OR 3.7; 95% CI 2.0-7.1, P < 0.001) or presented from a residential aged care facility (OR 9.1; 95% CI 3.9-21.2, P < 0.001) had greater odds of death in hospital. Comorbidities associated with death were obesity (OR 3.2; 95% CI 1.2-8.4, P = 0.02), a chronic cardiac condition (OR 6.0; 95% CI 2.7-13.3, P < 0.001), chronic hypertension (OR 4.3; 95% CI 1.9-9.8, P < 0.001) and receiving immunosuppressive treatment (OR 3.6; 95% CI 1.1-12.3, P = 0.04). There was a statistically significant association between death in hospital and oxygen saturation (OR 0.9; 95% CI 0.9-1.0, P = 0.01), an increased white blood cell count (OR 1.1; 95% CI 1.0-1.2, P = 0.04), and thrombocytopaenia (OR 2.4; 95% CI 1.0-5.8, P = 0.04).

For those variables that demonstrated a univariable association between in-hospital death and a positive SARS-CoV-2 test result, Table 4 also provides the corresponding positive and negative likelihood ratios and summarises the parameters of a clinical prediction model for death in hospital. The final set of four clinical variables in the COVED model for predicting death in hospital were age, triage category of 1 or 2, obesity and receiving immunosuppressive treatment.

The COVED Project represents the largest dataset of patients with suspected and confirmed COVID-19 in Australian EDs. The present study, COVED-5, provides: a summary of the demographics and baseline data for suspected and confirmed cases over the 8-month period between 1 April and 30 November 2020; a comparison of deaths and mechanical ventilation during Australia's second wave; and an analysis of the main determinants and predictors of death in hospital among SARS-CoV-2 positive patients.

Compared to SARS-CoV-2 negative patients, SARS-CoV-2 positive patients presenting to an ED were more likely to require mechanical ventilation or die in hospital. This confirms previous data regarding the increased risk of poor outcomes among patients with COVID-19, relative to other ED patients with similar symptoms. 6 Tables 3 and 4 Variable 1 July to 30 September 2020 (Table 3) 1 April to 30 November 2020 (Table 4) SARS Among patients who tested positive for SARS-CoV-2 in an ED, the odds of dying in hospital increased with age, being resident in an aged care facility, a triage assignment of category 1 or 2, lower oxygen saturations on arrival, obesity, receiving immunosuppressive treatment, thrombocytopaenia, a higher white blood cell count and a history of cardiac disease. The strongest model for predicting death combined the following risk factors: age, triage category of 1 or 2, obesity and receiving immunosuppressive therapy.

A reasonable interpretation of this COVED death prediction model is that age captures the univariable association with chronic cardiac conditions, hypertension and living in a residential aged care facility, but not the independent associations with obesity nor receiving immunosuppressive treatment. Similarly, triage effectively captures patients who are subsequently confirmed as being hypoxic. It is important to note that each of these variables independently contributes to an increased odds of death in hospital. For example, adjusted for age, there is an independent increase in the odds of death in hospital from being obese, receiving immunosuppressive treatment or having a high triage assignment.

These results are broadly consistent with the findings of overseas analyses, particularly in relation to the association of age, obesity and co-morbidities with poor outcomes. 10, [17] [18] [19] [20] [21] Globally, a large number of studies have used data of this nature to derive and validate COVID-19 severity prediction tools. A living systematic review has identified more than 100 prognostic models, 19 including the 4C mortality score and the QCOVID living risk prediction algorithm. 17, 18 Specific severity rules have also been developed for ED populations, including the Quick COVID-19 Severity Index and PRIEST score. 10, 22, 23 In addition to these de novo approaches, the performance of existing pneumonia and sepsis assessment tools has been assessed. 10, 24, 25 In general, these instruments rely heavily on clinical data, such as vital signs, to calculate the risk of severe disease. A recent study using data from 70 EDs in the UK suggests that the combination of the NEWS2 scoring system and demographic data (age, sex and performance status) can identify patients at risk of adverse outcomes with a high degree of sensitivity. 10 Until now, the low number of COVID-19 cases in the COVED registry had prohibited this type of analysis. COVED-5, therefore, provides the first local data in relation to the risk of poor outcomes for Australian patients testing positive for SARS-CoV-2 in the ED. This is highly relevant given the substantial global variation in COVID-19 experience to date, and Australia's relatively unique position in the world.

There are several considerations important to the interpretation of the present study. First, for several participating sites, data on SARS-CoV-2 negative patients were not available (Table 1 ). Second, as described in Table 4 , multiple clinical (presenting complaint and comorbidity) variables were missing more than 20% of observations. Third, the COVED Project's inclusion criteria remain defined by being tested for SARS-CoV-2 in the ED. Fourth, some of the data used in the previous analyses (COVED studies 1 to 4) have been incorporated into this overarching cumulative analysis of an expanded dataset (8 months and 12 EDs). Fifth, some of the clinical variables capturing presenting complaint, co-morbidities and clinical examination were necessarily subjective in definition, including obesity and receiving immunosuppressive treatment. Sixth, the findings of COVED-5 cannot be separated from the existing public health context over much of the study period; strict lockdowns where almost half of the participating EDs are situated (i.e. Melbourne, Australia) will have been a factor in the case-mix of ED presentations and generalisability of the results. Specifically, that no-one aged less than 50 years died from SARS-CoV-2 in the present study precludes any detailed analysis of risk factors for death in this age group. Finally, the present study does not describe the characteristics and outcomes of patients presenting to Australian EDs with the Delta variant of SARS-CoV-2, which has been associated with higher rates of hospitalisation. 3 This 'variant of concern' is now emerging as the predominant strain worldwide, including in Australia. 1, 4 Further research is required to define how infection with the Delta variant influences disease progression and outcomes among patients presenting to the ED.

Notwithstanding these considerations, COVED-5 provides important information on the outcomes of Australian ED patients who test positive for SARS-CoV-2. The findings will inform clinical judgement and decision-making regarding the goals, location, processes and systems of care for patients with suspected and confirmed COVID-19.

Among patients with suspected COVID-19 presenting to Australian EDs, those testing positive to SARS-CoV-2 had higher odds of mechanical ventilation and death in hospital compared with SARS-CoV-2 negative patients. For SARS-CoV-2 positive patients, age, triage category, obesity and immunosuppressive treatment were predictive of inhospital death. These findings will help inform clinical decisions and processes in Australian EDs. AUROC, area under the receiver operating characteristic curve; CI, confidence interval; IQR, interquartile range; OR, odds ratio; SBP, systolic blood pressure; WCC, white blood cell count.

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GMOR is currently a NHMRC Research Fellow at the National Trauma Research Institute, Alfred Hospital, Melbourne, Australia, leading the project titled: 'Maximising the usefulness and timeliness of trauma and emergency registry data for improving patient outcomes' (GNT1142691 

GMOR, BM, VT and PAC are section editors for Emergency Medicine Australasia.

Ethics approval was obtained from the Alfred Human Research Ethics Committee (Project No: 188/20) on 26 March 2020 and approved as a multi-site project (63444) on 9 April 2020. The requirement for patient consent was waived.

Data that support the findings of this study may be available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.