Predicting Death and ICU Admission in COVID-19 Patients in ED
Predicting Death and ICU Admission in COVID-19 Patients in ED
INTRODUCTION. The novel coronavirus designated SARS-CoV-2, has determined an international
 outbreak of respiratory illness named Covid-19. Patients with Covid-19 present primarily with
 fever, myalgia or fatigue, and dry cough. Based on available data from 5% to 10% among
 hospitalized patients will require ICU admission.

 In this context of overflow of critically ill patients, it is mandatory to establish clear
 and objective criteria to assess and predict a Covid-19 patient's need for ICU admission, and
 potentially predict death occurrence. Early Warning Scores (EWS) are used in hospitalized
 patients to predict clinical deterioration. Several study demonstrate the utility of EWS in
 ED to predict patient outcome.

 AIM. The objective of this study is to evaluate five EWSs, to predict the need for ICU
 admission and the mortality in patients admitted in ED with COVID-19.

 METHODS. This is a single-center, retrospective observational study. We will review the
 clinical records of all the patients consecutively admitted to our ED for Covid-19 over a
 three-weeks period (March 1 to 21, 2020). We will exclude from study cohort patients aged <18
 years old and pregnant women, and patients already on oro-tracheal intubation at ED arrival.
 Based on clinical records five EWS will be calculated: NEWS, NEWS2, qSOFA, MEWS, REMS.

 Study endpoints. The primary study endpoints will be death at 7 days, and need for ICU at 7
 days, since ED admission. As secondary endpoints we will evaluate need for ICU and death at
 24 and 48 hours since ED admission.

 Statistical Analysis Receiver operating characteristic (ROC) curve analysis will be used to
 evaluate the overall performance of the selected EWSs in predicting the defined adverse
 outcomes. According to Youden's index we will estimate the optimal cut-off points and
 corresponding sensitivity and specificity at selected score threshold values. The comparison
 between the ROC AUCs will be made according to DeLong method.
INTRODUCTION After the first cases identified in Wuhan city (China) on December 2019, the
 novel coronavirus designated SARS-CoV-2 has caused a global epidemic of respiratory illness
 named COVID-191. To date, more than, 3,000,000 cases have been reported worldwide, including
 more than 300,000 deaths.

 Typical COVID-19 patients present with fever, myalgia or fatigue, and dry cough. Severe cases
 progress to severe dyspnoea and hypoxemia within one week after the onset of symptoms 3-5. In
 hospitalized COVID-19 patients, the prevalence of hypoxemic respiratory failure is around
 20%, and more than 25% of them may require intensive care treatment.

 The increasing number of COVID-19 cases has challenged the healthcare systems worldwide.
 Given the current overflow of critically ill patients in the Emergency Departments (EDs), an
 early identification of patients who need admittance to an intensive care unit (ICU) because
 of an increased risk of unfavourable outcome is necessary. Although general guidelines for
 ICU admission and triage exist, only limited guidance is available for the specific setting
 of COVID-19 patients.

 In this context of overwhelming demand for medical assessment and triage in ED, early warning
 scores (EWS) may be useful. EWS are based on a rapid and quantitative assessment of changes
 in vital signs, and were developed to identify and track patients at risk of deterioration in
 non-critical areas of the hospital in order to ensure an early stabilisation and ICU transfer
 when appropriate and prevent avoidable cardiac arrest. However, in recent years these scores
 have been used in ED to predict ICU admission and mortality. Use of EWS has recently been
 proposed for the triage of COVID-19 patients in ED. However, their usefulness has not been
 demonstrated yet.

 METHODS Study design This is a retrospective observational study conducted in the ED of the
 largest urban teaching hospital in Rome, a referral center for COVID-19 in central Italy. The
 participants reviewed the electronic medical records (EMR) of all adults (>18y) patients
 admitted to ED for suspected COVID-19 over three consecutive weeks from March 1 to March 21,
 2020, tested for COVID-19 according to the WHO interim guidance.

 Inclusion and exclusion criteria Study will include only patients whose diagnosis is
 confirmed with real-time reverse-transcriptase-polymerase-chain-reaction assay of nasal and
 pharyngeal swab specimens.

 Will be excluded from the study cohort pregnant women, patients discharged from ED with
 normal chest x-ray findings, and patients who were already mechanically ventilated on ED
 arrival. For patients with more than one access to our ED, only the latest access will be
 included in the analysis.

 Study variables The following information will be extracted from digital clinical records:
 age, sex, clinical history and presentation, temperature, heart rate (HR), respiratory rate
 (RR), arterial blood pressure (BP), Glasgow Coma Scale (GCS) score, oxygen therapy,
 peripheral oxygen saturation (SpO2), and chest x-ray findings.Clinical signs, including SpO2,
 will be assessed on arrival at the ED. National Early Warning Score (NEWS), National Early
 Warning Score 2 (NEWS2), Quick Sepsis Related Organ Failure Assessment (qSOFA), Modified
 Early Warning Score (MEWS), and Rapid Emergency Medicine Score (REMS) will be calculated for
 each patient. For NEWS2 calculation, patient will be considered at risk of type 2 respiratory
 failure if had a confirmed history of chronic obstructive pulmonary disease (COPD).

 Study endpoints The primary study endpoints considered will be death or ICU admission within
 7 days from arrival at the ED. Secondary endpoints will be death or ICU admission within 24
 and 48 hours from ED arrival.

 Criteria for ICU admission The criteria for ICU admission of COVID-19 patients in include
 need for invasive respiratory support, or extra-pulmonary organ failure such as circulatory
 shock requiring vasopressors, or renal failure. These criteria are expected to be consistent
 throughout the study period.

 Statistical Analysis and sample size Continuous variables will be reported as median
 [interquartile range], and will be compared at univariate analysis by Mann-Whitney U test.
 Categorical variables will be reported as absolute number (percentage), and will be compared
 by Chi-square test (with Fisher's test if appropriate).

 Receiver operating characteristic (ROC) curve analysis will be used to estimate the overall
 performance of the evaluated scores in predicting the defined adverse outcomes. For each
 score threshold values will be calculated sensitivity, specificity, positive predictive value
 (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative
 likelihood ratio (-LR). The Youden index will be used to estimate the optimal cut-off points
 for sensitivity and specificity. The comparison between the ROC AUCs will be made according
 to DeLong method. A p value ≤ 0.05 will be regarded as significant. Data will be analyzed by
 IBM SPSS statistics v25® (IBM, IL, USA).

 Sample size. For a correct estimation of ROC Curve a minimum of 50 patients for each endpoint
 should be included in the analysis. Given the estimate flow of at least 300 COVID-19
 confirmed patients in the study period, and the actual rate of ICU admission in these
 patients (about 20%), the sample should be adequate for statistical estimation.

 Aim of the study The objective of the present study is to assess the ability of EWS to
 predict ICU admission and mortality in COVID-19 patients in the emergency department.

 Ethical considerations All the patients accessing the "COVID" ED signs a comprehensive
 ethical agreement for collection of blood samples and clinical data, for bio-bank and
 research purposes (Informative mod 147 25/06/2019).
Inclusion Criteria:

 -  COVID 19 confirmed patients.

 Exclusion Criteria:

 -  <18 years

 -  Pregnant women

 -  Asymptomatic and normal x-ray findings subjects