SummarySTUDY AIMS: To quantify mimics and chameleons of coronavirus disease 2019 (COVID-19), to analyse the diagnostic accuracy of the triage protocol, and to describe the resulting groups of mimics and chameleons – including their presenting symptoms and final diagnoses.
METHODS: Diagnostic accuracy study including all adult patients tested for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) at the emergency department of the University Hospital Basel, Switzerland during the first wave of pandemic in spring 2020. Diagnostic accuracy of triage was determined by calculating sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio. Triage to the group of suspected (+) and not suspected (–) COVID-19 was considered the index test, whereas a SARS-CoV-2 polymerase chain reaction test result was used as reference standard. Mimics were defined as false positives and chameleons as false negatives.
RESULTS: Of 2898 patients included in the analysis, 191 were true positives, 895 were false positives (mimics), 9 were false negatives (chameleons) and 1803 were true negatives. This resulted in a sensitivity of 0.95 (95% confidence interval [CI] 0.92–0.98) and a specificity of 0.67 (95% CI 0.65–0.69) for standardised triage. Among mimics, the main categories of final diagnoses were other infections (n = 513, 57.3%), cardiovascular diseases (excluding cerebrovascular) (n = 125, 14%), and non-infectious diseases of the respiratory system (n = 84, 9.4%). Fever (n = 357, 39.9% vs n = 104, 54.5%), cough (n = 466, 52.1% vs n = 126 66%), and smell or taste dysfunction (n = 60, 6.7% vs n = 24, 12.6%) were less frequently observed in mimics than in COVID-19 patients. Eight of nine COVID-19 chameleons presented with either nonspecific complaints (weakness and/or fatigue) or gastrointestinal symptoms.
CONCLUSION: The quantitative assessment of COVID-19 mimics and chameleons showed a high prevalence of mimics. Clinical differentiation between true positives and false positives is not feasible due to largely overlapping symptoms. Prevalence of chameleons was very low.
IntroductionCoronavirus disease 2019 (COVID-19) poses a challenge to emergency physicians, as most patients present with suspected but not confirmed COVID-19 to emergency departments (EDs). Although severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a respiratory virus, different atypical complaints have been observed [1–4], including cardiovascular , neurological  and neuropsychiatric  symptoms and manifestations.
Therefore, the triage process is of utmost importance, and protocols focus on a high sensitivity regarding early isolation of COVID-19 patients – some including atypical complaints  and others focusing on the original clinical World Health Organization (WHO) definition of COVID-19 [9, 10]. Nonetheless, false positives (initially isolated, but ultimately tested negative) and false negatives (initially not isolated, but ultimately tested positive) are a hazard, even under the most conservative approaches. Such false positives and false negatives have been termed “mimics and chameleons of COVID-19” . However, no attempts to quantify mimics and chameleons have been made.
Trade-offs, such as the high cost of isolation of too many patients (due to overtriage) versus safety concerns of “usual care” in too many patients (due to undertriage) are evident.
We therefore aimed to quantify mimics and chameleons of COVID-19 under a triage protocol focusing on the typical presentation with respiratory symptoms , to analyse the results of this protocol and to describe the resulting groups of mimics and chameleons – including their presenting symptoms and final diagnoses.
Study design and settingThis was a diagnostic accuracy study performed as a secondary analysis of the prospective COronaVIrus surviVAl (COVIVA, ClinicalTrials.gov NCT04366765) trial. In the COVIVA cohort, we consecutively included adult patients presenting with suspected SARS-CoV-2 infection to the ED of the University Hospital of Basel, a tertiary care centre with approximately 54,000 annual ED visits, aiming to cover the first wave of COVID-19 pandemic. In addition, data on all patients tested for SARS-CoV-2 as a routine surveillance measure were analysed retrospectively using hospital electronic health records for the current analysis.
Population and inclusion criteriaAll patients aged 18 years and older presenting with suspected SARS-CoV-2 infection to the ED of the University Hospital in Basel, Switzerland, during the first wave of COVID-19 pandemic between 22 March 2020 and 7 June 2020, were eligible for inclusion in the COVIVA study. At triage, SARS-CoV-2 infection was suspected in any patient with breathlessness, other respiratory symptoms or influenza-like symptoms, such as fever (i.e., feeling feverish), chills, sore throat, cough, myalgia, headache . Patients were not yet systematically asked if they had any smell or taste dysfunction (hyposmia or anosmia or hypogeusia or ageusia), but all presenting symptoms were recorded prospectively. All olfactory and gustatory impairments were summarised as smell or taste dysfunction. Patients were either referred from the Triage and Test Centre  for further work-up, transported by paramedics, or directly presented to the ED (self-referrals). In some cases, patients might have been tested before presenting to the ED. However, these results were not available to study personnel.
Formal triage was performed with the Emergency Severity Index (ESI) and was conducted according to the local standard operating procedure as described in medStandards (www.medstandards.com) (see supplementary figure S1 in the appendix), based on the WHO definition , as modified by the Bundesamt für Gesundheit (BAG; Federal Office of Public Health). Disease severity was determined with the National Early Warning Score (NEWS). Patients with suspected COVID-19 were evaluated in a dedicated respiratory sector in the ED, where all patients underwent nasopharyngeal SARS-CoV-2 swab testing. Patients were considered COVID-19 positive cases if one or multiple SARS-CoV-2 polymerase chain reaction (PCR) swab tests performed on the day of ED presentation or within 14 days before or after ED presentation was positive, whereas patients with negative SARS-CoV-2 swab test results within that time frame were considered COVID-19 negative. Patients not suspected of COVID-19 received usual care in the ED, without isolation. However, patients not suspected of COVID-19 underwent nasopharyngeal swab SARS-CoV-2 PCR tests for screening purposes only if they were hospitalised or a clinician deemed a test necessary during work-up. If test results at ED presentation or during the subsequent hospitalisation were positive, the patients’ data were included in order to quantitate chameleons of COVID-19.
Data collectionAll patients suspected of COVID-19 included in the COVIVA cohort underwent a comprehensive clinical assessment by the treating ED physician according to local standard operating procedures. The patients’ management was left to the discretion of the attending ED physicians. Study personnel were not involved in the care of patients.
Follow-upThirty days after discharge, patients suspected of having COVID-19 were contacted by telephone calls or in writing by research physicians or study nurses, and information about current health, hospitalisations and adverse events were obtained, guided by a predefined set of questions and item-checklists. Records of hospitals and primary care physicians, as well as national death registries, were screened for additional information, if applicable.
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