COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Most people with COVID-19 have a mild to moderate respiratory illness; others experience severe illness, such as COVID-19 pneumonia. Formal diagnosis requires laboratory analysis of nose and throat samples, or imaging tests like CT scans. However, the first and most accessible diagnostic information is from symptoms and signs from clinical examination. If initial diagnosis by symptoms and signs were accurate, the need for time-consuming, specialist diagnostic tests would be reduced.
Symptoms are experienced by patients. People with mild COVID-19 might experience cough, sore throat, high temperature, diarrhoea, headache, muscle or joint pain, fatigue, and loss of sense of smell and taste. Symptoms of COVID-19 pneumonia include breathlessness, loss of appetite, confusion, pain or pressure in the chest, and high temperature (above 38 °C).
Signs are evaluated by clinical examination, and include lung sounds, blood pressure and heart rate.
Often, people with mild symptoms visit their doctor (primary care physician) for an initial diagnosis. People with more severe symptoms might visit a hospital outpatient or emergency department. Depending on their symptoms and signs, patients may be sent home to isolate, may receive further tests or be hospitalised.
Why is accurate diagnosis important?
Accurate diagnosis ensures that people receive the correct treatment quickly; are not tested, treated or isolated unnecessarily; and do not risk spreading COVID-19. This is important for individuals and saves time and resources.
What did we want to find out?
We wanted to know how accurate diagnosis of COVID-19 and COVID-19 pneumonia is in a primary care or hospital setting, based on symptoms and signs from medical examination.
What did we do?
We searched for studies that assessed the accuracy of symptoms and signs to diagnose mild COVID-19 and COVID-19 pneumonia. Studies could include people with possible COVID-19, or people known to have – and not to have – COVID-19. Studies had to be in primary care or hospital outpatient settings only and include at least 10 participants with any symptom or sign that might be COVID-19.
The included studies
We found 16 relevant studies with 7706 participants. The studies assessed 27 separate signs and symptoms, but none assessed combinations of signs and symptoms. Seven were set in hospital outpatient clinics (2172 participants), four in emergency departments (1401 participants), but none in primary care settings. No studies included children, and only one focused on older adults. All the studies confirmed COVID-19 diagnosis by the most accurate tests available.
The studies did not clearly distinguish mild to moderate COVID-19 from COVID-19 pneumonia, so we present the results for both conditions together.
The results indicate that at least half of participants with COVID-19 disease had a cough, sore throat, high temperature, muscle or joint pain, fatigue, or headache. However, cough and sore throat were also common in people without COVID-19, so these symptoms alone are less helpful for diagnosing COVID-19. High temperature, muscle or joint pain, fatigue, and headache substantially increase the likelihood of COVID-19 disease when they are present.
How reliable are the results?
The accuracy of individual symptoms and signs varied widely across studies. Moreover, the studies selected participants in a way that meant the accuracy of tests based on symptoms and signs may be uncertain.
All studies were conducted in hospital outpatient settings, so the results are not representative of primary care settings. The results do not apply to children or older adults specifically, and do not clearly differentiate between milder COVID-19 disease and COVID-19 pneumonia.
The results suggest that a single symptom or sign included in this review cannot accurately diagnose COVID-19. Doctors base diagnosis on multiple symptoms and signs, but the studies did not reflect this aspect of clinical practice.
Further research is needed to investigate combinations of symptoms and signs; symptoms that are likely to be more specific, such as loss of sense of smell; and testing unselected populations, in primary care settings and in children and older adults.
How up to date is this review?
The review authors searched for studies published from January to April 2020.
The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.
Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing.
To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia.
On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.
Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19.
Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias.
We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present.
Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies.
We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups.