Signs and symptoms of COVID-19: new Cochrane evidence

Sarah Chapman looks at a new Cochrane ReviewCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. on how useful signs and symptoms are for diagnosing COVID-19.

There can’t be many of us that haven’t given some thought to the symptoms of COVID-19, the infectious disease caused by a recently discovered coronavirus. I’ve been reporting my symptoms, or lack of them, through the COVID symptom study app, and have seen how the range of symptoms asked about has expanded over the weeks. In the early days of lockdown, I suddenly lost my sense of taste; soon afterwards, this was added to a list of possible symptoms of COVID-19. After weeks of especially missing being able to taste tea, I now have a renewed appreciation of my favourite drink, but I’m none the wiser about whether I’ve had COVID-19.

According to the NHS website (at the time of writing this) the main symptoms of coronavirus are a high temperature, a new, continuous cough and a loss or change to your sense of smell or taste. It states, “most people with coronavirus have at least 1 of these symptoms.” But do they? In fact, just this week it’s been reported that only 22% of people testing positive for coronavirus say they have symptoms on the day of their test, based on an Office for National Statistics (ONS) survey, though this was based on a small sample, making it hard to draw firm conclusions. Some of these may have had symptoms earlier, or gone on to get symptoms, while others never had symptoms.

It would seem that we can’t assume that if you don’t have one of those listed symptoms, or indeed any other, then you probably haven’t got it. If you do have one or more of those symptoms, do these point to COVID-19? These symptoms, more than others? What about combinations of symptoms too?

Why it’s important to be able to diagnose COVID-19

Timely, accurate diagnosis of COVID-19 in people who consult their GP or go to hospital with symptoms is important to ensure that the right things happen to the right people (appropriate treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. and isolation measures, for example) and that resources aren’t wasted. Symptoms, along with signs assessed by clinicians – such as heart rateThe speed or frequency of occurrence of an event, usually expressed with respect to time. For instance, a mortality rate might be the number of deaths per year, per 100,000 people., provide early clues to what might be wrong with someone. If we can use these reliably to make a diagnosis, that’s helpful, not least because it reduces the need for specialist tests.

New Cochrane evidence on signs and symptoms of COVID-19

 A Cochrane Review aimed to bring together evidence published between January and April 2020 on the accuracy of any signs and symptoms, either alone or in combination, for diagnosing COVID‐19.

Studies could be included if they recruited people with suspected COVID‐19, or known cases with COVID‐19 and controls without COVID‐19, in primary care (GP practices) or in hospital outpatient departments, including emergency departments. Studies with people who got COVID-19 while in hospital were excluded.

The review authors did a broad and systematic search for studies, both published research studies and those which had not yet been peer-reviewed.

Here’s what they found

The review includes 16 studies with 7706 people. There were no studies in primary care settings. The prevalenceThe proportion of a population who have a particular condition or characteristic. For example, the percentage of people in a city with a particular disease, or who smoke. of COVID‐19 disease varied from 5% to 38%. All the studies confirmed COVID‐19 diagnosis by the most accurate tests available.

The studies looked at 27 signs and symptoms in four categories: systemic (such as fever), respiratory, gastrointestinal and cardiovascular, but NO studyAn investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. assessed combinations of different signs. There was a lot of variation between studies in symptoms and in results.

At least half of people with COVID-19 were found to have a cough, sore throat, high temperature, muscle or joint pain, fatigue, or headache, in at least one study. But lots of people without COVID-19 also had a sore throat and/or a cough. High temperature, muscle or joint pain, fatigue, and headache may be more useful indicators as they “substantially increase the likelihood of COVID‐19 disease when they are present.”

However, the authors make it clear that this does not take us much further forward. They conclude that the individual signs and symptoms studied here appear to be a poor basis for diagnosing COVID-19 and that “neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease.”

The review authors note various problems with the studies. For example, five of them only included people who had pneumonia on imaging, so a very specific populationThe group of people being studied. Populations may be defined by any characteristics e.g. where they live, age group, certain diseases.. The studies varied a lot and it wasn’t possible to combine results, but this may be possible in future updates. This is a ‘living systematic review’ which will be updated as often as is feasible, to take account of new research as it emerges.

Evidence gaps

There are also big gaps in the evidence. Doctors base diagnosis on a combination of signs and symptoms but the studies, only looking at single signs or symptoms, haven’t reflected that. Let’s hope future studies will do this. Also that they will clearly differentiate between milder COVID‐19 disease and COVID‐19 pneumonia, which the studies included here did not do.

There is a great need for studies of children, with none at all here. The authors point out that children may be misdiagnosed with COVID-19, based on “predefined, but not yet evidence-based symptoms”, and required to isolate, with negative impacts associated with that. We also need studies on older adults; the studies included here did not report results separately for different age groups, and we need studies with people presenting to primary care.

Finally, we need to know about other symptoms, such as loss of sense of smell.

Looking ahead

Researchers across the world are working incredibly hard to provide evidence to advance our knowledge of COVID-19 and help us manage it, so let’s hope that this living systematic reviewA Living Systematic Review is a systematic review which is continually updated, incorporating relevant new evidence as it becomes available. can soon be updated with more and better studies, with new evidence on signs and symptoms that are more helpful for diagnosis. Meanwhile, we can continue to follow official health advice but keeping in mind that there are many continuing uncertainties.

Take-home points

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References (pdf).

Sarah Chapman has nothing to disclose.