About 2 million people in the UK have persistent symptoms after COVID infection, termed long COVID.
Commonly reported long COVID symptoms, such as fatigue and shortness of breath, have a significant effect on people’s daily activities, quality of life and capacity to work.
But long COVID symptoms are much broader than this. In a new study published in the journal Nature Medicine, we identified 62 symptoms associated with long COVID. We also explored some of the factors linked to an increased risk of developing long COVID.
Much of the initial work undertaken to understand long COVID has been among people who were hospitalised, but most people infected with COVID have been managed in primary care. We therefore know relatively little about long COVID in people with typically milder initial infections.
In our study, we analysed electronic primary care records from more than 450,000 people in England with a confirmed diagnosis of COVID, and 1.9 million people with no prior history of COVID, from January 2020 to April 2021. We matched both groups very closely in terms of their demographic, social and clinical characteristics. We then assessed the relative differences in the reporting of 115 symptoms to GPs. For those who had COVID, we measured this at least 12 weeks after they were infected.
We found that people who had been diagnosed with COVID were significantly more likely to report 62 symptoms, only 20 of which are included in the World Health Organization’s clinical case definition for long COVID.
Some of these symptoms were expected, like loss of sense of smell, shortness of breath and fatigue. But some of the symptoms that we found to be strongly associated with COVID beyond 12 weeks were surprising and less well known, such as hair loss and reduced libido. Other symptoms included chest pain, fever, bowel incontinence, erectile dysfunction and limb swelling.
These differences in symptoms reported between the infected and uninfected groups remained even after we accounted for age, sex, ethnic group, socioeconomic status, body mass index, smoking status, the presence of more than 80 health conditions, and past reporting of the same symptom.
We also found that younger age, female sex, belonging to certain ethnic minority groups, lower socioeconomic status, smoking, obesity, and a wide range of health conditions were all associated with a higher risk of reporting persistent symptoms more than 12 weeks after COVID infection.
A group of conditions
Given the breadth and diversity of long COVID symptoms reported in surveys, long COVID is unlikely to represent a single condition, but rather a group of distinct conditions that occur as a consequence of COVID infection. Exploring how long COVID symptoms are different in different groups could help scientists understand the different disease processes in the body that cause long COVID.
Our analysis suggests that long COVID can be characterised into three distinct groups based on clusters of symptoms reported. The largest group, consisting of roughly 80% of people with long COVID in our study, faced a broad spectrum of symptoms, ranging from fatigue, to headache, to pain. The second largest group, representing 15%, predominantly had mental health and cognitive symptoms, including depression, anxiety, brain fog and insomnia. The third and smallest group, capturing the remaining 5%, had mainly respiratory symptoms such as shortness of breath, cough and wheeze.
Where to from here?
We were only able to assess symptoms reported during GP consultations. Of course, not everyone will report symptoms to a doctor, so our study was restricted to comparing the differences in symptoms reported between people with and without a history of confirmed COVID. It’s also possible some patients in the comparison group had COVID, but either didn’t get tested or didn’t notify their GP.
Nonetheless, our research validates what people with long COVID have been saying right through the pandemic about the breadth and diversity of their symptoms. It also reinforces that their symptoms cannot simply be attributed to other factors such as existing health conditions, or the effects of stresses related to living through the pandemic.
To support the millions of people in the UK and around the world afflicted with the chronic health effects of long COVID, doctors and researchers need comprehensive tools to capture the symptoms of long COVID, to provide the best care.
Patients with long COVID need tailored health services which recognise that long COVID is not a single condition but a diverse group of overlapping conditions needing individualised care.
Meanwhile, we need clinical trials to evaluate potential treatments targeting the spectrum of long COVID symptoms, which could hopefully improve the quality of life for people with long COVID.
Shamil Haroon, Associate Clinical Professor, Institute of Applied Health Research, University of Birmingham and Anuradhaa Subramanian, Research fellow, Institute of Applied Health Research, University of Birmingham
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