Evidence published in The Lancet suggests that one in eight adults (12.7%) infected with SARS-CoV-2 experience long COVID symptoms.
The study, which was performed in the Netherlands, is one of the first to analyse long COVID symptoms with symptoms in an uninfected population, also examining symptoms in people pre- and post-COVID-19 infection.
Professor Judith Rosmalen, the lead author of the study from the University of Groningen, said: “There is an urgent need for data informing the scale and scope of the long-term symptoms experienced by some patients after COVID-19 illness. However, most previous research into long COVID has not looked at the frequency of these symptoms in people who haven’t been diagnosed with COVID-19 or looked at individual patients’ symptoms before the diagnosis of COVID-19.
“Our study approach looks at the symptoms most often associated with long COVID, including breathing problems, fatigue and loss of taste and/or smell, both before a COVID-19 diagnosis and in people who have not been diagnosed with COVID-19. This method allows us to take pre-existing symptoms and symptoms in non-infected people into account to offer an improved working definition for long COVID and provide a reliable estimate at how likely long COVID-19 is to occur in the general population.”
Analysing the Lifelines COVID-19 Cohort
For their investigation, the researchers asked participants of the population-based Lifelines COVID-19 Cohort in the Netherlands to complete regular questionnaires on the 23 common long COVID symptoms. Between March 2020 and August 2021, the questionnaire was sent out 24 times.
This means participants who were infected during this period had the alpha-variant or earlier variants. Additionally, the data was collected before the vaccine rollout in the country, so the number of vaccinated participants was too small to analyse.
People were classified as COVID-10 positive if they had a test or a doctor’s diagnosis of the disease. Of the 76,422 participants, 4,231 had COVID-19 and were matched to 8,462 controls, matching for age, sex, and time of completing questionnaires.
One in eight adults develop long COVID symptoms
The team discovered that various long COVID symptoms were new or more severe between three and five months after the initial COVID-19 infection, compared to symptoms before a COVID-19 diagnosis and in the control group, meaning these symptoms can be viewed as the core long COVID symptoms.
Core long COVID symptoms included chest pain, difficulties breathing, pain when breathing, painful muscles, loss of taste and/or smell, tingling hands/feet, a lump in the throat, alternately feeling hot and cold, heavy arms and/or legs and general tiredness.
These symptoms’ severity plateaued three months following the initial infection with no further decline. Other symptoms that did not significantly increase between three and five months following a COVID-19 diagnosis included headache, itchy eyes, dizziness, back pain, and nausea.
Aranka Ballering, the first author of the study, commented: “These core symptoms have major implications for future research, as these symptoms can be used to distinguish between post-COVID-19 condition and non-COVID-19-related symptoms.”
The researchers observed that 21.4% of the COVID-19-positive participants who had submitted pre-COVID symptom data experienced at least one increased core symptom at moderate severity after three months or more following initial infection compared to 8.7% of the control group. This indicates that new or severely increased symptoms three months post-COVID can be linked to COVID-19 infection in 12.7% of patients.
Aranka Ballering added: “By looking at symptoms in an uninfected control group and in individuals both before and after SARS-CoV-2 infection, we were able to account for symptoms which may have been a result of non-infectious disease health aspects of the pandemic, such as stress caused by restrictions and uncertainty.
“Post-COVID-19 condition, otherwise known as long COVID, is an urgent problem with a mounting human toll. Understanding the core symptoms and the prevalence of post-COVID-19 in the general population represents a major step forward for our ability to design studies that can ultimately inform successful healthcare responses to the long-term symptoms of COVID-19.”
Study limitations
Limitations of the study included that there was no data from patients infected with the delta or omicron variants and that asymptomatic infection may have caused the prevalence of COVID-19 to be underestimated. Moreover, other symptoms such as brain fog have been identified as potentially relevant long COVID symptoms but were looked at during this study. Additionally, the research was performed in one region and did not include an ethnically diverse population.
Professor Rosmalen concluded: “Future research should include mental health symptoms (e.g., depression and anxiety symptoms), along with additional post-infectious symptoms that we could not assess in this study (such as brain fog, insomnia, and post-exertional malaise). We were unable to investigate what might cause any of the symptoms observed after COVID-19 in this study, but we hope future research will be able to give insights into the mechanisms involved.
“Furthermore, due to the timing of this study, we were unable to assess the effect of COVID-19 vaccination and different SARS-CoV-2 variants on long COVID symptoms. We hope future studies will provide answers on the impacts of these factors.”
