Summary
Background
Patients often report various symptoms after recovery from acute COVID-19. Previous studies on the post-COVID-19 condition have not addressed the prevalence and severity of these common symptoms before COVID-19 and in populations without SARS-CoV-2 infection.
Our objective was to analyze the nature, prevalence and severity of long-term symptoms related to COVID-19, while correcting symptoms present before SARS-CoV-2 infection and monitoring symptom dynamics in the population without infection.
Methods
This study is based on data collected in Lifelines , a multidisciplinary, prospective, population-based observational cohort study examining the health and health-related behaviors of people living in the north of the Netherlands. All Lifelines participants over the age of 18 received invitations to the digital COVID-19 questionnaires.
The longitudinal dynamics of 23 somatic symptoms surrounding COVID-19 diagnoses (due to the SARS-CoV-2 alpha [B.1.1.7] variant or earlier variants) were assessed using 24 repeated measurements between March 31, 2020 and August 2, 2021.
Participants with COVID-19 (a positive SARS-CoV-2 test or a medical diagnosis of COVID-19) were age-, sex-, and time-matched to COVID-19-negative controls. We recorded symptom severity before and after COVID-19 in participants with COVID-19 and compared it with matched controls.
Results
A total of 883,973 questionnaires were completed by 76,422 participants (mean age 53·7 years [SD 12·9], 46,329 [60·8%] were women). Of these, 4231 (5·5%) participants had COVID-19 and were matched with 8462 controls.
Persistent symptoms in COVID-19 positive participants between 90 and 150 days after COVID-19 compared to before COVID-19 and compared to matched controls included: chest pain, shortness of breath, pain when breathing, pain muscle, ageusia or anosmia, tingling in the extremities, lump in the throat, feeling of heat and cold alternately, heavy arms or legs and general tiredness .
In 12.7% of patients, these symptoms could be attributed to COVID-19, as 381 (21.4%) of 1,782 COVID-19-positive participants versus 361 (8.7%) of 4,130 negative controls for COVID-19 had at least one of these major symptoms increased substantially to at least moderate severity between 90 and 150 days after COVID-19 diagnosis or the coinciding time point.
Interpretation
To our knowledge, this is the first study to report the nature and prevalence of the condition post-COVID-19, while correcting for individual symptoms present before COVID-19 and symptom dynamics in the population without SARS-CoV-2 infection during the pandemic. More research is required that distinguishes potential mechanisms driving post-COVID-19-related symptomatology.
Comments
A Dutch study reports on the prevalence of long-term COVID symptoms in adults. The researchers compared the frequency of new or severely increased symptoms in an uninfected population with people who had been diagnosed with COVID-19, allowing for a more reliable estimate of the prevalence of long COVID than in previous studies.
Of adults who had COVID-19, 21.4% experienced at least one new or severely increased symptom three to five months after infection compared to before infection, compared to 8.7% of uninfected people followed over the same time period, suggesting one in eight COVID-19 patients (12.7%) in the general population experience long-term symptoms due to COVID-19.
The study also looked at people’s symptoms before and after SARS-CoV-2 infection. This made it possible to identify the core symptoms of long COVID: chest pain, difficulty breathing, pain when breathing, muscle pain, loss of taste and smell, tingling in the extremities, lump in the throat, sensation of hot and cold, heaviness in arms and/or legs, and general fatigue.
One in eight adults (12.7%) infected with SARS-CoV-2 experience long-term symptoms due to COVID-19, suggests a large Dutch study published in The Lancet .
The study provides one of the first comparisons of long-term symptoms after SARS-CoV-2 infection (often called ’long COVID’ ) with symptoms in an uninfected population, in addition to measuring symptoms in individuals before and after of COVID-19. 19 infection. Inclusion of uninfected populations allows for more accurate prediction of the prevalence of long-term COVID-19 symptoms, as well as better identification of the core symptoms of long COVID.
“There is an urgent need for data that informs the scale and extent of long-term symptoms experienced by some patients following COVID-19 illness.” says Professor Judith Rosmalen from the University of Groningen, lead author of the study. “However, most previous research on long COVID has not looked at the frequency of these symptoms in people who have not been diagnosed with COVID-19 nor has it looked at the symptoms of individual patients before COVID-19 diagnosis.”
Professor Rosmalen continues: “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 as in people who have not been diagnosed with COVID-19. “This method allows us to take into account pre-existing symptoms and symptoms in uninfected people to offer an improved working definition for long COVID and provide a reliable estimate of the probability of COVID-19 lasting in the general population.”
The researchers found that several symptoms were new or more severe three to five months after having COVID-19, compared to symptoms before a COVID-19 diagnosis and to the control group, suggesting that these symptoms may be seen as the core symptoms of long COVID.
The core symptoms recorded were chest pain, difficulty breathing, pain when breathing, muscle pain, loss of taste and/or smell, tingling in hands/feet, lump in throat, alternating sensation of heat and cold, heaviness in arms and /or legs and general fatigue . The severity of these symptoms stabilized at three months after infection and did not decrease further. Other symptoms that did not increase significantly three to five months after a COVID-19 diagnosis included headache, itchy eyes, dizziness, back pain and nausea.
PhD candidate and first author of the study, Aranka Ballering, says: "These core symptoms have important implications for future research, as these symptoms can be used to distinguish between the post-COVID-19 condition and non-COVID-related symptoms. 19".
Of study participants who had pre-COVID symptom data, researchers found that 21.4% (381/1,782) of COVID-19-positive participants, compared to 8.7% (361 /4130) of the control group, experienced at least an increase in core symptoms of moderate severity 3 months or more after SARs-CoV-2 infection. This implies that in 12.7% of COVID-19 patients, their new or severely increased symptoms three months after COVID-19 can be attributed to SARS-CoV-2 infection.
Aranka Ballering adds: “By looking at symptoms in an uninfected control group and in individuals before and after SARS-CoV-2 infection, we were able to explain symptoms that may have been the result of health aspects of non-infectious diseases. of the pandemic, such as the stress caused by restrictions and uncertainty.”
She continues: “The post-COVID-19 condition, also known as long COVID , is an urgent problem with a growing human toll. Understanding the core symptoms and 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 long-term symptoms of COVID-19. COVID-19.”
The authors acknowledge some limitations in the study. This study included patients infected with the alpha variant or earlier variants of SARS-CoV-2 and does not have data from people infected during the period when the delta or omicron variants caused the majority of infections. Furthermore, due to asymptomatic infection , the prevalence of COVID-19 in this study may be underestimated.
Another limitation of this study is that, since the beginning of data collection, other symptoms, such as brain fog , have been identified as potentially relevant to a definition of long COVID, but this study did not look at these symptoms. Additionally, the study was conducted in one region and did not include an ethnically diverse population.
Professor Judith Rosmalen says: “Future research should include mental health symptoms (for example, depression and anxiety symptoms), along with additional post-infectious symptoms that we were not able to assess in this study (such as mental confusion, insomnia and post-exertional malaise). We were not able to investigate what might cause any of the symptoms seen after COVID-19 in this study, but we hope that future research can provide insight into the mechanisms involved.
Additionally, due to the timing of this study, we were unable to evaluate the effect of vaccination against COVID-19 and different SARS-CoV-2 variants on long COVID symptoms. We hope that future studies will provide answers about the impacts of these factors.”
Writing in a linked comment, Professor Christopher Brightling and Dr Rachael Evans from the Institute of Lung Health at the University of Leicester (who were not involved in the study) note: “This is a significant advance on previous estimates of COVID prevalence long-term, as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.
The pattern of symptomatology observed by Ballering and colleagues was similar to previous reports with fatigue and shortness of breath among the most common symptoms, but interestingly, other symptoms such as chest pain were more of a feature in those with long COVID than in those with long COVID. uninfected controls. […] Current evidence supports the view that long COVID is common and can persist for at least 2 years , although severe debilitating disease is present in a minority. The long COVID case definition needs to be further improved, potentially to describe different types of long COVID, for which a better understanding of the mechanism is critical.”
