One in eight adults experiences long COVID

One in every eight individuals who has experienced COVID-19 may have persistent symptoms 3–5 months post-infection, according to an observational study from the Netherlands.

Participants were individuals enrolled in the prospective, population-based Lifelines cohort that comprised people living in the north of the Netherlands. The 76,422 adults (mean age 53.7 years, 60.8 percent female) who responded to digital COVID-19 questionnaires (883,973 completed) were included in the present study. The questionnaires, distributed 24 times to the same individuals between March 2020 and August 2021, included questions on 23 symptoms associated with long COVID.

The 5.5 percent (n=4,231) of patients with a COVID-19 infection* (mean age 52.4 years, 65.7 percent female) due to the SARS-CoV-2 alpha or previous variants were matched with 8,462 non–COVID-19 controls. The median follow-up period after COVID-19 diagnosis was 101 days and in the control group, 104 days after the matched timepoint.

The symptoms that were more severe in the post- vs pre–COVID-19 period and vs controls (core symptoms) were chest pain, breathing difficulties, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, alternately feeling hot and cold, heavy arms or legs, and general tiredness. [Lancet 2022;400:452-461]

“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,” remarked first author Aranka Ballering, a PhD candidate at the University Medical Center Groningen, Groningen, the Netherlands.

At 90–150 days after being diagnosed with COVID-19, 21.4 percent of patients experienced ≥1 symptom**, either new or increased to moderate severity, compared with pre–COVID-19 diagnosis. In the control group, 8.7 percent experienced ≥1 symptom which was new or increased to moderate severity (p<0.001).

As such, 12.7 percent of the long-term symptoms could be attributed to COVID-19. “Mean severity for these symptoms appeared to have reached a plateau at 3 months, with no further decline in mean severity thereafter,” the authors observed.

Conversely, headache, itchy eyes, dizziness, back pain, and nausea did not increase in severity at 90–150 days after COVID-19 diagnosis.

In the COVID-19 cohort, persistence of post-infection increased symptom severity was longer among women than men.

 

The importance of understanding long COVID

“After recovery from acute COVID-19, a substantial proportion of patients continue to experience symptoms of a physical, psychological, or cognitive nature,” said the authors.

“There is urgent need for data informing the scale and scope of the long-term symptoms experienced by some patients after COVID-19 illness,” said lead author Professor Judith Rosmalen, also from the University Medical Center Groningen.

“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,” she said.

“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,” said Ballering.

“[L]ong 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,” she continued.

 

What’s next?

The authors highlighted that the results do not apply to symptoms of long COVID following the delta, omicron, or later variants of the SARS-CoV-2 infection, or symptoms such as brain fog that have more recently been associated with long COVID. Furthermore, the prevalence of COVID-19 may have been underestimated due to asymptomatic infection. The results may also be limited by the majority White population.

The effect of ethnicity, age, sex, and underlying comorbidities on the risk of long COVID should be assessed in future research, as should mental health and other symptoms of long COVID (eg, anxiety, depression, brain fog, insomnia) and the impact and timing of COVID-19 vaccination.

“Further research will focus on … whether symptom clusters are associated with subtypes and distinct pathophysiological mechanisms underlying post–COVID-19 condition. We will also study genetic and environmental risk factors, and how post–COVID-19 condition affects (work) functioning and wellbeing,” the authors said.

“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,” added Rosmalen.