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One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published today in The Lancet indicates.
The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.
Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.
“This finding shows that post-COVID-19 condition is an urgent problem with a mounting human toll,” the study authors write.
The research design was novel, editorialists say in an accompanying commentary.
Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester, Leicester, United Kingdom, note, “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
Symptoms That Persist
The Lancet study finds that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.
The authors note that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.
Researcher Aranka V. Ballering, MSc, PhD candidate, told Medscape Medical News they found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.
Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.
Ballering, with the Department of Psychiatry at the University of Groningen in the Netherlands, said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
Closer to a Clearer Definition
The authors say their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.
“These symptoms have the highest discriminative ability to distinguish between post-COVID-19 condition and non–COVID-19-related symptoms,” they write.
Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.
Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.
Of 76,422 study participants, the 5.5% (4231) who had COVID were matched to 8462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
Effect of Hospitalization, Vaccination Unclear
Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.
Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.
However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.
Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.
The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.
The editorialists also note additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.
Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the Immunobiology Department at University of Arizona College of Medicine in Tucson, told Medscape Medical News he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.
However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal healthcare.
He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.
The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; Provinces of Drenthe, Friesland, and Groningen.
The study authors and Nikolich-Žugich have reported no relevant financial relationships.
Editorialist Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Editorialist Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick