Some Young People Have Long COVID Symptoms Despite Never Contracting COVID-19

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These findings suggest the World Health Organization's definition of post-COVID-19 condition (long COVID) may be too broad.

These findings suggest the World Health Organization's definition of post-COVID-19 condition (long COVID) may be too broad.

Image courtesy of Adobe Stock/ KMPZZZ

As COVID-19 prevention and treatment therapies become more advanced, the treatment focus has shifted to post-COVID-19 condition (PCC), or “long COVID.”

Mysteriously, long COVID is not limited to individuals at high risk of severe COVID-19 infection, such as persons who are older or immunocompromised. Many young people who only had mild acute infection go on to develop long COVID, yet the commonality and baseline risk factors of PCC remain unknown.

A new original investigation, published in JAMA Network Open, sought to determine the prevalence and associated risk factors of long COVID in young people after acute infection.

The prospective cohort study included nonhospitalized persons from 2 counties in southeast Norway, aged between 12-25 years. The individuals underwent reverse transcription-polymerase chain reaction (RT-PCR) testing to confirm their COVID-19 infection.

At the early stages of recovery and at a 6-month follow-up, participants underwent pulmonary, cardiac, and cognitive functional testing, immunological and organ injury biomarker analyses, and completed questionnaires. The investigators performed association analyses of 78 potential risk factors.

The team used the World Health Organization (WHO) case definition of long COVID, which broadly classifies any symptom occurring in the aftermath of acute COVID-19 as PCC. The WHO definition does not require symptom persistence since acute infection, nor significant disability.

A total of 382 COVID-19−positive and 85 COVID-19−negative young people were enrolled and participated in the entirety of the study. The cohorts were 38.1% male and 20.0% non-European ethnicity. After 6 months, the point prevalence of PCC according to the WHO definition was 48.5% in the COVID-19−positive group and 47.1% in the control cohort.

Interestingly, these results suggest that COVID-19 positivity was not associated with the development of long COVID. While the main risk factor for PCC was symptom severity at baseline, low physical activity and loneliness were also associated. Additionally, symptom severity was associated with personality traits. Biological markers had no correlation with the development of long COVID.

“The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors,” the study authors concluded. “This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC.”

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Paul Tambyah, MD, president of ISID
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