Study tracks long COVID's shifting course in general population

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In a recent study published in the journal Nature Communications, researchers examined the natural history of long COVID in a general population cohort.

Understanding the natural history and scale of long COVID is essential for social and healthcare planning. Most studies report long COVID prevalence at a single time point after infection, and there is limited information on temporal changes in long COVID. Besides, studies with serial outcome measures have been restricted to select population subsets and specific outcomes or have lacked a comparison group. Further, while long COVID might remain stable in some individuals, it may progress, subside, or relapse in others.

Study: Natural history of long-COVID in a nationwide, population cohort study. Image Credit: Lightspring / ShutterstockStudy: Natural history of long-COVID in a nationwide, population cohort study. Image Credit: Lightspring / Shutterstock

The study and findings

The present study examined the trajectory of long COVID in a general population cohort. The researchers used serial questionnaire data from the “Long COVID in Scotland study.” Of over four million questionnaires, 9% were completed by 288,173 individuals. From these, the team included persons who consented to link records necessary to obtain test results.

The team excluded individuals recruited beyond the six-month follow-up, persons with asymptomatic infections, and subjects with self-reported test-positive results that were not logged on the database. Thus, of the 160,781 eligible subjects, 80,332 had a lab-confirmed, symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the remainder never had an infection.

Among infected individuals, 12,947 provided six- and 12-month follow-up questionnaire data, and 4,196 completed questionnaires at both six- and 18-month follow-ups; the corresponding figures for non-infected subjects were 11,026 and 1,711, respectively. Six months after infection, 49.5% of subjects reported complete recovery, 43.6% had partial recovery, and 6.9% were unrecovered. At 12 months, the corresponding figures were 50.8%, 41.8%, and 7.4%, respectively.

Among those with partial recovery at six months, 21% and 22% improved by 12 and 18 months, whereas 8% and 10% reported deterioration, respectively. Among the unrecovered persons at six months, 404 improved to some extent by 12 months, and 28 recovered completely. Notably, 16% of subjects fully recovered at six months reported deterioration at 12 months.

Socioeconomic deprivation and depression pre-infection were more prevalent among subjects reporting deterioration in recovery between six and 12 months. Further, among people without complete recovery at six months, improvement was more likely among the most affluent but less likely among people with pre-infection depression and older individuals.

Likewise, among those with partial or complete recovery at six months, deterioration in recovery status at 12 months was more likely among people with depression and less likely among older and most affluent subjects. The percentage of individuals who reported at least one of the 26 symptoms was unchanged over time among the infected group but increased in the non-infected group.

The prevalence of new and persistent symptoms at 12 and 18 months compared to six months was higher among previously symptomatic subjects than non-infected individuals. There was a significant decline in the prevalence of confusion (brain fog) and altered smell/taste between six and 12 months post-infection. Notably, this reduction was specific to participants with improvements in recovery status.

Confusion was significantly more prevalent at six months post-infection among subjects with a history of anxiety or depression. Furthermore, infected subjects reported significant productive and dry cough prevalence increases from six to 12 months. Nevertheless, non-infected subjects also reported these symptoms more frequently over time.

Increased dry cough prevalence was associated with younger age and more preexisting conditions, especially anxiety or depression. More productive cough prevalence was associated with preexisting respiratory disease and the male sex. Of note, the late-onset cough was specific to people reporting deterioration in recovery. The prevalence of hearing problems increased in both groups between six and 12 months but was significantly higher in the infected group.

The higher prevalence of cough and hearing problems between six and 18 months was significant compared to the non-infected group. The median EuroQoL-5D visual analog scale (EQ-5D VAS) score decreased marginally from six to 12 months following infection. Nevertheless, a similar decline was also observed in the non-infected group. Notably, symptomatic infection was associated with a much larger decrease in VAS score.


Taken together, the study reported the long COVID trajectory in the general population relative to changes in symptoms and quality of life in never-infected people. The findings highlight no significant changes in self-reported recovery status or the percentage of individuals with symptoms beyond six months. Nonetheless, 12% of subjects reported deterioration, and an equivalent proportion had improvements in recovery. Confusion and altered smell/taste resolved over time for some people, while others had a late-onset cough or hearing troubles.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.


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