Study: Long-COVID in Scotland Study: a nationwide, population cohort study. Image Credit: RoundGlobalMaps/Shutterstock

The frequency, nature, determinants and impact of long-term COVID in Scotland

In a recent study posted on Research Square* researchers evaluated long-term consequences of coronavirus disease 2019 (COVID-19) in Scotland.

Study: Lung COVID in Scotland Study: A Nationwide Population Cohort Study† Image Credit: RoundGlobalMaps/Shutterstock

While most patients make a full recovery from COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), some experience prolonged COVID. The World Health Organization defined long-term COVID-19 in people with a history of COVID-19 as the persistence of symptoms for two months or longer, unexplained by an alternative diagnosis. This inaccuracy reflects the lack of a comprehensive understanding of the nature of the condition and its underlying mechanisms.

About the study

In the current study, researchers spent a long time analyzing COVID in the general public in Scotland. Long COVID in Scotland Study (Long-CISS) is an ambidirectional cohort study. Scottish people aged 16 years or older with a positive polymerase chain reaction (PCR) test for COVID-19 between April 2020 and May 2021 were eligible.

In addition, a matched control group of SARS-CoV-2 PCR negative humans was established. An online questionnaire was completed by participants who collected data on pre-existing comorbidities on index testing (first positive test or last negative test in the case of controls), current symptoms, quality of life and limitations in daily activities. Respondents completed three questionnaires on 6-, 12-, and 18-month post-index tests.

COVID-19 infection was defined as a positive PCR test result registered in the national database, and subjects were stratified into symptomatic or asymptomatic categories as reported by respondents. Severe illness was defined as hospitalization with the International Classification of Diseases Tenth Revision (ICD-10) code U07.1. The excluded were respondents who reported a PCR positive status but were not included in the national database.

Respiratory disease, depression, coronary heart disease and diabetes were defined using ICD-10 codes or self-reports. The study outcomes were 26 symptoms, quality of life, limitations in seven daily activities, hospitalization, intensive care unit (ICU), all-cause mortality, and recovery status (for symptomatic cases).


Of the 638,125 individuals invited to the survey, 16% (102,473) participated. The last cohort consisted of 96,238 subjects. The median age was 45 years; men made up 39% of the cohort and 91% of the participants were white. At least one pre-existing comorbidity was observed in 30% of respondents and at least one dose was vaccinated before the index test in 4%.

About 95% of the 33,281 SARS-CoV-2 positive respondents were symptomatic. Most individuals (82%) reported three symptoms. During the acute infection phase, fatigue was reported by 83% of subjects, 64% reported headache, and 63% had myalgia. All participants completed the first questionnaire (after six months), 20% completed the second questionnaire and only 809 respondents completed the last questionnaire.

Approximately 42% of symptomatic cases reported partial recovery at most recent follow-up and 6% had not recovered. Symptoms persisted in 21,525 subjects after symptomatic COVID-19, and the most common were headache, fatigue, muscle aches or weakness. After adjusting for possible confounders, people with the prior symptomatic disease were more likely to report 24 symptoms (out of 26) at follow-up.

The lack of recovery from symptomatic disease was associated with the severe clinical course (hospitalization), deprivation, older age, female gender, and pre-existing co-morbidities, including respiratory disease and depression. People with previous symptomatic infection showed no significantly increased risk of hospitalization, ICU admission, or death.

After adjusting for possible confounders, people with symptomatic COVID-19 more often reported reduced daily activities (mobility, work, sports and relationships). The asymptomatic illness was not associated with a higher risk of current symptoms, decreased daily activities, hospitalization, or all-cause mortality. At their most recent follow-up, those vaccinated before symptomatic disease were less likely to experience sustained changes in smell/taste, hearing problems, confusion or difficulty concentrating, and depression/anxiety.


The researchers noted that nearly half of the infected individuals had not recovered or had only partially recovered after 6 to 18 months of symptomatic COVID-19. The symptomatic disease was associated with many persistent symptoms, decreased quality of life, decreased daily activities, independent of sociodemographic factors, and comorbidities.

There was no evidence of lasting sequelae after asymptomatic disease. The strongest association for persistent symptoms was observed for cardiovascular symptoms such as chest pain, shortness of breath, palpitations and confusion. In addition, the authors found that severe illness, female gender, older age, pre-existing respiratory disease and deprivation were associated with lack of recovery.

However, vaccination before infection reduced the risk of seven persistent symptoms. Overall, the results indicated that after 6-18 months of symptomatic SARS-CoV-2 infection, adults were more likely to experience a wide range of symptoms, with poorer quality of life and reduced activities of daily living, which could not be explained. be through confounding.

*Important announcement

Research Square publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.

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