In a recent study posted to Research square, researchers evaluated long-term sequelae of coronavirus disease 2019 (COVID-19) in Scotland.
While most patients fully recover from COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), some experience long COVID. The World Health Organization defined long COVID in those with a history of COVID-19 as the persistence of symptoms for two months or more, unexplained by any alternative diagnosis. This imprecision reflects the lack of a comprehensive understanding of the nature of the condition and underlying mechanisms.
About the study
In the current study, researchers analyzed long 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 above 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 people was established. An online questionary was completed by participants that captured data on pre-existing comorbidities at index test (first positive test or latest negative test in the case of controls), current symptoms, quality of life, and limitations in daily activities. Respondents completed three questionaries at 6-, 12- and 18-months post-index tests.
COVID-19 infection was defined as a positive PCR test result registered on the national database, and subjects were stratified into symptomatic or asymptomatic categories as reported by respondents. Severe disease was defined as admission to a hospital with the U07.1 code of the International Classification of Diseases Tenth Revision (ICD-10). Those excluded were respondents who reported PCR-positive status but were not recorded on 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 across seven daily activities, hospitalization, intensive care unit (ICU) admission, all-cause mortality, and recovery status (for symptomatic cases).
Findings
Of the 638,125 individuals invited for the study, 16% (102,473) participated. The final cohort consisted of 96,238 subjects. The median age was 45 years; males constituted 39% of the cohort, and 91% of the participants were white. At least one pre-existing comorbidity was observed in 30% of the respondents, and 4% were vaccinated with at least one dose before the index test.
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 (at six months), 20% completed the second questionary, and just 809 respondents completed the final survey.
About 42% of the symptomatic cases reported partial recovery at the most recent follow-up, and 6% were not recovered. Symptoms persisted in 21,525 subjects after symptomatic COVID-19, and the most common were headache, fatigue, muscle ache, or weakness. After adjusting for potential confounders, people with the prior symptomatic disease were at higher odds of reporting 24 symptoms (out of 26) at follow-up.
The lack of recovery following symptomatic disease was associated with the severe clinical course (hospitalization), deprivation, older age, female sex, and pre-existing comorbidities, including respiratory disease and depression. People with prior symptomatic infection showed no significant increased risk of hospitalization, ICU admission, or death.
After adjusting for potential confounders, people with a symptomatic COVID-19 were more likely to report impaired daily life activities (mobility, working, exercising, and relationships). The asymptomatic disease was not associated with a higher risk of current symptoms, impairment of daily activities, hospitalization, or all-cause mortality. At their most recent follow-up, those vaccinated before the symptomatic disease had lower odds of persistent change in smell/taste, hearing problems, confusion or difficulty concentrating, and depression/anxiety.
Conclusions
The researchers noted that almost half of infected individuals had not recovered or only partially after 6 to 18 months of symptomatic COVID-19. The symptomatic disease was associated with many persistent symptoms, reduced quality of life, impaired daily activities, independent of sociodemographic factors, and comorbidities.
There was no evidence of lingering sequelae post asymptomatic disease. The strongest association for persistent symptoms was observed for cardiovascular symptoms such as chest pain, breathlessness, palpitations, and confusion. Moreover, the authors found that severe disease, female gender, older age, pre-existing respiratory disease, and deprivation were associated with the lack of recovery.
However, pre-infection vaccination reduced the risk of seven persistent symptoms. Altogether, 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 impaired activities of daily living, which were unexplained by confounding.
