Prevalence, determinants, and impact on general health and working capacity of post-acute sequelae of COVID-19 six to 12 months after infection: a population-based retrospective cohort study from southern Germany
Authors: Peter Raphael S. , Nieters Alexandra , Kräusslich Hans-Georg , Brockmann Stefan O. , Göpel Siri , Kindle Gerhard , Merle Uta , Steinacker Jürgen M. , Rothenbacher Dietrich , Kern Winfried V. ,   the EPILOC Phase 1 Study Group
Published: March 2022

AbstractBackgroundPost-acute sequelae of SARS-CoV-2 infection have commonly been described after COVID-19, but few population-based studies have examined symptoms six to 12 months after acute SARS-CoV-2 infection and their associations with general health recovery and working capacity.MethodsThis population-based retrospective cohort study in four geographically defined regions in southern Germany included persons aged 18-65 years with PCR confirmed SARS-CoV-2 infection between October 2020 and March 2021. Symptom frequencies (six to 12 months after versus before acute infection, expressed as prevalence differences [PD] and prevalence ratios [PR]), symptom severity and clustering, risk factors and associations with general health recovery, and working capacity were analysed.FindingsAmong a total of 11 710 subjects (mean age 44·1 years, 59·8% females, 3·5% previously admitted with COVID-19, mean follow-up time 8.5 months) the most prevalent symptoms with PDs >20% and PRs >5% were rapid physical exhaustion, shortness of breath, concentration difficulties, chronic fatigue, memory disturbance, and altered sense of smell. Female sex and severity of the initial infection were the main risk factors. Prevalence rates, however, appeared substantial among both men and women who had a mild course of acute infection, and PCS considerably affected also younger subjects. Fatigue (PD 37·2%) and neurocognitive impairment (PD 31·3%) as symptom clusters contributed most to reduced health recovery and working capacity, but chest symptoms, anxiety/depression, headache/dizziness and pain syndromes were also prevalent and relevant for working capacity, with some differences according to sex and age. When considering new symptoms with at least moderate impairment of daily life and ≤80% recovered general health or working capacity, the overall estimate for post-COVID syndrome was 28·5% (age- and sex-standardised rate 26·5%).InterpretationThe burden of self-reported post-acute symptoms and possible sequelae, notably fatigue and neurocognitive impairment, remains considerable six to 12 months after acute infection even among young and middle-aged adults after mild acute SARS-CoV-2 infection, and impacts general health and working capacity.Research in contextEvidence before this studyPrevious studies have shown that post-acute sequelae of COVID-19 are common, in particular among patients who had been admitted to hospital for COVID-19. Post-acute self-reported complaints and symptoms often are diverse, nonspecific and sometimes of unknown severity and functional relevance. We searched PubMed and medRxiv for studies published between January 2021 and February 2022, using search terms describing “long covid, post-acute sequelae of COVID-19, prevalence, and systematic review”, with no language restrictions. Searches with the terms “long covid”, “post-acute sequelae of COVID-19”, “post-covid condition” and “post-covid syndrome” were also done in PROSPERO, and we screened the website of the UK Office for National Statistics (www.ons.gov.uk) for long covid studies. We found more than 20 systematic reviews summarising post-acute symptom patterns among adults and a prevalence of “any” or “defined” symptoms (such as respiratory symptoms or symptoms related to mental health) or of medically assessed functional impairment (pulmonary or cardiac or neurocognitive function). Two reviews reported of health-related quality of life assessments. The prevalence of post-acute sequelae of COVID-19 or long covid/post-covid syndromes ranged between <10 to >70%, in part due to lack of uniform and clear case definitions, variable follow-up times, and non-inclusion of outpatients with initially mild disease. Most papers reviewed presented high heterogeneity and had a short follow-up, and there were very few papers estimating the prevalence of post-covid syndrome beyond six months after acute infection. The studies with the largest number of subjects were either including only patients after hospital admission, used online surveys of subjects with self-reported suspected and confirmed COVID-19 or electronic medical records only. We found one (small but) comprehensive population-based study from Switzerland assessing post-covid syndrome prevalence and associations with quality of life and health recovery with a follow-up time ranging from six to 10 months. Two further population-based studies from Switzerland and Norway investigated long covid symptoms among subgroups with ≥6 months (n=498) and 11 to 12 months (n=170) of follow-up after acute infection, respectively.Added value of this studyWith this large population-based study, we provide evidence of persistence of new symptom clusters (not present before acute infection) such as fatigue, neurocognitive impairment, chest symptoms, smell or taste disorder, and anxiety/depression beyond six months after acute infection, with a prevalence of >20% for each of these five clusters. We show that the three most frequent clusters (fatigue, neurocognitive impairment, chest symptoms) are often interfering with daily life and activities, often co-occur, and that both fatigue and neurocognitive impairment have the largest impact on working capacity, while long-term smell and taste disorders are reported relatively independent of other complaints. Age in this 18-65-year old adult population was not a major determinant of symptom prevalence, but we confirm severity of the initial infection and female sex as consistent risk factors for various manifestations of medium-term post-COVID syndrome, and age as risk factor for self-reported reduced working capacity, which overall and at population level exceeded 10%.Implications of all the available evidenceFuture research should include the medical validation of the key symptom clusters of post-COVID syndrome, determine the possible causes, and urgently address prognostic factors and therapeutic options. The described key symptom clusters contributed most to reduced general health status and working capacity in middle-aged adults. The findings of this study may also help develop a more consistent and relevant definition of post-COVID syndrome with major implications for research and medical practice.