Article
Clinical findings in adults with post-acute sequelae of COVID-19 in the second year after acute infection: population-based, nested case-control study
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Authors
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Raphael S. Peter
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
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Alexandra Nieters
- Institute for Immunodeficiency, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany
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Siri Göpel
- Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany
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Uta Merle
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
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Jürgen Steinacker
- Division of Sports and Rehabilitation Medicine, Department of Medicine, Ulm University Hospital, Ulm, Germany
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Peter Deibert
- Institute for Exercise and Occupational Medicine, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany
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Birgit Friedmann-Bette
- Department of Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany
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Andreas Nieß
- Department of Sports Medicine, University Hospital Tübingen, Tübingen, Germany
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Barbara Müller
- Institute of Virology, Department of Infectious Diseases, University Hospital Heidelberg, Heidelberg, Germany
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Claudia Schilling
- Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Sleep Laboratory, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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Gunnar Erz
- Department of Sports Medicine, University Hospital Tübingen, Tübingen, Germany
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Roland Giesen
- Division of Infectious Diseases, Department of Medicine II, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany
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Veronika Götz
- Division of Infectious Diseases, Department of Medicine II, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany
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Karsten Keller
- Department of Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany
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Philipp Maier
- Institute for Exercise and Occupational Medicine, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany
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Lynn Matits
- Division of Sports and Rehabilitation Medicine, Department of Medicine, Ulm University Hospital, Ulm, Germany
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Sylvia Parthé
- Institute of Virology, Department of Infectious Diseases, University Hospital Heidelberg, Heidelberg, Germany
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Martin Rehm
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
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Jana Schellenberg
- Division of Sports and Rehabilitation Medicine, Department of Medicine, Ulm University Hospital, Ulm, Germany
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Hans-Georg Kräusslich
- Institute of Virology, Department of Infectious Diseases, University Hospital Heidelberg, Heidelberg, Germany
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Dietrich Rothenbacher
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
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Winfried V. Kern
- Division of Infectious Diseases, Department of Medicine II, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany
| Published: | September 6, 2024 |
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Outline
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Introduction: We previously described a considerable burden of self-reported post-acute symptom clusters six to 12 months after acute SARS-CoV-2 infection in 18-65-year-old adults, notably fatigue, neurocognitive impairment, chest symptoms, smell or taste disorders, and anxiety or depression, among others [1]. The current study aimed to medically validate post-COVID syndrome (PCS) cases that were pre-defined in our previous population-based study.
Methods: PCS cases or controls were invited for a comprehensive outpatient clinical assessment. PCS cases were defined as no more than 80% recovery of general health or working capacity, and any new symptom of moderate to strong impairment compared to pre-COVID-19. Subjects that recovered to 100% and reported no new moderate to strong symptoms qualified as controls. Nine hundred eighty-two cases (participation rate 39.6%) and 576 age-sex frequency-matched controls (participation rate 32.0%) followed the invitation.
Participants answered a range of validated questionnaires (SF-12, CFQ-11, FLei, GAD-7, PHQ-9, PSQI, and COMPASS-31), underwent a physical examination, neuropsychological tests, routine laboratory investigations, resting electrocardiograms, echocardiograms, spirometry, and cardiopulmonary exercise testing (CPET).
Results: The mean age of participants was 48 years (65% female). The mean time between baseline and clinical assessment was 9.1 months for cases and 8.4 months for controls (median time since index infection: 17.2 months). A similar proportion of cases versus controls experienced a second SARS-CoV-2 infection (23%). 67.6% of the 982 participants pre-classified as cases continued to meet the case definition at the time of clinical assessment. The remaining cases (30.1%) had improved by the time of clinical assessment, but very few (2.2%) were classified as fully clinically recovered. Conversely, most (78.5%) of initial controls who participated in the clinical assessment were classified as stable controls.
The average scores of SF-12, CFQ-11, FLei, GAD-7, PHQ-9, PSQI, and COMPASS-31 differed substantially between persistent cases and stable controls in the expected direction after adjustment (sex-age class combinations, study centre, university entrance qualification). Less pronounced but statistically significant differences were observed in all neurocognitive tests (MoCA, SDMT, and TMT-B). Differences were observed for FEV1 and FVC, SpO2 at rest, and several CPET-derived variables, including lower VO2 max and a higher VE/VCO2 slope in persistent cases. VO2 max <85% of predicted was observed in 35.3% of persistent cases and 8.4% of stable controls. Exclusion of participants with pre-existing diseases did not alter these findings. No difference was found in the results of the resting echocardiogram. After adjustment for BMI and smoking status, we found no differences between persistent cases and stable controls in any of the laboratory investigations (including C-reactive protein, coagulation markers and virological analyses).
Conclusions: In a thorough medical examination 1.5 years after index infection, approximately one-third of subjects with persistent PCS showed findings that significantly differ from control subjects and are, in part, abnormal. These include impaired executive functioning, reduced cognitive processing speed, reduced exercise capacity and ventilator insufficiency. Routine laboratory assessments do not help discriminate PCS cases and controls.
The authors declare that they have no competing interests.
The authors declare that a positive ethics committee vote has been obtained.
References
- 1.
- Peter RS, Nieters A, Kräusslich HG, Brockmann SO, Göpel S, Kindle G, et al. Post-acute sequelae of covid-19 six to 12 months after infection: population based study. BMJ. 2022 Oct 13;379:e071050. DOI: 10.1136/bmj-2022-071050
