Post-acute sequelae of covid-19 six to 12 months after infection: population based study
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Abstract
Objectives
To describe symptoms and symptom clusters of post-covid syndrome six to 12 months after acute infection, describe risk factors, and examine the association of symptom clusters with general health and working capacity.
Design
Population based, cross sectional study
Setting
Adults aged 18-65 years with confirmed SARS-CoV-2 infection between October 2020 and March 2021 notified to health authorities in four geographically defined regions in southern Germany.
Participants
50 457 patients were invited to participate in the study, of whom 12 053 (24%) responded and 11 710 (58.8% (n=6881) female; mean age 44.1 years; 3.6% (412/11 602) previously admitted with covid-19; mean follow-up time 8.5 months) could be included in the analyses.
Main outcome measures
Symptom frequencies (six to 12 months after versus before acute infection), symptom severity and clustering, risk factors, and associations with general health recovery and working capacity.
Results
The symptom clusters fatigue (37.2% (4213/11 312), 95% confidence interval 36.4% to 38.1%) and neurocognitive impairment (31.3% (3561/11 361), 30.5% to 32.2%) 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. 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% (3289/11 536, 27.7% to 29.3%) among participants or at least 6.5% (3289/50 457) in the infected adult population (assuming that all non-responders had completely recovered). The true value is likely to be between these estimates.
Conclusions
Despite the limitation of a low response rate and possible selection and recall biases, this study suggests a considerable burden of self-reported post-acute symptom clusters and possible sequelae, notably fatigue and neurocognitive impairment, six to 12 months after acute SARS-CoV-2 infection, even among young and middle aged adults after mild infection, with a substantial impact on general health and working capacity.
Trial registration
German registry of clinical studies DRKS 00027012.
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SciScore for 10.1101/2022.03.14.22272316: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All study materials (i.e. participant information, informed consent form, and a standardised questionnaire) were included in the letter.
IRB: The study was conducted according to the Declaration of Helsinki, and ethical approval was obtained from the respective ethical review boards of the study centres in Freiburg (21/1484) and Ulm (337/21).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The identified symptom clusters were visualised by means of a co-occurrence network using Gephi 0.9.2. Gephisuggested: (Gephi, RRID:SCR_004293)Statistical procedures were … SciScore for 10.1101/2022.03.14.22272316: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All study materials (i.e. participant information, informed consent form, and a standardised questionnaire) were included in the letter.
IRB: The study was conducted according to the Declaration of Helsinki, and ethical approval was obtained from the respective ethical review boards of the study centres in Freiburg (21/1484) and Ulm (337/21).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The identified symptom clusters were visualised by means of a co-occurrence network using Gephi 0.9.2. Gephisuggested: (Gephi, RRID:SCR_004293)Statistical procedures were performed with the SAS statistical software package (release 9.4 SAS Institute Inc.) or R version 4.1.2. SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations include the self-reported nature of symptoms and sequelae without medical validation. Also, reporting bias has to be considered when reporting symptoms from the past, especially in subjects with neurocognitive sequelae. Furthermore, we had a limited response with some overrepresentation of older persons and female sex (appendix, table S4). Our study regions were located around medium sized university cities, with respondents having higher education than the general population, which may limit generalizability. As we only have a before-after comparison within infected subjects, we cannot differentiate between the impact of the pandemic itself and its consequences such as non-pharmaceutical and public health interventions on symptoms and symptom reporting from direct consequences of the virus infection. Finally, we used only one specific method for symptom clustering and cannot exclude that other methods would define different and presumably larger clusters.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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