Risk tools for predicting long-term sequelae based on symptom profiles after known and undetected SARS-CoV-2 infections in the population.

Journal: European journal of epidemiology
Published Date: May 19, 2025

Abstract

The aim was to determine the profile of long-term symptoms after known and undetected SARS-CoV-2 infections and to generate tools for risk and diagnostic assessment of Post-COVID syndrome (PCS). In the population-based Gutenberg COVID-19 Study (N = 10,250), sequential, systematic screening for SARS-CoV-2 was performed in 2020/2021. Individuals received a standardized interview on newly occurred or worsened symptoms since the infection or the pandemic. Robust Poisson regression models were fit to compare the frequency of symptoms between groups. Two scores were developed using machine learning techniques and prospectively validated in an independent cohort. Among n = 942 individuals, prevalence of long-term symptoms was 36.4% among individuals with known SARS-CoV-2 infection, 25.0% in those unknowingly infected, and 28.1% among the controls. Individuals with known infection more often reported smell (Prevalence ratio [PR] = 13.66 [95% confidence interval 4.99;37.41]) and taste disturbances (PR = 5.57 [2.62;11.81]), forgetfulness (PR = 2.88 [1.55;5.35]), concentration difficulties (PR = 2.83 [1.55;5.16], trouble with balance (PR = 2.74 [1.18;6.35]), and dyspnea (PR = 2.22 [1.18;4.19]) than controls. The risk score for predicting long-term sequelae based on symptoms during the acute infection had a cross-validated AUC of 0.74 and 0.72 when applied in an independent cohort (N = 6,570). The diagnostic score providing a probability of the presence of PCS had a cross-validated AUC of 0.66 and of 0.64 in the validation cohort (N = 3,176). Individuals with and without SARS-COV-2 infection reported persistent symptoms, but symptoms attributable to PCS were identified. The data-driven scores may help guide further diagnostic decisions in the initial management of PCS.

Authors

  • Rieke Baumkötter
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Simge Yilmaz
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Julian Chalabi
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Vincent Ten Cate
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Ayesha Syed Mamoor Alam
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Sepehr Golriz Khatami
    Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing, Sankt Augustin, 53757, Germany. sepehr.golriz.khatami@scai.fraunhofer.de.
  • Daniela Zahn
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Nora Hettich-Damm
    Department of Psychosomatic Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Untere Zahlbacher Str.8, 55131, Mainz, Germany.
  • Jürgen H Prochaska
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Irene Schmidtmann
    From the Department of Neuroradiology (S.A., N.F.G., L.B., M.K., M.A.B., A.E.O.), Institute of Medical Biostatistics, Epidemiology and Informatics (I.S., R.P.), and Department of Neurology (T.U., S.G.), University Medical Center Mainz, Johannes Gutenberg University, Langenbeckstr 1, 55131 Mainz, Germany; Siemens Medical Solutions USA, Boston, Mass (B.C.); and Siemens Healthcare, Erlangen, Germany (T.F., Z.H.).
  • Kristin Lehnert
    Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
  • Anke Steinmetz
    German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany.
  • Marcus Dörr
    Department of Internal Medicine B, Cardiology, Angiology & Pneumology, University Medicine of Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
  • Norbert Pfeiffer
    Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
  • Thomas Münzel
    Partner Site Rhine Main, German Center for Cardiovascular Research (DZHK), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Karl J Lackner
    Partner Site Rhine Main, German Center for Cardiovascular Research (DZHK), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Manfred E Beutel
    Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
  • Philipp S Wild
    Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. philipp.wild@unimedizin-mainz.de.

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