Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON)
Authors: Appel Katharina S. , Nürnberger Carolin , Bahmer Thomas , Förster Christian , Polidori Maria Cristina , Kohls Mirjam , Kraus Tanja , Hettich-Damm Nora , Petersen Julia , Blaschke Sabine , Bröhl Isabel , Butzmann Jana , Dashti Hiwa , Deckert Jürgen , Dreher Michael , Fiedler Karin , Finke Carsten , Geisler Ramsia , Hanses Frank , Hopff Sina M. , Jensen Björn-Erik O. , Konik Margarethe , Lehnert Kristin , de Miranda Susana M. Nunes , Mitrov Lazar , Miljukov Olga , Reese Jens-Peter , Rohde Gernot , Scherer Margarete , Tausche Kristin , Tebbe Johannes J. , Vehreschild Jörg Janne , Voit Florian , Wagner Patricia , Weigl Martin , Lemhöfer Christina ,   the NAPKON Study Group, Alsaad K. , Hamelmann E. , Heidenreich H , Hornberg C. , Kulamadayil-Heidenreich N. S. A. , Maasjosthusmann P. , Muna A. , Ruwe M. , Stellbrink C. , Buechner N. , Dashti Y. , Tessmer C. , Laumerich B. , Silberbaur I. , Bader S. , Engelmann M. , Fuchs A. , Langer A. , Maerkl B. , Messmann H. , Muzalyova A. , Roemmele C. , Altmann H. , Berner R. , Dressen S. , Koch T. , Lindemann D. , Seele K. , Spieth P. , Toepfner N. , Bonin S. V. , Feldt T. , Keitel V. , Killer A. , Knopp L. , Luedde T. , Lutterbeck M. , Paluschinski M. , Pereira J. P. V. , Timm J. , Kraska D. , Kremer A. E. , Leppkes M. , Mang J. , Neurath M. F. , Prokosch H. U. , Schmid J. , Vetter M. , Willam C. , Wolf K. , Arendt C. , Bellinghausen C. , Cremer S. , Groh A. , Gruenewaldt A. , Khodamoradi Y. , Klinsing S. , Vehreschild M. , Vogl T. , Addo M. , Almahfoud M. , Engels A. L. F. , Jarczak D. , Kerinn M. , Kluge S. , Kobbe R. , Petereit S. , Schlesner C. , Zeller T. , Baber R. , Bercker S. , Krug N. , Mueller S. D. , Wirtz H. , Boeckel G. , Meier J. A. , Nowacki T. , Tepasse P. R. , Vollenberg R. , Wilms C. , Dahl E. , Marx N. , Mueller-Wieland D. , Wipperfuerth J. , Brochhausen-Delius C. , Burkhardt R. , Feustel M. , Haag O. , Hansch S. , Malfertheiner M. , Niedermair T. , Schuster P. , Wallner S. , Cleef S. , Friedrichs A. , Kaeding N. , Koerner M. , Kujat C. , Oberlaender M. , Pape D. , Plagge M. , Rupp J. , Schunk D. , Cleef S. , Friedrichs A. , Kaeding N. , Koerner M. , Kujat C. , Oberlaender M. , Pape D. , Plagge M. , Rupp J. , Schunk D. , Barkey W. , Erber J. , Fricke L. , Lieb J. , Michler T. , Mueller L. , Schneider J. , Spinner C. , Winter C. , Bitzer M. , Bunk S. , Göpel S. , Haeberle H. , Kienzle K. , Mahrhofer H , Malek N. , Rosenberger P. , Struemper C. , Trauner F. , Frantz S. , Frey A. , Haas K. , Haertel C. , Herrmann J. , Isberner N. , Liese J. , Meybohm P. , Schmidt J. , Schulze P. , Brinkmann F. , Brueggemann Y. , Gambichler T. , Hellwig K. , Luecke T. , Reinacher-Schick A. , Schmidt W. E. , Schuette C. , Steinmann E. , Torres Reyes C. , Hafke A. , Hermanns G. , Nussbeck S. Y. , Santibanez-Santana M. , Zeh S. , Brochhagen L. , Dolff S. , Elsner C. , Krawczyk A. , Madel R. J. , Otte M. , Witzke O. , Becker K. , Doerr M. , Nauck M , Piasta N. , Schaefer C. , Schaefer E. , Schattschneider M. , Scheer C. , Stahl D. , Arlt A. , Griesinger F. , Guenther U. , Hamprecht A. , Juergens K. , Kluge A. , Meinhardt C. , Meinhardt K. , Petersmann A. , Prenzel R. , Brechtel M. , Laugwitz M. , Lee C. , Sauer G. , Schulze N. , Seibel K. , Stecher M. , Hagen M. , Schneider J. , Sikdar S. , Weismantel C. , Wolf L. , Günther K. , Haug J. , Haug F. , Fiessler C. , Heuschmann P. U. , Schmidbauer L. , Jiru-Hillmann S. , Bahls T. , Hoffmann W. , Nauck M. , Schaefer C. , Schattschneider M. , Stahl D. , Valentin H. , Chaplinskaya I. , Hanß S. , Krefting D. , Pape C. , Rainers M. , Schoneberg A. , Weinert N. , Kraus M. , Lorenz-Depiereux B. , Lorbeer R. , Schaller J. , Fricke J. , Krist L. , Rönnefarth M. , Schmidt S. , Bahmer T. , Hermes A. , Krawczak M. , Lieb W. , Schreiber S. , Tamminga T. , Herold S. , Heuschmann P. , Heyder R. , Hoffmann W. , Illig T. , Schreiber S. , Witzenrath M. 
Published: April 2024

Abstract
Purpose
The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score.

Methods
The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L).

Results
Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001).

Conclusion
The PCS score correlated with patients’ QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities.

Trail registration number
The cohort is registered at www.clinicaltrials.gov under NCT04768998.