Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS‑CoV‑2 infection: an analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort
Authors: Shi Yanyan , Strobl Ralf , Apfelbacher Christian , Bahmer Thomas , Geisler Ramsia , Heuschmann Peter , Horn Anna , Hoven Hanno , Keil Thomas , Krawczak Michael , Krist Lilian , Lemhöfer Christina , Lieb Wolfgang , Lorenz-Depiereux Bettina , Mikolajczyk Rafael , Montellano Felipe A. , Reese Jens Peter , Schreiber Stefan , Skoetz Nicole , Störk Stefan , Vehreschild Jörg Janne , Witzenrath Martin , Grill Eva ,   the NAPKON Study Group, Vehreschild Maria J. G. T. , Vehreschild Jörg J. , Dashti Hiwa , Laumerich Barbara , Pociuli Oliver , Büchner Nikolaus , Adler Sabine , Lehmann Mathias , Tasci Selcuk , Jorczyk Maximilian , Keller Thomas , Schroth Michael , Hower Martin , Eberwein Lukas , Zimmermann Tim , Herkenrath Simon-Dominik , Milovanovic Milena , Pauli Ramona , Simon Jörg , Hamelmann Eckard , Stellbrink Christoph , Tebbe Johannes-Josef , Stieglitz Sven , Wyen Christoph , Bosch Jan , Steinmüller Mirko , Allerlei Christoph , Böbel Markus , Heinitz Elke Natascha , Roecken Ariane , Münckle-Krimly Andrea , Guderian Christiane , Silberbaur Ingmar , Schäfer Harald , Raichle Claudia , Spinner Christoph , Schmeck Bernd , Altmann Heidi , Toepfner Nicole , Schmidt Wolfgang , Jensen Björn , Kremer Andreas , Blaschke Sabine , Dutzmann Jochen , Addo Marylyn , Bals Robert , Bercker Sven , Tepasse Phil-Robin , Hanses Frank , Müller-Wieland Dirk , Friedrichs Anette , Rupp Jan , Göpel Siri , Maschmann Jens , Dhillon Christine , Nattermann Jacob , Voigt Ingo , Obst Wilfred , Sprinzl Martin Franz , Scheer Christian , Teufel Andreas , Günther Ulf , Witzenrath Martin , Keil Thomas , Zoller Thomas , Schmidt Sein , Hummel Michael , Krist Lilian , Fricke Julia , Rönnefarth Maria , Treue Denise , Kretzler Ludie , Dang-Heine Chantip , Triller Paul , Jooß Andreas , Schlesinger Jenny , Liseweski Natalja , Pley Christina , Scheibenbogen Carmen , Hoeper Marius , Reuken Philipp A. , von Bergwelt Michael , Noth Rainer , Drömann Daniel , Vehreschild Maria J. G. T. , Rieg Siegbert , Vadasz Istvan , Koehler Philipp A. , Merle Uta , Schreiber Stefan , Heuschmann Peter , Störk Stefan , Friedrichs Anette , Petersmann Astrid , Ellert Claudia , Schmidt Georg , Vehreschild Janne , Milger Katrin , von Lilienfeld Marie , Witzenrath Martin , Witzke Oliver , Meybohm Patrick , Heuschmann Peter , Blaschke Sabine , Frank Sandra , Schreiber Stefan , Hein Thomas Illig. Alexander , Wittig Andrea , Simm Andreas , Friedrichs Anette , Reinacher-Schick Anke , Frey Anna , Iannaccone Antonella , Petersmann Astrid , Maasoumy Benjamin , Waschki Benjamin , Hoyer Bimba , van Oorschot Brigitt , van Schaik Carolina , Lemhöfer Christina , Polidori Christina , Klein Christine , Medenwald Daniel , Schulte Eva Christina , Grill Eva , Meinel Felix , Brinkmann Folke , Arabi Ghazal , Bickeböller Heike , Lindner Holger , Gagyor Ildiko , Hassel Jessica , Deckert Jürgen , Milger-Kneidinger Katrin , Ludwig Kerstin , Dörr Marcus , von Lilienfeld-Toal Marie , Möckel Martin , Weigl Martin , Nauck Matthias , Banas Miriam , Demir Muenevver , Lindenberg Nicole , Hettich Nora , Jung Norma , Witzke Oliver , Guntinas-Lichius Orlando , Meybohm Patrick , Berner Reinhard , Blaschke Sabine , Knauss Samuel , Frank Sandra , Baumeister Sebastian , Dolff Sebastian , Ugurel Selma , Stöcklein Sophia , Joos Stefanie , Vehreschild Winfred Häuser. Jörg Janne , Schons Maximilian , Hopff Sina , Brechtel Markus , Schmidt-Ibanez Cristina , Schneider Johannes , Jakob Carolin , Bernemann Franziska Voß. Inga , Kunze Sonja , Tauchert Maike , Illig Thomas , Fiessler Gabriele Anton. Cornelia , Kohls Mirjam , Miljukov Olga , Jiru-Hillmann Steffi , Reese Jens-Peter , Reese Peter Heuschmann. Jens-Peter , Heuschmann Peter , Hofmann Anna-Lena , Schmidt Julia , Ungethüm Kathrin , Horn Anna , Bahmer Michael Krawczak. Thomas , Lieb Wolfgang , Pape Daniel , Schreiber Stefan , Hermes Anne , Lehmann Irene , Maetzler Corina , Lorbeer Lukas Tittmann. Roberto , Lorenz-Depiereux Bettina , Kraus Monika , Schäfer Christian , Schaller Jens , Schattschneider Mario , Stahl Dana , Valentin Heike , Krefting Dagmar , Toepfner Matthias Nauck. Nicole , von Kalle Reinhard Berner. Christof , Thun Sylvia , Bartschke Alexander , Lysyakova Liudmila , Rudolph Stefanie , Nagel Julian Sass. Eike , Püntmann Valentina , Wolf Tammy , Azdad Thourier , Weis Franziska , Krückemeier Ira , Bohlender Simon , Desik Deniz , Laghchioua Layla , Heyder Ralf , Wiedmann Silke 
Published: May 2023

Abstract
Purpose
We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free.

Methods
COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled ≥ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan–Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free.

Results
Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49–59 years compared to < 49 years (aHR 0.70, 95% CI 0.56–0.87), female sex (aHR 0.78, 95% CI 0.65–0.93), lower educational level (aHR 0.77, 95% CI 0.64–0.93), living with a partner (aHR 0.81, 95% CI 0.66–0.99), low resilience (aHR 0.65, 95% CI 0.47–0.90), steroid treatment (aHR 0.22, 95% CI 0.05–0.90) and no medication (aHR 0.74, 95% CI 0.62–0.89) during acute infection.

Conclusion
In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant’s characteristics that are difficult to modify.