Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study.

Authors

Thomas Bahmer, Christoph Borzikowsky, Wolfgang Lieb, Anna Horn, Lilian Krist, Julia Fricke, Carmen Scheibenbogen, Klaus F Rabe, Walter Maetzler, Corina Maetzler, Martin Laudien, Derk Frank, Sabrina Ballhausen, Anne Hermes, Olga Miljukov, Karl Georg Haeusler, Nour Eddine El Mokhtari, Martin Witzenrath, Jörg Janne Vehreschild, Dagmar Krefting, Daniel Pape, Felipe A Montellano, Mirjam Kohls, Caroline Morbach, Stefan Störk, Jens-Peter Reese, Thomas Keil, Peter Heuschmann, Michael Krawczak, Stefan Schreiber

Year of publication

2022

Journal

EClinicalMedicine

Volume

51

Issue

-

ISSN

2589-5370

Impact factor

17.033

Abstract

Background

Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS.

Methods

COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742).

Findings

In Kiel-I (n = 667, 57% women), 90% of participants had received outpatient treatment for acute COVID-19. Neurological ailments (61·5%), fatigue (57·1%), and sleep disturbance (57·0%) were the most frequent persisting symptoms at 6-12 months after infection. Across sub-cohorts (Würzburg/Berlin, n = 316, 52% women; Kiel-II, n = 459, 56% women), higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index: r = -0·54/ -0·56, all p < 0·0001). Severe, moderate, and mild/no PCS according to the individual participant's PCS score occurred in 18·8%, 48·2%, and 32·9%, respectively, of the Kiel-I sub-cohort. In both validation sub-cohorts, statistically significant predictors of the PCS score included the intensity of acute phase symptoms and the level of personal resilience.

Interpretation

PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions.

Funding

The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).