TY - JOUR
T1 - Determinants of persistent symptoms after treatment for Lyme borreliosis
T2 - a prospective observational cohort study
AU - Vrijmoeth, Hedwig D.
AU - Ursinus, Jeanine
AU - Harms, Margriet G.
AU - Tulen, Anna D.
AU - Baarsma, M. E.
AU - van de Schoor, Freek R.
AU - Gauw, Stefanie A.
AU - Zomer, Tizza P.
AU - Vermeeren, Yolande M.
AU - Ferreira, José A.
AU - Sprong, Hein
AU - Kremer, Kristin
AU - Knoop, Hans
AU - Joosten, Leo A.B.
AU - Kullberg, Bart Jan
AU - Hovius, Joppe W.
AU - van den Wijngaard, Cees C.
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2023/12
Y1 - 2023/12
N2 - Background: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology. Methods: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice). Findings: Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms. Interpretation: Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated. Funding: Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS).
AB - Background: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology. Methods: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice). Findings: Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms. Interpretation: Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated. Funding: Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS).
KW - Erythema migrans
KW - Lyme borreliosis
KW - Persistent symptoms
UR - http://www.scopus.com/inward/record.url?scp=85179466548&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2023.104825
DO - 10.1016/j.ebiom.2023.104825
M3 - Article
C2 - 38016860
SN - 2352-3964
VL - 98
JO - eBioMedicine
JF - eBioMedicine
M1 - 104825
ER -