# Neurological and Immunological Insights Into Post-COVID-19 Syndrome: A Single-Center Retrospective Study

## TL;DR

This study explores the long-term effects of post-COVID-19 syndrome, focusing on symptoms like fatigue and immune markers such as ferritin and ANA.

## Contribution

The study identifies immune dysregulation as a potential underlying mechanism in post-COVID-19 syndrome through longitudinal biomarker analysis.

## Key findings

- Fatigue, sleep disturbances, and pain were the most common symptoms, with 82.4% of patients still experiencing fatigue at follow-up.
- Elevated ferritin levels were found in 78.1% of patients, and 40% had high ANA titers, indicating immune activation.
- Most patients with elevated ferritin and ANA remained above normal thresholds at follow-up, suggesting ongoing immune dysregulation.

## Abstract

Introduction

Following the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), post-COVID-19 syndrome (PCS) has emerged as a major health concern, affecting approximately 3.0-11.7% of infected individuals. While neuropsychiatric symptoms such as fatigue, pain, and sleep disturbances dominate the clinical picture, recent evidence suggests a pivotal role for immune dysregulation in the pathophysiology of PCS. This study aimed to analyze the clinical course and laboratory features of patients with PCS.

Methods

In this retrospective single-center study, 74 patients with PCS were evaluated between November 2020 and June 2022 at the Department of Neurology, University Hospital Bern. Clinical assessments included standardized questionnaires [Fatigue Severity Scale (FSS), Fatigue Scale of Motor and Cognitive Function (FSMC), Beck Depression Index II (BDI-II), Epworth Sleepiness Scale (ESS)] and laboratory investigations at two timepoints. Particular focus was placed on immune-related biomarkers, including ferritin and antinuclear antibodies (ANA).

Results

Fatigue, sleep disturbances, and pain were the most frequently reported symptoms. At follow-up (a mean duration of 14.4 weeks after the first consultation), both symptom burden and severity scores decreased significantly. Nevertheless, 82.4% of patients continued to report fatigue. Elevated ferritin levels were found in 78.1% of tested patients (mean: 306.9 µg/l), and ANA titres ≥1:160 were observed in 40% of patients without known autoimmune disease. At follow-up, 80% of patients with initially elevated ferritin and 68% with elevated ANA remained above normal thresholds, suggesting ongoing immune activation.

Conclusions

While symptom burden declined over time, most PCS patients continued to experience clinically relevant symptoms. The persistence of elevated ferritin and ANA levels underscores possible immune dysregulation and highlights the potential of these biomarkers in characterizing PCS. These findings underline the need for further studies investigating their diagnostic and therapeutic relevance.