Markers of oxidative stress during post-COVID-19 fatigue: a hypothesis-generating, exploratory pilot study on hospital employees
Hanna Hofmann, A. Önder, Juliane Becker, Michael Gröger, Markus Müller, Fabian Zink, Barbara Stein, Peter Radermacher, Christiane Waller
Abstract
Introduction Post-COVID-19 fatigue is common after recovery from COVID-19. Excess formation of reactive oxygen species (ROS) leading to oxidative stress-related mitochondrial dysfunction is referred to as a cause of these chronic fatigue-like symptoms. The present observational pilot study aimed to investigate a possible relationship between the course of ROS formation, subsequent oxidative stress, and post-COVID-19 fatigue. Method A total of 21 post-COVID-19 employees of the General Hospital Nuremberg suffering from fatigue-like symptoms were studied during their first consultation (T1: on average 3 months after recovery from COVID-19), which comprised an educational talk on post-COVID-19 symptomatology and individualized outpatient strategies to resume normal activity, and 8 weeks thereafter (T2). Fatigue severity was quantified using the Chalder Fatigue Scale together with a health survey (Patient Health Questionnaire) and self-report on wellbeing (12-Item Short-Form Health Survey). We measured whole blood superoxide anion ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:msubsup><mml:mrow><mml:mtext>O</mml:mtext></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow><mml:mrow><mml:mo>•</mml:mo><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> ) production rate (electron spin resonance, as a surrogate for ROS production) and oxidative stress-induced DNA strand breaks (single cell gel electrophoresis: “tail moment” in the “comet assay”). Results Data are presented as mean ± SD or median (interquartile range) depending on the data distribution. Differences between T1 and T2 were tested using a paired Wilcoxon rank sign or t -test. Fatigue intensity decreased from 24 ± 5 at T1 to 18 ± 8 at T2 ( p &lt; 0.05), which coincided with reduced <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msubsup><mml:mrow><mml:mtext>O</mml:mtext></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow><mml:mrow><mml:mo>•</mml:mo><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> formation (from 239 ± 55 to 195 ± 59 nmol/s; p &lt; 0.05) and attenuated DNA damage [tail moment from 0.67 (0.36–1.28) to 0.32 (0.23–0.71); p = 0.05]. Discussion Our pilot study shows that post-COVID-19 fatigue coincides with (i) enhanced <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:msubsup><mml:mrow><mml:mtext>O</mml:mtext></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow><mml:mrow><mml:mo>•</mml:mo><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> formation and oxidative stress, which are (ii) reduced with attenuation of fatigue symptoms.