AUTHOR=Hofmann Hanna , Önder Alexandra , Becker Juliane , Gröger Michael , Müller Markus M. , Zink Fabian , Stein Barbara , Radermacher Peter , Waller Christiane 

TITLE=Markers of oxidative stress during post-COVID-19 fatigue: a hypothesis-generating, exploratory pilot study on hospital employees

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1305009

DOI=10.3389/fmed.2023.1305009

ISSN=2296-858X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Method</title><p>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 (<inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><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></inline-formula>) 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”).</p></sec><sec><title>Results</title><p>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 <italic>t</italic>-test. Fatigue intensity decreased from 24 ± 5 at T1 to 18 ± 8 at T2 (<italic>p</italic> &lt; 0.05), which coincided with reduced <inline-formula><mml:math id="M2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><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></inline-formula> formation (from 239 ± 55 to 195 ± 59 nmol/s; <italic>p</italic> &lt; 0.05) and attenuated DNA damage [tail moment from 0.67 (0.36–1.28) to 0.32 (0.23–0.71); <italic>p</italic> = 0.05].</p></sec><sec><title>Discussion</title><p>Our pilot study shows that post-COVID-19 fatigue coincides with (i) enhanced <inline-formula><mml:math id="M3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><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></inline-formula> formation and oxidative stress, which are (ii) reduced with attenuation of fatigue symptoms.</p></sec>