Parasympathetic inflexibility as potential central precipitating and perpetuating factor for post-COVID-19 exhaustion symptoms

• Applicant: Dr. Magdalena Wekenborg
• Subject Area: Biological Psychology and Cognitive Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529032207

Exhaustion is the core symptom of a syndrome which persists beyond the acute phase of an infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). This syndrome is often referred to as Long COVID or post-COVID-19. Current estimates project that approximately 30% of the individuals infected with SARS-CoV-2 will develop post-COVID-19 exhaustion symptoms. According to the Johns Hopkins Coronavirus Resources Center, the number of confirmed SARS-CoV-2 infections exceeded 670 million cases worldwide in February 2023. Keeping this in mind, developing long-term planning for exhaustion symptom management amongst patients beyond acute stages of SARS-CoV-2 infections appears to be an urgent necessity. Understanding similarities and differences in underlying biological pathways between post-COVID-19 exhaustion symptoms and other, more researched pathologies would be of great importance especially with regard to the transferability of possible treatment strategies for the severe individual and societal consequences of exhaustion symptoms. Reductions in parasympathetic flexibility, as indicated by reduced vagally-mediated heart rate variability (vmHRV) appear to be a valid starting point for such a biological pathway, as the applicant could provide first evidence of reduced vmHRV being causally predictive of enhanced chronic stress associated exhaustion symptoms. Taken together with previous research on the central role of parasympathetic flexibility for an adequate response of biomarkers of acute inflammation (esp. interleukin 6 [IL-6]) in infections in general (cholinergic anti-inflammatory pathway) and in SARS-CoV-2 infections in particular, the applicant proposes a model on the role of parasympathetic inflexibility for post-COVID-19 exhaustion symptoms. The aim of the present project is to test central aspects of this model. This will be done by examining both: 1.the predictive power of pre-pandemic measurements of vmHRV and biomarkers of acute inflammation for post-COVID-19 exhaustion symptoms 2. as well as the interplay between vmHRV, biomarkers of acute inflammation and these exhaustion symptoms over a time span of one year after an acute infection with SARS-CoV-2 by combining laboratory methods with ecological momentary assessment.

• DFG Programme: Research Grants