1. Background
Due to the Post-COVID Syndrome (PCS), health care systems worldwide are confronted with an increasing number of patients who do not fully recover after SARS-CoV-2 infection [1, 2]. The exact pathomechanism is not yet understood and appears to vary individually. A portion of patients affected by PCS reports a clinical picture that shows significant overlap with the chronic, multisystem disease Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [1, 2]. Since there is no clinically validated biomarker for either condition and the diagnosis often relies on clinical symptoms [3], the exact number of affected individuals can only be estimated. In the case of ME/CFS, a prevalence of 0.3 to 0.8% is assumed [4]. We know that a subgroup (1-10%) of individuals previously infected with SARS-CoV-2 might develop PCS of the ME/CFS type, which is expected to double the prevalence of ME/CFS in the coming years [1, 2]. Similar to PCS, ME/CFS is often reported to begin with viral infections [5, 6]. Both conditions are suspected to involve altered immune functions such as chronic immune activation or immunodeficiencies, but also gastrointestinal dysregulation, mitochondrial dysfunctions and metabolic changes are described [5, 7-10]. In many cases, a recruitment of immune cells and the subsequent enhanced release of cytokines is suspected to detrimentally effect the otherwise tightly regulated pathways in the body.
Although, SARS-CoV-2 primarily targets the lungs causing respiratory symptoms, the infection affects multiple organ systems, including the GI tract. SARS-CoV-2 can cause direct injury to intestinal epithelial and endothelial cells or induce damage indirectly through immune responses. Significant changes to the intestinal microbiota were observed, disrupting local immune responses [7]. Additionally, it compromises the barrier’s structural integrity by altering the expression of tight junction proteins [11]. Persistent SARS-CoV-2 reservoirs in host organs are plausible, as other respiratory RNA viruses, such as latent respiratory syncytial virus or influenza A virus, have been observed to persist for extended periods in murine models [12, 13]. The angiotensin converting enzyme 2 (ACE-2) expressed in the epithelium of the GI tract serves as an entry site and as a reservoir for SARS-CoV-2. A systematic review and meta-analysis of studies reported GI symptoms in patients after COVID-19 were seen in 12% of non-PCS patients and in 22% of PCS patients, suggesting an even more important role of the GI tract in PCS than during the acute infection [14]. This raises the question, whether viral persistence, organ damage during acute COVID-19 or other persistent GI changes might be observed with PCS.
Our study aims to address this issue by combining medical record data of a prospective observational study with analysis of blood, saliva and stool samples of a well characterized PCS patient cohort. We focus not only on symptoms experienced during and after the disease, but also on complaints before SARS-CoV-2 infection to identify potential risk factors and predictive markers.