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.