Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Abstract

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.

Increased migratory/activated CD8+ T cell and low avidity SARS-CoV-2 reactive cellular response in post-acute COVID-19 syndrome

“…antibodies with the severity of cognitive symptoms and of M5R with fatigue in post COVID ME/CFS (83).…”

“…We suggest that the PAR2 antibodies function agonistically in the frame of PASC, however further studies are needed to assess our indirect results. Interestingly, Sotzny et al correlate levels of F2R/PAR-1 antibodies with the severity of cognitive symptoms and of M5R with fatigue in post COVID ME/CFS (83).…”

Chemotherapy-Induced, Broadly Reactive Autoantibodies in a Colon Cancer Patient

“…Monitoring the autoimmune status to different organs during cancer treatment, as in the herein described case, may help timely initiate measures to mitigate therapy-induced toxicity before the onset of symptoms. More generally, autoreactive antibodies have been shown to expand, for example, in patients with autoimmune diseases [ 14 ], following physical injury [ 16 , 17 ] or during COVID-19 [ 20 ], among others. Early and rapid diagnosis of autoantibody responses at tissue-level resolution may lead to a better prognosis for these patients as well.…”

SARS-CoV-2 infection induces the production of autoantibodies in severe COVID-19 patients in an age-dependent manner

“…Based on the multivariable regression results, we identified significantly increased titers of ageassociated autoantibodies against 16 targets, which underwent principal component analysis (PCA) with spectral decomposition 55,56 , as previously described 44,57 . This approach allowed us to measure the stratification power of the autoantibodies in distinguishing between severe COVID-19 patients and healthy controls while considering young and elderly groups.…”