Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dysautonomia tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2 vaccination of healthy controls (N = 89; 71 females; mean/median age: 39/49 years) were compared with corresponding values of PACVS-affected persons (N = 191; 159 females; mean/median age: 40/39 years) exhibiting chronic fatigue/dysautonomia (>= three symptoms for >= five months after the last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases in 11 receptor antibodies (by 25-50%, p < 0.0001), increases in two receptor antibodies (by 15-25%, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p < 0.0001) by increased Angiotensin II type 1 receptor antibodies (cut-off <= 10.7 U/mL, ROC-AUC = 0.824 +/- 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off >= 25.2 U/mL, ROC-AUC = 0.828 +/- 0.025) and increased IL-6 (cut-off <= 2.3 pg/mL, ROC-AUC = 0.850 +/- 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers.

Automated summary

SARS-CoV-2 mRNA vaccination may lead to chronic fatigue/dysautonomia known as post-acute COVID-19 vaccination syndrome (PACVS). Receptor autoantibodies and interleukin-6 (IL-6) were identified as somatic correlates of PACVS. Diagnostic blood markers, including increased Angiotensin II type 1 receptor antibodies, decreased alpha-2B adrenergic receptor antibodies, and elevated IL-6, can distinguish PACVS from normal post-vaccination state.