Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS)

Abstract

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years). Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented. Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms. Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis.

Keywords: PACVS; cognitive impairment; interleukin-6; interleukin-8; malaise/chronic fatigue; peripheral nerve dysfunction; post-acute COVID-19 vaccination syndrome.

Figure 1

Overlap of complex dysautonomia syndromes with symptoms reported by the PACVS study cohort. ME/CSF, POTS, MCAS, and SFN were assigned to the study participants according to published guidelines [4,5,7,8]. PACVS subjects were assigned a given syndrome if exhibiting n ≥ the cohort average of symptoms associated with that syndrome or if diagnosed after vaccination with that syndrome by a physician. A total of n = 31 PACVS subjects could not be assigned to any of the four syndromes (labeled “NONE”). Numbers indicate the n of study participants assigned to a given syndrome or syndrome intersection.

Figure 2

Hypothesis-free clustering of PACVS-associated symptoms. Hierarchical clustering of symptoms reported by the participants of the PACVS study cohort was performed using a modified Jaccard index considering distances of similarities and dissimilarities. The eight clusters indicated at the bottom were selected at the level h = 1.8 based on medical knowledge using the cut-tree function of the computer language R (details of clusters are in Table 2).

Figure 3

Matching of study participants to symptom clusters. Study participants were assigned to the eight clusters (Figure 2) based on the modified Jaccard index (mean of Jaccard index and Jaccard index of the negated values). Participants highlighted in red strongly matched the symptom cluster, those in white moderately matched the cluster, and those in blue matched the cluster poorly or not at all (value = 1: strong correlation with the cluster based on the modified Jaccard index; value = 0: no correlation with the cluster based on the modified Jaccard index).