key: cord-0694946-3aln5l9d
authors: Apiwattanakul, M.; Suanprasert, N.; Rojana-Udomsart, A.; Termglinchan, T.; Sinthuwong, C.; Tantirittisak, T.; Hanchaiphiboolkul, S.; Angchaisuksiri, P.; Srimahachota, S.; Wongsawat, J.; Stiudomkajorn, S.; Kiertiburanakul, S.; Techasaensiri, C.; Laisuan, W.; Manosuthi, W.; Doungngern, P.; Jaroenkunathum, W.; Jivapaisarnpong, T.; Panjangampatthan, A.; Chimmanee, J.; Chokephaibulkit, K.
title: Good recovery of immunization stress-related responses presenting as cluster of stroke-like events following CoronaVac and ChAdOx1 vaccinations
date: 2022-03-19
journal: nan
DOI: 10.1101/2022.03.15.22272434
sha: db78e1909f78a71dafde819b4926387b64efb707
doc_id: 694946
cord_uid: 3aln5l9d

Background: Immunization stress-related responses presenting as stroke-like symptoms may develop following COVID-19 vaccination. This study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination. Methods: We conducted a retrospective study of the secondary data of reported adverse events following COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score (i.e., defining the degree of severity/dependence, with higher scores indicating greater disability). The affected side was evaluated for associations with the injection site. Results: In total, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (53.8%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 90% of those receiving ChAdOx1 recovered well (modified Rankin scores <=2, indicating slight or no disability). Conclusions: Immunization stress-related responses presenting as stroke-like symptoms can develop following COVID-19 vaccination. Symptoms that are more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.

were reviewed by the AEFI committee. Causality and relationships to vaccination were 83 determined by consensus. 84 The first ISRR cluster was identified at the start of April 2021; the committee identified five 85 patients with stroke-like symptoms. These patients were healthcare workers (HCWs; i.e., the first 86 group to receive the vaccine in the country). Within one week, we identified many clusters of 87 stroke-like symptoms reported following vaccination, all of which occurred in HCWs. 88 This information spread rapidly through social networks and caused vaccine hesitancy. Impurity 89 or high vaccine specificity were suspected as probable causes. However, the relevant vaccine 90 types were investigated and no problems were found. The AEFI committee convened to review 91 these cases in a timely fashion and found that almost all of the reported cases were those of 92 ISRR. Thus, herein, we report on the clinical features of clustered ISRR presenting with . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) good outcome was defined as an mRS score of 0-2 (indicating slight or no disability), a poor 116 outcome was defined as an mRS score of 3-5 (indicating moderate to severe disability), and 117 mortality was categorized as an mRS score of 6. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

A theory that may explain the occurrence of vaccine-associated stroke-like symptomology based 197 on a mechanism involving complex regional pain syndrome and FND has been proposed in a 198 prior report (3). We note that most patients develop clinical symptoms of dysesthesia or . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 19, 2022. ; https://doi.org/10.1101/2022.03.15.22272434 doi: medRxiv preprint numbness in the same limb as the immunization site. We also note that the patients with stroke- Appropriate follow-up investigation is also essential so as not to miss real structural neurological 208 deficits as well as to provide appropriate investigation and treatment when necessary.

The ISRR clusters evaluated in our study were reported at the time the worldwide vaccine phobia The first case report of stroke-like symptomology occurring after CoronaVac vaccination in this 222 country described an acute prolonged motor aura (4). The patient in this case developed visual 223 symptoms within 15 min after vaccination, followed by left arm numbness and weakness. CT 224 and MRI findings were normal. We performed single-photon emission computerized 225 tomography with Tc-99 ethyl cysteinate dimer, demonstrating relative hypoperfusion to the right 226 cerebral hemisphere. However, in our study, most patients did not develop headaches. We also 227 note that adverse events were likely to be lateralized to the side of injection. We propose that the 228 underlying mechanisms for vaccine-associated ISSR may be of peripheral origin (e.g., pain 229 following vaccination) and may also be integrated with an autonomic response (i.e., a response 230 resembling a reflex sympathetic response, as in complex regional pain syndrome). According to 231 previous research, this symptomology may also involve the central nervous system, as 232 demonstrated by abnormalities in the postcentral gyrus and inferior parietal cortex, which are 233 responsible for afferent information processing (5, 6). This may explain the transient clinical 234 weakness seen in some of our enrolled patients.

ISRR was initially perceived as psychogenic within the medical community. However, these 236 symptoms are real and not iatrogenic. The initial confusion arose from the presenting 237 symptomology being caused by functional physiologic changes rather than by structural damage.

The same situation has been reported with many vaccines in the past (7-11). Many underlying 239 mechanisms have been proposed, including pain due to the vaccination process and/or 240 inflammation occurring after vaccination, which may activate the peripheral nerves and/or the 241 sympathetic nervous system, as explained in a prior description of the proposed complex 242 regional pain syndrome mechanism (3).

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The authors hypothesized that increased attention toward body signals and abnormal 254 expectations regarding the symptoms of vaccination-induced injury may be responsible for this 255 symptomology (13). This report confirms that the process of incident vaccine-associated 256 neurological disorders is more likely due to the vaccination process rather than to specific 257 vaccine constituents, since these events have occurred within various vaccine platforms.

As COVID-19 mass vaccination has been widely implemented among high-risk populations with 259 underlying diseases, we found that some true cases of stroke were simply temporally associated 260 with vaccination within the current study. This caveat provides precautionary information and 261 informs the provision of appropriate timely treatment (vs. empirically treating ISRR in the 262 absence of differential diagnosis). 263 We acknowledge several limitations of this report. Specifically, this evaluation was based on a 264 retrospective study within the secondary data and we may have therefore missed some critical 265 information (especially with respect to outcome data). The reported data regarding female . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 19, 2022. ; https://doi.org/10.1101/2022.03.15.22272434 doi: medRxiv preprint predominance could be due to the initial target population of the nationwide vaccine campaign, 267 which initially comprised HCWs who received preferential vaccination at the start of the vaccine 268 campaign, most of whom were young females (e.g., nurses, therapists). Moreover, we were 269 unable to identify the factors associated with ISRR in this descriptive study and instead present a . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Dr. Apiwattanakul had full access to all the data in the study and takes responsibility for the 288 integrity of the data and the accuracy of the data analysis. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted March 19, 2022. ; https://doi.org/10.1101/2022.03.15.22272434 doi: medRxiv preprint

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