BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines.
OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions.
METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements.
RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes.
CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.

UNASSIGNED: The sensation of throat closure after vaccination is concerning for anaphylaxis and leads to vaccine hesitancy.
UNASSIGNED: We characterized patients who developed laryngopharyngeal symptoms (LPhS) after coronavirus disease 2019 (COVID-19) vaccination and assessed risk factors for these symptoms.
UNASSIGNED: The study analyzed data from the COVID-19 vaccines adverse reactions registry (December 14, 2020, to June 13, 2022). Outcomes included the incidence of postvaccination LPhS and use of epinephrine. We identified and compared risk factors for COVID-19 postvaccination reactions between subjects with and without LPhS.
UNASSIGNED: A total of 158 subjects were enrolled onto the registry. LPhS were reported in 61 subjects (38.6%), of whom 52 (85.2%) received a subsequent dose. With initial vaccination, the use of epinephrine was higher in subjects with LPhS (20%) compared to those without (6%; P = .0094). Fifty-two subjects (85.2%) with LPhS received a subsequent COVID-19 vaccine dose with milder or no symptoms, and none needed treatment with epinephrine. Those with LPhS were more likely to have a history of drug allergies (P = .02), severe medication allergies (P = .03), gastroesophageal reflux disease (P = .018), and need for antireflux medications (P = .0085) compared to controls.
UNASSIGNED: In our registry, postvaccination LPhS were common. LPhS can mimic anaphylaxis and lead to more frequent use of epinephrine. Gastroesophageal reflux disease was more frequent in these subjects. Patients with subjective throat closure sensation can safely receive subsequent vaccine doses with close observation and reassurance. LPhS are not unique to COVID-19 vaccines. Patient and provider education regarding the role of gastroesophageal reflux disease as a risk factor for LPhS with vaccination can improve vaccine uptake.

mRNA-based COVID-19 vaccines are effective; however, persistent vaccine hesitancy is partly due to a misperception of their potential adverse events. Non-specific sensory symptoms (NSSS) following immunization are thought to be mediated by stress-related responses. In this case-control study, we evaluated NSSS from a cohort of 7,812,845 BNT162b2 first-dose recipients, of whom 10,929 reported an adverse event following immunization (AEFI). We found an overall frequency of 3.4% (377 cases) or 4.8 cases per 100,000 doses administered. Anatomically, the arms (61%) and face/neck region (36.2%) were the most commonly affected sites. The control group had significantly higher rates of reactogenicity-associated symptoms, suggesting that NSSS are reactogenicity-independent; in multivariable analysis, healthcare workers reported sensory symptoms less frequently (aOR 0.54; 95% CI 0.40-0.72;p < 0.001). This is the first study describing the topography and associated factors for developing NSSS among BNT162b2 recipients. The benign nature of these symptoms may help dissipate hesitation towards this vaccine.

The absence of a positive diagnosis of psychogenic non-epileptic seizures (PNES) in immunization stress-related response (ISRR) clusters may have not only a direct impact on affected patients\' health but may also reduce compliance to national vaccination programs. It is therefore crucial to develop efficient diagnostic tools and a feasible proposal for proper communication and treatment of ISRR.
To explore the psychogenic nature of patients\' convulsive seizures in a suspected outbreak of an ISRR cluster following human papillomavirus vaccination in Rio Branco, Brazil.
Twelve patients with convulsive seizures were submitted to prolonged intensive video-electroencephalography monitoring, brain magnetic resonance imaging, cerebrospinal fluid diagnostic testing, laboratory subsidiary examinations, and complete neurological and psychiatric evaluations.
Ten patients received the positive diagnosis of PNES, and two patients received the diagnosis of idiopathic generalized epilepsy. No biological association was found between the HPV vaccine and the clinical problems presented by the patients.
Prolonged VEEG monitoring can contribute significantly to the positive diagnosis of PNES in ISRR clusters and to avoid hesitancy to vaccinate.