Comparing reactions to COVID-19 and influenza vaccinations: data from patient self-reporting, smartwatches and electronic health records (preprint)

BackgroundPublic reluctance to receive COVID-19 vaccination is due in large part to safety concerns. We compare the safety profile of the BNT162b2 COVID-19 booster vaccine to that of the seasonal influenza vaccine, which has been administered for decades with a solid safety record and a high level of public acceptance. MethodsWe study a prospective cohort of 5,079 participants in Israel (the PerMed study) and a retrospective cohort of 250,000 members of Maccabi Healthcare Services. We examine reactions to BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 booster vaccinations and to influenza vaccination. All prospective cohort participants wore a Garmin Vivosmart 4 smartwatch and completed a daily questionnaire via smartphone. For the prospective cohort, we compare pre-vaccination (baseline) and post-vaccination smartwatch heart rate data and a stress measure based on heart rate variability, and we examine symptom severity from patient self-reports. For the retrospective cohort, we examine electronic health records (EHRs) for the existence of 28 potential adverse events during the 28-day period before and after each vaccination. FindingsIn the prospective cohort, 1,905 participants received COVID-19 vaccination; 899 received influenza vaccination. Focusing on those who received both vaccines yielded a total of 689 participants in the prospective cohort and 31,297 members in the retrospective cohort. Questionnaire analysis: For the COVID-19 vaccine, 39{middle dot}7% [95% CI 36{middle dot}4%-42{middle dot}9%] of individuals reported no systemic reaction vs. 66{middle dot}9% [95% CI 63{middle dot}4%-70{middle dot}3%] for the influenza vaccine. Individuals reporting a more severe reaction after influenza vaccination tended to likewise report a more severe reaction after COVID-19 vaccination (r=0{middle dot}185, p<0{middle dot}001). Smartwatch analysis: A statistically significant increase in heart rate and stress measure occurred during the first 3 days after COVID-19 vaccination, peaking 22 hours after vaccination with a mean increase of 4{middle dot}48 (95% CI 3{middle dot}94-5{middle dot}01) beats per minute and 9{middle dot}34 (95% CI 8{middle dot}31-10{middle dot}37) units in the stress measure compared to baseline. For influenza vaccination, we observed no changes in heart rate or stress measures. In paired analysis, the increase in both heart rate and stress measure for each participant was higher (p-value < 0{middle dot}001) for COVID-19 vaccination than for influenza vaccination in the first 2 days after vaccination. On the second day after vaccination, participants had 1{middle dot}5 (95% CI 0{middle dot}68-2{middle dot}20) more heartbeats per minute and 3{middle dot}8 (95% CI 2{middle dot}27-5{middle dot}22) units higher stress measure, compared to their baseline. These differences disappeared by the third day after vaccination. EHR analysis: We found no elevated risk of non-COVID-19 or - influenza hospitalization following either vaccine. COVID-19 vaccination was not associated with an increased risk of any of the adverse events examined. Influenza vaccination was associated with an increased risk of Bells palsy (1{middle dot}3 [95% CI 0{middle dot}3-2{middle dot}6] additional events per 10,000 people). InterpretationThe more pronounced side effects after COVID-19 vaccination compared to influenza vaccination may explain the greater concern regarding COVID-19 vaccines. Nevertheless, our findings support the safety profile of both vaccines, as the reported side effects and physiological reactions measured by the smartwatches faded shortly after inoculation, and no substantial increase in adverse events was detected in the retrospective cohort. FundingThis work was supported by the European Research Council, project #949850, and a Koret Foundation gift for Smart Cities and Digital Living. RESEARCH IN CONTEXT Evidence before this studyThe unprecedented global impact of COVID-19 led to the rapid development and deployment of vaccines against the virus, including vaccines using novel mRNA technology. Despite the promising effectiveness of mRNA vaccines in preventing severe outcomes of COVID-19, concerns have been raised regarding the safety profile of these new vaccines. These concerns led to a notable global public reluctance to become vaccinated. By contrast, the seasonal influenza vaccine has been administered for decades with a well-established safety record and a high level of public acceptance. We searched Google Scholar, PubMed, and preprint services (including medRxiv, bioRrxiv, and SSRN) for studies comparing the safety profile of the two vaccines between March 1, 2023 (our studys launch) and May 30, 2023, with no language restrictions, using the terms "safety of" AND ("COVID-19" OR "SARS-CoV-2") AND ("vaccine" OR "BNT162b2 (Pfizer-BioNTech) mRNA vaccine") AND "compared to" AND ("Influenza" OR "seasonal influenza" OR "flu") AND "vaccine". We found a study that compared the safety profile of the mRNA COVID-19 vaccine among 18,755 recipients with 27,895 recipients of the seasonal influenza vaccine using the WHO international database. The authors found a different safety pattern between the two vaccines with more systematic reactions following inoculation of the COVID-19 vaccine. Additionally, COVID-19 vaccines were associated with a higher risk of cardiovascular adverse events, while the influenza vaccine was associated with a higher risk of neurological adverse events. The remaining studies identified in our search compared the simultaneous administration of both vaccines to the administration of only COVID-19 vaccines. None of the studies conducted a paired analysis that compared reactions post-influenza vaccination and post-COVID-19 vaccination for the same individual; none examined the extent of physiological reaction (in terms of heart rate and heart rate variability) following the administration of COVID-19 or seasonal influenza vaccines; and none examined a cohort of individuals with data from before and after vaccination episodes or presented a comprehensive analysis to address concerns regarding the existence of potential rare adverse events following vaccination. Added value of this studyWe studied a prospective cohort of 5,079 participants in Israel (the PerMed study) from October 31, 2020 to September 30, 2022 and a retrospective cohort of 250,000 members of Maccabi Healthcare Services from July 31, 2021 and March 1, 2023. We examined reactions to BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccination (third or fourth shot) and to influenza vaccination. We compared the extent of reactions at the individual level, among individuals who received both vaccines separately. While the self-reported data and the continuous physiological measures from smartwatches revealed a higher rate of reactions following COVID-19 vaccination, these reactions faded soon after inoculation. We found no increase in risk of rare adverse events for either vaccine. We found a weak, albeit significant, correlation in the severity of the symptoms for the two vaccines (r=0{middle dot}185, p<0{middle dot}001): individuals who reported a more severe reaction after influenza vaccination tended to likewise report a more severe reaction after COVID-19 vaccination. We found no elevated risk of non-COVID-19 or - influenza hospitalization following the administration of either vaccine. COVID-19 vaccination was not associated with increased risk of any of the adverse events examined. Influenza vaccination was associated with an increased risk of Bells palsy (1{middle dot}3 [95% CI 0{middle dot}3-2{middle dot}6] additional events per 10,000 people). Implications of all the available evidenceOur study demonstrates the importance of accounting for continuous and objective surveillance of vaccines in both the clinical trial phase and the post-marketing phase, as it can aid in evaluating the safety profile of clinical trials and reduce vaccine hesitancy. The more pronounced side effects after COVID-19 vaccination compared to influenza vaccination may explain the greater concern regarding COVID-19 vaccines. Nevertheless, our findings support the safety profile of both vaccines, as the reported side effects and physiological reactions measured by the smartwatches faded shortly after inoculation, and no substantial increase in adverse events was detected in the retrospective cohort.

A case with prolonged headache after COVID-19 vaccination and later developed Bell's palsy.

PURPOSE: During COVID-19 pandemic, the authorization of emergent usage of new vaccine has raised suspicions and doubts about potential adverse events related to vaccination. Among the reported adverse events related to ChAdOx1/nCoV-19 vaccine, facial paralysis did not have an incident rate higher than natural occurrence like mRNA vaccines. However, temporal association between vaccination and facial palsy have been documented in several studies. Here, we report a case of an otherwise healthy 23-year-old Taiwanese female who experienced prolonged headache since the second day postvaccination and developed facial palsy on the tenth day. CASE REPORT: A 23-year-old Taiwanese female who was previously healthy experienced intermittent right side throbbing headache, general malaise, myalgia and fever. Headache, transient ear pain and right scalp numbness developed in the next few days but quickly resolved. On day ten after vaccination, signs of facial palsy on the right side of her face was noticed. The results of brain Magnetic Resonance Imaging (MRI) with contrast displayed no abnormality. Facial stimulation and blink reflex tests were compatible with right facial neuropathy. CONCLUSION: Reactivation of latent herpes virus has been suggested as one of the possible mechanisms underlying the phenomenon, but the causal pathophysiology related to the symptom needs further validation. Moreover, in the event of facial palsy post-vaccination, alternative diagnoses such as Guillain-Barre syndrome (GBS), Ramsey-Hunt syndrome, Lyme disease, trauma, central nervous system infection (CNS) infection, or stroke should also be considered.

Transient Bell's palsy following Covid-19 vaccination.

Bell's palsy is described as an acute, unilateral mononeuropathy of the facial nerve resulting in partial or complete paralysis of the face with no identifiable cause. Although facial palsy is often idiopathic, its development soon after the BB-152 Covid vaccine is exceedingly rare. We report a patient with transient acute-onset unilateral infranuclear facial palsy following vaccination, after an exhaustive work-up for other common causes was negative. With no detectable aetiology the likelihood of an association of the Covid-19 vaccine and Bell's palsy remains.

Association of SARS-CoV-2 Vaccination or Infection With Bell Palsy: A Systematic Review and Meta-analysis.

Importance: Bell palsy (BP) has been reported as an adverse event following the SARS-CoV-2 vaccination, but neither a causative relationship nor a higher prevalence than in the general population has been established. Objective: To compare the incidence of BP in SARS-CoV-2 vaccine recipients vs unvaccinated individuals or placebo recipients. Data Sources: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, and Google Scholar from the inception of the COVID-19 report (December 2019) to August 15, 2022. Study Selection: Articles reporting BP incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted with the random- and fixed-effect models using the Mantel-Haenszel method. The quality of the studies was evaluated by the Newcastle-Ottawa Scale. Main Outcomes and Measures: The outcomes of interest were to compare BP incidence among (1) SARS-CoV-2 vaccine recipients, (2) nonrecipients in the placebo or unvaccinated cohorts, (3) different types of SARS-CoV-2 vaccines, and (4) SARS-CoV-2-infected vs SARS-CoV-2-vaccinated individuals. Results: Fifty studies were included, of which 17 entered the quantitative synthesis. Pooling 4 phase 3 randomized clinical trials showed significantly higher BP in recipients of SARS-CoV-2 vaccines (77 525 vaccine recipients vs 66 682 placebo recipients; odds ratio [OR], 3.00; 95% CI, 1.10-8.18; I2 = 0%). There was, however, no significant increase in BP after administration of the messenger RNA SARS-CoV-2 vaccine in pooling 8 observational studies (13 518 026 doses vs 13 510 701 unvaccinated; OR, 0.70; 95% CI, 0.42-1.16; I2 = 94%). No significant difference was found in BP among 22 978 880 first-dose recipients of the Pfizer/BioNTech vaccine compared with 22 978 880 first-dose recipients of the Oxford/AstraZeneca vaccine (OR, 0.97; 95% CI, 0.82-1.15; I2 = 0%). Bell palsy was significantly more common after SARS-CoV-2 infection (n = 2 822 072) than after SARS-CoV-2 vaccinations (n = 37 912 410) (relative risk, 3.23; 95% CI, 1.57-6.62; I2 = 95%). Conclusions and Relevance: This systematic review and meta-analysis suggests a higher incidence of BP among SARS-CoV-2-vaccinated vs placebo groups. The occurrence of BP did not differ significantly between recipients of the Pfizer/BioNTech vs Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccination.

Observed-over-Expected analysis as additional method for pharmacovigilance signal detection in large-scaled spontaneous adverse event reporting.

BACKGROUND: The large-scale COVID-19 vaccination campaigns in 2021 and 2022 led to a rapid increase in numbers of received adverse event reports in spontaneous reporting systems. As background incidences of naturally occurring medical events became increasingly relevant for causality assessment of potential associations with the vaccines, a novel approach for signal detection was warranted. OBJECTIVES: This article illustrates the Observed-over-Expected (O/E) analysis as an additional method for signal detection and risk assessment in large-scaled spontaneous reporting systems. METHODS: All individual case safety reports (ICSRs) concerning idiopathic peripheral facial paralysis or Bell's palsy following administration of the COVID-19 vaccines (n = 291) manufactured by Pfizer/BioNTech (Comirnaty), Moderna (Spikevax), AstraZeneca (Vaxzevria) and Janssen (JCOVDEN) received by the National Pharmacovigilance Centre Lareb until 24th March 2022 were included in the O/E analysis, within a risk window of 7 and 14 days following immunisation. Dutch background incidence rates from 2019 and exposure of the Dutch population to the vaccines were obtained from the PHARMO institute and RIVM. The data was stratified in age groups, gender and administered dose in order to differentiate between population subgroups. RESULTS: Bell's palsy was reported more frequently than expected in several population subgroups following administration of all four COVID-19 vaccines, including children and adolescents. Among children, a high O/E ratio was found for boys aged 5-14 years after receiving the Pfizer/BioNTech vaccine. Regarding adolescents and young adults, women aged 15-24 years receiving Pfizer/BioNTech and Moderna, and men aged 15-24 years receiving Janssen developed Bell's palsy more often than expected. Furthermore, O/E ratios were high for individuals aged 25-64, regarding females receiving Pfizer, Moderna and AstraZeneca and males receiving Janssen. As facial paralysis was not labelled as an adverse event for the Janssen vaccine, this analysis contributed to signalling the association and warranting further regulatory action. CONCLUSIONS: The O/E method is a useful approach for signal detection of potential adverse reactions when handling large numbers of ICSRs. Further research is needed to attest to the causality on a clinical basis.

Facial Palsy in COVID-19 Patient: A Case Report.

Facial paralysis is one of the common problems leading to facial deformation. COVID-19 virus rarely has been shown to be associated with facial palsy. Here we present a case of a 60-year-old woman who presented with features of left lower motor facial palsy signs along with common features suggestive of COVID-19 infection. Brain imaging did not reveal any pertinent pathology but her polymerase chain reaction for COVID-19 was positive. This case highlights the fact that acute COVID-19 infection can be considered a cause of motor neuron facial palsy in the ongoing pandemic of COVID-19. Cases with neurological features suggestive of facial palsy therefore should be suspected of acute COVID-19 infection based on other pertinent findings of COVID-19 infection and thus polymerase chain reaction testing should be done. Keywords: case reports; COVID-19; facial palsy.

Evaluation of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Adults Aged 65 Years and Older: A Self-Controlled Study in the U.S. (preprint)

Background Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevations in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluations of the potential associations. Methods We conducted self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged 65 years and older. Adjusted incidence rate ratio (IRRs) and 95% confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following booster doses for AMI, PE, ITP, Bells Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). Results Among 3,360,981 individuals who received 6,388,542 primary series doses and 6,156,100 individuals with monovalent booster doses of either BNT162b2 or mRNA-1273, AE counts were: AMI (3,653 primary series, 16,042 booster), inpatient PE (2,470 primary, 5,085 booster), ITP (1,085 primary, 88 booster), DIC (254 primary), BP (3,268 booster), and Myo/Peri (1,295 booster). The IRR for inpatient PE cases following BNT162b2 primary series and booster was 1.19 (95% CI: 1.03 to 1.38) and 0.86 (95% CI: 0.78 to 0.95), respectively; and for mRNA-1273 primary series and booster, 1.15 (95% CI: 0.94 to 1.41) and 0.87 (95% CI: 0.79 to 0.96), respectively. The IRR for BP following BNT162b2 and mRNA-1273 booster was 1.17 (95% CI: 1.06 to 1.29) and 1.16 (95% CI: 1.05 to 1.29), respectively. Conclusion In these two studies of the U.S. elderly we did not find an increased risk for AMI, ITP, DIC, and Myo/Peri; the results were not consistent for PE; and there was a small elevated risk of BP after exposure to COVID-19 mRNA vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the elderly.

Facial nerve palsy following the administration of COVID-19 mRNA vaccines: analysis of a self-reporting database.

OBJECTIVES: Facial nerve palsy (or Bell's palsy) has occasionally been reported following the administration of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2 and mRNA-1273). Our study investigated such cases using a large self-reporting database from the USA (Vaccine Adverse Event Reporting System [VAERS]). METHODS: A disproportionality analysis, adjusted for age and sex, was conducted for VAERS reports from individuals who were vaccinated at the age of 18 years or over, between January 2010 and April 2021. RESULTS: The analysis revealed that the adverse events following immunization (AEFI) of facial nerve palsy, after administration of COVID-19 mRNA vaccines, was significantly highly reported, both for BNT162b2 (reporting odds ratio [ROR] 1.84; 95% confidence interval [CI] 1.65-2.06) and mRNA-1273 (ROR 1.54; 95% CI 1.39-1.70). These levels were comparable to that following influenza vaccination reported before the COVID-19 pandemic (ROR 2.04; 95% CI 1.76-2.36). CONCLUSIONS: Our pharmacovigilance study results suggest that the incidence of facial nerve palsy as a non-serious AEFI may be lower than, or equivalent to, that for influenza vaccines. This information might be of value in the context of promoting worldwide vaccination, but needs to be validated in future observational studies.

Hypoglossal nerve palsy after SARS-CoV-2 vaccination - report of two cases.

BACKGROUND: SARS-CoV-2 vaccination is associated with an increased risk for Bell's palsy and some other neurological disorders assumed to be of autoimmune origin. While facial nerve palsy is frequent and usually idiopathic, hypoglossal nerve palsy is rare, and a specific cause is almost always found. We firstly report two patients who developed isolated hypoglossal nerve palsy shortly after SARS-CoV-2 vaccination. CASE PRESENTATION: Two otherwise healthy patients, a 49-year-old man and a 39-year-old woman, developed unilateral hypoglossal nerve palsy 10 and 7 days after the second SARS-CoV-2-vaccination (AstraZeneca and BioNTech/Pfizer), respectively. In both subjects, needle electromyography showed denervation and rarefication of motor units. CT, MRI, examination of blood and CSF as well as ENT exam were unremarkable. In both subjects symptoms gradually improved. CONCLUSION: Due to close temporal relationship, the absence of other etiologies, and spontaneous improvement we suspect the vaccination as the cause for hypoglossal nerve palsy in both patients. This is further supported by the rarity of isolated hypoglossal nerve palsies, especially in idiopathic cases. We suggest the addition of hypoglossal nerve palsy to the list of neurological injuries potentially caused by SARS-CoV-2 vaccination.

Bell's Palsy Following SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis (preprint)

Background and Objective Bell's palsy (BP) has been considered as a serious adverse event following the SARS-CoV-2 vaccination. Many studies have reported BP following vaccination, although neither a causative relationship nor a prevalence of the condition higher than the general population has been established. The outcomes of interest were to compare BP incidence among (a) SARS-CoV-2 vaccine recipients, (b) nonrecipients in the placebo or unvaccinated cohorts, (c) different types of SARS-CoV-2 vaccines, and (d) SARS-CoV-2 infected vs. SARS-CoV-2 vaccinated individuals. Methods We performed a systematic search through MEDLINE (via PubMed), Web of Science, Scopus, Cochrane library, and Google Scholar from the inception to August 15, 2022. We included articles reporting individuals receiving any SARS-CoV-2 vaccine in whom BP had occurred. Studies reporting facial paralysis due to etiologies other than BP were excluded. Random- and fixed-effects meta-analyses using the Mantel-Haenszel method were conducted for the quantitative synthesis. Newcastle-Ottawa scale (NOS) was used to assess the quality. The study was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, and the protocol was registered with PROSPERO (CRD42022313299). Analyses were carried out using the R, version 4.2.1 (R package 'meta' version 5.2-0). Results Fifty studies were included, of which 17 entered the quantitative synthesis. First, pooling four phase-3 randomized controlled trials (RCT) indicated BP occurrence was significantly higher in SARS-CoV-2 vaccines (77, 525 doses) compared to placebo (66, 682 doses) (OR = 3.00, 95% CI = 1.10 - 8.18, I2 = 0%). Second, pooling nine observational studies of mRNA SARS-CoV-2 vaccine doses (13, 518,026) and matched unvaccinated individuals (13, 510,701) revealed no significant increase in the odds of BP in the vaccinated group compared to the unvaccinated group (OR: 0.70 (95% CI 0.42-1.16), I2=94%). The third meta-analysis suggested that post-vaccination BP among first dose Pfizer/BioNTech recipients (22,760,698) did not significantly differ from that in first dose Oxford/AstraZeneca recipients (22,978,880) (OR = 0.97, 95% CI = 0.82 - 1.15, I2 = 0%). According to the fourth meta-analysis, BP was significantly more commonly reported after SARS-CoV-2 infection (2,641,398) than after SARS-CoV-2 vaccinations (36,988,718) (RR = 4.03, 95% CI = 1.78 - 9.12, I2 = 96%). Conclusion Our meta-analysis suggests a higher incidence of BP among vaccinated vs. placebo groups. BP occurrence did not significantly differ between Pfizer/BioNTech and Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccines.

Concomitant Guillain-Barré syndrome and cerebral venous thrombosis complicating a SARS-CoV-2 infection: a case report.

Cerebral venous thrombosis associated to acute inflammatory axonal polyneuropathy during infection with SARS-CoV-2 (coronavirus-2) is unusual. We describe the case of a 66-year-old patient with typical clinical and electrophysiological criteria of acute axonal motor neuropathy, who was positive for SARS-CoV-2. The symptoms started with fever associated with respiratory symptoms, and complicated one week later by headaches, and general weakness. The examination showed bilateral peripheral facial palsy, predominantly proximal tetraparesis, and areflexia with tingling of limbs were found. The whole was concomitant with the diagnosis of an acute polyradiculoneuropathy. Electrophysiologic evaluation confirmed the diagnosis. Cerebrospinal fluid examination showed albuminocytologic dissociation, and brain imaging revealed sigmoid sinus thrombophlebitis. Neurological manifestations improved during treatment with plasma exchange and anticoagulants. Our case draws attention to the occurrence of cerebral venous thrombosis and Guillain-Barré syndrome (GBS) in patients with COVID-19. The neuro-inflammation induced by the systemic immune response to infection, can lead to neurological manifestations. Further studies should be conducted on the full clinical spectrum of patients with COVID-19 with neurological symptoms.

Epidemiology, clinical features, and treatment modalities of facial nerve palsy in COVID-19 patients: a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is responsible for a wide variety of multi-system clinical features. Facial nerve palsy (FNP) is identified as one of the neurological complications of the virus. This work aims to systematically review the clinical picture, laboratory/imaging findings, treatment options, and prognostic factors of FNP in COVID-19 patients. METHODS: Using six online databases, a search was conducted to include all articles with patients infected with COVID-19 and presenting with unilateral or bilateral FNP. Screening for eligibility and data extraction were done by three and four independent reviewers, respectively. Descriptive analyses and data visualizations were done using Google Sheets. Survival analysis and Kaplan-Meier plotting were done by R software. RESULTS: The data from 22 studies included 32 patients who were infected with COVID-19 and presented with clinical features of FNP. Fourteen patients were male while 18 were female. FNP affected 29 patients unilaterally and 3 patients bilaterally. The imaging findings confirmed that complications of FNP were COVID-19 related. Additionally, antivirals combined with steroids had the lowest median time (21, IQR = 8) to clinical improvement compared to steroid-only (30, IQR = 15) and antiviral-only (33, IQR = 3.5) treatments. CONCLUSION: This study has shown a potential correlation between the increased incidence of FNP and COVID-19. We have also found that combining antivirals with steroids may have better outcomes in patients with FNP and COVID-19 although the evidence to support this claim is not strong enough. Further studies are required to assess the extent of linkage between the two conditions and how to properly manage FNP when encountered in COVID-19 patients.

Parsonage Turner syndrome of the brachial plexus secondary to Covid-19 vaccine: A case report (preprint)

Parsonage Turner syndrome (PTS) is a peripheral inflammatory neuropathy of unknown etiology. We present a rare case of a patient with PTS post-covid-19 BNT162b2 mRNA vaccine. Symptoms occurred fifteen days after the second dose. The patient was treated with corticosteroids, analgesics and physical rehabilitation with a partial recovery.

New-onset Bell's palsy after neuroinvasive West Nile virus.

In this case report, a patient was diagnosed with new-onset Bell's palsy 3 weeks after the onset of neuroinvasive West Nile virus. This was the second case report of West Nile virus-associated Bell's palsy, highlighting the need to monitor these patients for peripheral neuropathies. This case report is also intended to raise awareness about the prevalence of West Nile virus in the USA.

Risk of serious adverse events after the BNT162b2, CoronaVac, and ChAdOx1 vaccines in Malaysia: A self-controlled case series study.

BACKGROUND: Rapid deployment of COVID-19 vaccines is challenging for safety surveillance, especially on adverse events of special interest (AESIs) that were not identified during the pre-licensure studies. This study evaluated the risk of hospitalisations for predefined diagnoses among the vaccinated population in Malaysia. METHODS: Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period. RESULTS: There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21). CONCLUSION: This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term.

Adverse events of special interest and mortality following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines in Hong Kong: A retrospective study.

BACKGROUND: Safety monitoring of coronavirus disease 2019 (COVID-19) vaccines is crucial during mass vaccination rollout to inform the choice of vaccines and reduce vaccine hesitancy. Considering the scant evidence directly comparing the safety profiles of mRNA and inactivated SARS-CoV-2 vaccines, this territory-wide cohort study aims to compare the incidence of various adverse events of special interest (AESIs) and all-cause mortality between CoronaVac (inactivated vaccine) and BNT162b2 (mRNA-based vaccine). Our results can help vaccine recipients make an informed choice. METHODS AND FINDINGS: A retrospective, population-based cohort of individuals who had received at least 1 dose of BNT162b2 or CoronaVac from 23 February to 9 September 2021 in Hong Kong, and had data linkage to the electronic medical records of the Hong Kong Hospital Authority, were included. Those who had received mixed doses were excluded. Individuals were observed from the date of vaccination (first or second dose) until mortality, second dose vaccination (for first dose analysis), 21 days after vaccination, or 30 September 2021, whichever came first. Baseline characteristics of vaccinated individuals were balanced between groups using propensity score weighting. Outcome events were AESIs and all-cause mortality recorded during 21 days of post-vaccination follow-up after each dose, except anaphylaxis, for which the observation period was restricted to 2 days after each dose. Incidence rate ratios (IRRs) of AESIs and mortality comparing between CoronaVac and BNT162b2 recipients were estimated after each dose using Poisson regression models. Among 2,333,379 vaccinated individuals aged 18 years or above, the first dose analysis included 1,308,820 BNT162b2 and 955,859 CoronaVac recipients, while the second dose analysis included 1,116,677 and 821,560 individuals, respectively. The most frequently reported AESI among CoronaVac and BNT162b2 recipients was thromboembolism (first dose: 431 and 290 per 100,000 person-years; second dose: 385 and 266 per 100,000 person-years). After the first dose, incidence rates of overall AESIs (IRR = 0.98, 95% CI 0.89-1.08, p = 0.703) and mortality (IRR = 0.96, 95% CI 0.63-1.48, p = 0.868) associated with CoronaVac were generally comparable to those for BNT162b2, except for Bell palsy (IRR = 1.95, 95% CI 1.12-3.41, p = 0.018), anaphylaxis (IRR = 0.34, 95% CI 0.14-0.79, p = 0.012), and sleeping disturbance or disorder (IRR = 0.66, 95% CI 0.49-0.89, p = 0.006). After the second dose, incidence rates of overall AESIs (IRR = 0.97, 95% CI 0.87-1.08, p = 0.545) and mortality (IRR = 0.85, 95% CI 0.51-1.40, p = 0.516) were comparable between CoronaVac and BNT162b2 recipients, with no significant differences observed for specific AESIs. The main limitations of this study include residual confounding due to its observational nature, and the possibility of its being underpowered for some AESIs with very low observed incidences. CONCLUSIONS: In this study, we observed that the incidences of AESIs (cumulative incidence rate of 0.06%-0.09%) and mortality following the first and second doses of CoronaVac and BNT162b2 vaccination were very low. The safety profiles of the vaccines were generally comparable, except for a significantly higher incidence rate of Bell palsy, but lower incidence rates of anaphylaxis and sleeping disturbance or disorder, following first dose CoronaVac versus BNT162b2 vaccination. Our results could help inform the choice of inactivated COVID-19 vaccines, mainly administered in low- and middle-income countries with large populations, in comparison to the safety of mRNA vaccines. Long-term surveillance on the safety profile of COVID-19 vaccines should continue.

Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform.

INTRODUCTION: We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy. METHODS: With the approval of NHS England we analysed primary care data from >17 million patients in England linked to emergency care, hospital admission and mortality records in the OpenSAFELY platform. Separately for each vaccine brand, we used a self-controlled case series design to estimate the incidence rate ratio for each outcome in the period following vaccination (4-42 days for GBS, 4-28 days for transverse myelitis and Bell's palsy) compared to a within-person baseline, using conditional Poisson regression. RESULTS: Among 7,783,441 ChAdOx1 vaccinees, there was an increased rate of GBS (N = 517; incidence rate ratio 2·85; 95% CI2·33-3·47) and Bell's palsy (N = 5,350; 1·39; 1·27-1·53) following a first dose of ChAdOx1 vaccine, corresponding to 11.0 additional cases of GBS and 17.9 cases of Bell's palsy per 1 million vaccinees if causal. For GBS this applied to the first, but not the second, dose. There was no clear evidence of an association of ChAdOx1 vaccination with transverse myelitis (N = 199; 1·51; 0·96-2·37). Among 5,729,152 BNT162b2 vaccinees, there was no evidence of any association with GBS (N = 283; 1·09; 0·75-1·57), transverse myelitis (N = 109; 1·62; 0·86-3·03) or Bell's palsy (N = 3,609; 0·89; 0·76-1·03). Among 255,446 mRNA-1273 vaccine recipients there was no evidence of an association with Bell's palsy (N = 78; 0·88, 0·32-2·42). CONCLUSIONS: COVID-19 vaccines save lives, but it is important to understand rare adverse events. We observed a short-term increased rate of Guillain-Barré syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.

A case of facial nerve palsy in a pediatric patient associated with Covid-19.

BACKGROUND: Pediatric facial nerve palsy is acute and mostly idiopathic; other causes are post-infectious forms. CASE PRESENTATION: We describe a rare case of facial nerve palsy associated with COVID-19 in a 5-year-old boy. The diagnosis of post-infectious COVID-19-related facial paralysis was made by serology positivity for a previous infection (IgG positive, IgM and IgA weakly positive), in the presence of a negative molecular nasopharyngeal swab and in the absence of other etiologies. Early treatment with steroids (1 mg/day for 7 days followed by tapering) and supportive care solved the problem. CONCLUSION: In a child with facial paralysis, COVID-19 must be considered as the cause and both nasopharyngeal swab and serology must be performed.

Surge of Bell's Palsy in the era of COVID-19: Systematic review.

BACKGROUND AND PURPOSE: With the progression of coronavirus infectious disease 2019 (COVID-19), various neurological manifestations have been noticed in infected patients, and Bell's Palsy (BP) is one of the peripheral neuropathies among those. BP has been associated with various other viral agents. Its evidence in patients with COVID-19 signifies the possibility of association between BP and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This research was undertaken to evaluate the number of published cases of BP as the only major neurological manifestation in patients with COVID-19 from March 2020 to December 2021 and to investigate the association of SARS-CoV-2 and BP. METHODS: A systematic review of the published English literature was performed using an electronic search in the PubMed/Medline, Scopus, Research Gate, Research Square, and Google Scholar databases, using keywords such as "COVID-19" OR/AND "SARS-CoV-2" OR/AND "Bell's palsy" OR/AND "facial nerve palsy" OR/AND "neurological" OR/AND "manifestation". RESULTS: The search strategy revealed 32 relevant publications with a total of 46 patients. BP was the initial manifestation in 37% of cases, and in 63% of cases it developed after COVID-19 symptoms; 71.7% of cases showed complete recovery, and 21.7% showed only partial relief from BP. CONCLUSIONS: Although the number of documented cases in this research is low, evidence of BP as the only major neurological manifestation in patients with COVID-19 signifies an important clinical finding and the possibility of another viral etiology of BP. More evidence is needed to establish the exact correlation between these two entities.