Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

Case report: Atypical case of autoimmune glial fibrillary acidic protein astrocytopathy following COVID-19 vaccination refractory to immunosuppressive treatments.

A 54-year-old Japanese man presented with headache and fever the day after SARS-CoV-2 vaccination. He became deeply unconscious within a week. Brain MRI showed periventricular linear enhancements and a few spotty lesions in the cerebral white matter. Cerebrospinal fluid (CSF) testing showed mild pleocytosis. He was treated with intravenous methylprednisolone and plasma exchange. However, the white matter lesions enlarged to involve the brainstem and cerebellum, and long cord spinal lesions appeared. Anti-glial fibrillary acidic protein (GFAP) antibody was positive in the CSF and serum, and he was therefore diagnosed as autoimmune GFAP-astrocytopathy (GFAP-A). In addition, high-dose immunoglobulin therapy was administered twice, but his symptoms did not improve; the white matter lesions enlarged further, and modified Rankin Scale score increased to 5. A brain biopsy specimen showed infiltration of macrophages and CD4 + lymphocytes together with neuron and oligodendrocytic injuries and glial scar. Although GFAP-A generally responds well to steroids, the present case developed GFAP-A following SARS-CoV-2 vaccination, with refractory to intensive immunosuppressive therapy and atypical pathologic findings of infiltration of CD4 + lymphocytes and demyelination.

Optic neuritis and mydriasis after vaccination: a case report.

BACKGROUND: Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria. CASE REPORT: A 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months. CONCLUSION: This study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.

A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases.

INTRODUCTION: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. METHODS: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. RESULTS: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. CONCLUSIONS: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.

Immunogenicity and safety of Sinovac-CoronaVac booster vaccinations in 12-17- year-olds with clinically significant reactions from Pfizer-BNT162b2 vaccination.

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.

Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Effects of COVID-19 vaccine safety framing on parental reactions.

As a major concern shared by parents globally, COVID-19 vaccine safety is typically being messaged to the public in a negative frame in many countries. However, whether the COVID-19 vaccine safety framing have an effect on parents when vaccinating their children is unclear. Here we implement an online survey with a convenience sample of 3,861 parents living in mainland China, all over 18 years old and with at least one child under 18. The parents were randomly assigned to receive information about COVID-19 vaccine safety in either a negative frame (incidence of side effects) or a positive frame (the inverse incidence of side effects), to compare parental reactions to a range of questions about communication, risk perception, trust, involvement and behavioral intention. We found that parents were more likely to regard vaccine safety as relevant to policy support and as a higher priority for government when receiving positively framed information (p = 0.002). For some specific subgroups, parents in positive framing group showed lower risk perception and higher trust (p<0.05). This suggests that positive framing of COVID-19 vaccine safety messages show more effective performance than negative framing in terms of involvement, as well as trust and risk perception in specific subgroups, which may lead to a reflection on whether to adjust the current widespread use of negative framing. Our findings inform how governments and health care workers strategically choose the framing design of COVID-19 vaccine safety information, and have important implications for promoting COVID-19 vaccination in children in the future.

COVID-19 Vaccine Injury Compensation Program: Lessons Learned From a Review of 10 Implementing Countries.

National vaccine injury compensation serves as a crucial and significant safety net for individuals affected by government-recommended vaccines during a pandemic, contributing to the community's overall safety. In the Republic of Korea, compensation for adverse events resulting from coronavirus disease 2019 (COVID-19) vaccinations has been provided through the National Vaccine Injury Compensation Program introduced in 1995. However, there have been limitations with these measures during the COVID-19 pandemic owing to strict criteria for substantiating causality between the vaccine and injury, its nontransparent process of determining whether to compensate, and the compensation amount that is not practically calculated. This article reviewed the Vaccine Injury Compensation Programs in 10 major countries to present implications for improving the Korean system. Expanding the scope of national accountability is essential to compensate for the consequences of adhering to national policies during public health crises. Therefore, valuable insight can be obtained from examining the systems in Germany, Japan, and Taiwan, which have implemented more relaxed criteria for determining causality in compensation cases; Thailand's system, which provides the mandatory payment of preliminary compensation for damage caused by vaccination; systems in Germany, France, and Japan, which offer compensation for vaccine injuries from a practical perspective; and systems in France and the United Kingdom, which have a process allowing the assessment records to be shared with the claimants. Furthermore, a dedicated agency for vaccine injury compensation, as seen in France, the United Kingdom, and Australia, is necessary to enhance the efficiency of the Korean system.

Dermatologic Reactions Following COVID-19 Vaccination: A Case Series.

We describe 7 patients with various dermatologic reactions following COVID-19 vaccination, including herpes zoster (HZ) infection, herpes zoster ophthalmicus (HZO), herpes labialis, and urticaria. Although the reactions described here may be related to COVID-19 vaccination, continued vaccination is recommended, as it is the most effective way to protect against serious COVID-19 infection.

Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

Background: The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. Methods: We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. Results: The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. Conclusion: The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

Live vaccinations in dermatology for immunosuppressed patients: a narrative review.

Given the higher susceptibility to infectious disease in patients receiving immunosuppressive therapies for inflammatory dermatologic conditions, immunization is important in this population. While live vaccines protect against life-threatening diseases, they can be harmful in immunosuppressed patients given the risk of replication of the attenuated pathogen and adverse reactions. The utilization of live vaccines in immunosuppressed patients depends on multiple factors such as the vaccine and therapy regimen. To provide an overview of evidence-based recommendations for the use of live vaccines in patients receiving immunosuppressive therapies for dermatological conditions. A literature search of the PubMed database was performed using keywords live vaccine, live-attenuated vaccine, dermatology, immunosuppressed, and immunocompromised, and specific immunosuppressive therapies: corticosteroids, glucocorticoids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, biologics. Relevant articles written in English were included. Using these keywords, 125 articles were reviewed, of which 28 were ultimately selected. Recommendations for live vaccines can be determined on a case-by-case basis. Measles, mumps, rubella, varicella (MMRV) vaccines may be safely administered to patients on low-dose immunosuppressive agents while the yellow fever vaccine is typically contraindicated. It may be safe to administer live MMRV boosters to children on immunosuppressive therapies and the live herpes zoster vaccine to patients on biologics. Given poor adherence to immunization guidelines in immunosuppressed patients, dermatologists have a critical role in educating patients and general practitioners regarding live vaccines. By reviewing a patient's vaccination history and following immunization guidelines prior to initiating immunosuppressive therapies, physicians can mitigate morbidity and mortality from vaccine-preventable diseases.

Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

An analysis of reported cases shoulder injury related to vaccine administration of after COVID-19 vaccination.

To prevent COVID-19, the COVID-19 vaccine has been widely administered worldwide, but various complications accompany this vaccine. The aim of this study was to investigate the demographic patterns, clinical features, diagnostic findings, and treatment outcomes associated with shoulder injury related to vaccine administration (SIRVA). This study examined 22 patients with SIRVA following COVID-19 vaccination from the Web of Science (WOS) and PubMed databases. The patients were categorized based on sex, age, type of COVID-19 vaccine received, dose administered, latency of symptom onset, and the presence of specific clinical manifestations. Patients, evenly distributed by sex (12 females, 10 males), and aged 21 to 84 years (mean age 46.6), were analyzed. SIRVA cases were reported across all age groups. The Pfizer - BioNTech COVID-19 vaccine had the highest incidence (n = 8), followed by the Oxford/AstraZeneca COVID-19 vaccine (n = 4). Symptoms, primarily shoulder pain (n = 22) and shoulder mobility disorders (n = 18), occurred within three days post-vaccination. Some patients also reported shoulder swelling (n = 5) and fever (n = 2). Imaging revealed nonspecific X-ray findings, supraspinatus tendon calcification (n = 2), and shoulder edema and inflammation on MRI (n = 12). This study provides insights into the clinical aspects of SIRVA related to COVID-19 vaccination. Recognition and appropriate management of these complications are crucial for optimal patient outcomes.

Factors influencing adverse events following COVID-19 vaccination.

Various novel platform technologies have been used for the development of COVID-19 vaccines. In this nested cohort study among healthcare workers in Australia and Brazil who received three different COVID-19-specific vaccines, we (a) evaluated the incidence of adverse events following immunization (AEFI); (b) compared AEFI by vaccine type, dose and country; (c) identified factors influencing the incidence of AEFI; and (d) assessed the association between reactogenicity and vaccine anti-spike IgG antibody responses. Of 1302 participants who received homologous 2-dose regimens of ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech) or CoronaVac (Sinovac), 1219 (94%) completed vaccine reaction questionnaires. Following the first vaccine dose, the incidence of any systemic reaction was higher in ChAdOx1-S recipients (374/806, 46%) compared with BNT162b2 (55/151, 36%; p = 0.02) or CoronaVac (26/262, 10%; p < 0.001) recipients. After the second vaccine dose, the incidence of any systemic reaction was higher in BNT162b2 recipients (66/151, 44%) compared with ChAdOx1-S (164/806, 20%; p < 0.001) or CoronaVac (23/262, 9%; p < 0.001) recipients. AEFI risk was higher in younger participants, females, participants in Australia, and varied by vaccine type and dose. Prior COVID-19 did not impact the risk of AEFI. Participants in Australia compared with Brazil reported a higher incidence of any local reaction (170/231, 74% vs 222/726, 31%, p < 0.001) and any systemic reaction (171/231, 74% vs 328/726, 45%, p < 0.001), regardless of vaccine type. Following a primary course of ChAdOx1-S or CoronaVac vaccination, participants who did not report AEFI seroconverted at a similar rate to those who reported local or systemic reactions. In conclusion, we found that the incidence of AEFI was influenced by participant age and COVID-19 vaccine type, and differed between participants in Australia and Brazil.

Adverse Events Following COVID-19 Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. METHODS: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization's global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12-17 years, ICSRs following any vaccines on adolescents aged 12-17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. RESULTS: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents; myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05-27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89-9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72-1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44-0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59-2.09) were not significantly higher following COVID-19 vaccination. CONCLUSION: In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

The early safety profile of simultaneous vaccination against influenza and Respiratory Syncytial Virus (RSV) in patients with high-risk heart failure.

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events.

Risk of abducens nerve palsy following COVID-19 vaccination.

PURPOSE: To investigate the prevalence and risk of new-onset abducens nerve palsy and acute-onset diplopia following mRNA COVID-19 vaccination. METHODS: In this retrospective, population-based study, patient data from the COVID-19 Research Network of TriNetX was searched via the TriNetX Analytics platform for patients who received specific vaccinations based on Common Procedural Technology codes. We recorded instances of newly diagnosed abducens nerve palsy and diplopia within 21 days following each vaccination event. RESULTS: Of the 3,545,224 patients (mean age at vaccination, 46.2 ± 21.3 years) who received the mRNA COVID-19 vaccine, 12 (<0.0001%) patients had a new diagnosis of abducens nerve palsy and 453 (0.013%) had acute-onset diplopia within 21 days of first dose of COVID-19 vaccination. After propensity score matching, the relative risk for new abducens nerve palsy diagnosis after the first dose of COVID-19 vaccination was not significantly different from that after influenza (RR, 0.77), Tdap (RR, 1.0), or the second dose of the COVID-19 vaccinations (RR, 1.00). Furthermore, there was a lower risk of abducens nerve palsy diagnosis after the first dose of the COVID-19 vaccination compared with the risk after COVID-19 infection (RR, 0.15). CONCLUSIONS: The risk of a new abducens nerve palsy diagnosis following the first dose of the COVID-19 vaccine is lower than the risk associated with COVID-19 infection itself. There is no evidence to suggest a causal relationship between COVID-19 vaccination and the development of abducens nerve palsy.

Evaluation of the safety profile of the quadrivalent vaccine against human papillomavirus in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia.

BACKGROUND: Cervical cancer eradication is one of the main goals for 2030 by the World Health Organization, which can only be achieved with high vaccination rates against Human Papilloma Virus. In Colombia, more and better scientific evidence is required to increase confidence in vaccination. The objective of this study is to evaluate the safety profile of the quadrivalent vaccine against HPV in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia. METHODS: We designed a cohort study based on national HPV vaccination records and incident diagnostic data for the diseases of special interest during 2012 and 2021. We included adolescent women between 9 and 19 years old and compared vaccinated and non-vaccinated cohorts using an Inverse Probability of Treatment Weighting (IPWT) method for each scenario disease and follow-up period (180 and 360 days). FINDINGS: The Odds Ratio (OR) of developing diseases of interest was estimated during two follow up periods, 180 and 360 days after the follow-up index date (Vaccination Day). The OR for developing rheumatoid arthritis was 4·4; CI95% (1·74 - 11·14), juvenile idiopathic arthritis was 2·76 IC95% (1·50 - 5·11), idiopathic thrombocytopenic purpura was 2·54 IC95% (1·28 - 5·02) and thyrotoxicosis was 2·86 IC95% (1·03 - 7·95), when comparing the vaccinated versus unvaccinated population. However, the temporal distribution of cases incident did not reveal a clear difference between the cohorts, since the rate of appearance of new cases has a constant linear behavior for the two groups. INTERPRETATION: For rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic thrombocytopenic purpura, and thyrotoxicosis; the application of the vaccine had an effect on the development of the disease. Nevertheless, our results should be interpreted with caution and be further studied, considering that the biological plausibility of the events occurred without a clear temporal pattern in relation to the exposure to the vaccine.