Real-world Effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among Children 5-11 years of age in Brazil: a prospective test-negative design study.

OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7% were female, 34.6% were obese, and 14.1% had chronic pulmonary disease. Omicron accounted for 100% of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7%, 21.4% and 21.4%, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1% (95% CI, -133.7% to 61.8%) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).

Comparison of Transient and Persistent Adverse Events After COVID-19 Vaccination: A Retrospective Analysis.

OBJECTIVE: Most reported adverse events following COVID-19 vaccination have been transient. However, persistent adverse events may occur with some frequency. This study aimed to analyze patient background characteristics and trends, with a focus on whether adverse events following COVID-19 vaccination were transient or persistent. METHODS: A retrospective study was performed at a single institution in Japan. PATIENTS: The study cohort included 47 patients who presented with symptoms after COVID-19 vaccination between May 2021 and September 2023. The patients were classified into two groups based on the duration of symptoms: transient group, less than four weeks; persistent group, greater than or equal to four weeks. Data on age, sex, body mass index, smoking history, underlying conditions, type of COVID-19 vaccination, number of doses, onset, symptoms, and treatments were collected retrospectively. RESULTS: The median age was 51.0 years and 74.5% were females, with a particularly high proportion of women in their 40s. The use of the bivalent omicron-containing booster vaccine (BA.1) was significantly more common in the persistent group than in the transient group (p = 0.0267). Onset in the transient group was more common after the first vaccination, whereas onset in the persistent group was more common after the second and subsequent vaccinations (p = 0.003). Regarding symptoms, pain was more frequent in the persistent group than in the transient group (60% vs. 13.6%; p = 0.001). CONCLUSIONS: This study investigated the presence of persistent symptoms, especially pain, after COVID-19 vaccination. Persistent symptoms were frequently reported after the second vaccination. It should be noted that the study does not negate the usefulness of COVID-19 vaccines.

SARS-CoV-2-Vaccine-Related Endocrine Disorders: An Updated Narrative Review.

The emergence of the COVID-19 pandemic has led to the rapid and worldwide development and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aimed to explore the current knowledge on potential adverse endocrine effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pituitary, adrenal, diabetes, and gonadal events are also reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar searches were performed. Case reports, case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines are accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of the endocrine disorders linked to COVID-19 vaccines.

Systemic and Mucosal Immunogenicity of Monovalent XBB.1.5-Adapted COVID-19 mRNA Vaccines in Patients with Inflammatory Bowel Disease.

Recently updated COVID-19 mRNA vaccines encode the spike protein of the omicron subvariant XBB.1.5 and are recommended for patients with inflammatory bowel disease (IBD) on immunosuppressive treatment. Nonetheless, their immunogenicity in patients with IBD against rapidly expanding virus variants remains unknown. This prospective multicenter cohort study is the first study to investigate the immunogenicity of XBB.1.5-adapted vaccines in patients with IBD. Systemic and mucosal antibodies targeting the receptor-binding domains (RBDs) of the omicron subvariants XBB.1.5, EG.5.1, and BA.2.86, as well as their neutralization were quantified before and two to four weeks after vaccination with monovalent XBB.1.5-adapted mRNA vaccines. Vaccination increased levels of serum anti-RBD IgG targeting XBB.1.5, EG.5.1, and BA.2.86 (1.9-fold, 1.8-fold, and 2.6-fold, respectively) and enhanced corresponding neutralization responses (2.3-fold, 3.1-fold, and 3.5-fold, respectively). Following vaccination, anti-TNF-treated patients had reduced virus neutralization compared to patients on treatments with other cellular targets. 11.1% and 16.7% of patients lacked EG.5.1 and BA.2.86 neutralization, respectively; all these patients received anti-TNF treatment. At mucosal sites, vaccination induced variant-specific anti-RBD IgG but failed to induce RBD-targeting IgA. Our findings provide a basis for future vaccine recommendations while highlighting the importance of frequent booster vaccine adaptation and the need for mucosal vaccination strategies in patients with IBD.

Challenging Pandemic Law: From Vaccine Mandates to Judicial Review of Vaccine Approvals.

Over recent years, dozens of legal challenges have been instituted in response to government action during the COVID-19 pandemic. While public health orders have been challenged on several grounds, few cases have succeeded. Fewer cases still have called into question decisions made by the Therapeutic Goods Administration (TGA) to approve the COVID-19 vaccines. This section provides a brief update on one recent, partially successful COVID-19 health directions case before examining two applications in the Federal Court of Australia seeking judicial review of the TGA's approval of the COVID-19 vaccines. The section argues that, while both TGA applications were dismissed for lack of standing, they illustrate how and why third parties will ordinarily not be entitled to challenge administrative decisions about therapeutic goods.

Short- and long-term outcomes of cardiac adverse events following COVID-19 immunization managed in a Canadian pediatric center.

BACKGROUND: Numerous reports have described the clinical presentation of cardiac adverse events following immunization (AEFI) with COVID-19 vaccines but long-term outcome studies are limited, especially in the pediatric population. METHODS: This is a single center retrospective case series of pediatric patients with cardiac AEFI following the Pfizer/BioNTech mRNA COVID-19, diagnosed between May 2021 and May 2022, and managed following a standardized protocol. Follow up information is presented up to 12 months post diagnosis. The incidence rate of cardiac AEFI was estimated for Ottawa residents. RESULTS: All cases were male (N = 17) with an average age of 16 years (range = 12-17). The majority of cases occurred after the 2nd (12/17) or 3rd vaccine dose (4/17) and were manifested mostly as myopericarditis (15/17). Average interval between the 1st and 2nd vaccine (n = 12) doses was 38 days (21-69 days). All patients improved promptly on non-steroidal anti-inflammatory drugs without recurrence. Five patients reported negative impact on quality of life and mental health, including 2 cases that led to new vaccine hesitancy, not only to COVID-19 vaccine, but also to other routine vaccines. The rate of cardiac AEFI was estimated for residents of the city of Ottawa and found to be 12.01 cases (CI 90 5.98-21.68) per 100,000 doses following the 2nd dose and 16.56 cases (CI 90 5.66-37.90) per 100,000 doses following the 3rd dose for males aged 12 to 17 years. CONCLUSIONS: Twelve months following the AEFI, all patients clinically recovered from their myopericarditis, but some reported negative impact on quality of life and mental health, including new vaccine hesitancy. This highlights the importance for timely and systematic evaluation of AEFI and the need to provide support, follow up and vaccine counseling in individuals experiencing an AEFI.

Estimating vaccine effectiveness against COVID-19 using cause-specific sick leave as an indicator: a nationwide population-based cohort study, Norway, July 2021 - December 2022.

BACKGROUND: Due to changes in testing policy and increased use of rapid tests, other indicators for SARS-CoV-2 infections are needed to monitor vaccine effectiveness (VE). We aimed to estimate VE against COVID-19 sick leave (> 3 days, certified by a medical professional) among employed individuals (25-64-years-old) in Norway. METHODS: We performed a nationwide cohort study by collating data from the Emergency preparedness register for COVID-19. We used adjusted Cox proportional hazard models with vaccine status as a time-varying covariate and presented results as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals. Separate models were run against sick leave and against SARS-CoV-2 infections during the Delta period (June-December 2021), and against sick leave during the Omicron period (January-December 2022) when SARS-CoV-2 PCR-testing was replaced by rapid self-tests and infections were underreported. RESULTS: We included 2,236,419 individuals during the Delta period, of whom 73,776 (3.3%) had a reported infection and 54,334 (2.4%) were registered with sick leave. Of the 2,206,952 included individuals in the Omicron period, 300,140 (13.6%) were registered with sick leave. During the Delta period, 55% (26,611) of individuals who had registered sick leave also had a positive test, compared to 32% (96,445) during the Omicron period. The VE against sick leave during the Delta period followed a similar waning pattern to that against SARS-CoV-2 infections. After the second and third dose, the lowest aHRs were estimated for 2-7 days after vaccination for both sick leave (0.25; 95%CI 0.24-0.26 and 0.26; 95% CI 0.24-0.29) and infection ( 0.16; 95% CI 0.15-0.17 and 0.18; 95% CI 0.16-0.19) respectively. During the Omicron period, aHRs for sick leave were higher than during the Delta period, but the lowest aHRs were still found in 2-7 weeks after receiving the second (0.61; 95% CI 0.59-0.64) or third dose (0.63; 95% CI 0.62-0.64). CONCLUSION: Our results showed that sick leave could be a relevant indicator for VE in the surveillance of COVID-19 and a finding that may be important in the surveillance of other respiratory infection.

Alopecia areata following COVID-19 vaccine: a systematic review.

BACKGROUND: To date, multiple cases of adverse reactions to COVID-19 vaccines have been reported worldwide. Alopecia areata (AA) is an uncommon type of adverse reaction reported in some articles and has a significant social and psychological impact on patients. Our study aimed to review the AA and COVID-19 vaccine literature. METHODS: This systematic review was conducted by searching for articles on AA following COVID-19 vaccines in international databases such as Embase, MEDLINE, PubMed, Web of Knowledge, and Ovid from December 2019 to December 30, 2023. We included studies that provided data for AA patients following COVID-19 vaccination with at least one dose. Data on sex, age, country/region of origin, vaccine type, days between vaccination and symptom presentation, manifestations of AA, trichoscopy and histopathological findings, treatment, and outcomes were included. RESULTS: In total, 579 explored studies were identified and assessed, and 25 articles with a total of 51 patients were included in the review. Twenty-seven (52.9%) patients developed new-onset AA following receiving the COVID-19 vaccine, and AA recurrence or exacerbation occurred after receiving the COVID-19 vaccine in 24 (47.1%) patients with preexisting disease. Five vaccines were reported to cause AA in all cases. The Pfizer vaccine (45.1%) was the most frequently reported, followed by the ChAdOx1 nCoV-19 vaccine (27.5%), Moderna mRNA-1273 (19.6%), Sinopharm (3.9%) and SinoVac (3.9%). AA occurred most frequently within one month after the 1st dose, and then, the incidence decreased gradually with time. Topical or systemic corticosteroids were used in 38 patients. Eleven patients were treated with a Janus Kinase inhibitor (jakinib) inhibitor, eight with tofacitinib, and three with an unspecified jakinib. However, 3 of the 11 patients experienced exacerbations after treatment. CONCLUSION: AA after COVID-19 vaccination is rare, and physicians should be aware of this phenomenon to improve early diagnosis and appropriate treatment.

The COVID-19 Vaccines Evaluation Program: Implementation, Management, and Experiences, 2021-2023.

In 2021, China's domestically produced coronavirus disease 2019 (COVID-19) vaccines received approval from regulatory bodies and were administered worldwide. Due to a low number of infections within China during that period, it became imperative to evaluate the vaccines' real-world effectiveness through international studies. To facilitate this, China CDC launched the COVID-19 Vaccines Evaluation Program (COVEP). This program formed research collaboration agreements with health institutes across five World Health Organization regions, addressing key questions about vaccine performance through ten cooperative agreements. The findings from COVEP projects reinforced confidence, both domestically and globally, in the effectiveness of the vaccines produced in China. Moreover, the outcomes observed internationally were frequently mirrored by later studies conducted within China. COVEP thus pioneered a novel approach for fostering cross-national research collaborations, addressing significant public health issues and exemplifying a framework for international cooperation. This approach is in line with the strategic objectives and other development efforts of China CDC's national disease control and prevention initiatives.

COVID-19 vaccination initiation and completion in a multicenter cohort study of insured US transgender and cisgender adults.

PURPOSE: Transgender and gender-diverse (TGD) people may have been disproportionately impacted by the COVID-19 pandemic, yet little is known about vaccination status in this population. This multicenter cohort study of insured adults examined the rates of COVID-19 vaccine initiation and completion in TGD persons compared to matched cisgender persons. METHODS: A cohort of TGD persons and matched cisgender persons enrolled in Kaiser Permanente health plans in Northern and Southern California between 12/1/2020 and 7/31/2021 were analyzed. COVID-19 vaccination initiation and completion rates were compared across groups using Cox regression models. RESULTS: Among transmasculine persons, the HR (95 % CI) estimates for COVID-19 vaccination initiation and completion were, respectively, 1.35 (1.30-1.40) and 1.78 (1.71-1.85) compared with cisgender women and 1.34 (1.29-1.40) and 1.81 (1.73-1.88) compared with cisgender men. Among transfeminine persons, the corresponding HRs (95 % CIs) for vaccination initiation and completion were 1.35 (1.30-1.40) and 1.78 (1.71-1.85) compared with cisgender women and 1.34 (1.29-1.40) and 1.81 (1.73-1.88) compared with cisgender men. CONCLUSION: Findings from this cohort of insured adults demonstrated that TGD persons initiated and completed COVID-19 vaccination at higher rates compared to matched cisgender persons. Further work is needed to understand vaccination rates and determinants in the broader TGD populations.

Medical occurrence and safety of SARS-CoV-2 vaccination outside of the hospital setting.

During COVID-19 pandemic, vaccination has been strongly recommended and advocated to prevent COVID-19 infection and adverse outcomes, particularly among at-risk populations. The vaccination against SARS-CoV-2 (COVAC) occurred at off-site locations capable of accommodating large crowds, distinct from the hospital setting, where a team of intensivists, emergency physicians, and nurses, ensuring prompt medical attention (medical occurrences, MO) in cases of adverse event following immunization. Our aims were to estimate the incidence of MO, and to assess its association with demographics, and vaccine characteristics. Our retrospective cohort study included all subject aged 12 years and older who received vaccinations at two large out-of-hospital vaccination hubs (Fiera Milano City, Palazzo delle Scintille), between April 12th and August 31st, 2021. Nine hundred and ninety-five thousand and twenty-eight vaccinations were administrated. MOs incidence rate was 278/100,000 doses (95% confidence interval (CI) 268-289). Most MOs were mild (86.27%) and mainly observed in subjects who received the Comirnaty vaccine; 92 MOs (3.32%) were severe and mostly occurred in recipients of the Vaxzeria vaccine. The incidence rate for hospital transfers following vaccination was 4.7/100,000 doses (95% CI 3.5-6.2) and any level of anaphylaxis occurred in 0.4 cases per 100,000 administrated doses (95% CI 0.3.-0.7). Sex, age, type of vaccine and first dose were associated with incidence of MO. Our results showed a low incidence rate in MOs after COVAC, mainly mild and support the feasibility, effectiveness and safety of vaccinations administered in hubs with a dedicated SEU located outside of the hospital setting.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.

Reflections on the Advisory Committee on Immunization Practices During the COVID-19 Pandemic.

Pediatricians and primary care providers serve an important role in building trust with families and communities. To support the critical role of front-line providers, this perspective seeks to reflect on the work of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices to support COVID-19 pandemic response efforts. Although Advisory Committee on Immunization Practice (ACIP) recommends vaccines for all age groups, this perspective focuses on the pediatric lens and is tailored to Academic Pediatrics. ACIP adapted from in-person meetings 3 times yearly to virtual meetings on an emergency basis to ensure a thorough review and presentation of all the components of the evidence to recommendation framework, including explicit consideration of equity in the decision-making process. The need for diverse enrollment in clinical trials was highlighted as critical for supporting recommendations and enhancing trust. Near real-time vaccine safety surveillance was implemented at scale and emphasized the importance of collaboration between federal partners engaged in vaccine safety in the United States and extended to other countries with similar safety surveillance systems to enable early recognition and response to safety concerns. A key equity opportunity for future pandemics is to shorten the time between vaccines being available for adults and young children.

Development of a high-performance liquid chromatography using rhodamine B hydrazide as the derivatization reagent for determination of ß propiolactone residues in inactivated COVID-19 vaccines.

ß-propiolactone (BPL) is an alkylating agent used for inactivation of biological samples such as vaccines. Due to its known carcinogenic properties, complete hydrolysis of BPL is essential, and the detection of trace amounts is crucial. In this study a novel High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) method was developed. Rhodamine B hydrazide (RBH) was synthesized and utilized as a derivatizing reagent to react with BPL. The reaction was optimized in a weak acidic solution, resulting in a high yield. The separation of the RBH-derivatized BPL was achieved on a C8 column and detected by a UV detector at a wavelength of 560 nm. The method's validation demonstrated a high linearity (r2 > 0.99) over a concentration range of 0.5-50 µg/mL, with detection and quantification limits of 0.17 µg/mL and 0.5 µg/mL, respectively. The average recovery of samples was 85.20 % with a relative standard deviation (RSD) of 1.75 %. This method was successfully applied for BPL residue analysis in inactivated COVID-19 vaccines. This novel derivatization method offers a promising solution for monitoring BPL residues in the vaccine production process for quality control purposes and compliance with regulatory standards.

Unstable angina pectoris in a young male after first dose of COVID-19 MRNA- vaccine.

Some side effects regarding COVID-19 vaccination have been reported. The most common reports of cardiovascular issues were myocarditis and pericarditis. Although inflammation is the most common cause in this matter, there were only a few reports about ischaemic cases related to COVID-19 vaccines. These reports also commonly included older men who received a second dose of mRNA vaccination. We present a 25-year-old man with chest pain mimicking a heart attack after receiving the first dose of the mRNA COVID-19 vaccine. There were no known preceding cardiovascular risk factors. Workups were done, and the diagnosis made was unstable angina pectoris. This may remind physicians to increase awareness of cardiovascular side effects in this vaccination era, as it may be encountered even in younger patients. The patient was seen at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, in August 2022.

Immunogenicity of BNT162b2 as a first booster after a ChAdOx1 primary series in a Thai geriatric population living with frailty.

OBJECTIVES: Impact of frailty towards immunogenicity and reactogenicity of BNT162b2 boosters administered via intramuscular or intradermal routes in a Thai geriatric population DESIGN: Prospective, randomized, open-labeled. SETTING: Siriraj Hospital, Thailand. PARTICIPANTS: Geriatric adults aged ≥65 years. INTERVENTION: 10 µg intradermal or 30 µg intramuscular BNT162b2 (Pfizer-BioNTech). MEASUREMENTS: Anti-SARS-CoV-2 receptor binding domain IgG, neutralizing antibodies (NAb), and interferon-gamma producing cells against Wuhan and Omicron BA.4/5. Analyses were stratified based on participants' Clinical Frailty Scale. RESULTS: A total of 139 participants were included in the analysis. Two-four weeks post-booster administration, NAb titers against Wuhan but not Omicron BA.4/5 were significantly lower among frail participants than non-frail participants who received intramuscular administration. Spike-specific T cell responses were similar for frail and non-frail participants, regardless of administration route. Frail participants who received intradermal BNT162b2 had fewer local adverse events (AEs), but higher systemic AEs than non-frail participants. CONCLUSION: Similar immune responses across vaccine routes warrants further evaluation of intradermal BNT162b2 in frail geriatric populations. Frail participants may be more sensitive to reporting systemic AEs. REGISTRATION OF CLINICAL TRIALS: The parent study was registered under the Thai Clinical Trials Registry (TCTR20220112002).

Longitudinal Follow-Up Study on the Side Effects of COVID-19 Vaccines: A Telephonic Questionnaire Approach.

BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted urgent efforts to develop and deploy effective vaccines. Covishield and Covaxin are two prominent COVID-19 vaccines authorized for emergency use; however, concerns regarding their safety persist. OBJECTIVE: This longitudinal follow-up study aimed to comprehensively assess and compare the demographic characteristics, frequencies, severities of reported side effects, and associations between vaccine type and demographic factors among individuals vaccinated with Covishield and Covaxin. METHODS: A telephonic questionnaire was used to collect data from individuals who attended COVID-19 vaccination programs between January 1, 2021, and January 1, 2022. Logistic regression analysis was performed to investigate the associations between vaccine type, demographic factors, and likelihood of experiencing side effects. RESULTS: Covaxin recipients exhibited a lower incidence of mild flu-like illness (16 cases) and post-vaccination infection (55 cases) than Covishield recipients (110 and 98 cases, respectively). However, Covaxin recipients reported more cases of soreness at the injection site (139 cases) than did Covishield recipients (172 cases). Logistic regression analysis revealed significantly higher odds of experiencing side effects among Covaxin recipients than among Covishield recipients (OR = 1.687, p < 0.001). Age was inversely associated with the likelihood of experiencing side effects (OR = 0.982, p < 0.001), while sex and ethnicity also exhibited significant associations. CONCLUSION: This study provides valuable insights into the safety profiles of the Covishield and Covaxin COVID-19 vaccines. These findings underscore the importance of ongoing surveillance and evaluation of vaccine safety and tolerability to inform public health policies and vaccination strategies.

Whole Exome Sequencing in Vaccine-Induced Thrombotic Thrombocytopenia (VITT).

Background: In February 2021, a few cases of unusual, severe thrombotic events associated with thrombocytopenia reported after vaccination with ChAdOx1 nCoV-19 (Vaxzevria) or with Johnson & Johnson's Janssen vaccine raise concern about safety. The vaccine-induced thrombotic thrombocytopenia (VITT) has been related to the presence of platelet-activating antibodies directed against platelet Factor 4. Objectives: We investigated VITT subject genetic background by a high-throughput whole exome sequencing (WES) approach in order to investigate VITT genetic predisposition. Methods: Six consecutive patients (females of Caucasian origin with a mean age of 64 years) were referred to the Atherothrombotic Diseases Center (Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence) with a diagnosis of definite VITT underwent WES analysis. WES analysis was performed on the Illumina NextSeq500 platform. Results:WES analysis revealed a total of 140,563 genetic variants. Due to VITT's rare occurrence, we focused attention on rare variants. The global analysis of all high-quality rare variants did not reveal a significant enrichment of mutated genes in biological/functional pathways common to patients analyzed. Afterwards, we focused on rare variants in genes associated with blood coagulation and fibrinolysis, platelet activation and aggregation, integrin-mediated signaling pathway, and inflammation with particular attention to those involved in vascular damage, as well as autoimmune thrombocytopenia. According to ACMG criteria, 47/194 (24.2%) rare variants were classified as uncertain significance variants (VUS), whereas the remaining were likely benign/benign. Conclusion: WES analysis identifies rare variants possibly favoring the prothrombotic state triggered by the exposure to the vaccine. Functional studies and/or extensions to a larger number of patients might allow a more comprehensive definition of these molecular pathways.

Menstrual Cycle Disturbances after COVID-19 Vaccination: A Cross-Sectional Study.

BACKGROUND: Following COVID-19 vaccination, some women suffered from menstrual cycle disturbances. This study aimed to investigate menstrual cycle disturbances after COVID-19 vaccination in women of reproductive age. MATERIALS AND METHODS: This cross-sectional study was performed on 407 vaccinated women in the vaccination center of Imam Hossein Hospital (Tehran, Iran) between October 2021 and October 2022. They were interviewed based on a research-made checklist which consisted of two areas of questions about the baseline characteristics of participants and menstrual cycle characteristics to explore menstrual characteristics following COVID-19 vaccination. RESULTS: The prevalence of menstrual disturbances was higher after the third dose (38.3%) compared with the second (27.9%) and first (17.7%) doses (P<0.001). After the first dose, a history of polycystic ovarian syndrome [PCOS, odds ratio (OR)=7.35, 95% confidential interval (CI)= (3.64-14.82), P<0.001] and menstrual disturbances with unknown etiology [OR=15.23, 95% CI=(6.30-36.80), P<0.001] could predict menstrual disturbances. After the second dose, a history of menstrual disturbances with unknown etiology [OR=3.83, 95% CI=(1.47-9.94), P=0.006] and menstrual disturbances after the first dose [OR=201.96, 95% CI= (40.99-994.90), P<0.001] were predictors of menstrual disturbances. After the third dose, a history of menstrual disturbances with unknown etiology [OR=3.09, 95% CI= (1.00-9.52), P=0.048], menstrual disturbances after the first [OR=9.82, 95% CI=(1.38-69.69), P=0.022] and second [OR=7.83, 95% CI=(1.46-41.92), P=0.016] doses could predict menstrual disturbances. CONCLUSION: We detected that many women experienced various menstrual disturbances after vaccination against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Furthermore, a history of menstrual abnormalities (before COVID-19 vaccination and following the previous doses of these vaccines) was associated with developing menstrual disturbances.