Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.

BACKGROUND: The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the baseline rate varies with age. Time-varying baseline risk adjustments with data from unexposed cohorts are utilised. Self-controlled risk interval (SCRI), with a shorter observation period, can also mitigate the problem by studying a control period close to the risk period. OBJECTIVE: An Indian rotavirus vaccine has previously been studied using SCCS. The risk of intussusception in the high-risk windows (21 days after vaccination) was comparable to the background risk. The aim was to re-analyse data of an existing SCCS study using alternate statistical methods to examine vaccine safety. METHODS: We examined the mean age of intussusception in the vaccinated and the unvaccinated. We performed an SCRI analysis of the surveillance data from the SCCS study, limiting the observation period to 180 days. We analysed the time-to-intussusception from the last vaccination. Finally, we performed an SCCS analysis, excluding unvaccinated cases from the analysis. RESULTS: We found that the mean age of intussusception was significantly lower in the vaccinated (205 days) compared to the unvaccinated (223 days) (p-value 0.0026). The Incident Risk Ratio (IRR) on SCRI analysis was 1.62 (95% CI 1.07-2.44). There were significantly more intussusceptions in the first 30 days after vaccination compared to the next 30-day window. (92 vs 63 p-value = 0.009). We found that excluding unvaccinated infants from the SCCS analysis demonstrated significantly increased risk for the risk period 1-21 days after the 3rd dose (IRR 2.47, 95% CI 1.70-3.59). The risks of intussusception were missed in traditional SCCS analysis using unvaccinated infants as controls. CONCLUSION: Traditional risk adjustments using data from unexposed cohorts in SCCS may not be appropriate for investigating the risk of intussusception where vaccination lowers the mean age of intussusception.

Overt Hypothyroidism Status Post Pfizer-BioNTech Vaccination: A Case Study.

Coronavirus disease (COVID-19) is among the most contagious viral illnesses, affecting millions worldwide. Although precautions such as social distancing, hand sanitizing, and the use of masks decreased the transmission of the virus, the situation went uncontrolled until vaccination came to light. Vaccination was vital in limiting the incidence, prevalence, and severity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the mechanism, several types of vaccines, such as Pfizer-BioNTech, Moderna, AstraZeneca, Johnson & Johnson, and Covaxin, were approved by the US Food and Drug Administration (FDA). A booster dose was implemented as the vaccine's effectiveness decreased with time. Several side effects, such as fever, soreness around the injection site, fatigue, chills, muscle weakness, and headache, have been reported after vaccination with Pfizer-BioNTech, but thyroid dysfunction is relatively rare. Several case reports and even case series describing links between COVID-19 vaccination and various types of thyroid dysfunction have appeared in the literature. However, the exact reasons have yet to be explained. This report presents the case of a healthy 50-year-old woman diagnosed with overt hypothyroidism three weeks after the administration of the Pfizer-BioNTech vaccine.

Acute encephalomyelitis in a 52-year-old male post messenger ribonucleic acid severe acute respiratory syndrome coronavirus 2 vaccination: a case report.

BACKGROUND: Acute disseminated encephalomyelitis is a well-known, but rare, side effect of some vaccines, or symptom following a febrile illness. CASE: A 69-year-old, otherwise healthy Hispanic male presented with acute fever, confusion, and later progressive weakness after receiving the first dose of the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 vaccine. Considering the progressive deterioration of the patient, despite being on multiple immunosuppressive agents, a brain biopsy was obtained, which revealed nonspecific meningoencephalitis. CONCLUSION: In this case, we highlight the need for a regulatory framework to assist clinicians and patients with coverage of treatment for acute disseminated encephalomyelitis. The use of intravenous immunoglobulin in conjunction with glucocorticoids seems to be an effective treatment option.

Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.

Multiple sclerosis (MS) is an autoimmune disease in which the body's immune system destroys myelin causing disruption of signals from the brain to the rest of the body. MS can be triggered by a variety of reasons. In this study, we present the case of a patient who developed neurological symptoms immediately (one day) after receiving the hepatitis B vaccine. The temporality of symptoms makes us question whether there is an association between the hepatitis B vaccine and MS. We would like to emphasize the importance of considering MS as a side effect of the hepatitis B vaccine and adding MS to the differential diagnosis of a patient who presents with neurological symptoms after receiving the hepatitis B vaccine.

Viral Versus Vaccine-Associated Acute Transverse Myelitis With Neuromyelitis Optica Immunoglobulin G Antibody and Myelin Basic Protein: A Case Report.

Transverse myelitis is a rare spinal cord disorder caused by local inflammation. Usually, this occurs as a complication from infection or autoimmune disease; however, there have been reported idiopathic causes such as vaccinations. A 73-year-old female with a medical history significant for Hashimoto's thyroiditis presented with new-onset paresthesias in her lower extremities. Her symptom onset was about five weeks after receiving influenza and tetanus, diphtheria, and pertussis (TDaP) vaccines. Magnetic resonance imaging (MRI) of the spine revealed an increased T2 signal of the lower cervical and thoracic spine. Lumbar puncture was also performed, and cerebrospinal fluid (CSF) serology showed elevated myelin basic protein (MBP) at 108.3 ng/mL (reference range: 0-5.5 ng/mL). Serology panel revealed Coxsackie virus type B4 antibody at 1:80 (reference range: <1:10) and Echovirus type 6 antibody at 1:640 (reference range: <1:10). Neuromyelitis optica (NMO) immunoglobulin G (IgG) antibody was 24.6 U/mL (reference range: <2.9 U/mL). She was diagnosed with acute transverse myelitis (ATM) and treated with alternating steroids and plasma exchange (PLEX) therapy for five days each. This case highlights the possible associations of vaccines with transverse myelitis. Although ATM is a rare disorder with serious complications, it has a favorable prognosis in the setting of rapid detection and treatment. Vaccine-related ATM remains controversial, but patients with these adverse reactions need to be cautioned regarding potential recurrence risk.

Thrombocytopenia and pneumonitis associated with BNT16B2b2 mRNA COVID-19 vaccine: A case report.

An 80-year-old Japanese male patient with Behçet's disease presented with a seven-day history of fever, cough, and progressive shortness of breath after receiving a second dose of the BNT16B2b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). The initial diagnosis was community-acquired pneumonia, and antibiotic treatment was started but proved ineffective. Twenty days after onset, his platelet count was significantly decreased. We suspected vaccine-induced pneumonitis and thrombocytopenia. After administration of prednisolone and intravenous immunoglobulin, and platelet transfusions, his platelet count normalized. The pneumonia symptoms improved three weeks after onset. Herein, we also summarize previous reports of cases of pneumonitis and thrombocytopenia associated with SARS-CoV-2 vaccination.

Acute pancreatitis as an adverse effect of COVID-19 vaccination.

While vaccination against COVID-19 has significantly improved the morbidity and mortality of the disease, with the increase in the administration of COVID-19 vaccines, it is more likely to observe their rare side effects in the clinical settings. Herein, we report a case of an 82-year-old man with history of coronary artery disease, prostate cancer in remission, gastroesophageal reflux disease, and hypothyroidism, who presented with acute pancreatitis few hours after receiving the third dose of Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, without other identified etiology. His symptoms were mild and he was discharged in a stable condition after improvement in his condition with supportive care.

Acute Extensive Deep Vein Thrombosis After Heterogeneous Administration of Moderna mRNA Booster Vaccine: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) struck the world in 2019 and led to the development of the multisystem coronavirus disease-2019 (COVID-19) causing a worldwide pandemic. Vaccines with boosters were developed due to novel mutations of SARS-CoV-2. Heterogeneous vaccination emerged with the perception that mixing vaccines can provide better protection. We present the case of a 68-year-old male patient who developed extensive acute deep vein thrombosis (DVT) of the left lower extremity, two weeks following the Moderna mRNA booster vaccine (mRNA-1273). His first two doses were AstraZeneca ChAdOx1-S [recombinant]. He was started on a heparin drip and prescribed rivaroxaban. We discuss the possible etiology of this DVT, the mechanism of action of the Moderna mRNA vaccine, the association of DVT with vaccine-induced inflammation, implications of heterogeneous vaccine combinations, and recommendations to advise people on possible thrombogenic adverse effects prior to mRNA vaccine administration.

Small Fiber Neuropathy Associated With the Moderna SARS-CoV-2 Vaccine.

Efforts of controlling viral transmission began soon after the first cases of coronavirus disease 2019 (COVID-19) infections were identified. Initial efforts were related to contact precautions, hand hygiene, and mask-wearing; however, it was soon evident that a robust global immunization drive was the most effective way to curb disease transmission. In the United States, the first doses of COVID-19 vaccines were rolled out soon after the FDA granted emergency use authorization for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. What this also meant was that many of the routine phases that any new drug or vaccine goes through before being released publicly were bypassed. Over the past two years, various side effects and reactions have been seen after COVID-19 vaccine administration, the most common being local injection site events (e.g., pain, redness, swelling) and systemic effects (e.g., fatigue, headaches, myalgias). We report the case of a 64-year-old female who developed bilateral lower extremity numbness and tingling within weeks of receiving the third dose of Moderna SARS-CoV-2 vaccine. The patient underwent extensive testing to ascertain the diagnosis. She had negative autonomic testing and normal nerve conduction study/electromyography (EMG), which did not reveal large fiber neuropathy. Eventually, the patient underwent a skin biopsy, which revealed small fiber neuropathy. This case report highlights the importance of keeping a broad differential for rare side effects, such as small fiber neuropathy, that are currently being seen and reported in the literature.

Central Retinal Vein Occlusion Following the First Dose of COVID Vaccine.

The reports of vascular adverse events in the eye following COVID-19 vaccination are infrequent. We report the case of a healthy male who developed central retinal vein occlusion in his left eye three days following administration of the first dose of Covishield vaccine. As the underlying systemic and ocular risk factors were absent and laboratory investigations were normal, vein occlusion appeared to probably result from the vaccine. The patient developed retinal hemorrhages and non-perfusion ischemic areas all over the fundus. The macular edema was reduced with intravitreal triamcinolone acetonide, but the visual gain was not much, which appears to be due to the time lag in his initial presentation to the Ophthalmology Department. A close watch should be kept for ophthalmic adverse events to have an early intervention.

Vaccine Adverse Event Mining of Twitter Conversations: 2-Phase Classification Study.

BACKGROUND: Traditional monitoring for adverse events following immunization (AEFI) relies on various established reporting systems, where there is inevitable lag between an AEFI occurring and its potential reporting and subsequent processing of reports. AEFI safety signal detection strives to detect AEFI as early as possible, ideally close to real time. Monitoring social media data holds promise as a resource for this. OBJECTIVE: The primary aim of this study is to investigate the utility of monitoring social media for gaining early insights into vaccine safety issues, by extracting vaccine adverse event mentions (VAEMs) from Twitter, using natural language processing techniques. The secondary aims are to document the natural language processing techniques used and identify the most effective of them for identifying tweets that contain VAEM, with a view to define an approach that might be applicable to other similar social media surveillance tasks. METHODS: A VAEM-Mine method was developed that combines topic modeling with classification techniques to extract maximal VAEM posts from a vaccine-related Twitter stream, with high degree of confidence. The approach does not require a targeted search for specific vaccine reaction-indicative words, but instead, identifies VAEM posts according to their language structure. RESULTS: The VAEM-Mine method isolated 8992 VAEMs from 811,010 vaccine-related Twitter posts and achieved an F1 score of 0.91 in the classification phase. CONCLUSIONS: Social media can assist with the detection of vaccine safety signals as a valuable complementary source for monitoring mentions of vaccine adverse events. A social media-based VAEM data stream can be assessed for changes to detect possible emerging vaccine safety signals, helping to address the well-recognized limitations of passive reporting systems, including lack of timeliness and underreporting.

Eruptive Angiomatosis Triggered by COVID-19 Vaccination.

Despite meeting strict standards of quality, safety, and effectiveness, rare systemic and cutaneous side effects of coronavirus disease 2019 (COVID-19) vaccinations continue to be reported throughout the world. We report a case of eruptive cherry angiomatosis in a female following her first dose of COVID-19 vaccination with subsequent crops appearing after the second dose. The biopsy revealed dilated capillaries within the superficial dermis consistent with the clinical diagnosis.

SARS-CoV-2 Antibody Response After a Third Dose of the BNT162b2 Vaccine in Patients Receiving Maintenance Hemodialysis or Peritoneal Dialysis.

RATIONALE & OBJECTIVE: Recent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared with the general population, suggesting the possible value of a third booster dose. We characterized the humoral response after 3 doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD). STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 69 French patients (38 HD and 31 PD) treated at a single center who received 3 doses of the BNT162b2 vaccine. FINDINGS: Humoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least 3 weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 years [interquartile range (IQR), 53-76 years], 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7,554 [IQR, 2,268-11,736] AU/mL after the third dose. Three patients were nonresponders (anti-S1 antibody level < 0.8 AU/mL), and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, 1 of the 3 initial nonresponders produced anti-spike antibody, and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe after a third vaccine dose. LIMITATIONS: Observational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood. CONCLUSIONS: A third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.

COVID-19 Vaccine-Related Thrombosis: A Systematic Review and Exploratory Analysis.

Introduction: The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Two vaccine types were developed using two different technologies: viral vectors and mRNA. Thrombosis is one of the most severe and atypical adverse effects of vaccines. This study aimed to analyze published cases of thrombosis after COVID-19 vaccinations to identify patients' features, potential pathophysiological mechanisms, timing of appearance of the adverse events, and other critical issues. Materials and Methods: We performed a systematic electronic search of scientific articles regarding COVID-19 vaccine-related thrombosis and its complications on the PubMed (MEDLINE) database and through manual searches. We selected 10 out of 50 articles from February 1 to May 5, 2021 and performed a descriptive analysis of the adverse events caused by the mRNA-based Pfizer and Moderna vaccines and the adenovirus-based AstraZeneca vaccine. Results: In the articles on the Pfizer and Moderna vaccines, the sample consisted of three male patients with age heterogeneity. The time from vaccination to admission was ≤3 days in all cases; all patients presented signs of petechiae/purpura at admission, with a low platelet count. In the studies on the AstraZeneca vaccine, the sample consisted of 58 individuals with a high age heterogeneity and a high female prevalence. Symptoms appeared around the ninth day, and headache was the most common symptom. The platelet count was below the lower limit of the normal range. All patients except one were positive for PF4 antibodies. The cerebral venous sinus was the most affected site. Death was the most prevalent outcome in all studies, except for one study in which most of the patients remained alive. Discussion: Vaccine-induced thrombotic thrombocytopenia (VITT) is an unknown nosological phenomenon secondary to inoculation with the COVID-19 vaccine. Several hypotheses have been formulated regarding its physiopathological mechanism. Recent studies have assumed a mechanism that is assimilable to heparin-induced thrombocytopenia, with protagonist antibodies against the PF4-polyanion complex. Viral DNA has a negative charge and can bind to PF4, causing VITT. New experimental studies have assumed that thrombosis is related to a soluble adenoviral protein spike variant, originating from splicing events, which cause important endothelial inflammatory events, and binding to endothelial cells expressing ACE2. Conclusion: Further studies are needed to better identify VITT's pathophysiological mechanisms and genetic, demographic, or clinical predisposition of high-risk patients, to investigate the correlation of VITT with the different vaccine types, and to test the significance of the findings.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.

The Usefulness of a Duplex RT-qPCR during the Recent Yellow Fever Brazilian Epidemic: Surveillance of Vaccine Adverse Events, Epizootics and Vectors.

From 2016 to 2018, Brazil faced the biggest yellow fever (YF) outbreak in the last 80 years, representing a risk of YF reurbanization, especially in megacities. Along with this challenge, the mass administration of the fractionated YF vaccine dose in a naïve population brought another concern: the possibility to increase YF adverse events associated with viscerotropic (YEL-AVD) or neurological disease (YEL-AND). For this reason, we developed a quantitative real time RT-PCR (RT-qPCR) assay based on a duplex TaqMan protocol to distinguish broad-spectrum infections caused by wild-type yellow fever virus (YFV) strain from adverse events following immunization (AEFI) by 17DD strain during the vaccination campaign used to contain this outbreak. A rapid and more accurate RT-qPCR assay to diagnose YFV was established, being able to detect even different YFV genotypes and geographic strains that circulate in Central and South America. Moreover, after testing around 1400 samples from human cases, non-human primates and mosquitoes, we detected just two YEL-AVD cases, confirmed by sequencing, during the massive vaccination in Brazilian Southeast region, showing lower incidence than AEFI as expected.