Post-authorization safety surveillance of Ad.26.COV2.S vaccine: Reports to the Vaccine Adverse Event Reporting System and v-safe, February 2021-February 2022.

BACKGROUND: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. METHODS: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. RESULTS: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. CONCLUSION: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.

Adverse events with risankizumab in the real world: postmarketing pharmacovigilance assessment of the FDA adverse event reporting system.

Background: Risankizumab, a humanized IgG1 monoclonal antibody that selectively inhibits IL-23, is currently approved for the treatment of moderate-to-severe plaque psoriasis and Crohn's disease. The real-world safety study of risankizumab in a large- sample population is currently lacking. The aim of this study was to evaluate risankizumab-associated adverse events (AEs) and characterize the clinical priority through the data mining of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses were performed by calculating the reporting odds ratios (RORs), deemed significant when the lower limit of the 95% confidence interval was greater than 1, to quantify the signals of risankizumab-related AEs from the second quarter (Q2) of 2019 to 2022 Q3. Serious and non-serious cases were compared, and signals were prioritized using a rating scale. Results: Risankizumab was recorded in 10,235 reports, with 161 AEs associated with significant disproportionality. Of note, 37 PTs in at least 30 cases were classified as unexpected AEs, which were uncovered in the drug label, such as myocardial infarction, cataract, pancreatitis, diabetes mellitus, stress, and nephrolithiasis. 74.68%, 25.32%, and 0% PTs were graded as weak, moderate, and strong clinical priorities, respectively. A total of 48 risankizumab-related AEs such as pneumonia, cerebrovascular accident, cataract, loss of consciousness, cardiac disorder, hepatic cirrhosis, and thrombosis, were more likely to be reported as serious AEs. The median TTO of moderate and weak signals related to risankizumab was 115 (IQR 16.75-305) and 124 (IQR 29-301) days, respectively. All of the disproportionality signals had early failure type features, indicating that risankizumab-associated AEs gradually decreased over time. Conclusion: Our study found potential new AE signals and provided valuable evidence for clinicians to mitigate the risk of risankizumab-associated AEs based on an extensive analysis of a large-scale postmarketing international safety database.

Spontaneously reported adverse events following COVID-19 basic and booster immunizations in the Netherlands.

INTRODUCTION: The rapid roll-out of novel COVID-19 vaccines made near real-time post-marketing safety surveillance essential to identify rare and long-term adverse events following immunization (AEFIs). In light of the ongoing booster vaccination campaigns, it is key to monitor changes in observed safety patterns post-vaccination. The effect of sequential COVID-19 vaccinations, as well as heterologous vaccination sequences, on the observed post-vaccination safety pattern, remains largely unknown. METHODS: The primary objective of this study was to describe the profile of spontaneously reported AEFIs following COVID-19 vaccination in the Netherlands, including the primary and booster series. Reports from consumers and healthcare professionals were collected via a COVID-19 vaccine-tailored online reporting form by the National Pharmacovigilance Centre Lareb (Lareb) between 6 January 2021 and 31 August 2022. The data were used to describe the most frequently reported AEFIs per vaccination moment, the consumer experienced burden per AEFI, and differences in AEFIs reported for homologous and heterologous vaccination sequences. RESULTS: Lareb received 227,884 spontaneous reports over a period of twenty months. Overall, a high degree of similarity in local and systemic AEFIs per vaccination moment was observed, with no apparent change in the number of reports of serious adverse events after multiple COVID-19 vaccinations. No differences in the pattern of reported AEFIs per vaccination sequence was observed. CONCLUSION: Spontaneous reported AEFIs demonstrated a similar reporting pattern for homologous and heterologous primary and booster series of COVID-19 vaccination in the Netherlands.

COVID-19 vaccine safety inquiries to the centers for disease control and prevention immunization safety office.

BACKGROUND: Following the authorization and recommendations for use of the U.S. COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC)'s Immunization Safety Office (ISO) responded to inquiries and questions from public health officials, healthcare providers, and the general public on COVID-19 vaccine safety. METHODS: We describe COVID-19 vaccine safety inquiries, by topic, received and addressed by ISO from December 1, 2020-August 31, 2022. RESULTS: Of the 1978 COVID-19 vaccine-related inquiries received, 1655 specifically involved vaccine safety topics. The most frequently asked-about topics included deaths following vaccination, myocarditis, pregnancy, and reproductive health outcomes, understanding or interpreting data from the Vaccine Adverse Event Reporting System (VAERS), and thrombosis with thrombocytopenia syndrome. CONCLUSIONS: Inquiries about vaccine safety generally reflect issues that receive media attention. ISO will continue to monitor vaccine safety inquiries and provide accurate and timely information to healthcare providers, public health officials, and the general public.

Oral side effects of COVID-19 vaccines in 32 European countries: Analysis of EudraVigilance reports.

The recent reports of oral side effects (SEs) following COVID-19 vaccination warrant further investigation into their prevalence, severity, and aetiology. This study was conducted to synthesize the first-ever population-level evidence about oral SEs of COVID-19 vaccines in Europe. The European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance) database was accessed in August 2022 to extract summary data of all potential oral SEs reported after COVID-19 vaccination. The data were reported descriptively and cross-tabulated to facilitate sub-group analysis per vaccine type, sex, and age group. Dysgeusia was the most commonly reported oral SE (0.381 case per each 100 received reports), followed by oral paraesthesia (0.315%), ageusia (0.296%), lip swelling (0.243%), dry mouth (0.215%), oral hypoaesthesia (0.210%), swollen tongue (0.207%), and taste disorder (0.173%). Females had significantly (Sig. < 0.001) a higher prevalence of all most common (top 20) oral SEs, except for salivary hypersecretion, which was equally prevalent among females and males. The present study revealed a low prevalence of oral SEs, with taste-related, other sensory and anaphylactic SEs being the most common SEs in Europe, similar to what was found earlier among the US population. Future studies should explore the potential risk factors of oral sensory and anaphylactic SEs to verify whether they are causally linked to COVID-19 vaccines.

Imprecision in adverse event reports following immunization against HPV in Japan and COVID-19 in the USA, UK, and Japan-and the effects of vaccine hesitancy and government policy.

INTRODUCTION: Erroneous reports of adverse events following immunization (AEFIs) likely exacerbated the 2013 collapse of Japan's HPV immunization program. A similar phenomenon characterized the first months of COVID-19 immunization programs in the USA, UK, and Japan with high rates of reported anaphylaxis. These reports illustrate the susceptibility of supposedly objective medical judgments to public anxiety. PURPOSE AND METHODS: This study documents inaccuracies in reported AEFIs using three quantitative methods. RESULTS: One of these quantitative methods revealed that false-positive rates for anaphylaxis reports following HPV and later COVID-19 vaccination ranged from 74 to 91 percent. However, unlike HPV vaccinations in Japan, anaphylaxis reports following COVID-19 vaccines fell in Japan, the USA and the UK in the latter months of 2021. Nevertheless, false-positive rates for anaphylaxis reports remained high, suggesting a high degree of imprecision in serious AEFI reports from many countries for many vaccines. Japan's HPV immunization program indicates that media reports, patient hesitancy, healthcare providers' perspectives on vaccine safety, and consistency of government messaging, all influence report number and accuracy. A parallel publication analyzes in depth how such factors affect AEFI reports. CONCLUSION: Confidence in the safety of the COVID-19 vaccines may have been bolstered trough rapid monitoring of AEFI reports and communication of these findings. This may partly explain the different trajectories of serious AEFI following HPV immunizations in Japan and COVID-19 immunizations in the USA, UK, and Japan.

Acute renal failure and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections: Analysis using the US FDA adverse event reporting system.

BACKGROUND: Recently, antivirals, including remdesivir, have been repurposed to treat COVID-19 infections. Initial concerns have been raised about the adverse renal and cardiac events associated with remdesivir. OBJECTIVE: This study aimed to analyse the adverse renal and cardiac events associated with remdesivir in patients with COVID-19 infections using the US FDA adverse event reporting system. METHOD: A case/non-case method was used to determine adverse drug events associated with remdesivir as the primary suspect drug between January 1, 2020, and November 11, 2021, for patients with COVID-19 infections. Cases were reports for remdesivir with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'Renal and urinary disorders' or 'cardiac' disorders. To measure disproportionality in reporting of ADEs, frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, and EBGM > 1 for ADEs with ≥4 reports. Sensitivity analyses were undertaken by excluding reports for non-Covid indications and medications strongly associated with AKI and cardiac arrhythmias. RESULTS: In the main analysis for remdesivir use in patients with COVID-19 infections, we identified 315 adverse cardiac events comprising 31 different MeDRA PTs and 844 adverse renal events comprising 13 different MeDRA PTs. Regarding adverse renal events, disproportionality signals were noted for "renal failure" (ROR = 2.8 (2.03-3.86); EBGM = 1.92 (1.58-2.31), "acute kidney injury" (ROR = 16.11 (12.52-20.73); EBGM = 2.81 (2.57-3.07), "renal impairment" (ROR = 3.45 (2.68-4.45); EBGM = 2.02 (1.74-2.33). Regarding adverse cardiac events, strong disproportionality signals were noted for "electrocardiogram QT prolonged" (ROR = 6.45 (2.54-16.36); EBGM = 2.04 (1.65-2.51), "pulseless electrical activity" (ROR = 43.57 (13.64-139.20); EBGM = 2.44 (1.74-3.33), "sinus bradycardia" (ROR = 35.86 (11.16-115.26); EBGM = 2.82 (2.23-3.53), "ventricular tachycardia" (ROR = 8.73 (3.55-21.45); EBGM = 2.52 (1.89-3.31). The risk of AKI and cardiac arrythmias were confirmed by sensitivity analyses. CONCLUSION: This hypothesis-generating study identified AKI and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections. The relationship between AKI and cardiac arrhythmias should be further investigated using registries or large clinical data to assess the impact of age, genetics, comorbidity, and the severity of Covid infections as potential confounders.

Analysis of COVID-19 mRNA Vaccine-induced Mouth Ulcers Using the Japanese Adverse Drug Event Report Database.

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

Capillary leak syndrome following COVID-19 vaccination: Data from the European pharmacovigilance database Eudravigilance.

Capillary leak syndrome (CLS) emerged as new adverse event after immunization (AEFI) associated to COVID-19 vaccination. CLS is a rare condition characterized by increased capillary permeability, resulting in hypoalbuminemia, hypotension, and edema mainly in the upper and lower limbs. Our pharmacovigilance study aims to evaluate the CLS onset following receipt of COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) compared to viral vector vaccines (Ad26.COV2-S and ChAdOx1-SARS-COV-2). We carried a cross-sectional study using all Individual Case Safety Reports (ICSRs) reporting a COVID-19 vaccine as suspected drug and CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. We applied the Reporting Odds Ratio (ROR) 95% CI for the disproportionality analysis. During our study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19(ChAdOx1-SARS-COV-2 = 36; Ad26.COV2-S = 9). The mRNA COVID-19 vaccines were reported in 39 ICSRs (BNT162b2 =33; mRNA-1273 =6). Majority of ICSRs were reported by healthcare professionals (71.4%). Majority of the patients were adult (58.3%) and the female gender accounted in more than 65% of ICSRs referred both to classes vaccines. In particular, women were more represented in ICSRs referred to mRNA-1273 (83.3%) and to ChAdOx1-SARS-COV-2 (72.2%). The CLS outcome was more frequently favorable in mRNA ICSRs (33,3%) than the viral vector ones (13.3%). Among the ICSRs reporting CLS with unfavorable outcome, we found also 9 fatal cases (BNT162b2 = 1; ChAdOx1-SARS-COV-2 = 4; Ad26.COV2-S = 4). From disproportionality analysis emerged a lower CLS reporting probability after vaccination with mRNA vaccines compared to viral vector-based ones (ROR 0.5, 95% CI 0.3-0.7; p <0.001).Our findings, even if subject to the limitations of spontaneous reporting systems, suggest a small but statistically significant safety concern for CLS following receipt of COVID-19 viral vector vaccines, in particular with Ad26.COV2-S. Cytokine-release following T-cell activation could be involved in CLS occurrence, but a precise mechanism has been not yet identified. COVID-19 vaccines remain attentive as possible triggers of CLS.

Quality of MedDRA® Coding in a Sample of COVID-19 Vaccine Medication Error Data.

INTRODUCTION: In recent years, there has been increasing interest from regulatory agencies and scientific organisations into the recording, coding and reporting of medication errors. Accuracy and consistency in the handling of medication error reports ensure the safety and effectiveness of medicines and provide reliable information to both healthcare professionals and patients. OBJECTIVE: The authors have examined a sample of Medical Dictionary for Regulatory Activities (MedDRA®) coded reports that describe medication errors to assess the accuracy and consistency of MedDRA® coding, and to identify the main types of coding errors for the newly introduced COVID-19 vaccines. METHODS: The sample of coded terms was assessed by two MedDRA® experts applying the Four Eyes Principle. It included 1500 reported terms drawn from the Uppsala Monitoring Centre database reported up to 25 August, 2021, describing medication errors for COVID-19 vaccines with their assigned MedDRA® terms. RESULTS: One third of the records could not be assessed because of incomplete or unclear verbatims. In one third, MedDRA® term assignments were correct, but another third of the sample was not adequately coded. The most frequent coding errors corresponded to vague MedDRA® Preferred Term assignments despite more detailed information being available in the verbatim for a more precise coding. This observation is similar to findings in the EudraVigilance database, where some of the most frequently assigned MedDRA® terms for medication errors also represent vague concepts. CONCLUSIONS: The findings indicate that understanding of medication error documentation and of the importance of accurate extraction of information from case narratives, as well as knowledge of MedDRA® content and coding guidelines need to be reinforced. The authors provide useful references to training opportunities and to the applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use-Endorsed Guides for MedDRA® users.

Reports analysis of psychotropic drugs related adverse reactions in Australia and Poland during the COVID 19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused significant changes to the global health care system AIMS: It is unknown whether the COVID-19 pandemic influenced the occurrence of adverse drug reactions (ADR) of antidepressive agents, benzodiazepines, and antipsychotics plus mood stabilizers (AaMS). The study was designed in order to compare the incidence of ADR during the COVID-19 pandemic with the period preceding the pandemic in Poland and Australia, different in terms of their COVID-19 prevention strategy. METHOD: We analysed ADR from the three surveyed pharmacological groups of drugs observed in Poland and Australia in the period prior to, and during the COVID-19 pandemic RESULTS: In Poland, a noticeable increase in the reported ADR of the assessed drug groups was observed during the COVID-19 pandemic. The highest was for antidepressive agents, but the reporting of ADR for benzodiazepines and AaMS drugs also increased significantly. In the case of ADR in Australian patients, the increase in the number of reported ADR for antidepressive agents was modest compared to that seen in Poland, but still noticeable, and there was a significant increase in ADR for benzodiazepines CONCLUSIONS: This study showed that the COVID-19 pandemic has had an impact on the incidence of ADR reported among both Polish and Australian patients but the modality of this was different.

COVID-19 Vaccine Safety First Year Findings in Adolescents.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Is PEGylation of Drugs Associated with Hypersensitivity Reactions? An Analysis of the Italian National Spontaneous Adverse Drug Reaction Reporting System.

BACKGROUND AND OBJECTIVE: Evidence highlights the allergenic potential of PEGylated drugs because of the production of anti-polyethylene glycol immunoglobulins. We investigated the risk of hypersensitivity reactions of PEGylated drugs using the Italian spontaneous adverse drug reaction reporting system database. METHODS: We selected adverse drug reaction reports attributed to medicinal products containing PEGylated active substances and/or PEGylated liposomes from the Italian Spontaneous Reporting System in the period between its inception and March 2021. As comparators, we extracted adverse drug reaction reports of medicinal products containing the same non-PEGylated active substances and/or non-PEGylated liposomes (or compounds belonging to the same mechanistic class). A descriptive analysis of reports of hypersensitivity reactions was performed. Reporting rates and time to onset of hypersensitivity reactions were also calculated in the period between January 2009 and March 2021. As a measure of disproportionality, we calculated the reporting odds ratio. RESULTS: Overall, 3865 adverse drug reaction reports were related to PEGylated medicinal products and 11,961 to their non-PEGylated comparators. Around two-thirds of patients were female and reports mostly concerned patients aged between 46 and 64 years. The frequency of hypersensitivity reactions reporting was higher among PEGylated versus non-PEGylated medicinal products (11.7% vs 9.4%, p < 0.0001). The hypersensitivity reaction reporting rates were higher for PEGylated medicinal products versus non-PEGylated medicinal products, with reporting rate ratios that ranged from 1.4 (95% confidence interval 0.8-2.5) for pegfilgrastim versus filgrastim to 20.0 (95% confidence interval 2.8-143.5) for peginterferon alpha-2a versus interferon alpha-2a. The median time to onset of hypersensitivity reactions was 10 days (interquartile range: 0-61) for PEGylated medicinal products, and 36 days (interquartile range: 3-216) for non-PEGylated comparators. Statistically significant reporting odds ratios were observed when comparing the reporting of hypersensitivity reactions for PEGylated versus non-PEGylated medicinal products (reporting odds ratio: 1.3; 95% confidence interval 1.1-1.4). However, when using all other drugs as comparators, the disproportionality analysis showed no association with hypersensitivity reactions for PEGylated nor non-PEGylated medicinal products, thus suggesting that many other triggers of drug-induced hypersensitivity reactions play a major role. CONCLUSIONS: The findings of this analysis of the Italian spontaneous adverse drug reaction database suggest a potential involvement for PEGylation in triggering drug-related hypersensitivity reactions, especially clinically relevant reactions. However, when comparing both PEGylated and non-PEGylated drugs under study to all other drugs no disproportionate reporting of hypersensitivity reactions was observed, probably due to a masking effect owing to the presence in the same database of other medicinal products increasing the threshold required to highlight a safety signal when the entire database is used as a reference.

Real-World Monitoring of COVID-19 Vaccines: An Industry Expert View on the Successes, Challenges, and Future Opportunities.

Pharmacovigilance leaders from major vaccine developers describe the learnings from the coronavirus disease 2019 (COVID-19) pandemic in the area of pharmacovigilance and pharmacoepidemiology. The authors aim to raise awareness of the co-operation among vaccine developers, highlight common challenges, advocate for solutions, and propose recommendations for the future in the areas of real-world safety and effectiveness, safety reporting and evaluation, and regulatory submissions. To enable timely evaluation of real-world safety and effectiveness, multi-sponsor study platforms were implemented, resulting in quicker recruitment over wide geographical areas. Future gains could be derived by developing geographically flexible, common protocols and/or joint company-sponsored studies for multiple vaccines and a collective strategy to build low/middle-income country (LMIC) sentinel sites. Safety reporting, signal detection and evaluation was particularly challenging given the unprecedented number of adverse events reported. New methods were required to manage increased report volume while maintaining the ability to quickly identify and respond to new data that could impact the benefit-risk profile of each vaccine. Worldwide health authority submissions, requests for information and differing regulatory requirements imposed significant burden on regulators and industry. Industry consensus on the safety reporting requirements and joint meetings with regulatory authorities markedly reduced this burden for all stakeholders. The most impactful innovations should be undertaken rapidly and expanded to other vaccines and therapeutics, with a multi-stakeholder approach. The authors of this paper make future recommendations and have launched an initiative named BeCOME (Beyond COVID Monitoring Excellence) with a focus on actions in each of the highlighted areas.

Serious adverse event following immunization and thromboembolic events associated with COVID19 vaccination: An analysis of nationwide causality assessment from India.

BACKGROUND: Vaccines against the COVID-19 pandemic were introduced in late 2020. The present study has been conducted to study the serious Adverse Events Following Immunization (AEFIs) reported for COVID-19 vaccines from India. METHODS: Secondary data analysis of the causality assessment reports for the 1112 serious AEFIs published by the Ministry of Health & Family Welfare, Government of India, was conducted. For the current analysis, all the reports published till 29.03.2022 were included. The primary outcome variables analyzed were the consistent causal association and the thromboembolic events. RESULTS: The majority of the serious AEFIs assessed were either coincidental (578, 52%) or vaccine product related (218, 19.6%). All the serious AEFIs were reported among the Covishield (992, 89.2%) and COVAXIN (120, 10.8%) vaccines. Among these, 401 (36.1%) were deaths, and 711 (63.9%) were hospitalized and recovered. On adjusted analysis, females, the younger age group and non-fatal AEFIs showed a statistically significant consistent causal association with COVID-19 vaccination. Thromboembolic events were reported among 209 (18.8%) of the analyzed participants, with a significant association with higher age and case fatality rate. CONCLUSION: Deaths reported under serious AEFIs were found to have a relatively lower consistent causal relationship with the COVID-19 vaccines than the recovered hospitalizations in India. No consistent causal association was found between the thromboembolic events and the type of COVID-19 vaccine administered in India.

Remdesivir for COVID-19 and acute kidney injury: disproportionality analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. AIM: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. METHOD: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. RESULTS: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. CONCLUSION: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic.

Safety of COVID-19 vaccines in pregnancy: a VAERS based analysis.

PURPOSE: Since vaccination against COVID-19 is recommended in pregnant people, we aimed to provide further evidence on the safety profile of COVID-19 vaccines in pregnancy. METHODS: Data on COVID-19 vaccines adverse events following immunizations (AEFIs) in pregnant people were retrieved from the open-access Vaccine Adverse Event Reporting System (VAERS) from December 2020 to April 2022. RESULTS: From December 2020 to April 1, 2022, a total of 4,869 reports involving pregnant women at COVID-19 vaccination were reported to VAERS. Among vaccines recipients, most belonged to the age group between 30 and 39 years old (3,029; 62.21%) and nearly half experienced an adverse event within 48 h of immunization (2,344; 48.14%). Overall, 21,816 suspected adverse reactions associated with COVID-19 vaccines were reported, and for as many as 80.43% of patients, they were described as non-serious. Most reactions occurred after administration of the mRNA-1273 (53.34%) and the BNT162b2 (40.68%) vaccines, while only a small proportion were related to the Johnson & Johnson's vaccine (5.69%). The most common non-pregnancy specific adverse events were headache (482; 2.21%), fatigue (472; 2.16%), and pyrexia (436; 2.00%), while adverse pregnancy outcomes with the highest reporting rate were abortions spontaneous (762; 3.49%), and vaginal haemorrhage (229; 1.05%). CONCLUSION: This post-marketing survey on VAERS data have provided updated evidence on the safety of COVID-19 vaccines during pregnancy, thus supporting clinicians in recommending maternal immunization.

Real-life safety profile of mRNA vaccines for COVID-19: An analysis of VAERS database.

INTRODUCTION: Since the first COVID-19 messenger RNA vaccines became available globally for emergency or conditional use, post-marketing surveillance activities have been implemented for the monitoring of any adverse events that might arise in daily clinical practice and were not detected earlier during clinical trials. METHODS: Safety data concerning the BNT162b2 and the mRNA-1273 COVID-19 vaccines were collected from the Vaccine Adverse Event Reporting System (VAERS) for the period from December 2020 to October 15, 2021. In addition to a descriptive analysis of individuals who experienced an adverse event after vaccination, a case-non-case analysis was performed by using the Reporting Odds Ratio with 95 % confidence interval as statistical parameter for detecting differences in reporting rates between the two mRNA vaccines. RESULTS: At the cut-off date, a total of 758,040 reports were submitted to VAERS, of which 439,401 were related to the Pfizer-BioNTech (BNT162b2) vaccine and 318,639 to the Moderna vaccine (mRNA-1273). Most common adverse events following immunization for both mRNA vaccines were headache, fatigue, pyrexia, dizziness, nausea, pain, chills, and pain in extremity. A disproportionality was found for BNT162b2 as compared with mRNA-1273 for some events of special interest, such as myocarditis [ROR 2.00; 95 % confidence interval (CI), 1.93-2.06], Bell's palsy (1.34; 1.29-1.39), and anaphylactic shock (3.23; 2.96-3.53). CONCLUSION: Even if some rare adverse events were identified, our survey of post-marketing surveillance has provided further evidence of the favourable safety profile of mRNA vaccines.

Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature.

Background: Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature. Methods: Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of 'any AEFI', local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination. Results: The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females. Discussion: The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.

Reporting rates for VAERS death reports following COVID-19 vaccination, December 14, 2020-November 17, 2021.

PURPOSE: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). We aimed to provide information and context about reports of death to VAERS following COVID-19 vaccination. METHODS: This is a descriptive study evaluating reporting rates for VAERS death reports for COVID-19 vaccine recipients in the United States between December 14, 2020, and November 17, 2021. Reporting rates were calculated as death events per million persons vaccinated and compared to expected all-cause (background) death rates. RESULTS: 9201 death events were reported for COVID-19 vaccine recipients aged 5 years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within 7 days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Limitations of VAERS data include potential reporting bias, missing or inaccurate information, lack of a control group, and reported diagnoses, including deaths, are not causally verified diagnoses. CONCLUSIONS: Reporting rates for death events were lower than the all-cause death rates expected in the general population. Trends in reporting rates reflected known trends in background death rates. These findings do not suggest an association between vaccination and overall increased mortality.