Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Safety Monitoring of COVID-19 Vaccine Booster Doses Among Adults - United States, September 22, 2021-February 6, 2022.

During September 22, 2021-February 6, 2022, approximately 82.6 million U.S. residents aged ≥18 years received a COVID-19 vaccine booster dose.* The Food and Drug Administration (FDA) has authorized a booster dose of either the same product administered for the primary series (homologous) or a booster dose that differs from the product administered for the primary series (heterologous). These booster authorizations apply to all three COVID-19 vaccines used in the United States (1-3).† The Advisory Committee on Immunization Practices (ACIP) recommended preferential use of an mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer-BioNTech]) for a booster, even for persons who received the Ad26.COV2.S (Janssen [Johnson & Johnson]) COVID-19 vaccine for their single-dose primary series.§ To characterize the safety of COVID-19 vaccine boosters among persons aged ≥18 years during September 22, 2021-February 6, 2022, CDC reviewed adverse events and health impact assessments following receipt of a booster that were reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system managed by CDC and FDA. Among 721,562 v-safe registrants aged ≥18 years who reported receiving a booster, 88.8% received homologous COVID-19 mRNA vaccination. Among registrants who reported a homologous COVID-19 mRNA booster dose, systemic reactions were less frequent following the booster (58.4% [Pfizer-BioNTech] and 64.4% [Moderna], respectively) than were those following dose 2 (66.7% and 78.4%, respectively). The adjusted odds of reporting a systemic reaction were higher following a Moderna COVID-19 vaccine booster, irrespective of the vaccine received for the primary series. VAERS has received 39,286 reports of adverse events after a COVID-19 mRNA booster vaccination for adults aged ≥18 years, including 36,282 (92.4%) nonserious and 3,004 (7.6%) serious events. Vaccination providers should educate patients that local and systemic reactions are expected following a homologous COVID-19 mRNA vaccine booster; however, these reactions appear less common than those following dose 2 of an mRNA-based vaccine. CDC and FDA will continue to monitor vaccine safety and provide data to guide vaccine recommendations and protect public health.

Thromboembolic events after Ad.26.COV2.S COVID-19 vaccine: Reports to the Vaccine Adverse Event Reporting System.

PURPOSE: The Food and Drug Administration (FDA) has identified a potential safety concern for thromboembolic events (TEEs) after Ad.26.COV2.S COVID-19 Vaccine. We sought to characterize the frequency, severity, type, and anatomic location of TEEs reported to the Vaccine Adverse Event Reporting System (VAERS) following Ad.26.COV2.S. METHODS: Reports of TEEs after Ad.26.COV2.S were identified in VAERS, and demographics, clinical characteristics, and relevant medical history were summarized. For a subset of reports, physicians reviewed available medical records and evaluated clinical presentation, diagnostic evaluation, risk factors, and treatment. The crude reporting rate of TEEs was estimated based on case counts in VAERS and vaccine administration data. RESULTS: Through February 28, 2022, FDA identified 3790 reports of TEEs after Ad.26.COV2.S. Median age was 56 years, and 1938 individuals (51.1%) were female. Most reports, 2892 (76.3%), were serious, including 421 deaths. Median time to onset was 12 days post-vaccination. Obesity and ischemia were among the most commonly documented risk factors. Thrombocytopenia (platelet count less than 150 000/µl) was documented in 63 records (11.5%) and anti-platelet 4 antibodies in 25 (4.6%). Medical review identified cases of severe clot burden (e.g., bilateral, saddle, or other massive pulmonary embolism with or without cor pulmonale; lower extremity thrombus involving the external iliac, common femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins). The crude reporting rate was ~20.7 cases of TEE per 100 000 doses of Ad.26.COV2.S administered. CONCLUSIONS: Life-threatening or fatal TEEs have been reported after Ad.26.COV2.S, including bilateral massive pulmonary embolism or other severe clot burden.

Guillain-Barré Syndrome After High-Dose Influenza Vaccine Administration in the United States, 2018-2019 Season.

BACKGROUND: The Vaccine Safety Datalink (VSD) identified a statistical signal for an increased risk of Guillain-Barré syndrome (GBS) in days 1-42 after 2018-2019 high-dose influenza vaccine (IIV3-HD) administration. We evaluated the signal using Medicare. METHODS: We conducted early- and end-of-season claims-based self-controlled risk interval analyses among Medicare beneficiaries ages ≥65 years, using days 8-21 and 1-42 postvaccination as risk windows and days 43-84 as control window. The VSD conducted chart-confirmed analyses. RESULTS: Among 7 453 690 IIV3-HD vaccinations, we did not detect a statistically significant increased GBS risk for either the 8- to 21-day (odds ratio [OR], 1.85; 95% confidence interval [CI], 0.99-3.44) or 1- to 42-day (OR, 1.31; 95% CI, 0.78-2.18) risk windows. The findings from the end-of-season analyses were fully consistent with the early-season analyses for both the 8- to 21-day (OR, 1.64; 95% CI, 0.92-2.91) and 1- to 42-day (OR, 1.12; 95% CI, 0.70-1.79) risk windows. The VSD's chart-confirmed analysis, involving 646 996 IIV3-HD vaccinations, with 1 case each in the risk and control windows, yielded a relative risk of 1.00 (95% CI, 0.06-15.99). CONCLUSIONS: The Medicare analyses did not exclude an association between IIV3-HD and GBS, but it determined that, if such a risk existed, it was similar in magnitude to prior seasons. Chart-confirmed VSD results did not confirm an increased risk of GBS.

Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barré syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public.

Association of Receipt of the Ad26.COV2.S COVID-19 Vaccine With Presumptive Guillain-Barré Syndrome, February-July 2021.

Importance: As part of postauthorization safety surveillance, the US Food and Drug Administration (FDA) has identified a potential safety concern for Guillain-Barré syndrome (GBS) following receipt of the Ad26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccine. Objective: To assess reports of GBS received in the Vaccine Adverse Event Reporting System (VAERS) following Ad26.COV2.S vaccination. Design, Setting, and Participants: Reports of presumptive GBS were identified in a US passive reporting system (VAERS) February-July 2021 and characterized, including demographics, clinical characteristics, and relevant medical history. Exposures: Receipt of the Ad26.COV2.S vaccine; the comparator was the background rate of GBS in the general (unvaccinated) population that had been estimated and published based on a standardized case definition. Main Outcomes and Measures: Presumptive GBS; the reporting rate was analyzed, including calculation of the observed to expected ratio based on background rates and vaccine administration data. Because of limited availability of medical records, cases were not assessed according to the Brighton Collaboration criteria for GBS. Results: As of July 24, 2021, 130 reports of presumptive GBS were identified in VAERS following Ad26.COV2.S vaccination (median age, 56 years; IQR, 45-62 years; 111 individuals [86.0%] were < 65 years; 77 men [59.7%]). The median time to onset of GBS following vaccination was 13 days (IQR, 10-18 days), with 105 cases (81.4%) beginning within 21 days and 123 (95.3%) within 42 days. One hundred twenty-one reports (93.1%) were serious, including 1 death. With approximately 13 209 858 doses of vaccine administered to adults in the US, the estimated crude reporting rate was 1 case of GBS per 100 000 doses administered. The overall estimated observed to expected rate ratio was 4.18 (95% CI, 3.47-4.98) for the 42-day window, and in the worst-case scenario analysis for adults 18 years or older, corresponded to an estimated absolute rate increase of 6.36 per 100 000 person-years (based on a rate of approximately 8.36 cases per 100 000 person-years [123 cases per 1 472 162 person-years] compared with a background rate of approximately 2 cases per 100 000 person-years). For both risk windows, the observed to expected rate ratio was elevated in all age groups except individuals aged 18 through 29 years. Conclusions and Relevance: These findings suggest a potential small but statistically significant safety concern for Guillain-Barré syndrome following receipt of the Ad26.COV2.S vaccine. However, the findings are subject to the limitations of passive reporting systems and presumptive case definition, and they must be considered preliminary pending analysis of medical records to establish a definitive diagnosis.

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures: Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

Logistic Regression Likelihood Ratio Test Analysis for Detecting Signals of Adverse Events in Post-market Safety Surveillance.

The Vaccine Adverse Event Reporting System (VAERS) and other product surveillance systems compile reports of product-associated adverse events (AEs), and these reports may include a wide range of information including age, gender, and concomitant vaccines. Controlling for possible confounding variables such as these is an important task when utilizing surveillance systems to monitor post-market product safety. A common method for handling possible confounders is to compare observed product-AE combinations with adjusted baseline frequencies where the adjustments are made by stratifying on observable characteristics. Though approaches such as these have proven to be useful, in this article we propose a more flexible logistic regression approach which allows for covariates of all types rather than relying solely on stratification. Indeed, a main advantage of our approach is that the general regression framework provides flexibility to incorporate additional information such as demographic factors and concomitant vaccines. As part of our covariate-adjusted method, we outline a procedure for signal detection that accounts for multiple comparisons and controls the overall Type 1 error rate. To demonstrate the effectiveness of our approach, we illustrate our method with an example involving febrile convulsion, and we further evaluate its performance in a series of simulation studies.

A new algorithmic approach for the extraction of temporal associations from clinical narratives with an application to medical product safety surveillance reports.

The sheer volume of textual information that needs to be reviewed and analyzed in many clinical settings requires the automated retrieval of key clinical and temporal information. The existing natural language processing systems are often challenged by the low quality of clinical texts and do not demonstrate the required performance. In this study, we focus on medical product safety report narratives and investigate the association of the clinical events with appropriate time information. We developed a novel algorithm for tagging and extracting temporal information from the narratives, and associating it with related events. The proposed algorithm minimizes the performance dependency on text quality by relying only on shallow syntactic information and primitive properties of the extracted event and time entities. We demonstrated the effectiveness of the proposed algorithm by evaluating its tagging and time assignment capabilities on 140 randomly selected reports from the US Vaccine Adverse Event Reporting System (VAERS) and the FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS). We compared the performance of our tagger with the SUTime and HeidelTime taggers, and our algorithm's event-time associations with the Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI). We further evaluated the ability of our algorithm to correctly identify the time information for the events in the 2012 Informatics for Integrating Biology and the Bedside (i2b2) Challenge corpus. For the time tagging task, our algorithm performed better than the SUTime and the HeidelTime taggers (F-measure in VAERS and FAERS: Our algorithm: 0.86 and 0.88, SUTime: 0.77 and 0.74, and HeidelTime 0.75 and 0.42, respectively). In the event-time association task, our algorithm assigned an inappropriate timestamp for 25% of the events, while the TARSQI toolkit demonstrated a considerably lower performance, assigning inappropriate timestamps in 61.5% of the same events. Our algorithm also supported the correct calculation of 69% of the event relations to the section time in the i2b2 testing set.

Decision support environment for medical product safety surveillance.

We have developed a Decision Support Environment (DSE) for medical experts at the US Food and Drug Administration (FDA). The DSE contains two integrated systems: The Event-based Text-mining of Health Electronic Records (ETHER) and the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment (PANACEA). These systems assist medical experts in reviewing reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and the FDA Adverse Event Reporting System (FAERS). In this manuscript, we describe the DSE architecture and key functionalities, and examine its potential contributions to the signal management process by focusing on four use cases: the identification of missing cases from a case series, the identification of duplicate case reports, retrieving cases for a case series analysis, and community detection for signal identification and characterization.

Allergic reactions after egg-free recombinant influenza vaccine: reports to the US Vaccine Adverse Event Reporting System.

The Vaccine Adverse Event Reporting System has received reports of allergic reactions following immunization with egg-free recombinant influenza vaccine, among patients with a self-reported egg allergy or previous allergic reaction to inactivated influenza vaccine. These results suggest that allergic reactions following influenza vaccination are not necessarily related to egg proteins.

Safety of Simultaneous Administration of Bivalent mRNA COVID-19 and Influenza Vaccines in the Vaccine Adverse Event Reporting System (VAERS).

INTRODUCTION: Bivalent mRNA coronavirus disease 2019 (COVID-19) vaccines may be simultaneously administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: The aim was to describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines during the period of September 1, 2022-March 31, 2023. We assessed the characteristics of these reports and described the most frequently reported AEs. Clinicians reviewed available medical records for reports of serious AEs and adverse events of special interest (AESI). RESULTS: During the period of 1 September 2022 through 31 March 2023, VAERS received 3689 reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. The median age of vaccinees was 59 years (interquartile range 39, 70 years); 342 reports (9.3%) were classified as serious. The most common AEs among non-serious reports were severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) infection (785, 23.5%), cough (592, 17.7%), and fatigue (568, 17.0%). The most common AEs among serious reports were Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (88, 25.7%), dyspnea (81, 23.7%), and condition aggravated (55, 16.1%). DISCUSSION: Reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19) was expected due to Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) reporting requirements. CDC and FDA will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines.

Adverse events after recombinant human BMP2 in nonspinal orthopaedic procedures.

BACKGROUND: The FDA has approved recombinant human bone morphogenetic protein 2 (rhBMP-2) for treating acute, open tibial shaft fractures. However, the nature and frequency of complications after the use of rhBMP-2 in nonspinal orthopaedic surgery have not been well characterized. QUESTIONS/PURPOSES: To determine what types of adverse events have been reported after the use of rhBMP-2, whether they were severe enough to require additional surgery, and after what types of operations these adverse events occurred. METHODS: Adverse events reported to the FDA's Manufacturer and User Facility Device Experience database were reviewed and summarized. RESULTS: Through December 31, 2011, the FDA has received 62 reports of adverse events involving rhBMP-2 in nonspinal orthopaedic procedures. Surgical site infections and other wound complications, heterotopic bone, pseudarthrosis, and local inflammation were among the most commonly reported adverse events. Almost half of the reports (30 reports; 48%) stated that the patients required secondary interventions to address the reported adverse events. The majority (49 reports; 79%) described adverse events occurring after unapproved uses, such as management of tibial plateau fractures, treatment of congenital pseudarthrosis of the tibia, and humeral reconstruction. CONCLUSIONS: Serious adverse events can occur after the use of rhBMP-2 in nonspinal orthopaedic procedures and may necessitate additional surgery. Most events in this analysis occurred after off-label uses. Postmarketing review of adverse event reports remains an important approach for identifying potential safety concerns.

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.

Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States.

Importance: Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring. Objective: To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines. Design, Setting, and Participants: This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included. Exposures: Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine. Main Outcomes and Measures: Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates. Results: Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods. Conclusions and Relevance: This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.