Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older

BackgroundMonitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. MethodsWe evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FindingsFour outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines. InterpretationThis early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.

Reporting Rates for VAERS Death Reports Following COVID-19 Vaccination, December 14, 2020-November 17, 2021

BackgroundDespite 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). ObjectiveTo provide information and context about reports of death to VAERS following COVID-19 vaccination. DesignDescriptive study; reporting rates for VAERS death reports. SettingUnited States; December 14, 2020, to November 17, 2021. ParticipantsCOVID-19 vaccine recipients. MeasurementsReporting rates for death events per million persons vaccinated; adverse event counts; data mining signals of disproportionate reporting. Results9,201 death events were reported for COVID-19 vaccine recipients aged five 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 seven 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. Reported adverse events were non-specific or reflected the known leading causes of death. LimitationsVAERS data are subject to several limitations such as reporting bias (underreporting and stimulated reporting), missing or inaccurate information, and lack of a control group. Reported diagnoses, including deaths, are not causally verified diagnoses. ConclusionReporting rates for death events were lower than the expected all-cause mortality rates. Trends in reporting rates reflected known trends in background mortality rates. These findings do not suggest an association between vaccination and overall increased mortality. Funding SourceNo external sources of funding were used.

Reported Cases of Multisystem Inflammatory Syndrome in Children Aged 12 to 20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12-20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. MethodsWe investigated potential cases of MIS-C after COVID-19 vaccination reported to CDCs health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDCs Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. FindingsWe identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12-20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12-20 years had received [≥]1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1{middle dot}0 case per million persons receiving [≥]1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0{middle dot}3 cases per million vaccinated persons. InterpretationIn our case series, we describe a small number of persons with MIS-C who had received [≥]1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FundingThis work was supported by the Centers for Disease Control and Prevention Clinical Immunization Safety Assessment (CISA] Project contracts 200-2012-50430-0005 to Vanderbilt University Medical Center and 200-2012-53661 to Cincinnati Childrens Hospital Medical Center. Research in context panelO_ST_ABSEvidence before this studyC_ST_ABSMultisystem inflammatory syndrome in children (MIS-C), also known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is an uncommon, but serious, complication described after SARS-CoV-2 infection that is characterized by a generalized hyperinflammatory response. A review of the literature using PubMed identified reports of six persons aged 12-20 years who developed MIS-C following COVID-19 vaccination. Search terms used to identify these reports were: "multisystem inflammatory syndrome in children", "MIS-C", "MISC", "multisystem inflammatory syndrome in adults", "MIS-A", "MISA", "paediatric inflammatory multisystem syndrome", and "PIMS-TS" each with any COVID-19 vaccine type. There were no exclusion criteria (i.e., all ages and languages). Added value of this studyWe conducted integrated surveillance for MIS-C after COVID-19 vaccination using two passive surveillance systems, CDCs MIS-C national surveillance and the Vaccine Adverse Event Reporting System (VAERS), and clinician or health department outreach to CDC, including through Clinical Immunization Safety Assessment (CISA) Project consultations. We investigated reports of potential MIS-C occurring from December 14, 2020, to August 31, 2021, in persons aged 12-20 years any time after receipt of COVID-19 vaccine to identify those that met the CDC MIS-C case definition. Any positive serology test was accepted as meeting the CDC MIS-C case definition, although anti- nucleocapsid antibody is indicative of SARS-CoV-2 infection, while anti-spike protein antibody may be induced either by SARS-CoV-2 infection or by COVID-19 vaccination. We investigated 47 reports and identified 21 persons with MIS-C after receipt of COVID-19 vaccine. Of the 21 persons with MIS-C, median age was 16 years (range 12-20 years), and 13 (62%) were male. Fifteen (71%) had laboratory evidence of past or recent SARS-CoV-2 infection (positive SARS-CoV-2 nucleic acid amplification test [NAAT], viral antigen, or serology test before or during MIS-C illness evaluation), and 5 (33%) of those 15 had illness onset after their second vaccine dose. Six (29%) of 21 persons had no laboratory evidence of past or recent SARS-CoV-2 infection, and five of those six (83%) had onset of MIS-C after the second vaccine dose. Implications of all the available evidenceDuring the first nine months of the COVID-19 vaccination program in the United States, >21 million persons aged 12 to 20 years received [≥]1 dose of COVID-19 vaccine as of August 31, 2021. This case series describes MIS-C in 21 persons following vaccine receipt during this time period; the majority of persons reported also had evidence of SARS-CoV-2 infection. The surveillance has limitations, but our findings suggest that MIS-C as identified in this report following COVID-19 vaccination is rare. In evaluating persons with a clinical presentation consistent with MIS-C after COVID-19 vaccination it is important to consider alternative diagnoses, and anti-nucleocapsid antibody testing may be helpful. Continued surveillance for MIS-C illness after COVID-19 vaccination is warranted, especially as pediatric COVID-19 vaccination expands. Providers are encouraged to report potential MIS-C cases after COVID-19 vaccination to VAERS.