Nebenwirkung Tod bei mRNA-Impfstoffen
In einer aktuell im Journal The Lancet veröffentlichten Studie mit dem Titel „Sicherheit von mRNA-Impfstoffen, die während der ersten 6 Monate des US-amerikanischen COVID-19-Impfprogramms verabreicht wurden: eine Beobachtungsstudie über Meldungen an das Vaccine Adverse Event Reporting System und v-safe“, betrachten die Wissenschaftler die offiziell gemeldeten Zahlen zu den Impfnebenwirkungen der mRNA-Impfstoffe.
Bei den in den ersten 6 Monaten nach Impfstart verabreichten 298.792.852 Impfdosen (was nicht gleichbedeutend mit der Anzahl an Personen ist!) kam es bei den gemeldeten Impfnebenwirkungen in 1.3% zur „schweren Nebenwirkung Tod (4.496 Todesfälle durch die Impfung )“ und in 6.6% zu „schweren Nebenwirkungen (22.572 Personen)“.
„Während des Studienzeitraums wurden in den USA 298 792 852 Dosen von mRNA-Impfstoffen verabreicht. VAERS bearbeitete 340 522 Meldungen: 313 499 (92.1 %) waren nicht schwerwiegend, 22 527 (6.6 %) waren schwerwiegend (ohne Todesfolge), und 4496 (1.3 %) waren Todesfälle. Mehr als die Hälfte der 7 914 583 v-safe-Teilnehmer berichteten selbst über lokale und systemische Reaktionen und zwar häufiger nach der zweiten Dosis (4 068 447 [71.7 %] von 5 674 420 Teilnehmern für lokale Reaktionen und 4 018 920 [70-8 %] für systemische) als nach der ersten Dosis (4 644 989 [68.6 %] von 6 775 515 Teilnehmern für lokale Reaktionen und 3 573 429 [52.7 %] für systemische). Schmerzen an der Injektionsstelle (4 488 402 [66.2%] von 6 775 515 Teilnehmern nach der ersten Dosis und 3 890 848 [68.6%] von 5 674 420 Teilnehmern nach der zweiten Dosis), Müdigkeit (2 295 205 [33.9%] Teilnehmer nach der ersten Dosis und 3 158 299 Teilnehmer [55.7%] nach der zweiten Dosis) und Kopfschmerzen (1 831 471 [27.0%] Teilnehmer nach der ersten Dosis und 2 623 721 [46.2%] Teilnehmer nach der zweiten Dosis) wurden am häufigsten in den Tagen 0-7 nach der Impfung berichtet. Am häufigsten wurde am Tag nach der Impfung über Reaktivität berichtet; die meisten Reaktionen waren mild. Nach der zweiten Dosis (1 821 421 [32.1 %]) wurde häufiger über Arbeitsunfähigkeit, Unfähigkeit zur Ausübung normaler Tätigkeiten oder das Aufsuchen eines Arztes berichtet als nach der ersten Dosis (808 963 [11.9 %]).”
Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme: an observational study of reports to the Vaccine Adverse Event Reporting System and v-safe
In December, 2020, two mRNA-based COVID-19 vaccines were authorised for use in the USA. We aimed to describe US surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), a passive system, and v-safe, a new active system, during the first 6 months of the US COVID-19 vaccination programme.
In this observational study, we analysed data reported to VAERS and v-safe during Dec 14, 2020, to June 14, 2021. VAERS reports were categorised as non-serious, serious, or death. Reporting rates were calculated using numbers of COVID-19 doses administered as the denominator. We analysed v-safe survey reports from days 0–7 after vaccination for reactogenicity, severity (mild, moderate, or severe), and health impacts (ie, unable to perform normal daily activities, unable to work, or received care from a medical professional).
During the study period, 298 792 852 doses of mRNA vaccines were administered in the USA. VAERS processed 340 522 reports: 313 499 (92·1%) were non-serious, 22 527 (6·6%) were serious (non-death), and 4496 (1·3%) were deaths. Over half of 7 914 583 v-safe participants self-reported local and systemic reactogenicity, more frequently after dose two (4 068 447 [71·7%] of 5 674 420 participants for local reactogenicity and 4 018 920 [70·8%] for systemic) than after dose one (4 644 989 [68·6%] of 6 775 515 participants for local reactogenicity and 3 573 429 [52·7%] for systemic). Injection-site pain (4 488 402 [66·2%] of 6 775 515 participants after dose one and 3 890 848 [68·6%] of 5 674 420 participants after dose two), fatigue (2 295 205 [33·9%] participants after dose one and 3 158 299 participants [55·7%] after dose two), and headache (1 831 471 [27·0%] participants after dose one and 2 623 721 [46·2%] participants after dose two) were commonly reported during days 0–7 following vaccination. Reactogenicity was reported most frequently the day after vaccination; most reactions were mild. More reports of being unable to work, do normal activities, or of seeking medical care occurred after dose two (1 821 421 [32·1%]) than after dose one (808 963 [11·9%]); less than 1% of participants reported seeking medical care after vaccination (56 647 [0·8%] after dose one and 53 077 [0·9%] after dose two).
Safety data from more than 298 million doses of mRNA COVID-19 vaccine administered in the first 6 months of the US vaccination programme show that most reported adverse events were mild and short in duration.
US Centers for Disease Control and Prevention.
In December, 2020, two mRNA COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech]; and mRNA-1273 [Moderna]) were granted emergency use authorisation (EUA) by the US Food and Drug Administration (FDA) as two-dose series and recommended for use by the Advisory Committee on Immunization Practices (ACIP).1, 2 In clinical trials, both mRNA COVID-19 vaccines showed acceptable safety profiles;3, 4 the most frequently reported local and systemic symptoms were injection-site pain, fatigue, and headache. Reactogenicity was more frequently reported after dose two than after dose one and among participants younger than 65 years than among older participants.3, 4, 5Post-authorisation safety monitoring can characterise the safety profiles of mRNA-based COVID-19 vaccines in large and heterogeneous populations.6 Phased administration of COVID-19 vaccines in the USA began with health-care workers and long-term care-facility residents and was expanded to the general population during spring 2021; however, implementation plans varied by state.7 The major sources of initial US safety data were the Vaccine Adverse Event Reporting System (VAERS), a spontaneous, passive reporting system;8 and v-safe,9 a new active monitoring system. VAERS was established in 1990 as the US early warning system to rapidly detect adverse events that might occur following vaccinations. V-safe was established in 2020 specifically for monitoring COVID-19 vaccine safety in the USA and collects information on reactogenicity and effects on health following COVID-19 vaccination.Research in contextEvidence before this studyWe searched PubMed for articles published up to Dec 29, 2021, using the terms (“BNT162b2” OR “mRNA-1273” OR “mRNA COVID-19 vaccine”) AND (“reactogenicity” OR “side-effects” OR “adverse effects” OR “health impact”), not restricted by language or type of publication. Among 429 results, few publications described health impacts following vaccination by BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). Available literature included reports of manufacturer-sponsored phase 1–3 clinical trials, observational and cross-sectional studies among specific groups (eg, transplant recipients or employees of a specific health-care system), and reviews or society recommendations that discussed reactogenicity and adverse events following mRNA vaccination.Added value of this studyIn this large, observational study, we assessed reactogenicity, health impacts, and adverse events reported following mRNA COVID-19 vaccination during the first 6 months of the US vaccination programme to one active (v-safe) and one passive (Vaccine Adverse Event Reporting System) surveillance system. We found that reported reactions to mRNA vaccination were mostly mild in severity and transient in duration, and most reports were non-serious. Reactions and health impacts were reported more frequently in female than in male recipients, and in individuals younger than 65 years than in older individuals. Information on health impacts for individuals from v-safe is presented here for the first time.Implications of all the available evidenceThe findings from two complementary surveillance systems from the first 6 months of mRNA vaccine administration in the USA are consistent with pre-authorisation clinical trials and early post-authorisation reports. On the basis of our findings, mild-to-moderate transient reactogenicity should be anticipated, particularly among younger and female vaccine recipients. Vaccine safety data collected by the US monitoring systems will be used to update the benefit–risk assessments for COVID-19 vaccine recommendations.Previous reports from these systems have been issued.10, 11, 12, 13, 14 We aimed to review VAERS and v-safe data during the first 6 months of the US vaccination programme, when more than 298 million doses of mRNA COVID-19 vaccines were administered, to better characterise the safety profile of mRNA vaccines.
VAERS is a national spontaneous reporting system for detecting potential adverse events for authorised or licensed US vaccines.8 VAERS is co-administered by the US Centers for Disease Control and Prevention (CDC) and the US FDA. VAERS accepts reports from health-care providers and other members of the public primarily through online submissions and from vaccine manufacturers through electronic transmissions. The volume of mail, fax, and telephone reports is trivial compared with public online and manufacturer electronic submissions. Reports include information about the vaccinated person, type of vaccine administered, and adverse events experienced. A VAERS report can be submitted for any event experienced following receipt of a vaccine. We included all VAERS reports that were submitted for US residents who received mRNA vaccines and processed from Dec 14, 2020, to June 14, 2021, including any interval from vaccination to event report. Processed reports were quality checked, and submitted text on the adverse event was coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.8 Each VAERS report was assigned at least one and possibly more than one MedDRA preferred term; preferred terms do not necessarily indicate medically confirmed diagnoses and they include signs and symptoms of illness and the ordering and results of diagnostic tests.Based on the Code of Federal Regulations,15 VAERS reports were classified as serious if any of the following outcomes were documented: inpatient hospitalisation, prolongation of hospitalisation, permanent disability, life-threatening illness, congenital anomaly or birth defect, or death. Prespecified adverse events of special interest were selected for enhanced monitoring of COVID-19 vaccine safety on the basis of biological plausibility, previous vaccine safety experience, and theoretical concerns related to COVID-19, such as vaccine-mediated enhanced disease.16 VAERS staff requested death certificates and autopsy reports for reports of death. CDC physicians reviewed VAERS reports and available death certificates for each death to form an impression about cause of death. Impressions were assigned to one of the following categories: one of the 15 most common diagnostic categories from the International Classification of Disease, Tenth Revision, reported on US death certificates,17 COVID-19 related, other (ie, impression was not included in prespecified categories), or unknown or unclear if not enough information were available to determine a cause of death.
V-safe is a voluntary smartphone-based system that uses text messaging and secure web-based surveys to actively monitor COVID-19 vaccine safety for common local injection-site and systemic reactions.9 V-safe participants receive text messages that link to web-based health check-in surveys following vaccination, initially daily (days 0–7), then at longer intervals after vaccination. The system resets to the initial survey frequency after entry of another dose. We analysed survey reports from days 0–7 for reactogenicity, severity (mild, moderate, or severe), 9 and health impacts (ie, unable to perform normal daily activities, unable to work, or received care from a medical professional) that were submitted to v-safe between Dec 14, 2020, and June 14, 2021. Participants who reported receiving medical care were contacted and VAERS reports were completed, if clinically indicated.
We conducted descriptive analyses of available VAERS and v-safe data following dose one and dose two of BNT162b2 and mRNA-1273 vaccines among individuals aged at least 16 years. We stratified analyses by sex, age group, race and ethnicity, serious versus non-serious reports, and vaccine manufacturer; and for death reports, by time from vaccination to death (ie, onset interval) and cause of death. Reporting rates to VAERS were calculated for adverse events using the number of doses of mRNA vaccines administered during the 6-month period as the denominator. COVID-19 vaccine administration data were provided through CDC’s COVID-19 Data Tracker.18V-safe participants who responded to at least one health check-in survey during days 0–7 after vaccination were included in analyses. Descriptive statistics were calculated for participants’ characteristics (sex, age, and race and ethnicity), reaction (type and severity) and health impact by manufacturer, dose number, and number of days following vaccination.Analyses were done using SAS (version 9.4). Both VAERS and v-safe conduct surveillance as a public health function and are exempt from institutional review board review. Activities were reviewed by the CDC and done in accordance with applicable federal law and CDC policy.
Role of the funding source
Authors from the CDC, the funder, were responsible for study design, data analysis, data interpretation, and writing of the report.
From Dec 14, 2020, to June 14, 2021, 298 792 852 doses of mRNA COVID-19 vaccines were administered in the USA: 167 177 332 were BNT162b2 and 131 639 515 were mRNA-1273 (appendix p 2). A greater proportion of vaccines was administered to females (155 969 573 [53·2%]) than to males (134 373 958 [45·8%]). The median age at vaccination was 50 years (IQR 33–65) for BNT162b2 and 56 years (39–68) for mRNA-1273. 112 698 875 (38·4%) recipients were non-Hispanic White. Race and ethnicity was unknown for 102 227 532 (34·9%) of all vaccine recipients.During the study period, VAERS received and processed 340 522 reports: 164 669 following BNT162b2 and 175 816 following mRNA-1273 vaccination (table 1). Of these reports, 313 499 (92·1%) were classified as non-serious; 22 527 (6·6%) were serious, not resulting in death; and 4496 (1·3%) were deaths (table 1). 246 085 (72·3%) reports were among female participants and 154 171 (45·3%) reports were among those aged 18–49 years; median age was 50 years (IQR 36–64; table 1). 169 877 (49·9%) of those reporting race or ethnicity identified as non-Hispanic White, and for 75 334 (22·1%) race and ethnicity were unknown (table 1). The most common MedDRA preferred terms assigned to non-serious reports were headache (64 064 [20·4%] of 313 499), fatigue (52 048 [16·6%]), pyrexia (51 023 [16·3%]), chills (49 234 [15·7%]), and pain (47 745 [15·2%]; table 1). The most common MedDRA preferred terms assigned to serious reports were dyspnoea (4175 [15·4%] of 27 023), death (3802 [14·1%]), pyrexia (2986 [11·0%]), fatigue (2608 [9·7%]), and headache (2567 [9·5%]; table 1).