key: cord-0718148-knrneuvl authors: Singh, Amninder; Khillan, Ratesh; Mishra, Yogendra; Khurana, Sumit title: The Safety profile of COVID-19 vaccinations in the United States date: 2021-10-23 journal: Am J Infect Control DOI: 10.1016/j.ajic.2021.10.015 sha: de9f44c209af331c497f8d31c6e8c4e969479112 doc_id: 718148 cord_uid: knrneuvl BACKGROUND/AIM: Pfizer-BioNTech, Moderna, and Johnson & Johnson's Janssen are the three COVID-19 vaccines authorized for emergency use in the United States. This study aims to analyze and compare adverse events following immunization (AEFIs) associated with these COVID-19 vaccines based on Vaccine Adverse Effect Reporting System (VAERS) data. METHODS: We utilized VAERS data from 01(st) Jan 2021 to 30(th) April 2021 to analyze and characterize adverse effects post-vaccination with these authorized COVID-19 vaccines in the US population. RESULTS: A total of 141208 individuals suffered at least one AEFI following 239.97 million doses of COVID-19 vaccination. The frequency of side effects was 0.04%, 0.06%, and 0.35% following administration of Pfizer-BioNTech, Moderna, and Johnson & Johnson's Janssen vaccines, respectively. Most of the patients had mild systemic side effects, the most common being headache (0.01%) and fever (0.01%). The frequency of serious side effects including anaphylaxis (0.0003%) and death (0.002%) was extremely low. CONCLUSION: The three COVID 19 vaccines have a wide safety profile with only minor and self-limiting adverse effects. However, continued monitoring ad surveillance is required to review any unexpected serious adverse effects. The Coronavirus disease is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, in Johnson's Janssen is administered as a single dose. All three vaccines have shown good safety and efficacy profile in phase-3 clinical trials. 5,6,7(p26) Vaccine Adverse Event Reporting System (VAERS) works as a national warning system to detect early safety issues with licensed vaccines. VAERS system is supervised by the Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA). It accepts and analyzes adverse events following vaccination reported by healthcare providers, vaccine manufacturers, and the public, along with maintaining personal confidentiality. 8 This study aims to analyze and compare common adverse events following immunization (AEFIs) that are temporally associated after receiving the above three COVID-19 vaccines based on VAERS data from January 01, 2021, to April 30, 2021, in the US population. This report is based on the AEFIs information obtained from the VAERS data, reported between January 01 to April 30, 2021, for these three COVID-19 vaccines. Data presented in this report only represent the AEFIs reported to the VAERS. Signs and symptoms of adverse events are coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 24.0. 9 As a result, all the data is subjected to varying degrees of reporting bias, particularly underreporting, especially for mild or common reportable events. 10 There might also be increased reporting of a few side effects which can occur in response to media coverage and increased public awareness. In the case of multiple reports of a single case or event, subsequent reports are not included in the publicly available dataset. VAERS data obtained from the VAERS website was analyzed using the R programming language (Figure 1) . The frequency of all the individual, non-exclusive side effects for the respective vaccines was calculated. AEFI reports from VAERS where the disposition was reported as product substitution, interchange of vaccine products, incorrect dose administered, unknown vaccine manufacturer or unevaluable event, or any variation on these values have been excluded. Each AEFI report refers to an individual who suffered an adverse event after receiving a dose of the COVID-19 vaccine. An AEFI report may contain multiple adverse events. Therefore, the total number of adverse events can exceed the number of individual AEFI reports reported in a given time frame. AEFI reports that did not have an adverse event reported at data extraction have been excluded. Between January 01 and April 30, 2021, a total of 141208 individuals suffered at least one AEFI Table 1 . The frequency of AEFIs was higher in the population with age less than 60 yrs (61.42% of the AEFIs) than the elderly with age equal to or greater than 60 yrs. The frequency of AEFIs was higher in females (73.46% of the AEFIs) than in males. The most common AEFIs following administration of Pfizer-BioNTech vaccine include Table 3) . A total of 3662 deaths were also reported in the post-vaccination period. Most of the side effects (68.51%) were reported within less than 72 hours of vaccination, and very few side effects (10.20%) were reported post seven days of vaccination. Most of the reported AEFIs were self-limiting without any specialized care. Vaccines are one of the most cost-effective public health measures. 11 It usually takes 10 -15 years for vaccines to get authorization after safety and efficacy trials. 12 However, given the COVID-19 pandemic with high infectivity and mortality, emergency authorization to vaccines was given within development. 94.1%, and 66.3%, as per the available data. [13] [14] [15] It is important to note that though vaccines are a cost-effective method to control a disease, they carry inherent risks of minor and significant side effects. The safety efficacy and immunogenicity of the vaccines are checked before licensing in Phase 3 trials. 16 These phase 3 trials have a small sample size and therefore may not report rare adverse events. Moreover, these pre-licensing vaccine trials cannot be generalized as they are tested in a uniform population group. Hence, passive surveillance systems are necessary to monitor the frequency of adverse events post-licensing of a vaccine. Though the passive surveillance system is pragmatic and costeffective, it is difficult to determine causality as per their reports. 17 Our study analyses data from the VAERS for adverse effects of these three vaccines almost five Most of the side effects lasted for less than 7 days and did not require any hospitalization. The frequency of serious side effects, including anaphylaxis (0.0003%) and death (0.002%), was extremely low. Other rare AEFIs reported were Bell's palsy, myocarditis, Guillain-Barre syndrome and Transverse Myelitis. The highest frequency of anaphylaxis was seen in the Janssen vaccine (7.04 per million doses). The reported deaths mainly were in patients Age >80 yrs (40.3% of the total deaths) who were either in hospice care or with chronic illness & multiple co-morbidities. There are several reports in which the death cannot be temporally associated post-vaccine administration, and the causality could not be established. However, considering the total number of vaccine doses administered in such a short period, these events are unlikely to be clinically significant. The frequency of side effects observed in the C4591001, COVE, and ENSEMBLE study for Pfizer-BioNTech, Moderna, and Johnson & Johnson's Janssen was 27%, 88.6 %, and 48.6%, respectively. 5,6,7(p26) The most common local side effect was injection site pain, and the most common systemic side effects were headache and fever. Most of the side effects lasted for less than 7 days. There were no deaths in the Pfizer group, while three deaths were reported in Moderna and Janssen. However, the investigators did not attribute these fatal cases to vaccine adverse effects. The high incidence of adverse events in clinical trials is in sharp contrast to VAERS data. This disparity is likely due to underreporting of minor and self-limiting side effects. In a recently published article, the safety profiles of mRNA-based COVID-19 vaccines were studied in pregnant females. 18 This study consisted of 35,691 participants, had analyzed data from the VAERS, v-safe registry, and v-safe after vaccination health checker. It did not find any safety concerns related to pregnancy or teratogenicity. Moreover, the pattern of local and systemic side effects was similar to our study. In comparison to the clinical trials of the safety of these vaccines, there were no new adverse effects reported in the VAERS data in our study. 5,6,7(p26) The adverse effect profile was similar to the previous mRNA-based and influenza vaccines in the general population. 19, 20 It can be concluded that the findings observed in all three vaccines were broadly consistent with vaccine reactogenicity. Our study effectively presents the adverse events following vaccination against COVID 19 based on VAERS. The sample size is large for clinical application with a long duration of almost five months post-authorization. Though the vaccine's initial rollout's focus was on healthcare workers, elderly people, and clinically vulnerable people, it has now been administered to a very large (43.32 %) part of the general population. 1 The sample size is large for clinical application with a long duration of almost 6 months for monitoring vaccine-related events. However, this study is not without limitations. It is based on a passive surveillance system in which there is significant underreporting, as mentioned above, due to self-limiting side effects. Passive surveillance system often reports non-specific events with limitations to detect new or rare events. Also, the reports may get biased with public perception and prevailing concepts regarding vaccines. 21 We utilized self/ physician-reported data, which can introduce information bias, including misclassification or effect bias exposure. Also, some participants might be more likely to report symptoms than others, and there is the potential for users to drop out of reporting. The major drawback of VAERS data is that it cannot determine if the vaccine caused the reported major adverse event. This leads to confusion in the available data from VAERS. 22 There has been a misinterpretation of reports of deaths following vaccination as deaths due to vaccination by the public. VAERS accepts all reports of adverse health events following vaccinations. These adverse reports may represent true reports or maybe just circumstantial. Overall, a direct causal relationship between vaccine administration and adverse effects cannot be established by the VAERS reports only. In conclusion, our study analyzed extensive data of AEFIs in vaccines that are authorized for emergency use against COVID-19. The reported AEFIs were similar to those observed in the clinical trials with a lower frequency. Most of the adverse effects were minor and self-limited. These findings will provide the necessary safety profile for the public for future vaccination programs against COVID-19. This has to be backed up with large studies on the efficacy of these vaccines in preventing COVID-19. Further research on the mechanisms of immunogenicity and reactogenicity for these vaccines is needed. Hopefully, this will lead to better identification of patients likely to benefit from treatment without experiencing significant adverse events, thus ensuring the maximum therapeutic effect. The surveillance and monitoring for AEFIs must be continued to detect any new or rare adverse effects. Food and Drug Administration. 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