key: cord-1047423-3z3n65ge authors: Parida, Swayam Pragyan; Sahu, Dinesh Prasad; Singh, Arvind Kumar; Alekhya, G.; Subba, Sonu Hangma; Mishra, Abhisek; Padhy, Biswa Mohan; Patro, Binod Kumar title: Adverse events following immunization of COVID‐19 (Covaxin) vaccine at a tertiary care center of India date: 2022-02-21 journal: J Med Virol DOI: 10.1002/jmv.27655 sha: d38aa476bbf22df8e8920d7f77639c21776d549e doc_id: 1047423 cord_uid: 3z3n65ge The study aimed to assess the adverse events following COVID‐19 vaccine (Covaxin) immunization at a tertiary care institution and also assess the predictors of the adverse events following immunization (AEFI). The prospective observational study was conducted in a tertiary care institute among the Covaxin beneficiaries between June 28 and September 6, 2021. A total of 1826 participants were assessed for any local or systemic adverse events after seven days of vaccination. A telephonic interview was conducted, and the beneficiaries were assessed according to the adverse event grading. A total of 1826 participants were assessed for AEFI, and 544 (29.8%) reported at least one of the AEFI. No severe adverse events were reported, and about 1.6% had moderate AEFI. Pain at the injection site (14.6%), fever (9.7%), and myalgia (5.9%) were the common adverse events reported by the participants. AEFI incidence was higher in the first dose (38.1%) when compared to the second dose (26.4%), and this finding was significant with a p < 0.001. The major factors associated with AEFI were female sex, history of an allergic reaction, presence of comorbidities, acute infection in the past 3 months, and intake of chronic medications. Precaution needs to be taken while vaccinating individuals having allergies, comorbidities, acute infection in the last 3 months, and individuals on chronic medication. respectively. 7 After May 1, 2021, it was extended to the 18-44 years age group. The vaccination in India is done through one single portal (https://cowin.gov.in) throughout the country. 8 Since then, more than 800 million doses have been administered by September 20, 2021. 2 Of those, 719 million doses were of Covishield, and 91 million were of Covaxin. 8 As of September 20, 2021, the adverse events following COVID-19 vaccination was 0.005%. However, these numbers may be grossly underestimated as the mechanism of adverse event following immunization (AEFI) reporting was not known to all. An AEFI is any untoward medical occurrence that follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. 9 As per the Government of India, anyone having any AEFI after receiving any COVID-19 vaccine can contact the helpline number: +91-11-23978046 (Toll free-1075), technical helpline number: 0120-4473222, helpline Email Id: nvoc2019@gov.in, or can contact the vaccination center where they took vaccination. 10 There have been few studies related to AEFI after COVID-19 vaccination in recent times. The majority of the studies were on Covishield (ChAdOx1) and BNT162b2. In the Phase I trial of Covaxin, 5% of participants reported local adverse events, and 14% reported systemic adverse events. 11 There were no other studies that assessed adverse events following Covaxin vaccination. This study aimed to assess the adverse events following Covaxin and also to assess the factors associated with AEFI among Covaxin beneficiaries. The prospective cohort study was conducted between June 28 and September 6, 2021. The study was conducted at the All-India Institute of Medical Sciences, Bhubaneswar, an institute of national importance in the eastern part of India. Beneficiaries who took either the first dose or second dose of Covaxin (BBV152) during the study period and provided consents were included in the study. The beneficiaries were followed up for 1 week after the vaccine dose. The minimum sample size required for the study was estimated to be 1825, taking 5% prevalence (p) of AEFI from the study by Ramanathan et al. 11 relative precision (ε) as 20%, and confidence interval of 95%. The sample size was calculated using nMaster software using the formula Z α 2 (1p)/ε 2 p. The study was commenced after receiving ethical approval from the Institute Ethics Committee of All India Institute of Medical Sciences, Bhubaneswar (reference number: T/IM-NF/CM&FM/21/20). Ten percent of each day's vaccine beneficiaries were selected using a simple random method with the help of a random number list generated by Microsoft Excel until a sample size of 1826 was achieved. The study age group included 18-44 years and more than 45 years age group, and they were selected proportionately. The study participants were observed for 30 min postvaccination to look for any immediate adverse events. A trained interviewer conducted a telephonic interview to assess the adverse events following the Covaxin vaccination. The telephonic follow-up was conducted once between the 7th and 10th day of vaccination. Solicited local adverse events like pain at the injection site, tenderness/soreness, erythema, swelling/induration, pruritus associated with injection, and solicited systemic adverse events like pain, fever, nausea/vomiting, headache, fatigue, myalgia, acute allergic reaction, rash, and joint pain were assessed. All the unsolicited adverse events reported by the study participants were also reported. The adverse events were graded based on the US Food and Drug Administration (FDA) document for the toxicity grading scale for healthy volunteers in preventive vaccine trials. 12 The adverse events were graded as mild, moderate, severe, and potentially life-threatening based on the severity (Table S1 ). Data analysis was done by Statistical Package for Social Sciences Version 22 (SPSS Inc.). The proportion of AEFI reported was calculated. The Χ 2 test was applied to find out the association between outcome and predictor variables. By logistic regression analysis, the odds ratio with 95% CI was calculated for various risk factors of AEFI. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio using the variables that were significant in bivariate analysis. A p < 0.05 was considered significant. A total of 2267 participants were interviewed to achieve a sample size of 1826. The nonresponse rate was 19.5%. The mean age of the participants was 40.02 ± 13.34 years. The maximum age of the participants was 88 years, and the minimum age was 18 years. Onefourth of the participants, 469 (25.7%), were from the age group of 40-49 years. Male participants (1000, 54.8%) were more than that of the female participants (826, 45.2%). Among the 1826 participants, 523 (28.6%) beneficiaries took the first dose, and 1303 (71.4%) took the second dose. Government services (497, 27.2%) and homemakers (499, 27.3%) were the major occupations of the participants. More than two-fifths of the participants (794, 43.5%) were graduates (Table 1) . Only 5.8% of the study participants had any of the comorbidities. Fourteen (0.8%) of the participants were taking steroids during the COVID-19 vaccination, and 3 (0.2%) had temporarily stopped steroids though they were taking so previously. Only one participant was taking immunomodulators, and 3 temporarily stopped medication for the vaccination. Only 26 (1.4%) participants had known allergy to any kind of food, drug, pollen, dust or other allergens, and 169 (9.3%) were not aware of their status. Only 85 (4.7%) of the participants were taking medication for chronic diseases in the last 6 months. Only 4 (0.2%) had COVID-19 infection in the last 3 months, and 4 (0.2%) were admitted to the hospital in the last 3 months. A history of acute infection was observed in 37 (2.0%) of the participants ( Table 2) . A total of 544 cases of AEFI are reported during the study. Among them, 29 (5.3%) reported moderate symptoms, and the rest 515 (94.7%) were mild in nature. No severe cases were reported. More than one AEFI was reported in 219 (12.0%) of the study participants, and 325 (17.7%) of the participants had reported only one AEFI. Pain at the injection site (267, 14.6%) was the most common AEFI, followed by fever (178, 9.7%) and myalgia (107, 5.9%). The proportion of cases reporting AEFI was more after the first dose (199, 38.1%) than that of the second dose (345, 26 .4%), and the difference was also found to be statistically significant. However, no statistically significant difference was reported for individual AEFI for the first and second dose except that for the pain at the injection site (p < 0.001) and joint pain (p = 0.026). We did not find any immediate adverse event ( Table 3) . The younger population had more AEFI than the older ones. Individuals aged 60 years or more were 0.66 times less likely to have AEFI than those aged 18-29 years. Females were 1.30 times more likely to have AEFI when compared to males, and the difference was found to be statistically significant (p = 0.010). Individuals with any comorbidities were 2.08 times more likely to have AEFI than those having no comorbidity (p < 0.001). AEFI was 2.39 times more reported among individuals with a history of allergic reaction than those with no previous history (p = 0.028). Individuals who took medication for chronic disease reported 2.07 times higher AEFI than those who were not taking medication (p = 0.001). Individuals who had an acute infection in the last 3 months reported 3.99 times more AEFI than those who did not have an acute infection in the last 3 months (p < 0.001). Individuals having COVID-19 infection in the last 3 months and history of hospital admission in the last 3 months had 7.10 times more AEFI, but the difference was not significant statistically. On multivariate logistic regression, gender, and past history of acute infection in the last 3 months were found to be significantly associated with AEFI (Table 4) . Only 27 (5%) of the study participants consulted any physician for the adverse events, and 54 (9.9%) took self-medication. None of the participants got admitted for any of the adverse events. The majority of the participants took tablet Paracetamol for their symptoms. 16 The difference may also be due to the difference in age of the participants in the study. The frequency of AEFI decreased with an increase in age in our study. The result is in accordance with other published trials of viral vector vaccines. 17, 18 In our study, 18-29 years (younger) age group patients were 34.6%, whereas it was 48.4% in South India, and a majority of the AEFI were reported among the younger age groups. Kaur et al. 19 also reported higher AEFI among the younger participants. The proportion of AEFI was 38.1% after the first dose and 26.4% after the second dose. This finding was similar to a study conducted by Kaur et al. 19 in North India; they have reported 40% and 16.6% of the AEFI among first and second-dose beneficiaries, respectively. We did not find any serious adverse events in our study. Kim The common adverse events reported in our study were injection site pain, tenderness, fever, headache, fatigue, and myalgia. These are also the common adverse events reported in the Phase 2 trial of the BBV152 vaccine. 15 However, the incidence of reactogenicity was higher in our study than in the clinical trial results. We did not find any serious adverse events in the first 7 days, and this was in accordance with the trial results. 15 However, few serious adverse events were reported in the studies from ChAdOx1 in India, Korea, and Nepal. 14, 19, [21] [22] [23] Other than gender, other significant predictors for AEFI in our study were comorbidities, history of steroid intake, history of allergy, history of medication in last 6 months, and history of acute infection in the Therefore, we had only four participants having infections in the last 3 months, and the variable could not be analyzed further. A higher incidence of reactogenicity was reported in participants with previous SARS-CoV-2 infection. 24, 25 In our study, 9.9% of the participants had taken self-medication. Most of the participants took tablets of Paracetamol for adverse events. In our Institute, we provide four tablets of Paracetamol tablets to all the beneficiaries after vaccination. This finding was similar to a study by Shrestha et al. 22 in Nepal, where 55% of the participant with AEFI took self-medication. Covaxin (BBV152), for which reactogenicity was assessed in our study, was an inactivated vaccine. The majority of the compared studied are mRNA-based vaccines, which are likely to have higher reactogenicity than the inactivated vaccine. 26 This may explain the lower reactogenicity in our study than other studies. WHO. Coronavirus Disease (COVID-19) Dashboard WHO Coronavirus Disease (COVID-19) Dashboard. Accessed Ministry of Health and Family Welfare Government of India. COVID-19 India Ministry of Science and Technology. DBT-BIRAC supported ZyCoV-D developed by Zydus Cadila Receives Emergency Use Authorization. Press Information Bureau. Accessed PIB'S bulletin on COVID-19. 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The data that support the findings of this study are available from the corresponding author upon reasonable request. Abhisek Mishra http://orcid.org/0000-0002-4745-3379Binod Kumar Patro http://orcid.org/0000-0003-0019-4522