Adverse Effects Following Immunization (AEFI) with CovaxinTM and Vaccine Reluctance among Adolescent Teenagers (14-18 Years) and Their Parents: A Descriptive Cross-Sectional Study in Delhi, India

Introduction

Immunization against Covid-19 is relatively new to curb Corona virus pandemic, which originated in Wuhan, China in 2019 [1]. A variety of vaccines against Covid-19 were developed using fast track technology globally and received emergency approvals for use (EAU) including first indigenous vaccine (CovaxinTM) of India. CovaxinTM (BBV152, whole virion inactivated vaccine) was the second Covid-19 specific vaccine preceded by Covishield™ (adenovirus vector vaccine) in India [2].

Initially Covishield™ developed by Serum Institute of India and Oxford-AstraZeneca became part of vaccination drive with effect from on January 16, 2021 in Health care professionals (HCPs) and front line workers (FLWs) [3]. On Jan 3, 2021, 'Covaxin™' (BBV152, Bharat Biotech) got approval for emergency use in adult population by DCGI [4]. The safety data on AEFI with Covaxin™ is required to educate public, avoid misinformation, which will overcome vaccine hesitancy [5].

AEFI can be defined as any untoward medical occurrence following immunization which does not necessarily have a causal relationship to the vaccine [5]. Vaccination against Covid-19 is new and therefore needs to be continuous monitoring of AEFI through post marketing as surveillance [6]. The purpose of vaccine surveillance is to identify serious and unexpected AEFI, to reduce the associated morbidity and mortality, to educate public, avoid misinformation and to overcome vaccine hesitancy among eligible population [5, 7, 8].

Till date adequate studies have been done on AEFI by Covid-19 vaccines in adult and elderly populations. But safety data on AEFI using Covaxin™ among children and adolescents is relatively inadequate. This is to note that only Covaxin™, which is made available for vaccinating Indian population under 18 years of age at the time of study proposal submission. There is an urgent need to generate safety data on Covaxin™ among teenagers in India.

Vaccine reluctance/hesitancy has also been seen among adolescents and parents. Vaccine reluctance is hesitancy of people to accept vaccine that has been made safe and effective to protect them against an Infectious disease [9].

The present study is a descriptive cross-sectional study conducted on Indian adolescent teenagers (14-18 years of age), willing to participate in the study. The primary objective of the study is to estimate prevalence of AEFI with Covaxin™ among adolescents between ages 14-18 years. The secondary objective is to determine factors responsible for causing vaccine hesitancy among adolescents (14-18 years of age) and their parents during mass vaccination drive in India. Study has been conducted to bridge the gaps in literature pertaining to AEFI and vaccine reluctance, targeted exclusively to 14-18 years of age group. The data generated will be beneficial to all stakeholders and policy makers for opting right decisions for strengthening mental and physical well-being of teenagers, following re-opening of schools almost after 2 years in India. This could also prove useful for motivating, creating awareness and convincing parents and school going children about benefits of getting vaccinated, to avoid future lockdowns in schools for their positive physical and mental health.

Methodology

Questionnaire was validated for the content and face validation before conducting the study, by getting the questionnaire filled among 20 known participants. Questionnaire was edited and updated as per feedback by participants. These 20 participants were excluded from the main study. The final questionnaire was approved by Institutional Ethical Committee (IEC), Jamia Millia Islamia, and Delhi. (IEC approval no.2/6/390/JMI/IEC/2022).

A questionnaire link was generated and request message to fill the Google questionnaire form was shared in Whatsapp groups and emails among known and unknown contacts to achieve target sample size. Questionnaire with information regarding purpose of study and benefits of study was accessed by participants by clicking on the link shared as mentioned above. Participants were invited to participate following acceptance to informed consent/assent as asked on first page of Google form. Each participant was asked multiple choice questions (MCQs) related to demography followed by MCQs related to CovaxinTM including reasons for any hesitancy/reluctance for vaccination at any time. Participants submitted their responses at last page after attempting questionnaire by clicking on ‘Submit’ icon. The acknowledgement was provided to each participant on submission of responses.

Responses received were saved in Google drive and downloaded in a Microsoft excel spread sheet which was later transferred to IBM-SPSS version 22 Chicago, USA for statistical analysis. Quality control of data collection was done and maintained by checking entries/ responses on daily basis by principal Investigator and co-investigator. Personal identity of participants was never revealed at any point of time of study conduct.

Data Analysis

Results from the data obtained were depicted in the form of tables, charts and graphs as percentages. IBM-SPSS version 22 Chicago, USA was used for analysis of results.

Results

Following are the observations and results depicted in the form of tables, pie charts and graphs as shown below.

The mean age of the participants (N=262) was 16 years (ranging from 14-18 years). Out of 262 participants, 7.3% reported history of pre-existing medical illness/co- morbidity. Around 100 (38.2%) participants had to take any form of analgesic drug before or after the vaccination. None of the participants reported any active clinical symptom at the time of vaccination (Table 1).

Table I: Demographic details of participants. N=Sample size The AEFI symptoms following first and second dose of CovaxinTM, experienced by the participants are shown in Figure 1. Out of 262 participants, 92 (35%) reported local symptoms of pain and swelling following first dose in contrast to 52 (20%) participants experiencing pain and swelling following second dose. The most common symptom was fever in 97 (37%) and in 50, (19.1%) followed by generalized body ache in 71 (27.1%) and in 29, (11.1%) following first and second dose of vaccine respectively (Figure 1).

Click to enlarge

Statistical Analysis

Data Analysis was done using IBM-SPSS version 22 Chicago, USA.

Discussion

In India, only CovaxinTM was approved for vaccinating teenagers of more than 14 years till 18 years of age at the time of study proposal submission. CovaxinTM roll out for vaccinating adolescents was done on 10 January 2022 after undergoing through the rigorous, multistage testing process and phase III clinical trials to ensure it’s the safety [10].

There are very limited studies on the AEFI with CovaxinTM on Indian population. We did not find any study on AEFI during literature search, for CovaxinTM among adolescent teenagers (14-18 years of age). The majority of the studies available in search literature were on CovishieldTM (ChAdOx1) and BNT162b2.

In our study, the most common AEFI symptoms after the first and second dose were fever (37% & 19.1%) followed by generalized myalgia (27.1% & 11.1%) and local pain/ swelling at injection site (13% & 7.3%) and respectively. AEFI reported by subjects in our study are 2-3 times higher compared to available studies on CovaxinTM. Houshmand B, et al in their study have shown similar adverse effects as found in our study except for very rare adverse effects in the form of diarrhea, arthralgia, nasal and oral bleeding with CovaxinTM in middle age adults [11]. The difference in response may be related to higher immune response seen in children and adolescents compared to adults and elderly.

In the study by Ella R, et al. (2021) in their phase III trials of CovaxinTM, 12.5% adult participants experienced at least one AEFI. No serious adverse effects were reported by subjects except for Immune thrombocytopenia (1/5959) participants. Overall AEFI were lower following second dose (4.3%) compared to first dose (5.9%) of CovaxinTM. Frequently reported local Adverse effects were local injection site pain, induration and erythema and common systemic adverse effects were headache, myalgia and mild to moderate grade fever. Around 9% subjects reported AEFI within 7 days post vaccination. Only 0.1% and 0.04% subjects reported immediate adverse effects within 30 minutes of vaccination following first and second dose respectively [12].

In contrast to study by Ella R et al, we in our study found that majority of subjects (22.3%) experienced adverse effects up to the duration of 24-48 hours following first and second dose of vaccine, the symptoms resolved after 2nd day post vaccination. Only 4.9% of subjects had AEFI symptoms beyond 72 hours (3 days) post first dose and 2.1% subjects had AEFI symptoms beyond 72 hours (3 days) post second dose of vaccine. In general, the AEFI were mild, self limiting and tolerable in most of the subjects following first in 127 (48.4%) and second dose in 181 (71.7%) respectively. AEFI symptoms were relatively more after first dose compared to second dose of CovaxinTM. This finding was similar to a study conducted by Kaur, et al. (2021) in North India; they have reported 40% and 16.6% of the AEFI among first and second dose beneficiaries, respectively [13, 14].

Study by Zhu F et al on AEFI of adenovirus vaccine, found a 69% overall AEFI incidence within 14 days post vaccination in subjects aging 6-17 years. Also overall AEFI in the vaccine group was significantly higher than that in the placebo group (22%). In contrast to the RNA vaccine, fewer adverse events were reported in the adenovirus vector vaccine group following Dose 2 than after Dose 1. The most common adverse events with adenovirus vaccine were injection-site pain, fever, headache, and fatigue. Most adverse events were not serious and resolved in few days. Incidence of local and systemic adverse events, were higher in the vaccine group than in the placebo group [15].

The reported AEFI in our study was higher than that of the Phase 2 trial of CovaxinTM. Ella et al reported 21% AEFI for BBV152 (CovaxinTM) with 6 µg Algel IMDG and 17% with 3 µg Algel IMDG. However, Kamal, et al. (2021) reported a 57% rate of AEFI among the study participants.  The difference may be due to the difference in vaccines [16, 12].

Kaur, et al. (2021) in their study finding, shown majority of the AEFI to be among the younger age groups compared to elderly [13]. In our study 7.3% of participants had pre- existing medical conditions including diabetes, bronchial asthma, hypertension, cutaneous allergies, polycystic ovarian disease, liver and renal stones, thyroid dysfunction and migraine. Also hypersensitivity in the form of allergic rash within one week, were to the extent of 0.8% (2) and 0.4% (1) following first and second dose respectively.

In our study, few participants reported additional AEFI beyond study questionnaire. Self reported adverse effects in our study were positive Covid-19 test within 14 days of vaccination, excess hair fall, altered taste sensation, profound generalised weakness and fatigue. These AEFI symptoms were more following first dose compared to second dose except for hair fall (7.2% after second dose compared to 1.9% after first dose). Hair fall was significant with a p < 0.05 (Figure 2). Few studies have also reported similar adverse effects post vaccination [17, 18].

We did not find any serious adverse events in our study. Kim, et al. (2021) in South Korea reported only one serious AEFI in the form of severe vomiting [19]. In our study, overall 38.2% of the participants had self-medicated with analgesic antipyretic (paracetamol) pre and post vaccination. Our finding was similar to a study by Shrestha, et al. (2021) [20]. In our study we also made an attempt to explore the factors responsible for vaccine hesitancy (Figure 5). Vaccine hesitancy rapidly rose due to growing number of cases who developed vaccine-related severe or permanent adverse events such as myocarditis, hypertension, acute respiratory failure, septic shock, sudden hearing loss, and thrombo- embolic events [21, 22, 23].

Our study present a well-documented safety profile of CovaxinTM, even in co-morbid younger patients (14-18 years of age) may ameliorate the safety concerns associated with vaccine. Vaccination plays an important role in protecting the health of children. In the previous study by MacDonald NE, few determinants of vaccine hesitancy have been categorized as contextual influences (due to historic, political, environmental and health systems), individual and group influences arising due to personal/group perception of subject/subjects and vaccine-/vaccination-specific issues directly related to vaccine contents or vaccination process. We consider that these determinants are largely influenced by disseminating correct information about vaccine, AEFI reporting and causality assessment influences these determinants. Although vaccination should certainly not be made compulsory, it is important that parents make the right decision by allowing children to be vaccinated without hesitation [24].

Strengths and Limitations of Study

To our best of knowledge, present prospective observational study is the first ever study on AEFI of CovaxinTM and vaccine hesitancy among 14-18 years age, in India. Certain notable limitations in our study are probability of selection bias which could have risen due to incorporating subjects reporting more AEFI unintentionally.

Conclusion and Recommendations

Present study has indicated an acceptable safety profile of COVID-19 vaccine (CovaxinTM) approved for 14-18 years of age group in India. The study will encourage children, adolescents and their parents to take vaccine shots to curb resurgence of pandemic. Overall, CovaxinTM is well tolerated and projects a good safety profile in young adolescents even with pre-existing co-morbidities. Since CovaxinTM is a killed (inactivated vaccine), it appears to be relatively safer compared to other available vaccines available in India. Monitoring and assessment of long-term adverse events needs to be done through active surveillance. There is a need to address safety concerns related to vaccine using Television, social media and print media. Adequate and valid explanation and preparation for expected adverse effects (AEs) is essential to promote widespread vaccination coverage.

Acknowledgement

We are thankful to Indian Council of Medical Research (ICMR), Delhi for providing the opportunity to take on this STS-ICMR research project. Our sincere gratitude to our participants, without whom the study could not have been possible.

Financial Support

It is a self-funded research project.

Conflict of Interest

None declared