INTRODUCTION:

The SARS-CoV-2 is spreading across the world at an alarming rate.¹ For controlling -19 infection different types treatment were launched.² In India the COVID - 19 vaccine was launched on 16^th January, 2021. Based on the guidance from National Expert Group on Vaccine Administration for Covid-19 (NEGVAC), COVID-19 vaccine will be introduced in a phase wise manner. The groups prioritization will depend upon the disease incidence and prevailing pandemic situation.³

First phase focusing on health care workers, frontline workers and population at higher risk.⁴

The scientific community plays an important role in prevention and slowing rate of COVID- 19 infection by inventing more than 40 new vaccines, a few of them obtained the Food and Drug Administration’s (FDA) Emergency Use Authorization (EUA) and are now used in many countries.⁵ Immunization prevent deaths and for last 3-4 decades it played a pivotal role in tackling infectious disease throughout the globe Immunization.⁶Despite of positive results negative results also noted for vaccines which are named as adverse events. The Vaccine Adverse Event Reporting System (VAERS) is a vaccine safety surveillance program co-sponsored by the CDC and FDA. It collects and analyzes reports of adverse events following vaccination. It is followed in many countries, such as the USA. It is a passive surveillance based on reports given by doctors or paramedical staff.⁷

Haryana state of India follows all rules and regulations set by central Government in 2015. Central government had given some guidelines regarding Adverse Event Following Immunization by vaccine which are broadly classified into three categories: common minor AEFI, which includes fever, rash, and local reactions; Serious AEFI, which results in hospitalization, death, or significant disability; and severe AEFI, which includes any adverse event of increased severity.^8,9

Nuh, district is the most backward district of India which is situated rural area of Haryana state on the National Highway 248 with estimated population of 10.89 lacs and area of 1507 square kilometer as per 2011 census.¹⁰It has a Shaheed Hasan Khan Mewati Government Medical College (SHKM GMC) which is the only tertiary health care hospital in Nuh, where vaccination programme was organized successfully under the guidelines of Haryana. The COVISHEILD manufactured by Serum Institute of India) and AstraZeneca COVID-19 VACCINE¹¹ was the main vaccine which was available in this hospital.

So, to check the AEFIs at different days after COVID – 19 vaccination in the health care workers this study was framed in Shaheed Hasan Khan Mewati govt. medical college, Nalhar, Nuh, Haryana, India.

Aim and objective:

To assess the profile of adverse events following immunization of Covid – 19 vaccination.

Material and methodology:

Study subjects: Students (MBBS) above the age of 18 years, faculty members (including Junior residents, PGs, Senior residents and all the professors) and other subjects up to the age of 55 years.

Study site:

The study was conducted in the SHKM Government Medical College, Nalhar, Nuh. The study was approved by the Institutional ethics committee with reference number EC/OA/24/2021 and written informed consent is obtained from all patients.

Study design:

Cross sectional and prospective observational study (Follow up period of 15 days for all those subjects who were vaccinated for covid-19 in SHKM, GMC Hospital to look for AEFI. Active surveillance was done on days 3,6 and 9 after days of vaccination for AEFI). Any AEFI noted will be managed as per the standard guidelines.

Study period:

A period of 3 months or till the desired sample size recruited in the study.

Sample size:

The sample size of more than 300 subjects will be taken in the study.

Procedure:

All the study subjects including interns, faculty members and other health care workers who were working in SHKM Medical College and Hospital were directly approached and the importance of the study were discussed with them. After their willingness and consent taken in the form of informed consent they were given a questionnaire form to give their response or opinion. Questionnaire form filled with their response is to be collected and data generated. This data had been incorporated in excel software and appropriate statistical tools was applied accordingly.

All protective measures had been taken during the course of the study as per the guidelines from Ministry of Health and Family Welfare department of India.

Eligibility of the participants:

To be eligible for the study, the study subjects will have to fulfill all of the following

Inclusion criteria:

a) Students, faculty and other health care workers who are engaged with SHKM Medical College.

Exclusion criteria:

a) Other than health care workers of SHKM Medical College.

b) Subjects below 18 years of age and above 55 years of age.

Statistical analysis:

After compilation of collected data, analysis was done using Statistical Package for Social Sciences (SPSS), version 24 (IBM, Chicago, USA). Percentages of participants were calculated in respective different study variable AEFI to estimate the results of the study.

RESULTS:

A total of 550 individuals were screened of whom 150 refused to participate in the study. Of the included 400 participants and were visiting the centres for their ﬁrst and second dose of vaccine respectively. Out of 400 participants 156 female and 244 male were enrolled in the study respectively (Tab.1). At the time of analysis, a signiﬁcant percentage of the subset who were enrolled while receiving the ﬁrst dose was yet to receive their second dose, as timing of second dose had been considered 28 days, after initiation of our study.

These individuals shall be included for safety and effectiveness analysis in the future. For the other 400 individuals who were enrolled in the study while receiving the second dose of vaccine, detailed enquiry was made about any AEFIs during their ﬁrst dose of vaccine as per protocol described in methods section. They were subsequently followed up after their second dose. Out of 550 individuals 400 enrolled participant had been found AEFIs after first and 269 after second dose of covid-19 vaccination and were compared only percentage basis respectively. In the study age wise AEFIs percentage of participants were also calculated. In the present study different systemic diseases percentage also calculated. (table. 1)

The baseline characteristics of the study participants are mentioned in Table 1

Profile of Adverse Events After COVID 19 Vaccination:

AEFIs recoded after first dose:

Total of 550 vaccine recipients, AEFIs were reported in 400, fever 150(37.50%), shivering 64(16.75%), generalized malaise 5(01.25%), local site pain 138(34.5%), headache 30(9.5%), skin rashes 10(2.5%), URI 3(0.75%) respectively (Table 2).

AEFIs recoded after second dose:

Total of 550 vaccine recipients, AEFIs were reported in 269, fever 78(28.99%), shivering 51(18.95%) generalized malaise 5(1.85%) local site pain 120(44.60%) headache 10(3.71%) skin rashes 3(1.11%) URI 2(0.5%) respectively (Table 2).

DISCUSSION:

In India 1,11,24,527 Confirmed COVID-19 cases and 1,57,248 deaths have been reported as of March 2 2021.Vaccines will provide a lasting solution by enhancing Immunity and containing the disease spread and it is one of the most cost-effective interventions for disease prevention.^12,13 Hence, in the generic sense, the process of artificial induction of immunity, in an effort to protect against infectious disease, is known as immunization.¹⁴ In the present study adeverse event following the immunization also reported in the hospital so we discussed them briefly.

57 Corona vaccine developed from them 40 are in phase I-II and 17 in phase III-IV among them several vaccines show the efficacy 95% in phases III during December 2020 mid period. National regulatory authority permitted 6 vaccine for public use: two RNA vaccines (Tozinameran from Pfizer-Biotech and Mrna 1273 from Moderna), two conventional inactivated vaccines (BBIBP-CorV from Sinopharma and CoronaVac from Sinovac) and two viral vector vaccines (Gam COVID- Vac from Gamaleya Vac Research institute and AZD1222 from the university of oxford and AstraZeneca). India indigenous COVAXIN vaccine for COVID-19 develop by Bharat Biotech with collaboration ICMR and Serum Institute of India tie up

with oxford and Astra Zeneca for manufacture COVISHIELD vaccine but still in confusion that it is useful for new strain or not. Vaccine stimulates the broad antibodies response against to entire protein spike, so the efficacy of vaccine will not be hampered by mutations.¹⁵

Bion Tech Chief executive says that vaccine will work for this variant also because the protein on variant are 99% same as the COVID-19 but more research studies and data needed for completely sure.¹⁶

AEFI surveillance has a very important role to guide vaccine safety prompt management of adverse events and to reduce any negative effect on a vaccination program. A study from the Serum Institute of India demonstrated that an indigenously produced covid-19 vaccine has a good immunogenicity and safety profile. Most adverse reactions following COVID-19 vaccination, regardless of the type of vaccine used, concern known and transient adverse reactions such as: headache, fatigue, malaise, fever, nausea, pain in the body. These usually appear on the first or second day after vaccination and last around 2-3 days. Most people tolerate these transient adverse reactions well, while others experience significant discomfort during the first few days after vaccination.¹⁷

In the present study, the most common adverse event was fever following the local site pain which is similar to the finding of the study conducted by Joshi et al. and Aherkar et al but their study was conducted on measles vaccine.¹⁸

In our study, we did not find any serious or severe AEFIs. Probable mechanisms of development of all these events are postulated to be live viral activity, injection related direct needle trauma, immune-mediated reaction, and cytokines production.¹⁹In our study, we did not find any serious or severe AEFIs

In the present study total of 550 vaccine recipients, AEFIs were reported in 400, fever 150(37.50%), shivering 64(16.75%), generalised malaise 5(01.25%), local site pain 138(34.5%), headache 30(9.5%), skin rashes 10(2.5%), URI 3(0.75%) respectively). And after second Total of 550 vaccine recipients, AEFIs were reported in 400, fever 78(28.99%), shivering 51(18.95%) generalised malaise 5(1.85%) local site pain 120(44.60%) headache 10(3.71%) skin rashes 3(1.11%) URI 2(0.5%) respectively AEFIs were seen in 72.72% participants after first dose and around 49.81% participants after second dose. These results were similar to U. Kaur et al.²⁰ This observation reactogenicity is much less compared to 60-88% reactogenicity observed in phase 1 and phase 2/3 clinical trials of Oxford-AstraZeneca's ChAdOx1vaccine in the UK based population (AZD1222).^21,22

In our study, the frequency of AEFIs decreased with age, in 21-30 yrs was 196(49.00%), 31-40yrs was 144(33.25%), 41-50yrs was 45(11.25%) and 51-60yrs was 15(3.75%) respectively, Participants which shows that increasing age is associated with lesser risk of AEFIs is in concordance with the published clinical trials analysing various viral vector-based vaccines The methodology followed in our study was very similar to the study conducted by Joshi et al. and Aherkar et al However, they reported AEFIs with MR vaccine at 9 months of age.^23,24

In the present study some systemic disease also plays a significant role in developing AEFIs. Main systemic diseases were related to thyroid status, history of allergy and hypertension status. In hypothyroidism individuals AEFIs was observed more as compared to those with normal thyroid function. Reason might be decrease in immune response due thyroxine stimulatory action on neutrophils, natural killer cells and macrophages.^25,26 Secondly, the S protein, adjuvants of the vaccine including polysorbate and EDTA can also interact with thyroxine or the hypothyroid state.²⁷ Other systemic diseases also augment the AEFIs but their impact were non significant.

Limitations:

Limitations of the study include:

1. The completion of study duration was short due to which long-term AEFIs could have been not recorded.

2. The study was conducted in one of most backward area of India where network problem at glance so minor ailments may not be search out.

3. No grading of AEFIs was done for cause specification.

4. The study was conducted at a tertiary care centre only not in primary health care centre, camp set up and private institutes where vaccine storage, the skill of the person vaccinating and socioeconomic background of the parents of the child vaccinated may be different.

5. In the last the study was framed to record the common AEFIs instead uncommon/ rare AEFIs.

CONCLUSION:

In the present study the main aim was to find the possible adverse events of the COVID - 19 vaccines through active surveillance which helped in finding and reporting of minor adverse events that could have Been missed in the passive reporting of AEFIs. According to study Younger individuals with diabetes Mellitus or hypertension or hypothyroidism are at increased risk of AEFIs and vaccines should be administered to such individuals with supervision of speciality concerned. The COVID-19 vaccine injected in hospital health care workers is found to be safe for use in except for a few minor reactions. More studies are required to evaluate the delayed and rare AEFIs.

Table 1. Characteristics of the study population.

Gender
Female Total enrolled -	156 (39.00%)
Male Total enrolled -	244(61.00%)
Age of participants developed AEFIs 0ut of 400 AEFIs
21- 30	196(49.00%)
31-40	144(33.25%)
41-50	45(11.25%)
51-60	15(3.75%)
Systemic diseases in relation to developed AEFIs	(N=400)
Individuals with diabetes mellitus; N (%)	20(5.00%)
Individuals with hypertension; N (%)	10(2.50%)
Individuals with hypothyroidism; N (%)	45(11.25%)
Individuals with hypothyroidism; N (%)	25(6.25%)
Individuals with asthma or COPD; N (%)	10(2.50%)
Individuals with coronary artery disease; N (%)	1(0.25%)
Individuals on antiplatelet drugs or anticoagulants; N (%)	0
Individuals with past history of or active tuberculosis; N (%)	0
Individuals with epilepsy; N (%)	0
Individuals with skin diseases; N (%)	3(0.75%)
Individuals with rheumatoid arthritis; N (%)	1(0.25%)
Individuals currently receiving other drugs N (%)	2(0.50%)

REFERENCES:

1. Rokade M. Khandagale P. Coronavirus Disease: A Review of a New Threat to Public Health. Asian J. Pharm. Res. 2020; 10(3):241-244. DOI: 10.5958/2231-5691.2020.00025.8

2. Vishnu KN. Uppala PK. Vangoori Y. Gudhanti SN. A Review on Covid- 19 Pandemic and its Global Effects. Asian Journal of Pharmaceutical Research.2021; 4:11 DOI: 10.52711/2231-5691.2021.00042

3. Ministry of Health and family welfare Government of India. Dated- 28/10/2020 Morning [cited 2021 Febuary 18]. Available onlin athttps://www.mohfw.gov.in/pdf/COVID19VaccineOG111Chapter16.pdf

4. Habibunisha H. RathinamVA. Nivethitha K.A. Study on perception on Covid- 19 vaccination among general public. Asian Journal of Nursing Education and Research. 2021; 11(4): 537-0.DOI 10.52711/2349-2996.2021.00127.

5. Agarwal AK. Agarwal Al. Mahor R. Pathak A. A Cross Sectional Study to identify managerial issues in the Implementation of vaccination of under-five Children for effective management of Immunization Center. Asian Journal of Management. 2021; 12(3): 265-0. DOI: 10.52711/2321-5763.2021.00040

6. Center for Disease Control and Prevention. Food and Drug Administration. Vaccine adverse event reporting system. VAERS form, https://vaers.hhs. gov/resources/vaers_form.pdf (accessed January 2020.

7. Health Department Government of Haryana. Media Bulletin on COVID-19, Dated- 31/01/2021 Morning [cited 2021 Febuary 06]. Available online at http://nhmharyana.gov.in/WriteReadData/userfiles/file/CoronaVirus/Daily%20Bulletin%20of%20COVID%2019%20as%20on%2005-02-2021.pdf

8. Yadav P. Rohane S. Velhal A. Adverse Drug Reactions and Comorbidities in Patient Treated for COVID-19. Asian Journal of Research in Chemistry. 2021; 14(6):451-4.DOI: 10.52711/0974-4150.2021.00079

9. Mehta P et al. Identifying Backwardness of Mewat Region in Haryana: A Block-Level Analysis. New Delhi: Sehgal Foundation.(2015)

10. https://www.canada.ca/en/health-canada/services/drugs- health products/ covid19 industry/drugs vaccines-treatments/interim-order-import-sale-advertising drugs. html#a2.8.

11. Usha NS. Sushmitha HS. Kumar VG. A Study to assess side effects of first dose of Covid-19 Vaccination among GNM students studying at JSS School of Nursing Chamarajanagar. Asian Journal of Nursing Education and Research. 2021; 11(4):552-4.

12. Yadav R. Vaccines Other Than Specified in National Immunization Schedule among Parents of under- five Children. Int. J. Adv. Nur. Management2015; 3(1):64-68.

13. Aher VD. Banerjee S. Mahaur KK. Vaccine: An Ultimate Way of Immunization. Research J. Pharm. and Tech. March 2011; 4(3):369-374.

14. Balai MK. UK Variant COVID-19. Asian Journal of Nursing Education and Research. 2021; 11(4): 601-4. DOI: 10.52711/2349-2996.2021.00140

15. Kashyap S. BioN Tech CEO confident vaccine will work on new UK variant. One India News. 22 Dec. 2020. Accessed on 16 Jan.2021. Available at: https://www.oneindia.com/international/biontech-ceo-confident- vaccine-will-work-on-new-uk-variant-3192703.html

16. AEFI: surveillance and response. Operational guideline 2015. Ministry of health & family welfare Government of India, https://nhm.gov. in/New_Updates_2018/NHM_Components/Immunization/Guildelines_for_immunization/ AEFI_Surveillance_and_Response_Operational_ Guidelines_2015.pdf (accessed January 2020).

17. Singh AK. Wagner AL. Joshi J. Application of the revised WHO causality assessment protocol for adverse events following immunization in India. Vaccine 2017; 35: 4197–4202. DOI: 10.1016/j.vaccine.2017.06.027

18. Poland GA. Ovsyannikova IG. Jacobson RM. Adversomics: the emerging field of vaccine adverse event immunogenetics. Pediatr Infect Dis J 2009; 28: 431–433. DOI: 10.1586/14760584.2015.1038249

19. Kaur U et al. prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- ﬁrst results from India E Clinical Medicine 2021;38:101038. DOI: 10.1016/j.eclinm.2021.101038

20. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single blind, randomised controlled trial. Lancet 2020; 396: 467–78. DOI: 10.1016/S0140-6736(20)31604-4

21. Ramasamy MN. Minassian AM. Ewer KJ. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet 2020; 396: 1979–93. DOI: 10.1016/S0140-6736(20)32466-1

22. Joshi ND. Prajapati HK. Solanki KC. Pattern of adverse events following immunization in an Indian teaching hospital. Int J Med Sci Public Health 2013; 2: 62–68. DOI: 10.5455/IJMSPH. 2013.2 62-68.A

23. Aherkar RY, Deshpande and Ghongane BB. Study of the pattern of adverse events following immunization of children in a tertiary care hospital. PK Int J Basic Clin Pharmacol 2016;5:609–615. DOI:10.18203/2319-2003.ijbcp20161423

24. Zhu F-C. Guan X-H. Li Y-H. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2020; 396: 479–88. DOI: 10.1016/S0140-6736(20)31605-6

25. Rubingh J. van der Spek A. Fliers E. Boelen A. The role of thyroid hormone in the innate and adaptive immune response during infection. Compr Physiol2020; 10: 1277–87. DOI:10.1002/cphy.c200003

26. Brix TH. Hegedus L. Hallas J. Lund LC. Risk and course of SARS-CoV-2 infection in patients treated for hypothyroidism and hyperthyroidism. Lancet Diabetes Endocrinol 2021; 9: 197–9.

6. DOI: 10.3389/fendo.2021.779692

Received on 02.12.2021 Modified on 31.01.2022

Research J. Pharm. and Tech 2023; 16(1):179-183.

DOI: 10.52711/0974-360X.2023.00033

AEFI reported	After First dose (n=400) (72.72%)	Number of AEFIS after second dose			Percentage of AEFI out of total no. of participants (n =269) (49.81%)
AEFI reported	After First dose (n=400) (72.72%)	Within three days post vaccination	Within seven days post vaccination	Within nine days post vaccination
Fever	150(37.50%)	33 (42.00%)	44(56.41%)	1(1.28%)	78(28.99%)
Shivering	64(16.75%)	50(98.03%)	1(0.19%)	-	51(18.95%)
Generalised malaise	5(01.25%)	1(0.2%)	1(0.2%)	3(0.6%)	5(1.85%)
Local site pain	138(34.50%)	120(44.60%)	-	-	120(44.60%)
Headache	30(7.5%)	9(0.9%)	1(0.9%)	-	10(3.71%)
Skin rashes	10(2.5%)	1(0.5%)	1(0.5%)	-	3(1.11%)
URI	3(0.75%)	1(33.33%)	1(33.33%)	1(33.33%)	2(0.5%)