Assessment of safety and adverse drug reactions of COVID vaccination in the South Indian population: An observational prospective cross-sectional study

Abstract

Background

COVID vaccination is now offering a way to transit out of this phase of the pandemic. Two vaccines were approved by the Central Drugs Standard Control Organization (CDSCO) in India: Covishield and Covaxin. However, the vaccines are known to have Adverse Drug Reactions (ADRs) like fever, body pains, headache, pain, and swelling at the injection site.

Aim

To assess the Safety of ADRs with Covid Vaccination in the South Indian Population.

Method

This prospective, multi-centric study was carried out for six months (February 2021–July 2021). Subjects vaccinated against COVID were enrolled in the study. Informed consent was taken from the study participants, and required data (age, gender, type of vaccine, and ADRs) was collected through telephonic interviews. The data were analyzed by using the Chi-square test.

Results

A total of 3032 participants were enrolled in the study. The prevalence of ADRs is highly observed after the 2nd dose (51%) of COVID vaccination. ADRs were mainly experienced by females (55%) than males (45%). The incidence of fever and body pains was high in Covishield after dose one and Covaxin after dose 2. The pain at the injection site was high in Covaxin after dose 2. The WHO assessment scale and Naranjo's scale shows that ADRs are higher likely than probable.

Conclusion

We concluded that frequent ADRs that occurred with Covaxin and Covishield were fever, body pains, weakness, headache, and pain at the injection site. All the ADRs were mild and manageable with Paracetamol. So, the vaccines are safe to administer.

Highlights

• •Due to the rapid development of covid-19 vaccines, there is hesitancy among communities to take them.
• •This study assesses the ADRs that occur with Covaxin and Covishield.
• •Our study shows different ADRs caused by the Covid vaccination and their percentage incidence.
• •It also represents the severity of ADRs of Covid vaccination according to age, gender, and type of vaccine.
• •This study reported no severe or significant ADRs associated with covid-19 vaccines.

1. Introduction

COVID-19 infection is caused by severe acute respiratory syndrome - Coronavirus 2 (SARS-CoV2) [1]. The impact of COVID-19 was far-reaching worldwide, including more than 150 countries. Thus, the WHO declared this disease a global pandemic [2]. Vaccination is a simple, safe, and effective way of preventing harmful diseases. The vaccine administration uses the body's natural defence system to build resistance to the specific infection and strengthens the immune system [3].

COVID vaccination is now offering a way to transit out of this phase of the pandemic. Two vaccines have been granted by the Central Drugs Standard Control Organization (CDSCO) in India: Covishield and Covaxin. India's Bharat Biotech develops Covaxin, the Indian Council of Medical Research (ICMR), and the National Institute of Virology (NIV). It is an inactivated vaccine. The Generic name of Covaxin is BBV152 [4]. It is given as an intramuscular injection into the deltoid muscle of the upper arm in two doses with an interval of 4–6 weeks. The common ADRs observed are injection site pain/swelling/redness/itching, fever, headache, body pains/Malaise, nausea, vomiting, and rashes [5]. A Survey conducted by Swayam Pragyan Parida et al. has shown that pain at the injection site followed by fever and Myalgia were the most common ADRs of Covaxin [6].

Covishield is a recombinant replication-deficient chimpanzee adenovirus vector encoding the SARS CoV 2 spike glycoprotein. It is a viral vector vaccine. It is developed by the serum institute of India on the same patent technology as AstraZeneca. The Generic name of Covishield is ChAdOx1 to-19 (Serum Institute of India), AZD1222 (AstraZeneca) [7]. It is administered intramuscularly into the deltoid muscle in two doses at a volume of 0.5 ml each with a time interval of 12–16 weeks. The ADRs observed are injection site tenderness, warmth, pain, redness, itching, swelling or bruising, being unwell, tired (fatigue), fever with or without chills, headache, feeling sick, nausea, joint pains, or muscle ache [8]. A survey conducted by Maria Jose et al. at a tertiary care hospital in Kerala has resulted in ADRs such as fever, tiredness, pain at the injection site, chills, Myalgia, and headache [9].

According to WHO, Adverse Drug Reaction is “Any response to a drug which is noxious and unintended which occurs at normal doses used in man for prophylaxis, diagnosis or therapy of disease or the modification of the physiological function”. This definition excludes overdose that may be accidental or intentional, treatment failure drug abuse. An adverse event is “any unwanted medical occurrence during drug administration”. When an ADR is suspected, the assessment should include the collection of data, including demographics of the subject experiencing ADR, a list of all medications used at the time of ADR occurrence, and details of ADRs like time of onset, its duration, severity, treatment and outcome of the treatment. This data must be used to assess the relationship between the drug and suspected ADR. This assessment can be done by one or more standard ADR scales like the WHO and Naranjo's assessments [10].

2. Aim

The aims of this study are.

• ●To assess the safety of both COVID vaccines and prove that those are safe to use.
• ●Assess the patterns, severity, prevalence, and risk factors associated with COVID vaccination.

3. Materials and methods

This prospective observational multi-centric study was conducted for six months (December 2020 to May 2021). A suitable informed consent form and data collection form were designed. A total of 3032 subjects vaccinated against COVID gave their consent to participate in the study and were enrolled in it. Subjects who were non-cooperative were excluded. The data on age, gender, vaccine type, and ADRs was collected through telephonic interviews and an online questionnaire and was documented in the data collection form. The collected data were categorized and compared, and results were analyzed using the Chi-square test.

Inclusion criteria: The study enrolled all individuals receiving the vaccine during the study period.

Exclusion criteria: Uncooperative individuals and those who refused consent were excluded.

This study was reported in line with the STROCSS criteria [11]. The study was registered and approved by the institutional human ethical committee of St. Pauls College of Pharmacy, Hyderabad, Telangana, India (UIN: SPCP/2020-21/IHEC/002).

4. Statistics

Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software for windows (version 27.0, 2021; SPSS, Inc., Chicago, IL). The Chi-Square test was used for the analysis. A P-value less than 0.05 were considered to be statistically significant.

5. Results

The study enrolled a total of 3032 subjects. Of them, 900 (29.6%) were vaccinated with Covaxin and 2132 (70.3%) with Covishield. Males account for 1459 (48.1%), and females account for 1573 (51.8%).

All 900 subjects of the Covaxin vaccination received both doses. ADRs occurred in 251 participants after the 1st dose and 169 participants after the 2nd dose. Among 251 participants who received 1st dose, 109 (43.4%) were males, and 142 (56.5%) were females. Among 169 participants who received 2nd dose, 90 (53.2%) were males, and 79 (46.7%) were females.

Out of 2132 subjects with Covishield vaccination, all the subjects received 1st dose (1064 experienced ADRs), and 1793 subjects received 2nd dose (181 experienced ADRs).

Among 1064 subjects who experienced ADRs with a dose of Covishield, 461 (45.3%) were males, and 603 (54%) were females. Among 181 participants of the 2nd dose of Covishield, 83 (45.8%) were males, and 98 (54.1%) were females.

The prevalence of ADRs is highly observed after the 2nd dose (51%) of COVID vaccination, and females (55%) are more predominantly affected than males (45%).

The details of ADRs experienced by subjects after Covaxin and Covishield vaccinations and their percentage incidence are detailed in Table 1, Table 2, respectively.

Table 1.

Adverse drug events occurred with 1st and 2nd doses of Covaxin and their percentage incidence.

S No	Adverse drug event	1st dose ADRs (%)	2nd dose ADRs (%)
1	Body pains	99 (30.7%)	53 (33.9%)
2	Fever	76 (23.6%)	58 (37.1%)
3	Headache	64 (19.8%)	7 (4.4%)
4	Weakness	35 (9.9%)	12 (7.6%)
5	Pain at injection site	24 (7.4%)	21 (13.4%)
6	Cold	6 (1.8%)	2 (1.2%)
7	Drowsiness	5 (1.5%)	0
8	Giddiness	3 (0.93%)	2 (1.2%)
9	Chills	2 (0.6%)	0
10	Constipation	2 (0.6%)	0
11	Blurred vision	1 (0.3%)	0
12	Stomach upset	1 (0.3%)	0
13	Throat itching	1 (0.3%)	0
14	Tiredness	1 (0.3%)	0
15	Vomiting	1 (0.3%)	0
16	Cough	1 (0.3%)	1 (0.6%)
17	Loss of appetite	0	1 (0.6%)

Table 2.

Adverse drug events occurred with 1st and 2nd doses of Covishield and their percentage incidence.

S No.	Adverse drug event	1st dose ADRs (%)	2nd dose ADRs (%)
1	Fever	614 (38.3%)	78 (33.4%)
2	Body pains	543 (33.9%)	89 (38.1%)
3	Headache	153 (9.5%)	18 (7.7%)
4	Weakness	140 (8.7%)	30 (12.8%)
5	Pain at injection site	87 (5.4%)	7 (3%)
6	Vomiting	12 (0.75%)	3 (1.2%)
7	Chills	9 (0.56%)	0
8	Giddiness	8 (0.5%)	1 (0.4%)
9	Loss of appetite	5 (0.3%)	0
10	Cold	5 (0.21%)	1 (0.4%)
11	Stomach upset	4 (0.25%)	0
12	Drowsiness	3 (0.18%)	0
13	Cough	3 (0.18%)	0
14	Diarrhea	3 (0.18%)	3 (0.12%)
15	Neck pain	3 (0.18%)	0
16	Insomnia	2 (0.12%)	0
17	Eye irritation	2 (0.12%)	0
18	Allergy	1 (0.06%)	0
19	Dysuria	1 (0.06%)	0
20	Chest pain	1 (0.06%)	0
21	Throat pain	1 (0.06%)	0

Table 3 is a detailed comparative analysis of adverse drug events with Covaxin and Covishield.

Table 3.

Comparison of adverse drug events of Covaxin and Covishield.

S.No.	Dose	Adverse Event	Covaxin	Covishield	P- Value
1.	1	Fever	76 (8.4%)	614 (28.7%)	0.00001*
2.	2	Fever	58 (6.4%)	78 (4.4%)	0.001*
3.	1	Body pains	99 (11%)	543 (25.4%)	<0.00001*
4.	2	Body pains	53 (5.8%)	89 (5.1%)	0.05
5.	1	Headache	64 (7.1%)	153 (7.1%)	0.9527
6.	2	Headache	7 (0.7%)	18 (1%)	0.8544
7.	1	Weakness	35 (3.8%)	140 (6.5%)	0.006
8.	2	Weakness	12 (1.3%)	30 (1.7%)	0.8755
9.	1	Pain at injection site	24 (2.6%)	87 (4%)	0.067
10.	2	Pain at injection site	21 (2.3%)	7 (0.4%)	0.0001*

Fig. 1 shows the age-wise distribution of subjects concerning ADRs experienced with Covaxin and Covishield.

Fig 1.

Age wise distribution of subjects with respect to ADRs experienced with Covaxin and Covishield.

where 1 and 2 after the Covaxin and Covishield indicate the doses.

Fig. 2 is the classification of ADRs that occurred with Covaxin and Covishield according to the WHO assessment scale.

Fig 2.

Classification of ADRs occurred with Covaxin and Covishield according to WHO assessment scale.

Fig. 3 is the classification of ADRs that occurred with Covaxin and Covishield according to Naranjo's assessment scale.

Fig 3.

Classification of ADRs occurred with Covaxin and Covishield according to Naranjo's assessment scale.

6. Discussion

The present study was on the ADRs caused by the vaccines against COVID-19 infection. The ADRs were mostly seen in the age group of 18–30 years, followed by 46–60 years.

The study by Thirthankar Deb et al. [12] in a tertiary care hospital among healthcare workers in India has reported few ADRs associated with vaccination. On the other hand, Ashwini Mahadevaiah et al. [13] and Deep Kamal et al. [14] conducted similar studies. Those studies have shown that the first dose of vaccination shows a higher percentage of ADRs compared to the second dose of Covishield. Similar results were seen in our study, where Covishield's first dose showed a rate of ADRs of 49.9%, followed by the second dose of 10.9%.

The common ADRs caused by the COVID vaccines were fever, body pains, headache, vomiting, pain at the injection site, weakness, drowsiness, insomnia, chills, cold, cough, diarrhoea, allergy, dysuria, giddiness, chest pain, loss of appetite, throat pain, neck pain, stomach upset, eye irritation. All the ADRs caused by these vaccines were mild or moderate.

Our study's results have shown that the ADRs of Covishield vaccination are fever, body pains, headache, weakness, and pain at the injection site in a higher percentage of the population. Furthermore, an observational study on surveillance of adverse events of Covishield conducted by Dhanya Jose et al. [15], a cross-sectional study conducted on ADRs of Covishield by Sukhpal Kaur et al. [16], A comparative study conducted on adverse events of Covishield by Sushil Rayamajhi et al. [17] has shown the ADRs of fever, headache, weakness, pain at the injection site as the most common ADRs of Covishield which were similar to our studies. However, the data was different in the research reported by Dr Rajeev et al. [18] and a study conducted at the tertiary care institute of Eastern Uttar Pradesh by Bhushan Kamble et al. [19], which showed that Myalgia and tiredness were high.

Our studies have resulted in a high frequency of ADRs of Covaxin, such as Body pains, Fever, Headache, weakness and pain at the injection site, where similar results were seen in the study conducted by Swayam Pragyan Parida et al. [6]. But the studies conducted by Swayam Pragyan Parida et al. [6] have shown that ADRs were seen more after 1st dose when compared to 2nd dose, whereas our studies have resulted in more ADRs after 2nd dose compared to 1st dose.

The incidence of fever and body pains is high in Covishield after 1st dose and Covaxin after 2nd dose. The pain at the injection site is high in Covaxin after 2nd dose. The ADR assessment scales, such as the WHO and Naranjo's probability assessment scales, demonstrate that the possible condition is more elevated than probable with both Covaxin and Covishield-induced ADRs.

7. Conclusion

COVID-19 infection has been a worldwide pandemic. To fight against this pandemic emergency, vaccines were developed. However, the general population feared taking vaccination in the initial days with various myths and fears. In the present study, a safety assessment of ADRs of both COVID vaccines was done. The present study noticed that the common ADRs caused by both Covaxin and Covishield were fever, body pains, weakness, headache, and pain at the injection site. All the ADRs were assessed using WHO and Naranjo's assessment scales and confirmed to be under the categories of possible. No severe ADRs were found. All the ADRs subsided after administering Paracetamol 650 mg, QID, TID/SOS (frequency of administration depending on the requirement of the individual). Thus, the study shows that Covaxin and Covishield are safe to use.

Limitations

• 1.Due to the reinfection of Covid 19, the sample size was reduced in the second dose of Covishield.
• 2.During our study period, vaccination was primarily done for 45 years and above, so the population aged 18–44 years was less.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Ethical approval

This internet-medicated interventional study follows the guidelines and ethical principles of the British Psychological Society.

The study was registered and approved by the institutional ethical committee of St. Pauls College of Pharmacy, Hyderabad, Telangana, India (UIN: SPCP/2020-21/IHEC/002).

Sources of funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author contribution

All the authors have contributed to the study equally.

Registration of research studies

• 1Name of the registry: Institutional human ethical committee of St. Pauls College of Pharmacy, Hyderabad, Telangana, India
• 2Unique Identifying number or registration ID: SPCP/2020-21/IHEC/002
• 3Hyperlink to your specific registration (must be publicly accessible and will be checked): https://drive.google.com/file/d/1NPYTyK3-sV4hpm1RQMeraO44hAkslnOC/view?usp=sharing

Guarantor

Dr. Keerthi Thatikonda, Ms. Anusha Manda.

Consent

Participants have given their consent through an online procedure during data collection.

Declaration of competing interest

The authors have no relevant financial or non-financial interests to disclose.

Appendix A. Supplementary data

The following is the Supplementary data to this article: