|Year : 2022 | Volume
| Issue : 2 | Page : 104-109
Active surveillance of adverse events following the first dose of COVID-19 vaccination – Oxford–AstraZeneca (Covishield) vaccine
Sangeetha Merrin Varghese1, Grace Mary John2, Geomcy George3, Linda Jacob2, Mammen Paul2, Arun Sachu4, Abel K Samuel Johnson2, George Mateethra Chandy5
1 Department of Community Medicine, Believers Church Medical College, Thiruvalla, Kerala, India
2 Department of Clinical Pharmacy, Believers Church Medical College, Thiruvalla, Kerala, India
3 Department of Radiation Oncology, Believers Church Medical College, Thiruvalla, Kerala, India
4 Department of Microbiology, Believers Church Medical College, Thiruvalla, Kerala, India
5 Department of Gastroenterology, Believers Church Medical College, Thiruvalla, Kerala, India
|Date of Submission||12-Apr-2021|
|Date of Decision||25-Jun-2022|
|Date of Acceptance||19-Jul-2022|
|Date of Web Publication||22-Aug-2022|
Sangeetha Merrin Varghese
Cherical House, Channanikadu P.O, Kottayam - 686 533, Kerala
Source of Support: None, Conflict of Interest: None
Background: COVID-19 vaccines have been the most rapidly developed vaccines in history and consequently, fears of its safety and efficacy intrigue the minds of the common man. Aims: This study was intended to determine the adverse events following COVID-19 vaccination and thereby reduce vaccine hesitancy in the people. Methods and Materials: An active vaccine safety surveillance study was carried out on health-care workers of a tertiary care center in Central Kerala using a prestructured interview schedule documenting a description of adverse events following immunization (AEFI), time of occurrence, management and outcome of AEFI, knowledge about AEFIs, and fear of COVID-19 vaccination. A telephonic survey was carried out on 475 randomly selected COVID vaccine beneficiaries. Results: Overall, 86% of the participants reported at least one postvaccination symptom. Fever (51.8%), injection-site pain (46.9%), headache (29.3%), myalgia (28.4%), and fatigue/tiredness (25.1%) were the most common symptoms. None of the symptoms were severe/serious to warrant hospital admission. Side effects were more common in females (P = 0.003) and reactogenicity of the COVID-19 vaccine decreased with advancing age (P = 0.001). The vaccine did not have any difference in side effects among those who had previous COVID-19 infection. Conclusion: This study shows that COVID vaccines are safe in the Indian population and the side effects are similar to any other vaccine. It may help to dispel any fear and misinformation regarding COVID-19 vaccination and thus maximize the benefit of the nationwide immunization program.
Keywords: Adverse events, COVID-19 vaccination, safety
|How to cite this article:|
Varghese SM, John GM, George G, Jacob L, Paul M, Sachu A, Samuel Johnson AK, Chandy GM. Active surveillance of adverse events following the first dose of COVID-19 vaccination – Oxford–AstraZeneca (Covishield) vaccine. Saudi J Health Sci 2022;11:104-9
|How to cite this URL:|
Varghese SM, John GM, George G, Jacob L, Paul M, Sachu A, Samuel Johnson AK, Chandy GM. Active surveillance of adverse events following the first dose of COVID-19 vaccination – Oxford–AstraZeneca (Covishield) vaccine. Saudi J Health Sci [serial online] 2022 [cited 2022 Nov 30];11:104-9. Available from: https://www.saudijhealthsci.org/text.asp?2022/11/2/104/354167
| Introduction|| |
The COVID-19 pandemic and its devastating consequences to the health and economy of the different countries have prompted the most rapid vaccine development program in history and many vaccines are now licensed for emergency use in each country. Immunization is one of the most cost-effective public health interventions, preventing millions of deaths due to infectious diseases, every year globally. However, vaccine development is a long, complex process, often lasting 10–15 years and following a standard set of steps. The first stages are exploratory in nature, involve basic laboratory research, and often last 2–4 years. Then comes the preclinical stage wherein studies use cell culture and animal testing. Many candidate vaccines never progress beyond this stage because they fail to produce the desired immune response. Then the vaccine undergoes Phase-1, 2, and 3 clinical trials to evaluate the vaccine's safety, immunogenicity, dosage, schedule, and method of delivery. The emergence of COVID-19 vaccines has been hailed as a game changer, but the speed of their development and approval is a matter of concern for some people. Although the finishing line seems to be in sight, there is still much difficult terrain to cross as in dealing with vaccine hesitancy, seroconversion in the elderly, and so on.
Unlike drugs, the expectations from vaccinations are much higher and problems arising from the COVID-19 vaccine are less acceptable to the general public, especially the health-care workers when they are informed about the aforementioned facts. Covishield (AstraZeneca–Oxford ChAdOx1 n CoV-19), manufactured by the Serum Institute – the vaccine used against COVID-19 in the first phase of vaccination is Kerala, is generally considered safe and effective when used correctly. However, like medicinal products, vaccines are not free from adverse events.
Adverse events following immunization (AEFI) are defined as “any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the use of the vaccine.” The adverse event may be any unfavorable or unintended sign, an abnormal laboratory finding, a symptom, or a disease. Vaccines, settings, as well as the process of immunization are all potential sources of adverse events. The cause-specific classification of AEFIs by the Council for International Organizations of Medical Sciences and the World Health Organization lists vaccine product-related reaction, vaccine quality defect-related reaction, immunization error-related reaction, immunization anxiety-related reaction, and coincidental event. The Serum Institute of India has labeled side effects such as tenderness, pain, warmth, redness, itching, swelling, or bruises where the injection is given, generally feeling unwell, fatigue, chills, or feeling feverish, headache, nausea, and joint pain or muscle ache as the “very common” adverse effects to Covishield vaccine. “Uncommon” side effects are – dizziness, decreased appetite, abdominal pain, enlarged lymph nodes, excessive sweating, itchy skin, or rash.
Covishield vaccines have completed Phase 3 trials, but we do not know the postvaccination experience of our people in real-life settings. Knowledge about the symptoms that can occur after vaccination can lead to improved compliance and higher acceptance of subsequent doses. Allegations that COVID-19 vaccines cause adverse events must be dealt with rapidly and effectively. Failure to do so can undermine confidence in a vaccine and ultimately have dramatic consequences for immunization coverage and disease incidence. Appropriate actions must be taken to respond promptly, efficiently, and with scientific rigor to vaccine safety issues. This will help to dispel misinformation, minimize fear of adverse effects of COVID-19 vaccination and in turn help to maximize the benefits of immunization programs.
The study aimed to detect AEFIs to the first dose of COVID vaccine among the health-care workers in Central Kerala, and thereby alleviate fear and apprehension among those hesitant to take the COVID-19 vaccine. Furthermore, we tried to explore the factors that could influence AEFI such as age, gender, and previous COVID-19 infection. In addition, we also found the proportion of health-care workers who feared about AEFIs after COVID-19 vaccination.
| Methods|| |
The study was conducted in our institution (tertiary care center) after obtaining clearance from the Institutional Review Board (IEC/2021/06/216) between February 2021 and March 2021. It was an active vaccine safety surveillance study carried out on health-care workers of a tertiary care center in Central Kerala. Study participants were monitored at the vaccination session site for 30 min following the COVID vaccination. A telephonic survey was carried out to identify all AEFIs, 1 week after vaccination. The study included COVID-19 beneficiaries who were allocated by the Co-WIN portal during the 1st week of the first round of COVID-19 vaccination and who were willing to provide informed consent.
COVID-19 vaccination was conducted in a dedicated area adjacent to the emergency medicine department. This was to deal with any inadvertent reactions to the COVID vaccine. Only previously registered beneficiaries were allowed entry into the vaccination session site. The beneficiaries were checked for their possession of a Government certified ID card by a Vaccination officer-1, who was a hospital security guard who was solely posted on duty for the same. Vaccination officer-2 checked the eligibility of the beneficiaries based on a prestructured checklist and vaccinator officer vaccinated the beneficiaries.
The COVID vaccine checklist was prepared based on the recommendations of the Covishield Package Insert and WHO, collecting essential details of any previous allergy or anaphylaxis to food/drug/vaccine. Furthermore, the status of the beneficiaries with regard to pregnancy, lactation, and fever was also documented. A vaccination register was also maintained at the site to collect details of the vaccine (Batch no., Mfg date, and Expiry date), time of the opening of the vaccine vials, and time to discard the opened vial. Another register to ensure a compulsory waiting period of 30 min was also maintained, mentioning each beneficiary's time of injection and time to observe.
All beneficiaries who received their first dose of the COVID vaccine were compulsorily monitored for 30 min in the waiting area of the vaccination site following vaccination. Vaccination officer-3 and 4 were located in the waiting area for observation of the vaccinated beneficiaries as well as to provide postvaccination information and education. In addition, the vaccination session site had plenty of patient information and education posters in English and in the local language, regarding the vaccine, possible AEFIs, and postvaccination COVID protocol that will have to be inevitably followed by all beneficiaries. In case of any AEFIs, the beneficiaries were advised to visit the emergency medicine department and contact the vaccination team at any time for a week following the vaccination. After a week following vaccination, a telephonic follow-up was conducted with the study participants, irrespective of whether they had contacted the study team or not. The study team also had an AEFI case reporting format provided by the Kerala State, ready to collect the required data in case of a severe or serious AEFI.
The assessment of AEFI was done using a prestructured interview schedule documenting demographic details, description of AEFI, time of occurrence of AEFI, severity, seriousness, details of medical attention sought due to AEFI, management and outcome of AEFI, knowledge about AEFIs after any vaccination, and their fear of COVID-19 vaccination.
| Results|| |
A total of 475 participants were telephonically interviewed to monitor the adverse events following the administration of the COVID vaccine. Majority of the study participants were nurses (42%), 20% were doctors, and 38% were students, technicians, and supporting staff. Majority (73%) belonged to the age group of 20–40 years and 12% had a history of COVID-19 infection [Table 1].
Although 90.5% of the participants were aware of the side effects of the COVID-19 vaccination, only nearly one-eighth (12.8%) of the participants feared the side effects of COVID vaccination.
Overall, 86% of the participants reported at least one postvaccination symptom. Fever (51.8%), injection-site pain (46.9%), headache (29.3%), myalgia (28.4%), fatigue/tiredness (25.1%), chills (18.5%), joint pain (8.4%) nausea (4.4%), and dizziness (4.2%) were the most prevalent symptoms. Others included insomnia, somnolence, injection-site swelling, vomiting, decreased appetite, diarrhea, urticarial rashes, lymphadenopathy, sore throat, cough, and abdominal pain [Figure 1] and [Figure 2]. Urticarial rashes occurred in 0.4% of the participants within 30 min of vaccination and resolved with an injection of hydrocortisone and Pheniramine maleate. None of the symptoms reported in the survey were neither serious nor required hospitalization/intensive care unit admission. About 5.2% reported their symptoms to a doctor.
More than half (52%) of the beneficiaries reported to develop symptoms within 24 h of vaccination, 20.4% developed symptoms after 24 h, and only 5% developed symptoms after 48 h [Figure 3]. Of those who developed symptoms after 24 h, 25% belonged to the older age group (>50 years). Furthermore, nearly 10% developed symptoms within 4 h of vaccination. Among those who did not fear the side effects of the vaccine, 90% developed symptoms after 4 h, whereas compared to only 10% who developed symptoms before 4 h. This was found to be statistically significant with a Chi-square value = 4.264 and P = 0.039.
We find that percentage of people with symptoms after vaccination decreased as age increased. This finding was consistent across all age groups (P = 0.009). Furthermore, females were reported to have more symptoms when compared to males [P = 0.003 and [Table 2]].
Out of the surveyed beneficiaries, 12% had previous COVID-19 infection. Among these, 15.8% did not have any symptoms after vaccination. Although 50.9% developed symptoms within 24 h, >28% developed symptoms after 24 h. Furthermore, among those with previous COVID-19 infection, except for fever (54.4%), symptoms such as fatigue (29.8%), myalgia (28.1%), chills (15.8%), and headache (31.6%) were low when compared to those without previous COVID-19 infection. However, it was not statistically significant.
Among those who had postvaccination symptoms, 70.5% had consumed paracetamol (288/408). Of them, the majority were females (67.4%) compared to males (32.6%). There is a significant gender difference in paracetamol intake postvaccination [P = 0.001] and [Figure 4].
| Discussion|| |
The study was conducted to explore the vaccine side effects among the recipients of the Covishield vaccine. Vaccine reactions are generally classified as immune-mediated vaccine reactions which can present as local reactions at the injection site and multisystem (generalized reactions) such as systemic inflammatory response (fever or lethargy), mast cell degranulation, Immunoglobulin E (IgE)-mediated hypersensitivity (anaphylaxis), non- IgE-mediated hypersensitivity (anaphylactoid reactions), immune complex-mediated reaction (serum sickness), and organ-specific reactions by autoimmune or other undefined mechanisms such as urticarial rashes in the skin after vaccination. Fever is a relatively common inflammatory response following vaccination. For most vaccines, the fever is of short duration and there are no associated adverse reactions. Fever and symptoms such as fatigue and myalgia are consistent with an immune response commonly associated with vaccines. Our study also finds that fever was the most common symptom following the Covishield vaccination.
A few of our study participants also manifested immunization anxiety-related reactions (immunization stress-related responses). Stress responses to vaccination are manifested immediately before, during, or after vaccination. This may include acute stress responses including vasovagal reactions (e.g., fainting, palpitations, hyperventilation, and dizziness). They usually occur in the immediate time period surrounding a vaccine administered by the injectable route. An acute stress response or vasovagal reaction is usually transient and resolves spontaneously. This was consistent with our findings. Our study also finds that among those who did not fear the side effects of the vaccine, majority did not have immediate side effects such as acute stress responses. This finding was also statistically significant.
Our study demonstrates the association between age and postvaccination symptoms. There is a remarkable decline in symptoms with increasing age and was a consistent finding across all age groups. This was comparable to the results of the Phase 2/3 trial of the Covishield vaccine. However, more is yet to be known whether the presence of postvaccination symptoms reliably predicts antibody response. However, several studies have revealed that the presence of symptoms is known to correlate with neutralizing antibody levels in patients with COVID-19 infection. In general, we know that elderly individuals do not respond to immune challenges as robustly as the young, due to diminished production and function of lymphocytes in the body. However, to our relief, there is no predictive association between postvaccination symptoms and immune response. Antibody responses to the vaccine can occur regardless of local or systemic symptoms.
There was a striking gender difference in the occurrence of symptoms. Women reported more postvaccination symptoms. Furthermore, among men who reported symptoms, 66% of them adjusted without consuming paracetamol compared to women. This could be either due to increased severity of symptoms in women or lower threshold of women to withstand postvaccination discomfort. Although the use of paracetamol to relieve fever and discomfort is a common phenomenon, routine prophylactic use of paracetamol and other pain killers is not recommended, due to evidence of blunted immune response by reducing vaccine immunogenicity in studies conducted in infants following routine immunization. The WHO has also advised against the administration of prophylactic oral analgesics due to the potential for affecting vaccine response.,
This study shows that COVID vaccines are safe and the side effects are similar to any other vaccine. Although COVID-19 vaccines were produced in haste, (compared to the normal time required for developing a vaccine) these are found to be safe in the Indian population. Although the reactogenicity decreased in older age groups and the symptoms more in females, the vaccine did not have any difference in adverse effects in those who were previously affected with COVID-19. This study may help to dispel any fear and myths regarding COVID-19 vaccination and thus maximize the benefit of the nationwide immunization program.
| Conclusion|| |
The study concludes that COVID vaccines are safe and free from any severe or serious adverse effects when given to individuals after following the Vaccine Insert guidelines. The most common side effects were fever (51.8%), injection-site pain (46.9%), and headache (29.3%). Side effects were more common in females (P = 0.003) and reactogenicity of the COVID-19 vaccine decreased with advancing age (P = 0.001). The vaccine did not have any difference in side effects among those who had previous COVID-19 infection. This study may help to dispel any fear and misinformation regarding COVID-19 vaccination and thus maximize the benefit of the nationwide immunization program by reducing vaccine hesitancy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]