|Ahead of print publication
A longitudinal study to estimate adverse events following two doses of COVID-19 vaccination
Saurabh Bobdey, Rajesh Sahu, Arun Kumar Yadav, SK Kaushik, KS Sreekanth, Niharika Nagari, Kunal Koundinya
Department of Community Medicine, AFMC, Pune, Maharashtra, India
|Date of Submission||02-Sep-2021|
|Date of Decision||13-Oct-2021|
|Date of Acceptance||13-Oct-2021|
Arun Kumar Yadav,
Professor, Department of Community Medicine, AFMC, Pune-411040, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: On March 30, 2020, coronavirus disease 19 was declared pandemic and many countries of the world started working on the development of vaccine soon after China released the genetic structure of severe acute respiratory syndrome coronavirus 2. Drugs Controller General of India on January 3, 2021, accorded emergency use authorization to Oxford-AstraZeneca's ChAdOx1 nCoV-19 vaccine and vaccination drive commenced in India on January 16, 2021. The present study was conducted to determine the incidence adverse event following immunization (AEFI) among recipients of the first and second dose of the vaccine. Materials and Methods: A longitudinal descriptive study was conducted among 2529 vaccine beneficiaries who were asked about the side effects at 24 and 72 h after the first dose and second dose of vaccination with ChAdOx1 nCoV-19 vaccine. Passive surveillance was also done for 4 months. Results: AEFI was reported in 27.59%, 38.4%, and 19.96% of vaccines after both doses, first dose, and second dose, respectively. 14% did not report any AEFI with either dose of vaccine. Younger people had higher rates of AEFIs with both the doses. Pain at injection site and fever <102°F were the most common symptoms. Only three patients required admission after first dose and nil required admission after second dose, all three were discharged after 24 h observation without any complication or sequelae. Conclusion: The results of our study indicate that the vaccine has good safety profile and is recommended for use among 18–60 years. However, since majority of individuals in our study were young, studies may be undertaken in more than 60 years of age, persons with a history of allergy, and comorbidities to further evaluate safety profile of the vaccine among these groups of people.
Keywords: Adverse event following immunization, coronavirus disease 19, vaccination
|How to cite this URL:|
Bobdey S, Sahu R, Yadav AK, Kaushik S K, Sreekanth K S, Nagari N, Koundinya K. A longitudinal study to estimate adverse events following two doses of COVID-19 vaccination. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 7]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=338916
| Introduction|| |
On January 30, 2020, the World Health Organization (WHO) Director-General determined that the outbreak of coronavirus disease 19 (COVID-19) constitutes a Public Health Emergency of International Concern and declared it a pandemic on March 11, 2020. Since then, COVID-19 infection has caused significant mortality and morbidity throughout the world. Without a definitive treatment, the only way to control the situation is to develop herd immunity through an effective vaccination program.,
Vaccine is an important weapon in the armamentarium for the prevention of communicable disease, especially among the vulnerable. Typically vaccine development is a long, complex process, often lasting 10–15 years, involving four stages of clinical trials. However, due to the gravity of the current public health emergency and the importance of facilitating availability of vaccines to prevent COVID-19, the Food and Drug Administration (FDA) gave emergency use authorization (EUA) to certain vaccines after they met the minimum statutory criteria. Under an EUA, FDA may allow the use of unapproved medical products or unapproved uses of approved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, including that there are no adequate, approved, and available alternatives. Several vaccines have been approved in different countries and a number of vaccines are still in the pipeline and seeking EUA., Drugs Controller General of India has approved the Bharat Biotech vaccine against COVID-19, which is a locally manufactured inactivated vaccine named “Covaxin” in collaboration with the Indian Council of Medical Research on January 3, 2021, for emergency use along with the “Covishield” Oxford-AstraZeneca's ChAdOx1 nCoV-19 vaccine manufactured locally by the Serum Institute of India. On January 16, 2021, India started its national vaccination program against the severe acute respiratory syndrome coronavirus 2, and in the initial stage, only health-care workers and frontline workers were authorized to be vaccinated. With many factors playing a key role in vaccine acceptance, one such major issue is the speed with which COVID-19 vaccines have been manufactured and rolled out in the market., In the recent past, adverse event following immunization (AEFI) due to the ChAdOx1 nCoV-19 vaccine has been in focus due to serious adverse events being reported in European countries.
In such a scenario, timely detection and reporting of adverse events following COVID-19 vaccination is the most important step for ensuring immunization safety surveillance and response. The WHO has defined AEFI as “any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. The adverse event may be any unfavorable or unintended sign, abnormal laboratory finding, symptom or disease.”,
The study was conducted to determine the incidence and types of AEFI among recipients of the first/second dose of ChAdOx1 nCoV-19 vaccine.
| Materials and Methods|| |
The present study was a longitudinal descriptive study conducted among employees of a medical education institute in western Maharashtra. The study was conducted from January 16 to March 30, 2021. The study population was all individuals who were vaccinated during the period.
A standardized questionnaire was prepared to collect the data on the side effects. The questionnaire consisted of both close-ended and open-ended questions. The questionnaire was circulated among epidemiologists, public health experts, and pharmacologist for content validity. The training session was conducted for persons administering the questionnaire. The participants were asked about the side effects at 24 h and 72 h after the first dose and second dose of vaccinations. All the participants were actively contacted to know the side effects of vaccine. At least three calls were made if a participant did not respond to the first call. Home visits were made if the participants did not respond to any of the call.
The study was approved by the institutional ethical committee of the institute. The ones who have reported side effects were counseled and appropriate management administered. The passive surveillance of all the vaccines was done for 4 months.
The data were collected in an excel spreadsheet and data were analyzed using an electronic statistical package IBM SPSS for Windows, version 20.0. Armonk, NY, USA: IBM Corp. A P < 0.05 was considered statistically significant.
| Results|| |
A total of 2529 individuals received ChAdOx1 nCoV-19 vaccine from January 16, 2021, to March 31, 2021. The majority (83.15%) of the vaccine beneficiaries were males and <40 years of age (74.93%). AEFI was seen with both doses among vaccines in 698 (27.59%), only with first dose in 971 (38.4%) and in 505 (19.96%) only with the second dose. A total of 355 (14%) did not report any AEFI with vaccination. Age and gender distribution is shown in [Table 1]. No significant statistical association was found with gender (P = 0.30). There was a significant association with age, with younger people having higher rates of AEFIs with both the doses. AEFI symptoms were classified into local and systemic. Pain at the site of injection was the most common complaint after both first and second doses. Fever <102°F was the most common systemic symptoms [Figure 1]. Only three patients required admission and observation in the hospital after the first dose, one for breathlessness, one for hypotension, and one for a momentary loss of consciousness. All the three patients were discharged after 24 h of observation without any complication or sequelae. No vaccine beneficiary following the second dose suffered from any serious adverse effect requiring admission to the hospital. In passive surveillance of 4 months, no vaccines reported to MI room for any vaccine-related illness.
|Table 1: Distribution of adverse event following immunization as per dose and basic demographic characteristics|
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| Discussion|| |
The two important aspects of any vaccination program are vaccine efficacy and the safety of the vaccine. Our study is one of the earliest studies to estimate the incidence of AEFI with both first and second dose in a large cohort of recipients of ChAdOx1 nCoV-19 “Covishield” vaccine. The majority of the vaccine recipients of our study had minor AEFIs which were self-limiting, thus highlighting that the vaccine is safe to use in the age group of 18–60 years.
In our study, 1669 (65.94%) of vaccine recipients had mild-to-moderate AEFIs after the first dose and 1203 (47.56%) after the second dose. A retrospective study conducted in Korea among 994 HCW has reported a much higher incidence of 94.5% of AEFIs after the first dose of ChAdOx1 nCoV-19 vaccine. In comparison to our study, a much lower incidence of 40% after the first dose and 16% after the second dose has been reported in one of the preprint Indian study. Higher incidence of AEFI in our study may be due to better surveillance quality of our study, as our study employed active surveillance through an institutionalized mechanism and ensured good response rates during follow-up. Our results were comparable to the safety results of the clinical trial of ChAdOx1 nCoV-19 vaccine conducted in the United Kingdom, which employed much more reliable robust surveillance to capture AEFI data, wherein almost two-thirds of the vaccinated persons reported mild-to-moderate AEFIs.,, In our study, the incidence of AEFIs was lower with the second dose, which is in accordance to known phenomenon where reactogenicity to vaccine reduces with each subsequent dose.
The incidence of AEFI was higher in the younger age group as compared to older age group, which is an expected outcome of reactogenicity to any viral vector vaccine like Covishield. Similar results have been reported from the clinical trial results of ChAdOx1 nCoV-19 vaccine.,, Among the presented AEFIs, local AEFI of pain/tenderness/swelling at the injection site was much more common as compared to systemic AEFIs. Among the systemic AEFIs, low-moderate grade fever (Ist dose – 32.5%, IInd dose – 18.1), bodyache (Ist dose – 36.3%, IInd dose – 17.3%), and headache (Ist dose – 19.4%, IInd dose – 14.2%) accounted for majority of the vaccine recipients, whereas high-grade fever (Ist dose – 3.0%, IInd dose – 2.1%), skin rash (Ist dose – 0.6%, IInd dose – nil), nausea, vomiting, pain abdomen, loss of appetite, dizziness, numbness of the injected limb accounted for the AEFIs in only a few vaccine recipients. The incidence of severe AEFIs was just above 1% which included one incident of breathlessness, one of hypotension, and one incident of a momentary loss of consciousness. All the three patients were discharged after 24 h of observation without any complication or sequelae. There were no medium/long-term adverse sequelae requiring hospitalization on follow-up up to 4 months through institutional passive surveillance. In recent past certain European countries have reported incidents of thrombosis after receiving ChAdOx1 nCoV-19 vaccine which led to pausing the vaccination campaign in many. However, in our study, no such case of postvaccination thrombosis has been reported.
Our study had few limitations. First, only health-care workers were enrolled in the study as they were the first priority group to receive vaccine as per Government of India policy. Second, we could not record the status of comorbidity and thus could not analyze any association of it with AEFIs. Third, we could carry out active surveillance only up to 72 h after vaccination, although passive surveillance was conducted up to 4 months following the first dose. Nonetheless, in-depth surveillance of a large cohort (approximately 2500) postvaccination with reliable quality data and long-term passive surveillance are unique strengths of our study.
We found that after the ChAdOx1 nCoV-19 vaccination, majority of the recipient had only developed mild-to-moderate AEFIs and there were no long-term complications or mortality. Thus, based on the results, we can conclude that the vaccine has good safety profile and is recommended for use among 18–60 years. Further studies may be undertaken in more than 60 years of age, persons with a history of allergy and comorbidities to further evaluate safety profile among these groups of people.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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