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ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 7  |  Page : 72-76  

Hazards of vaccinating the way out of Covid-19 pandemic: Study of adverse events following immunization (Aefi) in India


Department of Community Medicine, AIIMS Nagpur, Ashok Chowk, Budhha Nagar, Nagpur, Maharashtra, India

Date of Submission18-May-2022
Date of Acceptance20-May-2022
Date of Web Publication25-Jul-2022

Correspondence Address:
Dr. Priti Nandkishor Tiwari
Ashok Chowk, Budhha Nagar, Nagpur, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_428_22

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  Abstract 


Context: The COVID-19 pandemic burdened the healthcare systems and led to unprecedented impact leading to global economic crisis. In India, the vaccines given emergency use authorization for restricted use were Covishield and Covaxin. The majority of the known adverse effects of COVID vaccine were reported to be mild but there are some serious and severe adverse events reported in COVID-19 vaccine trials including deaths. Aim: To make estimates of the adverse events following immunization (AEFI) burden in India based on Vaccine Adverse Effect Reporting System data model from the USA. Settings and Designs: The descriptive study was carried out in March–May 2022. Data were extracted from report of National AEFI Committee, Ministry of Health and Family Welfare (MOHFW), Immunization Division, Government of India. This study made different hypothesis based on assumption of levels of underreporting ranging from 0.1 to 5%. From these hypotheses, projected deaths and those requiring hospitalization because of AEFI were calculated. Results: More than half (51.34%) of adverse events following immunization were classified as coincidental by National AEFI Committee. Actual reported deaths by MOHFW were 387 but estimated deaths may be around 38,700–41,400 or even more. From the total AEFI deaths, 77.78% were labelled as coincidental deaths. A Maximum of 53.82% coincidental death were because of cardiac cause. Conclusion: Deaths reported by MOHFW are likely to represent gross underestimate of the real scenario in India.

Keywords: AEFI, COVID 19, deaths, hospitalization, vaccine


How to cite this article:
Tiwari PN, Kushwaha AS. Hazards of vaccinating the way out of Covid-19 pandemic: Study of adverse events following immunization (Aefi) in India. Med J DY Patil Vidyapeeth 2022;15, Suppl S1:72-6

How to cite this URL:
Tiwari PN, Kushwaha AS. Hazards of vaccinating the way out of Covid-19 pandemic: Study of adverse events following immunization (Aefi) in India. Med J DY Patil Vidyapeeth [serial online] 2022 [cited 2022 Sep 28];15, Suppl S1:72-6. Available from: https://www.mjdrdypv.org/text.asp?2022/15/7/72/351971




  Introduction Top


The COVID-19 pandemic burdened the healthcare systems and led to unprecedented impact leading to global economic crisis.[1] From the initial stage of this pandemic, scientists were focused on either repurposing the existing drugs or developing vaccines against COVID-19.[2] By January 2021, emergency approval was granted to nine vaccines by regulatory authorities in different parts of the globe.[3] The safety data were published for 11 vaccines as interim reports or clinical trial reports.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]

India embarked on an ambitious COVID vaccination drive on 16th January 2021 starting with Health care workers (HCWs). Later it was expanded to other groups. The vaccines given emergency use authorization for restricted use were Covishield and Covaxin.[17] Concern over hazards of mass vaccination were expressed by some scientists in field of public health who advocated targeting only specific high-risk groups.[18] In India as on 10th May 2022, total 1900 million doses had been administered to 867 million population, that is, 62.9% are now fully vaccinated.[19]

Adverse events following immunization (AEFI) can be common and minor, such as fever, local pain, and swelling. It may be severe, such as pain and swelling that spreads beyond the nearest joint or high-grade fever and serious AEFIs conditions requiring hospitalization or leading to death or disability.[20] Unprecedented rapid development of the COVID-19 vaccines followed by their rapid deployment before adequate trials and licensing have posed unique challenges in monitoring vaccine safety and mitigating any potential risks through a robust AEFI Surveillance system.

The majority of the known adverse effects of COVID vaccine were reported to be mild in studies conducted in different regions of world in terms of severity, such as headache, pain at the injection site, muscle pain, and fever.[10],[21] But there are some serious and severe adverse events reported in COVID-19 vaccine trials in Danish population including deaths.[22] Deaths and serious AEFIs because of vaccination in flu vaccines and Rotavirus vaccines have in the past resulted in halting of vaccinations.[23] There is no Voluntary Adverse Event Reporting System (VAERS) in India and thus majority of AEFI go unreported. Very few studies even on minor or serious and severe AEFIs are available from India.[24] Hence, to understand AEFI in India, the data available on the website of Ministry of Health and Family Welfare (MOHFW) were analyzed to assess the quantity and quality of AEFI in India following COVID vaccinations. An attempt has been made to make estimates of the AEFI burden based on VAERS data model from the USA. Recently, Supreme Court of India in their judgement on vaccine mandates by Jacob Puliyel as petitioner advised the government to ensure development of AEFI reporting on the lines of VAERS and ruled against vaccine mandates.[25]


  Materials and Methods Top


The descriptive study was carried out in March–May 2022. Data were extracted from report on Causality assessment result of serious AEFI following COVID-19 vaccination approved by National AEFI Committee, MOHFW, Immunization Division, Government of India.[26] A Total of13 AEFI documents were available. First document was released on 5th March 2021, whereas the most recent on 21st March 2022. According to VAERS in USA, only 5% of adverse events because of vaccination get reported. Such VAERS system does not exist in India. So, different hypothesis have been developed in this study based on assumption of levels of underreporting ranging from 0.1 to 5%. From these hypotheses, projected deaths and those requiring hospitalization because of AEFI were calculated. Another estimate was made based on VAERS model in the United States of America that recorded 23 deaths per million doses among people who received COVID-19 vaccine by 22 February 2022.[27] Assuming similar rates for India, projected deaths have been calculated for 1800 million doses.


  Investigation of AEFI in India Top


All the serious events, cluster AEFI, Suspected immunization error, causes significant parental or public concern, and reactions because of newly introduced vaccine needs to be investigated as per protocol by AEFI Committee.[28]


  Results Top


It was seen that 31.11% participants were greater than the age of 60 years [Table 1]. Requirement of hospitalization following immunization was the most common reason in 64.39% for reporting of AEFI. Whereas the remaining 35.61% were reported because of death. More than half (51.34%) of adverse events following immunization were classified as coincidental by National AEFI Committee. One fifth of all AEFI were vaccine product related [Table 2]. [Table 3] shows distribution of reported AEFI subjects according to reason for death. Cardiac cause was the most common reason for death in 46.51% cases followed by COVID-19 disease in 15.24% and stroke in 9.56%. Other reasons for death included causes, such as anaphylaxis, diabetic ketoacidosis, hypertensive emergency, pneumonia, COPD, sepsis, and multisystem inflammatory syndrome of children. Whereas remaining 3.66% deaths were classified as unexplained. [Table 4] shows that from the total AEFI deaths, 77.78% were labelled as coincidental deaths. To a Maximum, 53.82% coincidental death were because of cardiac cause. About one sixth (17.94%) of deaths were attributed to COVID-19 disease. [Table 5] shows Estimated AEFI from March 2021 to January 2022. Actual reported deaths by MOHFW were 387. But if we consider these reports are only 0.1% of actual, then total deaths projected are 3,87,000 and 38,700 at 1% level of reporting. USA reported 23 deaths per million dose. From this, projected Indian deaths per 1800 million doses are 41,400. A total of 5,600 deaths had been estimated for HCW if we consider 1% of the total reporting. The two figures based on 1% reporting and those at 23 deaths per million deaths are 38,700 and 41,400, respectively are quite comparable.
Table 1: Characteristics of reported AEFI

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Table 2: Classification of AEFI as per causality by national AEFI committee

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Table 3: Distribution of reported AEFI deaths according to cause (n=387)

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Table 4: Characteristics of coincidental AEFI including deaths

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Table 5: Estimated AEFI from March 2021 to January 2022

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  Discussion Top


The national AEFI guidelines provide complete guidance and other details for reporting, investigating, and conducting the causality assessment of cases reported as AEFIs. The AEFI surveillance system has been in place since 1988. AEFI Secretariat was established in 2012 within the MOHFW to strengthen AEFI surveillance in the country.[20] It is very crucial to establish the safety of the COVID-19 vaccines beyond any reasonable doubt when emergency approval is being granted to these vaccines without completion of all phases of clinical trials to large section of population.

In this study, requirement of hospitalization following immunization was the most common reason in 69.89% for reporting of AEFI. Whereas remaining 30.11% were reported because of death. Sudden cardiac death was the most common reason for death in 23.72% participants followed by COVID-19 disease in 18.25%, acute myocardial infarction in 10.95%, stroke in 09.49%, and acute coronary syndrome in 09.12%. Hannah G Rosenblum et al.[29] reported that from total AEFI, 92.1% were non-serious, 6.6% were serious, and 1.3% were deaths. Serious adverse events detected in VAERS and Vaccine Safety Datalink surveillance reported anaphylaxis, thrombosis with thrombocytopenia syndrome, myocarditis, and Guillain-Barré syndrome.[30],[31],[32],[33],[34]


  Limitations of the Study Top


The population profile and vaccines used in India and USA are different and the AEFI may also be qualitatively different in both scenarios. The data on only serious AEFI available on MOHFW website also restricts the scope of the findings and hides the true burden of AEFI. Most HCWs are not ready to label serious AEFI because of a belief that these vaccines are safe. Many deaths that occurred as a result of COVID infection in vaccinated group that are equally at risk to get infected would be discounted with no causality attributed to them because of vaccine. Those serious AEFI that occur after a long gap from vaccination may be labelled as not because of vaccine. Because mass roll out of vaccine was done, availability of control group further limits the scope for assessing the true burden of AEFI through case–control studies or cohort studies.


  Conclusion and Recommendations Top


A large proportion of AEFI, that is, 51.34% were classified as coincidental by National AEFI Committee. Actual reported deaths by MOHFW were 387 but estimated deaths may be around 38,700–41,400 or even more. An efficient platform for self-reporting such as VAERS should have been established before mass roll of COVID vaccines. There is a need for transparency and independence for causality assessment system so that decisions may be made rationally. There is a need for strengthening the methods of causality assessment and defining limits when vaccination may need to be halted on occurrence of serious AEFI. Mechanism for long-term AEFI and rare adverse events should be investigated before mass use especially in vulnerable groups, such as children, pregnant females, and immune compromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organisation: COVID-19 vaccines: safety surveillance manual. Available from: https://www.who.int/vaccine_safety/committee/Module_Regulatory_reliance.pdf?ua=1. [Last accessed on 2022 Mar 23].  Back to cited text no. 1
    
2.
World Health Organisation: WHO coronavirus disease (COVID-19) dashboard. Available from: https://covid19.who.int/. [Last accessed on 2021 Jan 28].  Back to cited text no. 2
    
3.
Craven J. RAPS: COVID-19 vaccine tracker. Available from: https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19vaccinetracker. [Last accessed on 2022 Apr 20].  Back to cited text no. 3
    
4.
Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. Lancet Infect Dis 2021;21:950-961. Epub 2021 Mar 8.  Back to cited text no. 4
    
5.
Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, 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.  Back to cited text no. 5
    
6.
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA vaccine against SARS-CoV-2—preliminary report. New Engl J Med 2020;383:1920-31.  Back to cited text no. 6
    
7.
Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike proteinnanoparticle vaccine. New Engl J Med 2020;383:2320-32.  Back to cited text no. 7
    
8.
Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime boost COVID-19 vaccine in two formulations: Two open, nonrandomised phase 1/2 studies from Russia. Lancet 2020;396:887-97.  Back to cited text no. 8
    
9.
Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 2020;586:589-93.  Back to cited text no. 9
    
10.
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New Engl J Med 2020;383:2603-15.  Back to cited text no. 10
    
11.
Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, de Groot AM, et al. Interim results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 vaccine. N Engl J Med 2021;384:1824-35. Epub 2021 Jan 13.  Back to cited text no. 11
    
12.
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111.  Back to cited text no. 12
    
13.
Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: Interim analysis of 2 randomized clinical trials. JAMA 2020;324:951-60.  Back to cited text no. 13
    
14.
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: A randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis 2021;21:39-51.  Back to cited text no. 14
    
15.
Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: A randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2020. doi: 10.1016/s1473-3099 (20) 30843-44.  Back to cited text no. 15
    
16.
Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. 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.  Back to cited text no. 16
    
17.
Juyal D, Pal S, Thaledi S, Pandey HC. COVID19: The vaccination drive in India and the Peltzman effect. J Family Med Prim Care 2021;10:3945-7.  Back to cited text no. 17
  [Full text]  
18.
Kushwaha A, Banerjee S. Vaccination in controlling COVID pandemic in India: A SWOT analysis. Med J DY Patil Vidyapeeth 2022;15:20-24.  Back to cited text no. 18
  [Full text]  
19.
20.
Adverse Events Following Immunization: Surveillance and response operational guidelines, MOHFW, 2015. Available from: http://itsu.org.in/repository-resources/AEFI-Surveillanceand-Response-Operational-Guidelines-2015.pdf. [Last Accessed on 2022 May 05].  Back to cited text no. 20
    
21.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-16.  Back to cited text no. 21
    
22.
Østergaard SD, Schmidt M, Horváth-Puhó E, Thomsen RW, Sørensen HT. Thromboembolism and the Oxford-AstraZeneca COVID-19 vaccine: Side-effect or coincidence? Lancet 2021;397:1441-3.  Back to cited text no. 22
    
23.
Hampton LM, Aggarwal R, Evans SJ, Law B. General determination of causation between Covid-19 vaccines and possible adverse events. Vaccine 2020;39:1478-80.  Back to cited text no. 23
    
24.
Jeon M, Kim J, Oh CE, Lee JY. Adverse events following immunization associated with coronavirus disease 2019 vaccination reported in the mobile vaccine adverse events reporting system. J Korean Med Sci 2021;36:1-8.  Back to cited text no. 24
    
25.
Jacob Puliyel Petitioner; Versus Union of India and Others. Available from: https://www.scconline.com/blog/post/2022/05/04/covid-19-forced-vaccination-immunisation-privacy-right-bodily-integrity-supreme-court-judgments-legal-news-research-updates-law/. [Last accessed on 2022 Jun 06].   Back to cited text no. 25
    
26.
Government of India Ministry of Health & Family Welfare Immunization Division. Available from: https://main.mohfw.gov.in/Organisation/Departments-of-Health-and-Family-Welfare/immunization/aefi-reports.  Back to cited text no. 26
    
27.
Reported adverse events. Centers for Disease Control and Prevention. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html. [Lastaccessed on 2022 Mar 15].  Back to cited text no. 27
    
28.
Causality assessment of an adverse event following immunization (AEFI). User manual for the revised WHO classification. Available from: https://apps.who.int/iris/bitstream/handle/10665/259959/9789241513654-eng.pdf?sequence=1&isAllowed=y.  Back to cited text no. 28
    
29.
Rosenblum HG, Gee J, Liu R, Marquez PL, Zhang B, Strid P, et al. Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme: An observational study of reports to the Vaccine adverse event reporting system and v-safe. Lancet Infect Dis 2022;3099:1-11.  Back to cited text no. 29
    
30.
Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, et al. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA 2021;326:1390-99.  Back to cited text no. 30
    
31.
US Centres for Disease Control and Prevention. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine—United States, December 14–23, 2020. MMWR Morb Mortal Wkly Rep 2021;70:46-51.  Back to cited text no. 31
    
32.
MacNeil JR, Su JR, Broder KR, Guh AY, Gargano JW, Wallace M, et al. Updated recommendations from the advisory committee on immunization practices for use of the Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—United States, April 2021. MMWR Morb Mortal Wkly Rep 2021;70:651-56.  Back to cited text no. 32
    
33.
Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, et al. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: Update from the advisory committee on immunization practices—United States, June 2021. MMWR Morb Mortal Wkly Rep 2021;70:977-82.  Back to cited text no. 33
    
34.
Rosenblum HG, Hadler SC, Moulia D, Shimabukuro TT, Su JR, Tepper NK, et al. Use of COVID-19 vaccines after reports of adverse events among adult recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna): Update from the advisory committee on immunization practices—United States, July 2021. MMWR Morb Mortal Wkly Rep 2021;70:1094-99.  Back to cited text no. 34
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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