key: cord-0971365-cw9kjb4l authors: Arora, Geetika; Taneja, Jyoti; Bhardwaj, Priya; Goyal, Shorya; Naidu, Kumar; Yadav, Sunita. K.; Saluja, Daman; Jetly, Sunita title: Adverse events and breakthrough infections associated with COVID‐19 vaccination in the Indian population date: 2022-03-21 journal: J Med Virol DOI: 10.1002/jmv.27708 sha: b4df4ee2782b3b58296df0191f8abb3e4c3b2c1a doc_id: 971365 cord_uid: cw9kjb4l Vaccines against COVID‐19 provide immunity to deter severe morbidities associated with the infection. However, it does not prevent infection altogether in all exposed individuals. Furthermore, emerging variants of SARS‐CoV‐2 impose a threat concerning the competency of the vaccines in combating the infection. This study aims to determine the variability in adverse events and the extent of breakthrough infections in the Indian population. A retrospective study was conducted using a pre‐validated questionnaire encompassing social, demographic, general health, the status of SARS‐CoV‐2 infection, vaccination, associated adverse events, and breakthrough infections in the Indian population. Informed consent and ethical approval were obtained as per Indian Council of Medical Research (ICMR) guidelines. Participants, who provided the complete information, were Indian citizens, above 18 years, and if vaccinated, administered with either Covishield or Covaxin, were considered for the study. Data have been compiled in Microsoft Excel and analyzed for statistical differences using STATA 11. The responses from 2051 individuals fulfilling the inclusion criteria were analyzed. Among 2051, 1119 respondents were vaccinated and 932 respondents were non‐vaccinated. Among 1119 vaccinated respondents, 7 were excluded because of missing data. Therefore, out of 1112 vaccinated, 413 experienced adverse events with a major fraction of younger individuals, age 18–40 years, getting affected (74.82%; 309/413). Furthermore, considerably more females than males encountered adverse consequences to vaccination (p < 0.05). Among vaccinated participants, breakthrough infections were observed in 7.91% (88/1112; 57.96% males and 42.04% females) with the older age group, 61 years and above (odds ratio, 3.25 [1.32–8.03]; p = 0.011), and males were found to be at higher risk. Further research is needed to find the age and sex‐related factors in determining vaccine effectiveness and adverse events. Ad26.COV2.S (August 2021). All these vaccines were rolled out to be given in two doses for optimum efficacy except Janssen's Ad26.-COV2.S and ZyCov-D that required one and three doses, respectively. [2] [3] [4] Only Covishield and Covaxin were rolled out in India by the time the current study was conducted. The efficacy of Covishield was found to be around 93%, after both the doses, based on the VIN-WIN cohort study carried out on over 1.59 million healthcare and frontline workers of the Indian Armed Forces. 5 Kulkarni et al. 6 reported that SII-ChAdOx1 nCoV-19 has a good safety profile and is highly immunogenic in the adult Indian population in comparison to AZD122. Desai et al. 7 showed 50% efficacy of two doses of BBV152 Collectively responses of 2064 participants were registered in the period spanning May 2021 to August 2021. The study was aimed to estimate the adverse events and breakthrough infections in vaccinated individuals and to draw comparisons on the basis of gender, age-groups, and status of comorbidities. A questionnaire was designed and pre-validated in two steps, first by following a pilot study using 200 volunteers, modified based on the inputs, and again 50 volunteers belonging to research and healthcare workers were recruited to validate the questionnaire. This validated questionnaire (see Supporting Information) was approved by the Institutional ethics committee (ACBR/IHEC/DS-09/08-2021) and was used to conduct the retrospective study. The survey was administered to subjects of India and above the age of 18 years with informed consent. In addition, the snowball sampling approach was utilized to increase the number of responses to the online survey. The Google survey form link was sent through WhatsApp, Facebook, emails, and other social media to the college students and colleagues of the authors and coauthors, friends, family members, and relatives. Further, they were requested to roll out the online questionnaire to as many people as possible ensuring randomization. The data collected was a mix of nonvaccinated and partially or fully vaccinated individuals. People who participated in the survey were requested to fill in the honest and appropriate information to the best of their knowledge and understanding. The study has no hidden or apparent agenda of intruding into participants' personal space and our objectives are strictly academic and research-oriented. People were given free will whether they want to choose to participate or not and no incentives were given for participation. The identity of the participants was kept hidden and only one reply per participant was accepted. Descriptive analyses were used for sociodemographic and categorical data. Multivariate logistic regression analysis was performed to find the correlation of adverse events and of breakthrough infections with sex, age, body mass index (BMI), and comorbidities. Chi-square and Fisher's exact tests were performed to obtain the p value to determine the significance by more than two authors independently. F I G U R E 2 100% stacked bar of the vaccination status of participants belonging to various age groups. Different colors in one bar represent the fraction of vaccinated and nonvaccinated respondents belonging to that age group 18-40, 41-60, and 61 years and above, respectively, who developed adverse events after vaccination (Figure 3 ). Furthermore, the younger age group of 18-40 years, as well as the female sex were found to be more positively correlated with adverse events associated with the vaccinations concerned (Table 2) . However, we found no correlation between comorbidity, BMI, and the occurrence of adverse events. (37/88) were of age group 41-60 years, and only 13.63% (12/88) belonged to the age group 61 years and above. Notably, when we performed multivariate regression analysis, the older age group (61 years and above) and males were found to be at higher risk of acquiring breakthrough infections (Table 3) . However, we found no link between comorbidity, BMI, and breakthrough infections. genes are located at sites on the X-chromosomes that are able to skip the process of X-chromosome inactivation. By the virtue of two X chromosomes contributing to the pool of ACE-2 enzyme, this becomes another reason why females have higher expression of ACE-2 and thus, higher protection against the ongoing pandemic than males. [20] [21] [22] Female physiology, hormones, and genes have certainly helped them survive better in the pandemic but the role of behavioral response seems to also contribute. 23 A study conducted in Spain highlights that women showed higher compliance with the safety measures, washed hands regularly, maintained physical distance in public, and cared more to wear masks and hence, steer clear of the infection. 24 As reported, we also found a conspicuous difference in the fraction of males and females who developed adverse events after receiving the vaccine against COVID-19. 25 Zydus Receives EUA from DCGI for ZyCoV-D, the Only Needle-free COVID Vaccine in the World Press Statement by the Drugs Controller General of India (DCGI) on Restricted Emergency Approval of COVID-19 Virus Vaccine COVISHIELD (AZD1222) VaccINe effectiveness among healthcare and frontline Workers of INdian Armed Forces: interim results of VIN-WIN cohort study A phase 2/3, participant-blind, observer-blind, randomised, controlled study to assess the safety and immunogenicity of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine) in adults in India Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility ChAdOx1 nCoV-19 effectiveness during an unprecedented surge in SARS COV-2 infections Occurrence of COVID-19 in priority groups receiving ChAdOx1 nCoV-19 coronavirus vaccine (recombinant): a preliminary analysis from North India Transmission event of SARS-CoV-2 delta variant reveals multiple vaccine breakthrough infections COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study Severe SARS-CoV-2 breakthrough reinfection with delta variant after recovery from breakthrough infection by alpha variant in a fully vaccinated health worker Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19 SARS and MERS: recent insights into emerging coronaviruses Age-related morbidity and mortality among patients with COVID-19 Should ACE2 be given a chance in COVID-19 therapeutics: a semi-systematic review of strategies enhancing ACE2 Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men Age-and gender-related difference of ACE2 expression in rat lung Coronavirus: why men are more vulnerable to Covid-19 than women? ACE2 expression and sex disparity in COVID-19 Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection How sex and age affect immune responses, susceptibility to infections, and response to vaccination A prospective observational safety study on ChAdOx1 nCoV-19 coronavirus vaccine (recombinant) use in healthcare workers-first results from India Sex and Gender and COVID-19 Vaccine Side Effects Yale School of Medicine Biological sex affects vaccine efficacy and protection against influenza in mice Sex differences in immune responses Changes in the immune system during menopause and aging Vaccination in the elderly: the challenge of immune changes with aging Tavares Da Silva f. The how's and what's of vaccine reactogenicity Adverse events and breakthrough infections associated with COVID-19 vaccination in the Indian population The authors would like to acknowledge all the participants and volunteers for collecting offline data from door to door. The authors thank Prof. Ravi Toteja (Principal, Acharya Narendra Dev College, University of Delhi) and Prof. Savita Roy (Principal, Daulat Ram College, University of Delhi) for their logistic support and cooperation. The authors would like to thank ICMR for providing fellowship to GA. The authors declare no conflict of interest. The present study has been approved by the Institutional Human The raw data will be provided on request.