A prospective observational study on BBV152 coronavirus vaccine use in adolescents and comparison with adults- first real-world safety analysis (preprint)

Background The BBV152 COVID-19 vaccine (COVAXIN) has recently been approved for adolescents. We provide the first real world safety data of COVAXIN use in adolescents and compare this with adults. Methods A prospective observational study is being conducted since January 2022. Enrolled adolescents and adults were contacted telephonically after 14 days of receiving the BBV152 vaccine. Primary outcome was vaccine safety assessed as rates of adverse events following immunization (AEFI). Severity grading of AEFIs was done using the FDA scale. Findings A total of 698 adolescents and 326 adults were enrolled. AEFIs occurred in 36.3% adolescents after first and in 37.9% after second dose. Systemic involvement was seen in 15-17% adolescents. Injection site pain and fever were the common AEFIs. Majority of AEFIs were mild-moderate. Severe and atypical AEFIs were observed in 0.9% and 0.6% adolescents respectively. Majority of AEFIs recovered in 1-2 days. In >2% adolescents, AEFIs were persisting at 14-day follow-up since the second dose. No difference in AEFI incidence and patterns was observed between adolescents and adults. Regression analysis showed females and those with history of allergy to be respectively at 1.5-times and 3-times increased risk of AEFIs among adolescents. Interpretation COVAXIN carries an overall favorable short term safety profile in adolescents. The observed AEFI rates in adolescents are much lower than that reported with mRNA vaccines. Female adolescents and those with history of allergy need watchfulness. With some AEFIs persisting at 14 days, a longer follow-up is recommended to strengthen the safety data of these vaccines. Funding No funding support

Persistent health issues, adverse events of significant concern, and effectiveness of COVID-19 vaccination- findings from a real-world cohort study of healthcare workers in north India (preprint)

Background: There is paucity of real-world data on COVID-19 vaccine effectiveness and safety from cohort designs. The current study aimed to evaluate vaccine performance during second wave in India. It also aimed to determine adverse events of significant concern (AESCs), and to ascertain the effect of vaccination on persistent health issues in individuals post COVID-19. Methods: A cohort study was conducted from July-2021 to December-2021 in a tertiary hospital of north India. The primary outcome was vaccine-effectiveness against COVID-19. Secondary outcomes were AESCs, and persistent health issues in those receiving vaccine. Regression analyses were performed to determine risk factors. Results: In 2760 healthcare workers (HCWs) included, 1033 COVID-19 events were reported. Around 6-17% vaccine effectiveness was observed against COVID-19 occurrence. One dose-recipients were at 1.6-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.5-times increased risk of moderate-severe COVID-19. AESCs were observed in 1.3% including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times and those receiving vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusion: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. Relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. Independent protection of prior SARS-CoV-2 infection was high and persistent health issues were common in individuals receiving vaccine post COVID-19. Recommendations of vaccinating those recovered from COVID-19 need further studies.

Patterns and predictors of COVID-19 occurrence and severity in vaccinated priority groups (preprint)

Background: Varying protection rates have been observed with approved COVID-19 vaccines post-approval, in various real-world studies. However, little data exists on the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The aim of the present study is to describe the patterns of presentation of COVID-19 in vaccinated individuals, and to determine the predictors of occurrence of COVID-19 and the predictors of severity in the vaccinated. Methods: : The study is a part of a prospective observational study ongoing since February 2021 in a tertiary teaching and research hospital of northern India. Individuals recruited in this study belong to a high-risk group comprising health care workers and elderly. COVISHIELD, based on ChAdOx1 nCoV-19 platform was the vaccine received by the participants based on policy on allocation.Primary outcomes of the study are the short term and long-term adverse events following immunization (AEFI) with COVID-19 vaccines. Secondary outcomes include the rates of occurrence of COVID-19 and severity of COVID-19. Data on these have been already reported. The clinical presentation, typical and atypical manifestations, time to symptomatic recovery and patterns of post-COVID-19 complaints were analysed in the current study. Logistic regression analysis was performed to predict the risk factors of occurrence of COVID-19 in the vaccinated and the determinants of severe forms of the disease in this group. Findings: 1500 individuals completed at least two month follow up. Of these, 418 developed laboratory confirmed or suspected COVID-19. Fever was the commonest symptom (72%), followed by features of rhinitis (41%) and cough (34%). Nearly 12% individuals had only one symptom or none. Cardiovascular involvement was seen in more than 2% of affected. Time to symptomatic recovery varied from 1-75 days and 11% had post COVID-19 complaints at two month follow up, most common being generalized weakness. Results of regression analysis showed 1.6 times higher odds of contracting the disease in females and young individuals < 40 years of age (P<0.001). Overweight individuals and those receiving only one dose were at 1.4 times and 3 times higher odds of contracting COVID-19 compared to those with normal body mass index and those who were fully vaccinated. Individuals receiving two doses at a gap of < 30 days were at 7 times higher odds of disease acquisition compared to those receiving the second dose at an extended gap of > 60 days (P=0.01).With respect to severity, males and those receiving only one dose each had 3 times higher odds of suffering from moderate to severe COVID-19 compared to females and fully vaccinated. Persons with pre-existing lung disease, such as asthma had 6 times higher odds of suffering from moderate to severe COVID-19 (P=0.024). No association with the occurrence or severity of disease was observed with any other co-morbidity or the use of renin-angiotensin-aldosterone system (RAAS) blockers. Interpretation Sex wise differences exist with respect to occurrence and severity of COVID-19. Two doses of vaccine, compared to one dose provide considerable protection against occurrence as well as severity. Full vaccination with extended dosing interval should be the optimal strategy and should be carried out when the community burden of cases is negligible. Future studies are needed to explore the sex wise differences in the propensity and severity of COVID-19. Further, the risk association of asthma phenotypes with COVID-19 needs to be investigated. Funding: The study received no funding support

Occurrence of COVID-19 in priority groups receiving ChAdOx1 nCoV-19 coronavirus vaccine (recombinant): a preliminary analysis from north India (preprint)

Background: In randomized controlled settings, vaccine efficacy close to 70% against symptomatic COVID-19 has been demonstrated by the ChAdOx1 nCoV-19 vaccine which is a recombinant chimpanzee adenovirus based vaccine expressing the SARS-CoV-2 spike protein. Post approval studies are however necessary to validate the findings in the real world.Methods: A prospective observational study is being conducted in a tertiary hospital of north India since 5th February 2021 with the primary objective of determining safety of COVID-19 vaccines and the secondary objective of assessing the rate of occurrence of COVID-19 in vaccinated group. High risk group comprising health care workers, other frontline workers (police, sanitary workers etc) and elderly citizens who were initially focus groups for vaccine roll-out in India, were enrolled in the study. The study included all vaccine recipients who provided consent and were enrolled at the time of receiving the first or second dose of COVISHIELD vaccine, and followed up telephonically.Results: Among 1650 enrolled vaccine recipients, 1500 participants of the study (Female/Male: 472/1028; mean age 38.8 years) completed at least 2 months of follow-up, after the second dose. The common comorbidities in study participants were hypertension (170, 11.3%), diabetes (142, 9.5%), and hypothyroidism (54, 3.6%). Of those who received a single dose of vaccine (n=65), laboratory confirmed SARS-CoV-2 infection was observed in 27 individuals (41.5%) and 3 were suspects. Severity wise, infections were mild in 21 out of 30 (70%) cases, moderate in five (16.7%) and severe in two (6.7%). Of those who received both doses of vaccine (n=1435), 388 were diagnosed as confirmed or suspect cases of SARS-CoV-2 infection. Of these 388, RT-PCR positivity was seen in 271 (18.9%) individuals, 82 (5.7%) were labelled as ‘suspects’ and 35 (2.4%) were RT-PCR negative suspects. Severity wise, majority of SARS-CoV-2 infections were ‘mild’ (331/388, 85.3%), followed by ‘moderate’ (33/388, 8.5%) and ‘severe’ (6/388, 1.5%). 404 out of the 1500 total participants were doctors including consultant/teaching faculty, resident doctors, and those in general practice. Among the 377 doctors who received both doses of vaccine, 160 were diagnosed as confirmed or suspect cases of SARS-CoV-2 infection. Of these, 131 (34.7%), 17 (4.5%) and 12 (3.2%) were laboratory confirmed cases, ‘suspects’ and RT-PCR negative suspects respectively. The infection was asymptomatic, ‘mild’, ‘moderate’ and ‘severe’ in 9 (5.6%), 130 (81.3%), 16 (10%) and 5 (3.1%) respectively. Breakthrough infections occurring at > 14 days after receiving the second dose were seen in 148 doctors who received both doses (39.2%), or 119 doctors (31.6%) if only laboratory confirmed cases were considered. Four deaths occurred in the study participants during the study period, two in partially vaccinated group and two in fully vaccinated group. Two of these participants, both in partially vaccinated group had developed SARS-CoV-2 infection during their follow-up.Conclusion: The disproportionately high occurrence of SARS-CoV-2 infection and COVID-19 in priority vaccinated groups in our study can be explained to some extent by the existence of variants such as the delta which might have escaped the vaccine generated immune protection. Despite the high incidence, the severity of COVID-19 was observed to be low. Since the ongoing study was primarily focused on adverse events following immunization (AEFIs) and enrolled only vaccinated individuals, the secondary outcome results lack a control unvaccinated group. However, the result of this preliminary analysis necessitates vigorous research on the performance of vaccines against variants, optimal timing of vaccination, need for boosters, and also optimal timings of effectiveness studies to guide future vaccination policy.

A prospective observational safety study on ChAdOx1 nCoV- 19 corona virus vaccine (recombinant) use in healthcare workers- first results from India (preprint)

Vaccines are an important public health measure for tiding over the COVID-19 pandemic. Several vaccines have been approved in different countries for emergency use. In India, two vaccines have been currently approved- COVISHIELD (Serum Institute of India (SII)) which is a recombinant simian adenovirus-based vaccine and COVAXIN (Bharat Biotech) which is an inactivated SARS-CoV-2 vaccine. Our current study provides the first post approval safety data on ChAdOx1 nCoV- 19 corona virus vaccine (recombinant) use in healthcare workers in northern India (n=804). Around one half of vaccinees developed adverse events at any time post vaccination with majority of reactions being mild to moderate in severity. AEFIs were seen in 40% participants after first dose and around 16% participants after second dose. This observed reactogenicity is much less compared to 60-88% reactogenicity rate observed with Oxford-AstraZenecas ChAdOx1 vaccine in the UK based population. Individually, fever, injection site pain and headache were the commonly observed AEFIs. Overall, the frequency of systemic events of severity grade 3 was only 0.5% and is much less than the reported rates for other recombinant adenoviral vaccines. The rate of serious AEFIs in our study was only 0.1% (n=1). There was a possibility of this AEFI being an immunization stress related response. No deaths were reported in the vaccinees in our study during the study period. Reactogenicity rate was observed to decrease with age and was higher in females. On the basis of interim findings of this safety study, it may be interpreted that the ChAdOx1 nCoV-19 corona virus vaccine (recombinant) (COVISHIELD, Serum Institute of India) carries a good safety profile overall.