Long-Term Safety Analysis of the ChAdOx1-nCoV-19 Corona Virus Vaccine: Results from a Prospective Observational Study in Priority Vaccinated Groups in North India.

INTRODUCTION: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. There is a scarcity of long-term safety data for many of these. OBJECTIVE: The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine and determine the risk factors of adverse events of special interest (AESIs) and persistent AESIs. METHODS: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital in North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Atypical adverse events developing after a booster dose of the COVID-19 vaccine were assessed. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of AESIs persisting for at least one month at the time of final telephonic contact. RESULTS: Of 1650 individuals enrolled, 1520 could be assessed at one-year post-vaccination. COVID-19 occurred in 44.1% of participants. Dengue occurred in 8% of participants. The majority of the AESIs belonged to the MedDRA® SOC of musculoskeletal disorders (3.7% of 1520). Arthropathy (knee joint involvement) was the most common individual AESI (1.7%). Endocrinal disorders such as thyroid abnormalities and metabolic disorders such as newly diagnosed diabetes developed in 0.4% and 0.3% of individuals, respectively. Regression analysis showed females, individuals with a pre-vaccination history of COVID-19, diabetes, hypothyroidism, and arthropathy had 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were at 1.66- and 2.23-times higher risk of persistent AESIs. Individuals receiving the vaccine after COVID-19 were at 2.85- and 1.94 times higher risk of persistent AESIs compared, respectively, to individuals with no history of COVID-19 and individuals developing COVID-19 after the vaccine. Among participants receiving a booster dose of the COVID-19 vaccine (n = 185), 9.7% developed atypical adverse events of which urticaria and new-onset arthropathy were common. CONCLUSION: Nearly half of the ChAdOx1-nCoV-19 vaccine recipients developed COVID-19 over one year. Vigilance is warranted for AESIs such as musculoskeletal disorders. Females, individuals with hypothyroidism, diabetes, and pre-vaccination history of COVID-19 are at higher risk of adverse events. Vaccines received after natural SARS-CoV-2 infection may increase the risk of persistence of adverse events. Sex and endocrinal differences and timing of the COVID-19 vaccine with respect to natural infection should be explored as determinants of AESIs in the future. Pathogenetic mechanisms of vaccine-related adverse events should be investigated along with comparisons with an unvaccinated arm to delineate the overall safety profile of COVID-19 vaccines.

Determinants of COVID-19 Breakthrough Infections and Severity in ChAdOx1 nCoV-19-Vaccinated Priority Groups.

The current analysis is a part of an ongoing observational study that began in February 2021 in the Sir Sunder Lal Hospital (Varanasi, Uttar Pradesh) in northern India and is expected to continue until June 2022. This analysis aimed to delineate the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The study enrolled health-care workers and the elderly receiving the COVID-19 vaccine at one of three centers linked to the study hospital. The participants received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine based on the chimpanzee adenovirus platform (manufactured in India by the Serum Institute of India). The adenovirus codes for the spike (S) protein of SARS-CoV-2. Participants were contacted by phone at pre-decided intervals and questioned about the occurrence of COVID-19, clinical presentation, severity, and persistence of symptoms. A logistic regression analysis was performed to predict the risk factors of occurrence and severity of COVID-19. Of the 1,500 participants included in the analysis, 418 developed COVID-19 (27.9%). Fever was the most common symptom (72%), followed by cough (34%) and rhinitis (26%). Cardiovascular involvement was seen in more than 2% of individuals, and 11% had post-COVID-19 complaints. Regression analysis showed 1.6 times greater odds of contracting the disease in females and in those younger than 40 years, 1.4 times greater odds in individuals who were overweight, and 2.9 times greater odds in those receiving only one dose, compared with respective comparators. Individuals receiving two doses at a gap of ≤ 30 days had 6.7 times greater odds of infection than those receiving at a > 60-day interval. There was no association between COVID-19 occurrence in the vaccinees and pre-vaccination history of SARS-CoV-2 infection. Males were at a 3.6 times greater risk, and persons with preexisting lung disease-mainly asthma-had a 5.9 times greater risk of experiencing moderate to severe COVID-19 than comparators. While an extended interval between the two vaccine doses seems to be a better strategy, gender differences and an association of asthma phenotypes with COVID-19 need to be explored.

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. 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 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-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 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.

Transformation in culinary behaviour during the COVID-19 pandemic: In-depth interviews with food gatekeepers in urban India.

COVID-19 and its associated regulatory measures including lockdowns, curfews, and physical distancing norms have significantly affected individual's dietary and culinary behaviours. Although there is ample empirical evidence available on dietary changes within the Indian context, very limited evidence exists about the factors influencing these dietary modifications and changes in culinary behaviours during COVID-19 lockdown. Therefore, the aim of this qualitative study was to explore the views of Indian household food gatekeepers towards meal planning, food purchasing, and meal preparation during the pandemic and its associated lockdowns. A convenience sample of 34 female gatekeepers from the Mumbai metropolis participated in online interviews. Interviews were conducted in English and Hindi (then translated in English), audio-recorded and transcribed verbatim. Underpinned by Template Analysis technique, transcribed data were analysed manually and using the NVivo software program. The interview structure guided the development of themes. The emerging themes included were: Increased household cooking; Involvement of children and male members in food-related activities; Experimentation in the kitchen; Adoption of meal planning skills; Increase in online food shopping; Bulk buying; Shortage of food items; Reduced consumption of outside home food; Increased variety of home-cooked meals; Increase in snacking and overall food intake; Determinants of food choices; and Family meals-a new norm. In the light of these findings, developing family-focussed, web-based nutrition programs to enhance gatekeepers' and their families' food literacy including declarative and procedural nutritional knowledge would be beneficial. The importance of organisational culinary behaviours such as planning meals in advance, shopping with a food list should be promoted to prevent hoarding and subsequently reduce strain on the food supply system. With a surge in domestic cooking, low cost nutritious recipes with the use of local and seasonal produce should be emphasized promoting healthy eating among the gatekeepers and their family members. The inclusion of food studies in the school curriculum will facilitate the development of culinary skills among children and youth. Also, there is a need for further research and surveillance to strengthen understanding of sustainability of healthy culinary behaviours practiced during the pandemic.

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

The ChAdOx1 nCoV-19 vaccine (Oxford University-Astra Zeneca) has demonstrated nearly 70% efficacy against symptomatic COVID-19 in trials and some real-world studies. The vaccine was the first to be approved in India in early January 2021 and is manufactured by the Serum Institute of India. Favorable short-term safety data of the vaccine in India in a real-world setting has been recently demonstrated. Here, we report secondary objective (COVID-19 occurrence) measures of the same ongoing prospective observational study in prioritized recipients of the vaccine. The findings are based on participants who could complete at least 2 months of follow-up (n = 1500; female/male: 472/1028; mean age: 38.8 years). Laboratory confirmed SARS-CoV-2 infection was observed in 27/65 participants (41%) who received a single dose and 271/1435 (19%) who received both doses. Specifically, among doctors, 18/27 (66.7%) one dose recipients and 131/377 (34.7%) fully vaccinated developed SARS-CoV-2 infection. The majority of the cases were mild in all groups, and most were breakthrough infections. The occurrence of "severe" COVID-19 was 7.7 times lower (0.4%) in fully vaccinated participants compared to partially vaccinated (3.1%). Four deaths were observed in the study. One of the four deaths was due to sepsis, two due to unspecified cardiac events, and one due to unspecified post-COVID-19 complications. The results of this preliminary analysis necessitate vigorous research on the performance of vaccines against variants, optimal timing of vaccination, 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.

BACKGROUND: We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India. METHODS: This continuing prospective observational study (February 2021 to May 2022) enrolled participants ≥18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed. FINDINGS: We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism. INTERPRETATION: COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings. FUNDING: No funding support.