|Year : 2022 | Volume
| Issue : 1 | Page : 101-108
Covishield™ (ChAdOx1) vaccine effectiveness and epidemiological risk factors of COVID-19 infection among frontline workers during second wave of COVID-19 pandemic, New Delhi: A case–control study
Kiran Kumar Maramraj, Sougat Ray, Kaushik Roy, Ajit Gopinath, Sudeep Naidu, Naveen Chawla
Department of Health Services, O/o Directorate General Medical Services (Navy), Government of India, New Delhi, India
|Date of Submission||28-Oct-2021|
|Date of Decision||21-Nov-2021|
|Date of Acceptance||29-Nov-2021|
|Date of Web Publication||26-Mar-2022|
Surg Capt (Dr) Kiran Kumar Maramraj
Department of Health Services, O/o Directorate General Medical Services (Navy), Government of India, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Frontline workers were the first cohorts vaccinated with Covishield™ (ChAdOx1 nCoV-19) vaccine with dose-interval of 4–6 weeks. We evaluated vaccine effectiveness (VE) of Covishield and studied epidemiological risk factors associated with COVID-19 during second wave of COVID-19 pandemic. Methods: We conducted a 1:3 case-control community-based study, as per WHO protocol. We identified case-patients from COVID-19 surveillance system and recruited controls from the same community as per the WHO protocol. Information was obtained through questionnaire; and all potential confounders were identified to evaluate VE. Results: We enrolled 243 case-patients and 712 controls. Adjusted VE of fully vaccinated was 74% (95% confidence interval [CI]: 53%–86%) against infection and 91% (95% CI: 78%–97%) against moderately severe disease. Pre-infection high-risk exposure events such as ccontact with COVID-19-positive patient, visit to a crowded place, and attending social-gathering in confined space were significantly associated with contracting infection, with odds ratios 10.1 (95% CI: 5.6–18.3), 6.0 (95% CI: 1.8–20.2) and 3.9 (95% CI: 1.4–10.5) respectively. The use of double-mask and past COVID-19 infection was 60% and 70% protective, respectively. Conclusion: Covishield vaccine is highly effective against infection and mainly against disease-severity during high-transmission settings. We recommend three-layer shield to minimize breakthrough and re-infections comprising of vaccination, double-masking, and avoiding “pre-infection high-risk exposure events.”
Keywords: COVID-19, Covishield, frontline worker, vaccine effectiveness
|How to cite this article:|
Maramraj KK, Ray S, Roy K, Gopinath A, Naidu S, Chawla N. Covishield™ (ChAdOx1) vaccine effectiveness and epidemiological risk factors of COVID-19 infection among frontline workers during second wave of COVID-19 pandemic, New Delhi: A case–control study. J Mar Med Soc 2022;24:101-8
|How to cite this URL:|
Maramraj KK, Ray S, Roy K, Gopinath A, Naidu S, Chawla N. Covishield™ (ChAdOx1) vaccine effectiveness and epidemiological risk factors of COVID-19 infection among frontline workers during second wave of COVID-19 pandemic, New Delhi: A case–control study. J Mar Med Soc [serial online] 2022 [cited 2022 Jul 4];24:101-8. Available from: https://www.marinemedicalsociety.in/text.asp?2022/24/1/101/339532
| Introduction|| |
Covishield™ is a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein (ChAdOx1 nCoV-19 Coronavirus vaccine/AZD1222). It is the Indian version of Oxford-AstraZeneca COVID-19 vaccine, manufactured by Serum Institute of India and is one of the primary vaccine bands being administered in India. The interval between the two doses of Covishield when introduced was 4–6 weeks, as recommended by the National Technical Advisory Group on Immunization (NTAGI) in India. Subsequently, it was extended to 6–8 weeks on March 23, 2021 and revised to 12–16 weeks on May 13, 2021, due to operational reasons as well as evolving scientific evidence.
A nationwide COVID-19 vaccination program was launched by the government of India on January 16, 2021, in a phased manner. The order of priority was health workers, frontline workers (FLWs), individuals aged >60 years, and those aged >45 years with comorbidities. From May 1, 2021, all citizens above the age of 18 years were included in the program., Indian Navy is one of the FLW cohorts who were vaccinated as part of the phase-1 vaccination program, with an interval of 4–6 weeks between the two doses.
Vaccine efficacy is a percentage reduction of disease in a vaccinated group compared to an unvaccinated group under the most favorable conditions of controlled clinical trial. Covishield™ manufacturer claimed the overall vaccine efficacy of 66.7% to 70.4% against COVID-19 infection and 100% against severe disease and death. Depending on interval between the two doses, the vaccine efficacy also varied between 53.3% (<6 weeks) to 78.8% (>12 weeks)., Vaccine effectiveness (VE) is a measure of how well vaccines work in the real world, outside of strict clinical trial settings. After giving emergency approval of the vaccines, it is a mandate for the approval authorities to monitor their real-world performance through multiple VE studies conducted across the country.
The primary objective of the study was to evaluate VE of Covishield vaccine in preventing laboratory-confirmed COVID-19 infection and the disease severity among FLWs of Naval community in New Delhi. The secondary objective was to determine epidemiological risk factors associated with COVID-19 infections in the same community during the second wave of COVID-19 pandemic.
| Methods|| |
We conducted a retrospective case-control study among FLWs of the Indian Navy community in Delhi from April 1, 2021, to July 15, 2021, as per the WHO protocol. A “case” for this study was defined as a laboratory confirmed COVID-19 positive individual from the Naval community in Delhi station detected between April 1, 2021, and June 30, 2021. A total of 550 cases were reported to the surveillance system from April 1, 2021, to June 30, 2021, out of which around 310 were tested by reverse transcription-polymerase chain reaction (RTPCR) and remaining by Rapid Antigen test. Only those tested by RTPCR were selected for the study with a response rate of around 78%. We administered the questionnaire mostly by in-person interviews and used E-mail for those who were not available. The study period represented high transmission period, corresponding to nationwide second wave. Cases were further classified as asymptomatic, mild, moderate, severe, and death as per the Ministry of Health and Family Welfare, Government of India classification. Mild COVID-19 patients were those who had Upper Respiratory Tract symptoms without breathlessness, moderate COVID-19 were those who had breathlessness or require oxygen support, severe cases were those who had breathlessness requiring oxygen support and were admitted to intensive care unit (ICU). A COVID-19 death was a death of an RTPCR-positive individual with no period of complete recovery between illness and death. Requirement of hospitalization (other than ICU) as an outcome was not taken into consideration for evaluation in this study, as the mild cases in this community (especially unmarried FLWs who stay in barracks) were also likely to get admitted to hospital for isolation requirements when home isolation facility is not available.
Controls were recruited from the same community, and they were comparable in approaching the same health care facility with similar health-seeking behavior. Controls were chosen from the community to reflect the population from which cases arise, in terms of exposure to virus and vaccination coverage. The community controls for FLW case-patients were randomly selected office colleagues (preferably working in the same section/room) and were enrolled within 14 days timeframe from the date of enrolment of case-patients to match the transmission settings. The nonresponse rate of controls was negligible being a closed and well-educated community.
The sample size was estimated using the WHO protocol. With a precision of estimate of ± 10%, type-1 error rate of 0.05, estimated vaccination coverage of 70% in the population under evaluation, with 3 controls per case, a minimum of 218 cases with 654 controls were required.
All the participants were administered a questionnaire by the interviewer with an informed consent form. The information on basic demographic details, exposure history to laboratory-confirmed COVID-19 cases, symptoms suggestive of COVID-19, and vaccination details were recorded. Data were entered into standard formats by the investigation team. “Epiinfo” © version 7.2.4 was used for statistical analysis of various epidemiological risk factors associated with COVID-19 infection. All potential confounders were adjusted using multivariable regression analysis and final VE estimates were calculated using the adjusted odds ratio (aOR) for vaccination using the formula VE = (1-[aOR]) ×100%.
Informed written consent and confidentiality of data were ensured. Ethical clearance of the study protocol was approved by a Government of India registered Institutional Ethical committee of Base Hospital and Army College of Medical Sciences, New Delhi.
Operational definitions of exposure variables
An individual is considered as fully vaccinated with Covishield 14 days after the date of second dose and partially vaccinated 21 days after the date of first dose and up to 14 days from the date of second dose. These definitions are consistent with the vaccine clinical trials.
Preinfection high-risk exposure event was defined as any exposure event of more than 15 min duration and associated with high infection transmission risk on any day within 14 days prior to symptom onset for case-patients, or 14 days prior to enrolment for controls., Four such events were considered akin to high-risk exposure and were evaluated during the study, namely, contact history with COVID-19-positive patient, visit crowded place (e.g., crowded marketplaces/shopping centers) and attending a social gathering in a confined enclosed space and outstation travel. Outstation travel in own vehicle was excluded and only in public transport (Bus, Train, Aircraft) was included.
Workplace settings are considered as high risk when there is a difficulty in adhering to prescribed physical distancing norms while working or more than 4 individuals working in one room or history of poor ventilation settings (poor ventilation is defined as lack of air-conditioning or lack of natural cross-ventilation when there is no air-conditioning).,, Living place settings are considered as high risk when more than two individuals sharing one room (or) more than four individuals living together as a single household unit (or) history of poor ventilation settings.,
A breakthrough COVID-19 infection was defined as the laboratory detection of SARS-CoV-2 in a respiratory specimen collected from a person >14 days after they have completed two recommended doses of COVID-19 vaccine. Past-COVID-19 infection was defined as RTPCR confirmed infection prior to 01 March 2021 (at least 4 weeks prior to commencement of study/second wave). The study period started from April 1, 2021, and a duration of around 4 weeks from symptom onset was considered adequate to provide protection.
| Results|| |
Distribution of characteristics among case-patients and controls
We enrolled a total of 243 case-patients and 712 controls for the study. The median age of case-patients was 34 years (range 23–55 years, interquartile range 29–43 years) and that of controls was also 33 years (range 20–55 years, interquartile range 29–42 years). Baseline characteristics of case-patients and controls are given in [Table 1]. Among the study participants, 778 (81%) were fully vaccinated, 121 (13%) partially vaccinated and 56 (6%) were unvaccinated. The breakdown of immunization status among case-patients and controls is shown in [Figure 1]. Among the case-patients, 28 (12%) were asymptomatic, 190 (78%) were mild and 25 (10%) were moderate. No severe cases or deaths due to COVID-19 were reported among FLWs.
|Table 1: Baseline characteristics of case-patients and controls – Frontline Workers, New Delhi, April to June 2021|
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|Figure 1: Vaccination status of the Frontline Workers, New Delhi, during second wave (April to June 2021)|
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Epidemiological risk factors of COVID-19 infection
Pre-infection high-risk exposure events such as contact with COVID-19-positive patient, visit crowded place, and attending social-gathering in confined space were significantly associated with contracting infection, with ORs 10.1 (95% confidence interval [CI]: 5.6–18.3), 6.0 (95% CI: 1.8–20.2), and 3.9 (95% CI: 1.4–10.5), respectively. However, history of domestic outstation travel was found to be statistically not significant. All the study participants had given the history of mask-use, either washable mask or disposable mask (at workplace settings and while traveling). The use of double-mask (defined as washable mask outside with disposable mask inside) during the high transmission settings was found to be 60% protective against the infection. Past COVID-19 infection was 70% protective [Table 2].
|Table 2: Epidemiological risk factors associated with COVID-19 infections among Frontline Workers, New Delhi, April to June 2021|
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Adjusted VE of fully vaccinated was 74% (95% CI: 53%–86%) against infection and that of partially vaccinated was 72% (95% CI: 42%–87%) [Table 3]. Adjusted VE of fully vaccinated was 91% (95% CI: 78%–97%) against severity of the disease and that of partially vaccinated was 87% (95% CI: 61%–99%) [Table 4].
|Table 3: Vaccine effectiveness against COVID-19 infection among Frontline Workers, Delhi, April to June 2021|
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|Table 4: Vaccine effectiveness against moderately-severe COVID-19 Disease, Delhi, April to June 2021|
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Breakthrough infections and past infections
Of 243 case-patients, 185 (76%) were breakthrough infections. Among these 185 breakthroughs, 155 (84%) were either mild or asymptomatic and disease severity was significantly less than the nonbreakthrough cases (P < 0.0001) [Figure 2]. Seven (3%) cases and 61 (9%) controls had COVID-19 infection in the past with OR 0.3 (95% CI 0.1–0.7) (P = 0.003) [Table 2]. Of the 7 case-patients who had COVID-19 infection in the past, 6 were mild/asymptomatic and only one was moderately severe.
|Figure 2: Disease severity among breakthrough infections among Frontline Workers, New Delhi, during second wave (April to June 2021)|
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| Discussion|| |
Indian Navy, being one of the priority-1 cohorts in the National COVID-19 vaccination program, got an early opportunity to evaluate the real-world performance of Covishield vaccine in India. We report 74% and 91% VE against COVID-19 infection and disease severity (of moderate-level and above) respectively, during the massive nationwide second wave. No severe infections or deaths were reported among the vaccinated. This meets the WHO's criteria of minimum standards of 50% protection. The study thus provides postauthorization confirmation of the effectiveness of the Covishield vaccine, which was conditionally approved by the national regulatory body in January 2021.,
Serum Institute of India, the manufacturer of Covishield vaccine, claims the vaccine efficacy ranging from 53.3% (for dose-interval <6 weeks) to 78.8% (for dose-interval >12 weeks) and overall efficacy 67%–70% against COVID-19 infection. The VE in our study was similar to the manufacturer's claim of overall efficacy. However, when corresponding efficacy with dose-interval of <6 weeks is taken into consideration, the VE was higher than the claimed efficacy. Our study findings are comparable to two clinical trials of AstraZeneca (~Covishield), and VE study of Bernal et al. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% among persons with the alpha variant and 67.0% among those with the delta variant. Contrarily, Ghosh et al. found a very high VE of 93%–95% against the infection, possibly due to a different study design (surveillance data analysis) and varied transmission settings during the study (high transmission during second wave and low transmission prior to that) [Table 4].
Among the partially vaccinated, the clinical trials showed 76% efficacy and maintained up to day 90 following a single dose. It increased to 81% among fully vaccinated, when dose interval was >12 weeks. In our study, VE of partially vaccinated was only marginally less than that of fully vaccinated, as the dose-interval was mostly 4 weeks between the two doses not exceeding 6 weeks.
No severe disease or deaths were reported among the vaccinated in our study and the finding is consistent with the manufacturer's clinical trials. The vaccine was also reported to be highly effective against disease severity in Oxford AstraZeneca study in England.,
Epidemiological risk factors of COVID-19 infection
Among specific pre-infection high-risk exposure events, contact with COVID-19-positive patient, visit crowded place, and attending a social gathering in a confined enclosed space were found to be highly significant risk factors for COVID infection. This is in consistent with WHO recommendations. The use of double-mask during the high transmission settings was found to be highly protective against the infection. This finding is in consistent with currently available studies., In addition to vaccine, our study thus finds double-masking and avoiding “pre-infection high-risk exposure events” as significant preventive factors against COVID-19 infection during high-transmission settings. These findings are represented in [Figure 3] in the form of a three-layer shield to minimize the breakthrough and re-infections.
|Figure 3: Three-layer shield to minimize COVID-19 breakthrough infections and reinfections|
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US CDC recommends that quarantine and testing are not required after domestic travel if fully vaccinated. Pombal et al. in their study stated that the risk of contracting COVID-19 infection during air travel is lower than from an office building, classroom, supermarket, or commuter train. Similarly, in our study, we found that outstation travel is not significantly associated with COVID-19 infection during high-transmission settings. This is possibly explained by the fact that when community transmission is local, the risk of outstation domestic travel is expected to similar to the local travel.
Breakthrough cases and past infections
Breakthrough cases tend to occur when vaccine efficacy/effectiveness is <100%. An Indian Council of Medical Research study showed 86% of the breakthrough infections in Indian during the second wave were caused by the Delta variant (B.1.617.2). In our study, 23% fully vaccinated participants had breakthrough infections, possibly occurred due to gaps in VE and emergence of the Delta variant as predominant variant during second wave.
Persons with past COVID-19 infection were included in the primary analysis of this study, as policy mandates vaccination to all individuals in target groups regardless of prior infection status. Hansen et al. estimated protective immunity against reinfection is approximately 80% in people younger than 65 years after 6 months. Krutikov et al. in their study found that the natural immunity due to COVID-19 infection substantially reduced the risk of reinfection for up to 10 months after primary infection. A study by David Alfego offers an encouraging timeline for the sustainability of antibodies up to 10 months from natural infection. In our study, protection due to natural immunity from the past infection was estimated to be 70%.
Strengths and limitations of the study
Our study is a community-based case-control design presented with primary data analysis. The study design comprehensively evaluated the important epidemiological risk factors of COVID-19 infections. The timing of the study has exclusively covered the high transmission settings after vaccination coverage stabilized at around 70%. Though the study population is a closed homogenous community with minimum selection biases, it was a relatively younger and predominantly male population. Therefore, results of the study may not be generalized to the entire population across the country. Being retrospective case-control design, the recall bias is likely to occur. The crowded place was not quantitatively defined and only examples were provided to the respondents.
| Conclusion|| |
Covishield, launched by the Government of India under Emergency Use Authorisation is considered effective against COVID-19 infection in high transmission settings, and highly effective against the disease severity. Since the protection from immunity (either due to the vaccine or past-infection) is <100%, breakthrough and reinfections are likely to occur in future. We recommend three-layer shield to minimize breakthrough and re-infections comprising of vaccination, double-masking, and avoiding “pre-infection high-risk exposure events.” Continued surveillance for emerging Variants of Concerns (which may adversely affect the VE) and prospective studies to evaluate the waning of VE are the recommended measures for way ahead.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]