key: cord-0326482-kukx6tbj authors: Issac, A.; Kochuparambil, J. J.; Elizabeth, L. title: SARS-CoV-2 Breakthrough Infections among the Healthcare Workers Post-Vaccination with ChAdOx1 nCoV-19 Vaccine in the South Indian State of Kerala. date: 2021-08-08 journal: nan DOI: 10.1101/2021.08.07.21261587 sha: 0a5027d4452fdcba6a353b181b7583121c0a95f7 doc_id: 326482 cord_uid: kukx6tbj Objective: The national COVID-19 vaccination campaigns in India, prioritized healthcare workers to be vaccinated with ChAdOx1 nCoV-19 (AZD1222). So, we aimed to ascertain the effectiveness of the ChAdOx1 nCoV-19 vaccine among the healthcare workers by characterizing the breakthrough infections which occurred 14 days after the second dose of the vaccine. Methods: We prospectively evaluated the Institutional Covid Vaccination Database to categorize the SARS-CoV-2 positive healthcare workers into 2 cohorts: infected vaccinated and infected unvaccinated cohort. Along with comparing the descriptive statistics of the cohorts, the relative risk (RR), relative risk reduction (RRR), and the vaccine effectiveness were calculated. The study population was compared for the significant difference by using the parametric model (binary logistic regression) for the Odds ratio and the non-parametric model (cox proportionality model) for the Hazard ratio. Results: Out of the 324 healthcare workers employed in our institution 243 (75%) were vaccinated. When 6.58% (16) of the vaccinated healthcare workers were tested positive, 43.75% (35) were infected in the unvaccinated cohort and the median time of infection in the vaccinated cohort was 65 days (range 20 - 91 days). While the cox proportionality model reveals that the age, sex, and the contact exposure status of the cohort are not significant factors for getting infected after being vaccinated, binary logistic regression proves that a significant relationship exists between the incidence of infection and the unvaccinated status (p = 0.001, OR = 4.278). Completing the two-dose of vaccination decreased the hazard of testing positive for the SARS-CoV-2 by 84.96 % when compared with the unvaccinated individuals, which is the effectiveness of the ChAdOx1 nCoV-19 vaccine. Conclusion: There is an increased risk of the third wave of COVID-19 infection in the upcoming months. So, primary infection control measures should be followed even if vaccinated, to prevent the risk of breakthrough infections. In India, the COVID-19 vaccination campaigns were originally conducted using the ChAdOx1 nCoV-19 vaccine (popularly known in India as Covishield) and BBB-152 (Covaxin) [1] . Healthcare workers and the frontline workers were prioritized in the initial phase of the vaccination campaign [2] . Earlier in May 2021, the vaccination opened to all individuals aged more than 18 years [3] and as of July 31, 2021, more than 10.35 crore Indians were fully vaccinated [4] ChAdOx1 nCoV-19 (AZD1222) vaccine had been extensively studied and the overall efficacy more than 14 days after the second dose was found to be 66.7% (95% CI 57.4-74.0) and 70·4% (95·8% CI 54·8-80·6) respectively in two studies [5] [6] . The vaccine effectiveness against hospitalization due to COVID-19 from day 22, after the first dose was 100%. This has provided an impetus to be authorized for use in several countries including India. Current data regarding the efficacy and the immunogenicity of the vaccine against the SARS-CoV-2 and the emerging variants propounds an overall efficacy of more than 65% in the majority of the studies [5] [6] [7] . The reduced risk of disease or infection among individuals which is attributed towards the vaccination in real-world conditions is termed as the effectiveness of the vaccine. World health organization has published standard interim guidelines for evaluating the effectiveness of COVID-19 vaccines [8] . According to the Ministry of Health and Family Welfare and ICMR, the breakthrough infection rates with the ChAdOx1 nCoV-19 vaccine were limited to 0.02% -0.04% [9] . Post-marketing real-life studies should be conducted rigorously to ascertain this level of effectiveness. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The vaccine being the final resort to fight against the COVID-19 pandemic, the incidence of breakthrough infections in fully vaccinated healthcare workers is quite distressing in the South Indian state of Kerala. World Health Organization states AZD1222 vaccine has 63.09% efficiency for symptomatic SARS-COV infection. The study is the foremost in evaluating vaccine effectiveness of 84.96% in fully vaccinated Healthcare workers in a Private Hospital of Kerala. The incidence of infections is more in the unvaccinated cohort (43.75%) than in the vaccinated cohort (6.58%). Factors like age, sex, and exposure status were found to have no relation to the incidence of breakthrough infections. Our study highlights the need for strict compliance of infection control practices even after vaccinations to prevent breakthrough infections. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint We conducted a single-center, prospective study by divided the groups into two cohorts [8] : infected vaccinated cohort and infected unvaccinated cohort (time frame of the study is presented in Figure 1 ). Breakthrough infections were defined as the COVID-19 infections occurring after 14 days of completing the primary series of vaccination. The symptomatic suspected cases, as well as the high-risk contacts of infected cases, were confirmed using RT-PCR screening with nasopharyngeal swabs. The data collection was conducted till July 15, 2021. Data were analyzed using SPSS version 20. All the hypothesis tests were two-sided and evaluated at a significance level of 0.05. The descriptive statistics of age, sex, department, and contact exposure grade were compared between the cohorts. The symptomatic profile and prognosis of vaccinated positive healthcare workers were evaluated along with reasons for not being vaccinated. The relative risk (RR) and relative risk reduction (RRR), were calculated to evaluate the decreasing incidence of testing positive against the SARS-CoV-2 after vaccination. The vaccine effectiveness was calculated using the following formula [11] : - The cohorts are compared and checked for the significant difference by using the parametric model (binary logistic regression) and the non-parametric model (time-dependent cox . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint proportionality hazard model). The event time observed was the number of days from the second dose until a COVID-19 infection was confirmed and the event was COVID-19 infection. Covariates tested were age, sex, and contact exposure status. Ethical approval is granted by the Institutional Ethical Committee of Mary Queen's Mission Hospital (MQMH/IRB/21-23-00) upon ensuring the confidentiality of the personal information of the Hospital staff. Written consent was waived and verbal consent is obtained prior to the data collection. We prospectively evaluated the 324 employees working in our hospital throughout the study . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) A detailed description of the study cohorts with the significance level is depicted in Table 2 . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. While the stepwise binary logistic regression analysis revealed a significant relationship exists between the incidence of infection and being unvaccinated (P = 0.001, OR = 4.278)., it also . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint proves that age (P = 0.814, OR = 1.006) and sex (P = 0.407, OR = 0.605) of the individuals are not significant independent factors for getting infected. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint the healthcare workers who were continuously exposed to the COVID-19 positive patients and their close contacts. Completing the full course of the vaccination decreased the risk of infection with the SARS-CoV-2 virus by 84.96% which is lower than the 91.8 -94.9% in the VIN-WIN cohort [12] and the study done by Benal JL et.al i.e, 89% (85% to 93%) [13] . The breakthrough infection rate among the vaccinated health care workers in the previous studies was found to be 18.65% and 13.3% [14, 15] and it is 6.58 % in our study. Comparison with other studies is mentioned in Table 4 . and 75% respectively similar to the findings of Sabnis R et.al [17] . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint In our study, the median days between the second dose and being tested positive for SARS-CoV-2 was 65 days which is much longer than reported in all the previous studies, which ranged from 5 days or 47 days [9, 12, 15, 16] . Also, none of the vaccinated HCWs who tested positive for SARS-CoV-2 were hospitalized, and there were no deaths, which in turn proves that vaccination reduces hospitalization by 100% which is more than the results observed in a study conducted in Scotland (88%) [18] and England (43%) [19] . Thus, we ascertain and uphold that the ChAdOx1 nCoV-19 vaccine is effective in protecting healthcare workers. The symptomatic profile of the infected vaccinated HCWs was found similar to that study from Siloam Teaching Hospital, Indonesia [16] . Nurses (43.75%) and the staffs with more positive patient contacts (68.75%) were more infected among the vaccinated samples, which agree with the fact that more infection control practices have to be followed in the hospital settings [20] . Hesitancy against COVID-19 vaccine [33.75% (27)], being the major reason for being unvaccinated and the same trend was observed worldwide [21] . Other reasons include breastfeeding and pregnancy, which might be due to the reason that only very limited studies regarding the safety of vaccines in these categories were conducted during the initial phase of vaccination. Limitations of the study is that this is a monocentric, observational study design with a small sample size and also the inability to adjust the confounding variables. Also, the study doesn't compare the efficacy of various other vaccines available in India. Another limitation is that we don't evaluate the immunogenicity of the vaccinated individuals and the results address the short-term effect of the vaccine. We need multi-national studies with a large sample size to provide more accurate results. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 8, 2021. ; Breakthrough infections among the healthcare workers amid vaccination campaigns remain a concern for all authorities worldwide. As plotted in the dotted linear forecast (Figure 2 ), there is an increased risk of the third wave of COVID-19 infection in the coming months. So, the basic infection control measures including face masking, hand hygiene, social distancing, and quarantine protocols should be followed even if vaccinated, to prevent the risk of breakthrough infections. ChAdOx1 nCoV-19 -Chimpanzee (Ch) Adenovirus-vectored vaccine (Ad), developed by the University of Oxford (Ox)to stimulate an immune response to novel coronavirus (nCoV-19) first identified in 2019. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 8, 2021. ; https://doi.org/10.1101/2021.08.07.21261587 doi: medRxiv preprint Strategy for COVID-19 vaccination in India: the country with the second highest population and number of cases. npj Vaccines COVID-19 vaccine hesitancy among medical students in India Ministry of Health and Family Welfare, India; Cowin Dashboard Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. 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