key: cord-0850842-wijqiktk authors: Sharma, P.; Mishra, S.; Basu, S.; Tanwar, N.; Kumar, R. title: Breakthrough infection with SARS-CoV-2 and its predictors among healthcare workers in a medical college and hospital complex in Delhi, India date: 2021-06-09 journal: nan DOI: 10.1101/2021.06.07.21258447 sha: 97d2d16c33fb6b4afd75183fbe6183b2d26dd021 doc_id: 850842 cord_uid: wijqiktk Introduction The study objective was to determine the breakthrough infection rate of Covid-19 (SARS-CoV-2) infection in those vaccinated with either BBV152 or AZD1222 (ChAdOx1-S) vaccine among healthcare workers (HCWs). Methods A cross-sectional analysis was conducted a medical college and hospital complex in Delhi, India through telephonic interviews among HCWs who had received at-least one dose of a Covid-19 vaccine during January to March 2021. Breakthrough infections were operationally defined as occurrence of Covid-19 infection 14 days after administration of two doses of either Covid-19 vaccine. Results We enrolled 326 HCWs with mean (SD) age of 29.1 (85.9) years including 212 (65%) males. Two hundred eighty (90.9%) HCWs were fully vaccinated while 46 (14.1%) were partially vaccinated. There were 168 (51.5%) BBV152 and 158 (48.5%) AZD1222 (ChAdOx1-S) recipients. A total of 36 (11%, 95% C.I. 8.1, 14.9) breakthrough infections were reported in the HCWs. The median (IQR) time until incidence of Covid-19 infection since receiving second dose of either Covid-19 vaccine was 46 (28.2, 54.7) days. Furthermore, Covid-19 infections occurred in 65 (19.9%, 95% C.I 15.9, 24.6) HCWs vaccinated with at-least one dose of vaccine but prior to receiving their second dose or <14 days post second dose. Most breakthrough infection cases (94.4%) were mild and did not require supplemental oxygen therapy. HCWs with past history of natural Covid-19 infection with recovery were 4.5 times less likely to experience a Covid-19 infection after partial vaccination. Conclusion Nearly one in nine HCWs experienced a Covid-19 breakthrough infection in the present study. Vaccines are considered the mainstay in halting and ending the Covid-19 pandemic which has caused over 172 million cases and 3.7 million deaths worldwide till date [1] . India launched the world's largest Covid-19 mass vaccination campaign from January' 2021 in a phased manner beginning with healthcare, sanitation and essential frontline workers, followed by the geriatric population, people with comorbidities, those aged > 45 years and finally the entire adult population [2] . The vaccines approved and deployed in India by the regulatory authority included AZD1222 [4] . The AZD122 (ChAdOx1-S/nCoV-19) recombinant vaccine against Covid-19 is a replicationdeficient adenoviral vector vaccine that expresses the SARS-CoV-2 spike protein gene [3] . BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine adjuvanted with Algel-IMDG to induce T-helper-1 cell (Th1) responses [4] . The efficacy of AZD1222 (ChAdOx1-S) after administration of two doses of the vaccines irrespective of interval between the doses has been reported as 63.1%, with possibly higher efficacy on longer intervals [3] . The interim phase-3 clinical trial data reported BBV152 to have efficacy of 78% against infection with SARS-CoV-2 [5] . However, the real-world effectiveness of vaccines may differ from the efficacy reported in clinical trials due to a multitude of factors including the dynamics of disease exposure, diminished antibody response in sub-groups like the elderly and the immunocompromised, and the emergence of newer mutant strains with greater infectivity and virulence [6, 7] . A small proportion of individuals will contract Covid-19 despite complete vaccination as no vaccine accords 100% protection against the disease, and occasionally newer virus variants evolve mechanisms for bypassing the vaccine induced antibody response. Breakthrough infections with reference to Covid-19 refers to the incidence of SARS-CoV-2 infections in individuals who have already been partially or completely vaccinated with any authorized Covid-19 vaccine [8] . According to the ICMR between 0.02 and 0.04% infections have occurred after partial or complete vaccination with either BBV152 or AZD1222 (ChAdOx1-S) [9] . However, healthcare workers (HCWs) represent a very high-risk group for contracting COVID-19 due . 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258447 doi: medRxiv preprint to sustained occupational exposure to the virus [10, 11] , and the breakthrough infection rate assessed in this cohort would provide crucial evidence in understanding the effectiveness of vaccination in preventing symptomatic disease and disease transmission. The study objective was therefore to determine the breakthrough infection rate of Covid-19 (SARS-CoV-2) infection in those vaccinated with either BBV152 or AZD1222 (ChAdOx1-S) vaccine among healthcare workers. Study design and setting: We conducted a cross-sectional study among healthcare workers of infections occurring post vaccination with at-least a single dose of vaccine but prior to receiving either the second dose or before 14 days after vaccination with the second dose. The independent variables included age, sex, time since vaccination, vaccine type, adherence to non-pharmaceutical measures post-vaccination and previous history of natural infection and recovery prior to vaccination. The sample size was calculated considering the prevalence of breakthrough infection among HCWs in India as 13.3% as reported in a study from a chronic care facility in Delhi [12] , at 95% confidence level, 4% precision, and 10% non-response. The minimum sample size was estimated as 270. The data was collected during a period of 7 days from May 31 to June 6 through telephonic interviews conducted by multiple trained investigators using the following sources in a consecutive order: (i). Registration records of all the healthcare workers vaccinated at the Covaxin administration site within the college campus during February-March 2021 (ii). Records of the medical interns affiliated to the MAMC who were vaccinated between January-March' 2021. . 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 June 9, 2021. (Table 2 ). In this study, nearly, one in five HCWs reported the incidence of Covid-19 infection after Vaccine seroconversion through robust anti-spike antibody response is likely to be induced after a single dose of AZD1222 (ChAdOx1-S) compared to BBV152 wherein two doses are usually required to stimulate adequate antibody levels [7] . This study also observed the rates of Covid-19 infection after administration of at-least a single dose of vaccine were higher in the BBV152 group compared to the AZD1222 group, although statistical significance was not attained. . 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258447 doi: medRxiv preprint Evidence from a previous study suggests that a single dose of either BBV152 or AZD1222 induced higher concentration of neutralizing IgG antibody in those having a history of natural infection and recovery from COVID-19 [13] . Similarly, in this study, a history of a natural infection and recovery from Covid-19 was observed to be protective against a subsequent Covid-19 infection or reinfection in those HCWs who had been administered at-least a single dose of Covid-19 vaccine. The rates of breakthrough infection observed in the present study (11%) were slightly lower than that observed during surveillance in a chronic care facility in Delhi, India (13.2%) where HCWs received either AZD1222 (ChAdOx1-S) or BBV152 [12] . However, another study in a large cohort of HCWs from a north Indian city vaccinated with AZD1222 (ChAdOx1-S) reported the incidence of Covid-19 breakthrough infections to be only 1.6% (48 out of 3,000) while 2.6% tested positive after receiving at-least one dose of the vaccine [14] . In contrast, Hacisuleyman et al. report the incidence of breakthrough infection as just 0.5% in a cohort of 417 health care workers who had previously received two doses the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine [15] . The period of observation in this study coincided with a massive wave of the Covid-19 epidemic in Delhi during April and May 2021 which witnessed 0.737 million cases including 11,075 deaths [16] . Furthermore, the emergent evidence from genomic analysis also reveals that the Covid-19 variants of concern, B.1.617.2 (Delta) and B.1.1.7 (Alpha) having ~50% higher transmissibility were primarily responsible for the surge in cases during the same period. These variants also constituted the predominant lineages found in the breakthrough infections cases due to a probable immune escape mechanism that could occasionally bypass the vaccine induced immunity [17] . Moreover, diminished neutralizing antibody activity and limited protectiveness against the delta variant of the SARS-CoV-2 has been observed in most of the currently available Covid-19 vaccines globally especially prior to complete vaccination with both vaccine doses [18, 19] . The strengths of the study are that it was conducted in real-world settings with the period of observation inclusive of the peak of the Covid-19 pandemic in Delhi, India when health systems were overwhelmed resulting in large scale viral exposure of HCWs providing either outpatient or inpatient treatment services. However, there are certain study limitations. First, since infection status of the HCWs was based on self-report in the absence of a mandatory testing policy, mostly symptomatic breakthrough infections diagnosed with RT-PCR or the . 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258447 doi: medRxiv preprint Ag test were likely to be captured while asymptomatic infections also capable of viral transmission were potentially omitted. Second, although, we observed high rates of transmission in the household members of the HCWs, the vaccination status in the infected household members was not recorded. Third, comorbidity status was not ascertained in the participants although the likelihood of underlying morbidities in the HCWs was less considering their low median age. Consequently, future studies should assess the extent of vaccine induced antibody response and protection after vaccination with Covid-19 vaccines in patients with diabetes, heart disease, chronic kidney disease, and older people at risk of reduced protection in addition to pre-existing concerns causally linked with the occurrence of severe disease. A final limitation is that the sample size was not adequately powered to detect statistically significant differences between subgroups. In conclusion, breakthrough infections represent a major public health challenge in ending the Covid-19 pandemic. Robust surveillance through large-scale epidemiological studies to identify the predictors of breakthrough infection among individuals at risk, and rapid genomic analysis for early recognition of emerging variants of concern that have greater capability of causing breakthrough infections warrant continued prioritization. . 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 June 9, 2021. 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258447 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) The copyright holder for this preprint this version posted June 9, 2021. . 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 June 9, 2021. ; https://doi.org/10.1101/2021.06.07.21258447 doi: medRxiv preprint Last accessed on 6 th June, 2021. 2. PM Launches pan India rollout of COVID-19 vaccination drive Last accessed on 6 th June, 2021. 3. World Health Organization. COVID-19 Vaccines Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial Covaxin efficacy 78% in Phase 3 analysis Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Antibody Response after First-dose of ChAdOx1-nCOV (Covishield) and BBV-152 Health Care Workers in India: Preliminary Results of Cross-sectional Coronavirus Vaccineinduced Antibody Titre Breakthrough case investigations and reporting 000 people infected after getting vaccinated, Covaxin works against mutant viruses: Govt. 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