key: cord-0332515-fvdy4yv7 authors: Sushila Kataria, Rashmi Phogat; Pooja Sharma, Vikas Deswal; Sazid Alam, Manish Singh; Kuldeep Kumar, Vaibhav Gupta; Padam Singh, Rohit Dutt; Smita Sarma, Renu Saxena; Trehan, Naresh title: Is Covid-19 seroprevalence different in health care workers as per their risk of exposure? A study from a tertiary care hospital in National Capital Region of India date: 2021-02-12 journal: nan DOI: 10.1101/2021.02.10.21251543 sha: 4d054ff1536307fcb7eb492c2223abf3efe7deb0 doc_id: 332515 cord_uid: fvdy4yv7 nan The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), causing the coronavirus disease 2019 (Covid- 19) , has severely ravaged health systems, economic and social progress globally in 2020. This novel coronavirus spread rapidly to more than 213 countries/territories worldwide and consequently led to a global pandemic (World Health Organization (WHO) since its detection in Hubei province of China in December 2019 [1] . On 30 Jan 2020, WHO declared the novel coronavirus outbreak a public health emergency of international concern (PHEIC), its highest level of alarm [2] . Covid-19 reached the Indian shores of Kerala on Jan 27, 2020 [3] . Worldwide massive responses were put into action, including lockdowns, social distancing measures, quarantine and several drugs, technologies swung into action to minimize morbidity and mortality. Despite all the best efforts of humankind, over 84474195 confirmed cases and 1848704 lives worldwide have been lost to Covid-19 disease [2]. On 23 March 2020, the Government of India ordered a nationwide lockdown .This lockdown and its variants were extended for three more times before the "Unlock" was started on June 8, 2020.The infectious nature of the disease initiated the race to develop and deploy safe and effective vaccine. There are currently more than 50 Covid-19 vaccine candidates in trials [4] . On Dec 11, 2020 . On 16 January 2021, India started its national vaccination programme against the SARS-CoV-2 which is responsible for the Covid-19 pandemic. The drive prioritises healthcare and frontline workers, and then those over the age of 50 or suffering from certain medical conditions. Several studies have found that the SARS-CoV-2 seroprevalence (the percentage of the population with serum containing antibodies that recognize the virus) has remained below 20% even in the most adversely affected areas globally, such as Spain and Italy [7] [8] [9] . The data that is available from India shows a variable seroprevalence in HCW ranging from 2.5% from two different hospitals in Srinagar [10] to 11.94% in a tertiary care center in Kolkata [11] . The variation in rates of seroprevalence being reported from the world and from India, limited availability of the vaccine, and vaccine hesitancy prompted us to evaluate the seroprevalence in HCW at our hospital prior to the national vaccine drive. This paper All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21251543 doi: medRxiv preprint analyses the baseline seroprevalence findings of a prospective, observational, real world study to evaluate the safety, immunogenicity and effectiveness of the national vaccine roll out. This study is the part of the baseline evaluation of a larger prospective cohort study evaluating the safety, immunogenicity and effectiveness of the Covid-19 vaccine given as the national vaccine roll out in health care workers. The study was approved by the Institutional Ethics Committee and was conducted in a fifteen hundred bedded tertiary care hospital in the National Capital Region of Delhi, which has treated over ten thousand hospitalized Covid-19 patients. The data was collected between 12 January and 13 February 2021. The hospital has listed 6962 HCW registered for vaccination in the national vaccine roll out. All health care personnel who consented to participate in the real world cohort for the evaluation of the Covid-19 vaccine were eligible for participation. Further we have excluded those who had participated in any covid prophylactics or drug trials, or had received immunoglobulins and/or convalescent plasma within the three months preceding the planned administration of the vaccine (Jan 16, 2021). Those who were ineligible to receive the vaccine due to history of hypersensitivity reactions, or active Covid-19 disease were also excluded from participation. The informed consent process followed by a baseline questionnaire was completed by a doctor. The baseline questionnaire collected information on basic socio-demographic characteristics (Age and gender), health information (comorbidities, previous Covid-19 diagnosis, use of any supplements including alternative medicine), and work related information (role in the hospital, the type of exposure at work ie working in a Covid-19 ward, radiology or emergency etc). 3 ml of blood was then collected in Serum Separated Tube graded the results. The assay detection range is from 3.8 to 400 AU/mL .SARS CoV-2 S1/S2 IgG. < 15 AU/mL were reported negative. Test results >=15.0 AU/mL were graded positive. The fully automated LIAISON® has been calibrated and validated according to the laboratory SOP, ie 3 samples (high, medium and low value) were run 5 times a day for 5 consecutive days. Their mean, SD and CV% were calculated, which were within normal limits. One positive and one negative kit controls were also processed daily for internal quality control. The instrument was calibrated once daily before processing the samples and also for every new lot kit used. Inter-Lab Comparison (ILC) and Repeat -split testing was conducted as per standard laboratory quality assurance protocol. For data capture each participant was assigned a unique study code, which facilitated linking of participant data with barcode of serum sample. The data were entered into e-HIS (electronic health information system) template which is protected and exported into Excel sheets. Quality assurance (QA) of the data was taken care of by an independent QA coordinator. Initial analysis was done on the characteristics of the study participants according to role in the hospital, nature of exposure, demographics (age and gender), habits perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted February 12, 2021. ; Of the 3258 participants tested for IgG serology (S1 and S2 proteins), 1504 (46.2%) were positive (i.e. had an antibody titre more than/equal to 15 AU/ml) ( Table 3 &Figure 1). All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in People with a past history of Covid-19 disease were found to have significantly higher antibody levels as compared to those without history of Covid-19 (p = 0.0001) (Figure 2 ). . All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Importantly, history of Covid-19 provides double the protection, in particular those who had it recently. Also those in the age group of 60 years or more have 52% higher risk as compared to those under 60 years of age (Table 5) . The unifying hope for ending the global Covid-19 pandemic is the development of adequate population-level herd immunity to halt the continuing cycles of infection and disease. Although no data exist to define the exact threshold necessary to achieve herd immunity against Covid-19, modelling and extrapolation from similar diseases suggest that more than 60%, and perhaps up to 80%, of the population may need immunity for the viral replication Indeed, there are reasons to be optimistic that prior exposure to the virus does lead to All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted February 12, 2021. Immunoglobulin G titres rise during the weeks following infection as active plasma cells secrete antibody into systemic circulation. Those titres then wane as the plasma cells actively secreting the antibodies senesce, whereas resting memory B and T lymphocytes continue to circulate for years to decades and can mediate long-term immunity to infection even in the face of waning antibody titres [18] . Herd immunity is an age-old concept, which is an indirect protection conferred by immune individuals to the susceptible ones in a given population against a specific pathogenic infestation. Herd immunity protects by limiting the spread of the disease [19] . The basic reproductive number (R 0 ) determines the minimum percentage (Y) of the population required to be immune to achieve the herd immunity for the entire population. As described before, R 0 = 2-3 as per recent reports [17] If R 0 = 2, then Y = [(2 − 1)/2] × 100 = 50%. Therefore, for R 0 = 2-3, nearly 50% to 66.66%* (threshold) of the population is required to be immune against Covid-19 for the protection of susceptible individuals in a given population through herd immunity. It is unclear how many people have contracted the causative coronavirus (SARS-CoV-2) unknowingly. Signorelli et al report seroprevalence in the most effected province of Northern Italy (Bergamo) and its effect on the second wave [20] . The first wave impacted this region particularly violently (1332.9 per 100,000 population). The serosurveillance of 42% Covid-19 antibody positivity was the highest level recorded so far in European seroprevalence studies. It was noted that the second wave impacted Bergamo lesser All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21251543 doi: medRxiv preprint (257.6 per 100,000 population) than the neighbouring provinces. This may indicate the evolution of an epidemiological picture of herd immunity [21] . Seroprevalence studies help to evaluate the extension of epidemics. Seroprevalence is also an excellent evaluation of the prevention measures of the health care staff [22] . The prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult populations of various countries such as the Netherlands (2.7%) [23] , Turkey (2.7%) [24] , Spain (11.2%) [25] , a public hospital in New York (27%) [26] . Studies in health care workers showed an equivalently wide spread 14.5% in the Scottish study [27] , 1.2% (Japan) [28] 3.66% in Rome [29] . Indian data from two metropolitan studies (Srinagar and Kolkata) show a variation in the prevalence in health care workers ranging from 0.6% to 11.94% [10] [11] . Seroprevalence in our study was high at 46.2% (CI 44.4 -47.9%), this might be due to the changing profile of the seroprevalence in the community from 24.71 % in October 2020 [30] to more than 50% as per Delhi government fifth serosurvey conducted in January, 2021 or due to higher risk of exposure to Covid-19 patients due to the nature of the hospital (focused Covid care hospital). Seroprevalence was significantly lower in clinical HCW (41.4%) as compared to non-clinical HCW workers (50.2%) (p = 0.0001). This may be due to awareness, vigilance and proper use of PPE, other preventive methods in this group of HCW [31]. Seroprevalence was significantly lower in age > 60 years (30.6%) as compared to age ≤ 60 years (46.4%) (p = 0.023) and this has also been reflected in other studies as with advancing age immune response is hampered [32] . Participants with h/o Covid-19 were found to have significantly higher seroprevalence as compared to those without h/o of Covid-19 (81.2% vs. 40.2%; p = 0.0001). Importantly, history of Covid-19 provides double the protection, in particular those who had it recently. Also those in the age group of 60 years or more have 52% higher risk as compared to those under 60 years of age. Seroprevalence in healthcare workers at our hospital is high at 46.2%. It is higher in nonclinical HCW than in clinical HCW and the risk of acquiring Covid-19 infection was higher in clinical HCW and we feel this subgroup would benefit most from vaccination. History of Covid-19 provides double the protection, in particular those who had it recently. All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21251543 doi: medRxiv preprint Timeline: WHO's COVID-19 response First confirmed case of COVID-19 infection in India: A case report Treatments and vaccines for COVID-19 Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States SARS-CoV-2 seroprevalence in healthcare workers of dedicated-COVID hospitals and non-COVID hospitals of District Srinagar Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India Genomic evidence for reinfection with SARS-CoV-2: a case study Estimated SARS-CoV-2 Seroprevalence in the US as of COVID-19: Herd immunity and convalescent plasma transfer therapy The reproductive number of COVID-19 is higher compared to SARS coronavirus High seroprevalence of SARS_COV-2 in Bergamo: evidence for herd immunity or reason to be cautious? 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