key: cord-0699448-7kb7qwm0
authors: Dudeja, M.; Shaikh, A.; Islam, F.; Alvi, Y.; Ahmad, M.; Kashyap, V.; Singh, V.; Rahman, A.; Panda, M.; Shree, N.; Nandy, S.; Jain, V.
title: Assessment of Potential Risk Factors for COVID-19 among Health Care Workers in a Health Care Setting in Delhi, India -A Cohort Study
date: 2022-03-02
journal: nan
DOI: 10.1101/2022.02.28.22271674
sha: 01e529746579d1ee90c0c6bfc2c786e27c32c36b
doc_id: 699448
cord_uid: 7kb7qwm0

Introduction : Health care workers (HCW) are among the most vulnerable for contracting the COVID-19 infection. Understanding the extent of human-to-human transmission of the COVID-19 infection among HCW is critical in management of this infection and for policy making. We did this study to observe seropositivity and estimate new infection by seroconversion among HCW and predict the risk factors for infection. Methods : A cohort study was conducted at a tertiary dedicated COVID-19 hospital in New Delhi during first and second wave of the COVID-19 pandemic. All HCW working in the hospital during the study period who come in contact with the patients, were our study population. The data was collected by a detailed face to face interview along with serological assessment for anti- COVID-19 antibodies at baseline and endline, and assessment of daily symptoms. Prediction of potential risk factors for seroprevalence and seroconversion was done by logistic regression keeping the significance at p<0.05. Results : A total of 192 HCW were recruited in this study, out of which, 119 (61.97%) at baseline and 108 (77.7%) at endline were seropositive for COVID-19. About two-third (63.5%) had close contact, 5.2% had exposure during aerosol procedures, 30.2% had exposure with a patients body fluid while majority (85.4%) had exposure to contact surface around the patient. Almost all were wearing PPE and following IPC measures during their recent contact with a COVID-19 patient. Seroconversion was observed among 36.7% of HCWs while 64.0% had a serial rise in titer of antibodies during the follow-up period. Association of seropositivity was observed negatively with doctors [OR:0.353, CI:0.176-0.710], COVID-19 symptoms [OR:0.210, CI:0.054-0.820], comorbidities [OR:0.139, CI: 0.029 - 0.674], and recent Infection Prevention Control (IPC) training [OR:0.250, CI:0.072 -0.864], while positively associated with partially [OR:3.303, CI: 1.256-8.685], as well as fully vaccination for COVID-19 [OR:2.428, CI:1.118-5.271]. Seroconversion was positively associated with doctor as profession [OR: 13.04, CI: 3.39 - 50.25] and with partially [OR: 4.35, CI: 1.070 -17.647], as well as fully vaccinated for COVID-19 [OR: 6.08, CI: 1.729 - 21.40]. No significant association was observed between adherence to any of the IPC measures and PPE (personal protective equipment) adopted by the HCW during the recent contact with COVID-19 patients and seroconversion. Conclusion : A high seropositivity and seroconversion could be either due to exposure to COVID-19 patients or concurrent immunization against COVID-19 disease. In this study the strongest association of seropositivity and seroconversion was observed with recent vaccination. IPC measures were practiced by almost all the HCW in these settings, and thus were not found to be affecting seroconversion. Further study using anti N antibodies serology, which are positive following vaccination may help us to find out the reason for the seropositivity and seroconversion in HCW.

families. Besides the increased psychological burden, due to the heightened patient care burden and lack of empathy; their overall wellness is something which is the need of the hour. (6) .

Starting from, line listing, diagnosis, treatment, rehabilitation, home visits to prevention; all of those require the health work force to plunge into as front liners. To add to these sufferings are the financial insecurities, violence, wrath of families affected and governmental mismanagements. HCW providing COVID-19 care are at increased risk of acquiring infection if there is slightest breach in personal protection. They are valuable and scarce resources who cannot be spared for getting isolated for treatment and quarantine. Their health in terms of disease status and mentation besides being a concern for themselves also affects the hospital service delivery. The WHO reported that one in ten health workers is infected with the virus. Infection is more common among nursing staff while death is seen more among doctors, with highest case fatality rate seen in age group over 70 years (7) . They also have a role in the implementation of adequate IPC measures in health care facilities. Several advisories and directives have been updated by the Ministry of Health and Family Welfare EMR Division, for managing this crisis among Health care workers. They stressed for activating Hospital Infection Control Committee (HICC) and identifying nodal officer to respond to Health Associated Infections (HAIs) and following updated guidelines.

Investigating the extent of for COVID-19 infection and assessing the potential risk factors among health workers is essential for characterizing virus transmission patterns, preventing future infections of health workers and preventing the health-care-associated spread of COVID-19.

With the emergence of mutant forms and the rising disarray between the health system and the political clutter, it's a priority to safeguard the frontliners and make them battle ready.

So, we did this study with the objective of (1) to understand the extent of human-to-human transmission of COVID-19 by estimating the seroconversion among HCW in recent contact with . CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint a COVID-19 patient; (2) to characterize the range of clinical presentations of infection (3) to evaluate the effectiveness of infection prevention and control (IPC) measures among HCW; and (4) to find out risk factors for seroconversion and serological response.

This was a prospective cohort study carried out among health care workers (HCW) between December 2020 to June 2021, the period covered India's intense second wave of COVID-19 pandemic.

Hakeem Abdul Hameed Centenary Hospital (HAHC), which is a dedicated COVID-19 Hospital of 200 beds, located in South East Delhi, India. The study population included all the health personnel who were working in this hospital and had come in contact or been exposed recently to a COVID-19 patient receiving care.

Inclusion criteria All HCW exposed to COVID-19 patient receiving care in this health care facility within 72 hours of confirmation of the diagnosis with exposure either to  Close contact (within 1 m) to laboratory-confirmed case  or exposed to case's blood or body fluids,  or exposed to case's used materials, devices or equipment,  or environmental surface around case including his/her bed, table, wheelchair, ward corridor etc.

. CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02. 28.22271674 doi: medRxiv preprint They were enrolled irrespective of their use of Personal Protective Equipment (PPE), any symptoms, and vaccination status.

 HCW who also works in another healthcare facility  HCW who had already suffered from COVID-19 before the start of the study  HCW who are COVID-19 infected or have a confirmed COVID-19 case among their household/close contacts.

 HCW who are so clinically serious that they cannot participate in the study.

For determining sample size, we used methods of Kelsey, Fleiss and Fleiss with continuity correction. The ratio of unexposed to expose is kept as 1:1. We hypothesize a 36% outcome in the unexposed group based on the previous studies (8) (9) (10) . With a risk ratio of 1.7 and Odds ratio of 2.8, we got the sample size of 138, which was increased to 180 considerating the attrition rate at 25%.

 Healthcare worker: Any staff in the healthcare facility involved in the provision of care for a COVID-19 infected patient. It included those who have been present in the same area as the patient as well as those who may not have provided direct care to the patient but who have had contact with the patient's body fluids, potentially contaminated items or environmental surfaces.

o Category I -All doctors like teaching faculty, residents, demonstrators and medical interns.

o Category II -Nurses and nursing assistants . CC-BY 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) 

Once a confirmed case of COVID-19 was detected, identification of healthcare workers who came in contact with the patient or their contaminated objects was done by the Covid Surveillance Unit by interviewing patient and/or their attendant(s) were to understand their movement history in the hospital and to do tracing of the contacts in the hospital in the past 72 hours. The identified HCW contacts were called and informed about their potential contact and about the ongoing study. They were provided with Patient Information Sheet. If they agreed to be a part of the study, then written informed consent was obtained. Participants were also recruited through selfreporting of contacts and referrals. All details were maintained in master register of the project. CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint All HCW recruited into the study completed a researcher-administered, translated, questionnaire at baseline which covered: The participants were provided with a symptom's diary having common symptoms of COVID-19 for self-administration during the 21 days follow-up period. The participants were regularly followed up to check the filling of symptoms diary. The endline visit was scheduled at 22-28 days from the first visit during which endline assessment and second serum sample was collected. The serum samples were tested for antibodies against COVID-19 using the WANTAI serological testing kit. A value of above 1 was considered as positive. These paired serological samples allowed for detection of seroconversion, for better understanding of the secondary infection attack rate.

Two millilitre of blood was collected by venepuncture from all healthcare workers who were enrolled in the study. The first sample collected after enrolment was considered as the 'baseline blood sample'. All the subjects were recalled after 21 days (from the date of baseline sample collection) for the collection of endline blood sample. (Protocal deviation 1: In initial proposal, we planned to call only those who were sero-negative at baseline, later after protocol deviation . CC-BY 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 March 2, 2022. all HCW were called for endline). The paired samples testing protocol helped in detection of asymptomatic carriers and understand the pattern of seroconversion.

The sample collected in appropriate and labelled blood vial was allowed to stand upright for 30 minutes at room temperature followed by centrifugation at 2500 rpm for 5 minutes. The samples are then sent to testing laboratory by placing the vials in a carrier box in upright position. The blood collection staffs were well trained in safe specimen handling practices and spill decontamination protocols and used appropriate PPE during the sample collection process.

Wantai SARS-CoV-2-Ab ELISA kit detects total antibodies against SARS-CoV-2 virus and is based on the principle of two-step incubation antigen "sandwich" enzyme immunoassay. Briefly, 100 ml of patient's serum is added to polystyrene microwell strips pre-coated with recombinant SARS-CoV-2 antigen. Three wells are marked as negative calibrator and 2 wells as positive calibrator. 50 ml of negative and positive calibrator are added to respective wells and the plate is incubated at 37 0 C for 30 minutes. Post incubation the wells were washed 5 times with diluted wash buffer. 100μl of HRP-Conjugate was then added to each well and the pate was incubated at 37 0 C for 30 minutes. The wells were washed again washed 5 times and 50μl of Chromogen Solution A and then 50μl of Chromogen Solution B was added into each well. The plate was then incubated at 37°C for 15 minutes in dark. 50μl of Stop Solution was added into each well and mixed gently. Absorbance was measured using PR4100 microplate reader, Bio-Rad, USA (dual filter) with reference wavelength at 600~650nm. Cut-off value (C.O.) was calculated as C. O= Nc + 0.16 (Nc = the mean absorbance value for three negative calibrators). The tested serum samples were stored at -80 0 C with proper labelling (11) .

Negative results were reported for specimens with absorbance (A) less than the Cut-off value, which meant that no SARS-CoV-2 antibodies were detected with WANTAI SARS-CoV-2 Ab . CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint ELISA (A / C.O. < 1). Specimens with absorbance equal to or greater than the Cut-off value were considered positive, which indicated that SARS-CoV-2 antibodies was detected using WANTAI SARS-CoV-2 Ab ELISA A / C.O. ≥ 1). All the study participants were provided with their baseline and endline antibody results and counselling was done depending on the results.

Data was collected and managed in Microsoft excel with appropriate coding and later cleaned for any possible errors. The questionnaires were checked if they were complete and consistent.

For analysis SPSS (version 26) was used. The frequency tests were performed after determining clear values for the outcomes. Categorical data were presented as percentage (%). Pearson's chisquare and bivariate logistic regression was done to evaluate the independent associations of multiple factors. All tests are performed at a 5% level of significance, and thus the p value less than 0.05 (p value < 0.05) was taken as significant association.

Ethical considerations for doing the study were undertaken and all norms of confidentiality, autonomy, beneficence and consent were taken care of. Study started after approval by the Research Project Advisory Committee (RPAC) and Institutional Ethics committee (IEC) of HIMSR. Other necessary permissions from hospital and medical college were obtained. Written informed consent in English / Hindi was obtained from each participant before their enrolment in the study. All the project staff were trained in and followed Good Clinical Practice. All the participants who needed RTPCR test were offered the same by Hospital. All the participants with poor IPC practices were recommended for refresher IPC training . CC-BY 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.

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Out of a total of 405 HCW approached, 192 were recruited in this study. All of them were interviewed and blood sampling for serology was done at the baseline visit. Out of them, 139

were also included at end line serology assessment, reason of lost to follow up are highlighted in More than half of them were paramedic and a quarter were doctor and nurse. About 63% were unvaccinated at baseline which was least among doctors. (Figure 3 ). All the HCW had taken Covishield (AstraZeneca/ChAdOx1 nCoV-19) vaccine. We found incubation period of 7.9 ± 6.8 days in our study population. Median incubation period was also similar 7.5 days as shown in Table 1 [Insert Figure . CC-BY 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 March 2, 2022. Mean ± SD 7.9 ± 6.8

Median ( profession. Majority of nurses and doctors were exposed in direct contact including face to face and aerosol and direct patient body fluid exposure.

[Insert Figure 4 here]

Usage of various PPE during recent contact with COVID-19 positive patient is shown in figure   4 . We observed a trend in adherence to PPE with almost all were following the PPE protocol during high-risk procedure including aerosol procedure while less so during direct face to face contact. Almost three-fourth of the HCW were wearing mask, while face shield and glasses were used by only one-fourth during face to face prolong exposure. We also observed that majority of the participants were wearing almost all the PPE while Aerosol Procedure and body fluids exposure. [Insert Figure 5 here] Table   4 ). Rhinitis 0 (0%) 0 (0%) 4 (2.9%) 1 (0.9)

Muscle aches 1 (0.5%) 0 (0%) 2 (1.4%) 1 (0.9) Joint ache 1 (0.5%) 1 (0.8%) 0 (0%) 0 (0%)

Loss of appetite 1 (0.5%) 0 (0%) 0 (0%) 0 (0%)

. CC-BY 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) Other symptoms 1 (0.5%) 1 (0.8%) 0 (0%) 0 (0%)

[Insert Figure 6 here] Figure 6 : Seroconversion rate and antibody titre increase of HCW at endline Figure 6 shows seroconversion rate and serial rise in antibody titre between baseline and endline among HCW. We had observed that more than one third (36.7%) of the HCW became positive for the antibody against COVID-19 at endline who were negative at baseline. In term of rise in titre, it was observed in 64.0% of HCW. The seroconversion rate was 63.2% among doctors, 42.9% in nurses and 13.0% in paramedical staff. Doctors antibody titre was observed to increase maximum (71.4%) while in nurses it was seen in 53.8%. (Table 3 ) In our study we did not observe any association of type of exposure type as well as adherence of PPE and IPC practices with both seroconversion and serial rise in titre of antibodies against the COVID-19 after 3-4 weeks. (Table 5 & Table 6 ) . CC-BY 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 March 2, 2022. As shown in Supplementary Table 6 , the nurses were found to be using most of the PPE during the recent close contact with the COVID-19 case, while paramedics were less adherent, doctors were in between the two in usage of PPE. This association was found to be statistically significant in all the type of PPE.

We did this study with the objective of assessing human to human transmission by measuring the seroconversion of COVID-19 among recently exposed healthcare workers and to evaluate the effectiveness of infection prevention and control measures. This was done in New Delhi, the city which was hard hit during first and second wave of COVID-19 pandemic in India. In this we collected information about the exposure to COVID-19 and their risk factors, along with the serological testing at baseline and after 3-4 week, along with daily symptoms by symptoms diary.

Our results show that the seropositivity was 62.0%. We found that seropositivity significantly and negatively associated with doctor as profession, having symptoms, comorbidities, recent IPC training while positively associated with partially as well as fully vaccinated for COVID-19.

. CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02. 28.22271674 doi: medRxiv preprint This research confirms the previous studies of higher seroprevalence of antibodies against the COVID-19 among health care workers. We are of the opinion that these may be due to higher risk of transmission as well as the ongoing immunization program against COVID -19. We also observed seroconversion in 36.7% HCW while 64.0% had serial rise in titre of antibodies during our follow-up period. The seroconversion was higher in doctors, and nurses (63.2% and 42.9% respectively) in comparison to paramedics staff (13.0%). The seroconversion was positively associated with doctor as profession and with partially, as well as fully vaccinated for COVID-19. None of the HCW who were smokers and with any comorbidity had seroconversion. We observe a negative and significant relationship of serial rise in titre of antibodies with recent influenza like illness (ILI), smoker, HCW with comorbidities, and the recent full IPC training, while positively associated with partially, as well as full vaccination for COVID-19. Adherences to the infection prevention measure adopted by the HCW during the recent contact with COVID-19 patients was not found to be significantly associated with seroconversion or serial rise in titre.

Among the HCW we enrolled, more than half were paramedical staff and males and belonging to young age group. Studies done among HCW have varied finding, with majority supporting the similar health care worker profiles like our study. (12) . With regard to comorbidity, our finding are in contrast to the healthcare setting in Chile, where comorbidities were seen in almost half while smoking in a quarter of them (13) . Only a few (5.7%) of the HCW had symptoms at the baseline, and majority of those who had symptoms were seropositive. This is supported by countrywide sero-survey which observed majority of the seropositive participants were not having any kind of symptoms (14) . It has been found in studies done across the continent that majority of the COVID-19 patients are asymptomatic, while only a few require hospitalization (15) . Our findings is contrast to the observations of researcher from Spain, where they found . CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint higher proportion of HCWs with comorbidities and COVID-19-compatible symptoms in the previous months (16) .

We also documented incubation period in our study which was 7.9 ± 6.8 days (median: 7.5; IQR:1.0 -15.0). The CDC reports incubation period of COVID-19 to extending up to 14 days with median of 4-5 days (17) .

We observed that all the doctors and nurses and almost all paramedical staff were wearing some kind of PPE when they were exposed to COVID-19 patient. This was expected because the of mandatory PPE policy adopted by the hospital where this study was conducted. The PPE adherence was seen high risk procedure, but less in low risk activity specially by the paramedics, who were even found to be significantly non adherent in usage of PPE. We did not observe any significant association usage of individual PPE with seroconversion as well as increase in titre.

Studies has shown appropriate use of PPE to be the most critical defence against COVID-19 infection among HCW (18) (19) (20) . This could not be observed in our study may be due to the very high adherence of appropriate PPE in high-risk places, leading to non-significant relation as well as due to the confounding by vaccination of the HCW.

While two-third doctors and a majority of nurses (82%) were performing appropriate hand hygiene practices while in contact with COVID-19 patient, only half of the paramedical staff were following the same. This could be due to the fact that doctors and nurses are involved in direct patient care, while paramedical staff, who are not directly involve in patient care may consider themselves at lesser risk. This may be further due to the differences in information available about importance of adherence to IPC practices. Unlike our study, an international study observed higher knowledge and practice of PPE in non-physicians in comparison to physicians (21) . Similar to ours, a study also observed that resident doctors and paramedic reported lower adherence to PPE (22) This along with not performing hand hygiene practices . CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint could be one of the major potential for exposure to the COVID-19. Previous studies have also stressed on IPC practices among various categories of HCW (23) (24) .

In this study HCW were exposed to close contact exposure, face to face prolong exposure, aerosol generating procedure, exposure with patients material, patient's body fluid, and environment surface exposure. All of these exposures made them a high-risk group for contracting COVID-19. There are many studies which demonstrate HCW being infected due to these procedures(25) (26) . Inspite of this, we did not observe any association of type of exposure with seroconversion except among those exposure to patient material. This might be due to good adherence to PPE and IPC measures in our hospital setting, as well as due to confounding by concurrent vaccination program. 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint expected since COVID-19 vaccines are given to produce antibodies by the immune system (29) .

This was true in our study where we observed the strongest association of vaccination with seroconversion.

The seropositivity at baseline was 62% while at endline was observed to be 77.7%. Our study findings are supported by a study where positive IgG response was observed in 48.4 % and 77.8 % at baseline and follow up respectively (30) . The latest sero-survey in India, observed low seropositivity among general population. A sero-survey done in Delhi has also observed low seropositive rate in contrast to our study (31) . One Indian study found doctors have higher risk of seropositivity than other HCWs which is similar to our study finding (14) . Globally the seroprevalence among HCW varied from 3% in Finland to 55.9% in Brazil (32) . It was also found that seropositivity was higher in HCWs involved in COVID-19 patient management(33), although a study from Chile found no statistical difference in seropositivity among HCW involved in direct clinical care of patients with COVID-19 and those working in low risk areas (34) . We are in an opinion that high seroprevalence in our study papulation is due to the high vaccination rates, which was also one of the strongest risk factors observed in our study.

We also observed various factors associated with seropositivity at baseline. our study, while those who had any symptom had lower risk of seroconversion. These are in contrast to study from similar settings in New Delhi observed seropositivity to be associated with male sex (31), while one from Germany observed use of PPE to be protective (35) . A study from . CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint Spain reported high odds of seropositive among those having any COVID-19 symptom in the previous months, although found no association with profession, working in high risk unit, close contact with a COVID-19 case, comorbidities and sex, partially supporting our findings (16) .

Higher seroprevalence in paramedical staff in comparison to doctors (71.6% vs 47.1%) as well as those working in low-risk area in comparison to high-risk area (67.9% vs 54.7%). This could be explained by strict adherences to IPC measure and higher use of PPE as seen among allied health workers in our study, who are more often responsible for managing patients in high-risk setting. The health care setting where this study took place, had a dedicated IPC committee, COVID surveillance Unit and proper PPE mandate, leading to better adherence of IPC measures and higher availability of PPEs in comparison to other hospitals and effective contact tracing.

The seroconversion was documented to be 36.7 % among HCW, was 63.2% in doctors, 42.9% in nurses and 13.0% in paramedics staff. We also observed that 64.0% had increase in titre of antibodies during our follow-up period. Studies done across the globe have varied rates of seroconversion. In a large prospective study in UK it was 0.77% (36), 5.4% in Italy(37), 24% in Chile (13) while 44% from Paediatric Dialysis Unit in USA (38) . Seroconversion among HCW for H1N1 in 2009 was also documented as 6.5% (39) .This variation could be due to different settings and study period. A study from Germany observed rise in titre among 72% of HCW during the follow-up period (35) We are in an opinion that high seroconversion in our study papulation is due to the concurrent vaccination program -which was also one of the strongest risk factors observed in our study -rather than secondary infection from COVID-19 case to which HCW was exposed. Seroconversion was positively associated with doctor as profession [OR: 8.87 ]. None of the HCW who were smokers, with any comorbidity as well as those who had attended adequate IPC training had seroconversion. We observed higher seroconversion among females, higher age group and those working in high-risk setting, but did not reach the level of significance (p>0.05).

Our study findings are supported by the various studies done different part of the world(13) (40) .

Negative association of smoking and seroconversion found in our study is also supported by study from Chile, where they found smokers showing lower seroconversion (13) . Unlike our study, researchers in Italy have observed symptoms to be positively associated (37) , while more nurses in comparison to allied physicians were significantly more associated with seroconversion for H1N1 in the past (39) .

Inspite of best of our effort , we had a limitation due to concurrent vaccination drive among HCW which confounded our study and thus prevented us in understanding the development of secondary infection among HCW. This could be solved by confirming the infection with RT-PCR testing, but doing it after every contact of HCW with COVID-19 patients would be nonpractical and unethical during the time, our health care system was overwhelmed with requirement of COVID testing. We also had a higher attrition then expected, which could bring bias, although the profile of responders and non-responders did not vary significantly.

Our study observed higher seroprevalence among HCW and its associated with vaccination for COVID-19. The seropositivity was high among paramedical staff but more doctors were seroconverted and increased titre after the exposure to COVID-19 patient. Doctors as well as . CC-BY 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 March 2, 2022. ; https://doi.org/10.1101/2022.02.28.22271674 doi: medRxiv preprint vaccinated HCW were found to be highly associated with seroconversion and protective against the COVID-19. Hence, it is strongly recommended to increase the vaccination coverage for all cadre of HCWs.

This confounding of infection with vaccination may be curtailed using anti N antibodies serology, in future research. It was also observed that PPE, hand hygiene and IPC measures in the facility practiced and are protective. However, these are better followed by nurses and doctors than the paramedical staff. Therefore, imparting frequent IPC trainings to the paramedical staff is vital in preventing COVID-19. We are in opinion that it would be appropriate to regularly test all healthcare workers for COVID-19, using both PCR and serological assays, irrespective of exposure or symptom history so as to protect this workforce.

This study was supported by grants from the World Health Organization under UNITY studies.

We are thankful to hospital admiration of HIMSR, New Delhi including Dr. G.N Qazi, CEO, and Dr. Ajaz Mustafa, MS. We also would like to sincerely thank all the study participants for their time and cooperation in completing this project. 

We declare no competing interests.

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Data sharing requests should be directed to the corresponding author.

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Wantai : COVID-19 Serology and Molecular Tests

Prevalence and Predictors of Stress, anxiety, and Depression among Healthcare Workers Managing COVID-19 Pandemic in India

Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile

SARS-CoV-2 seroprevalence among the general population and healthcare workers in India

COVID-19: Clinical features -UpToDate

Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital | Nature Communications

Centers for Disease Control and Prevention

Personal protective equipment and intensive care unit healthcare worker safety in the COVID-19 era (PPE-SAFE): An international survey

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. Cochrane Database Syst Rev

Healthcare Workers' Knowledge, Attitude, and Practice Regarding Personal Protective Equipment for the Prevention of COVID-19

Are health care workers following preventive practices in the COVID-19 pandemic properly? -A crosssectional survey from India

Personal protective equipment recommendations based on COVID-19 route of transmission

Protocol for assessment of potential risk factors for 2019-novel coronavirus (COVID-19) infection among health care workers in a health care setting

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COVID-19: Infection control for persons with SARS-CoV-2 infection -UpToDate

Aerosol-generating otolaryngology procedures and the need for enhanced PPE during the COVID-19 pandemic: a literature review

Coronavirus Pandemic (COVID-19). Our World Data

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet

Immune response to SARS-CoV-2 in health care workers following a COVID-19 outbreak: A prospective longitudinal study

Seroprevalence of antibodies to SARS-CoV-2 and predictors of seropositivity among employees of a teaching hospital in New Delhi, India. Osong Public Health Res Perspect

SARS-CoV-2 infections among healthcare workers at Helsinki University Hospital, Finland, spring 2020: Serosurvey, symptoms and risk factors

Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care

Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile

SARS-CoV-2 Seroprevalence among Health Care Workers-A Voluntary Screening Study in a Regional Medical Center in Southern Germany

The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers

Dynamics of the seroprevalence of SARS-CoV-2 antibodies among healthcare workers at a COVID-19 referral hospital in

Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit

Risk Factors for Pandemic (H1N1) 2009 Virus Seroconversion among Hospital Staff, Singapore. Emerg Infect Dis

Seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies among healthcare workers with differing levels of coronavirus disease 2019 (COVID-19) patient exposure