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PROTOCOL
Year : 2021  |  Volume : 14  |  Issue : 2  |  Page : 123-127  

Sero-surveillance of SARS-CoV2 infection among health-care workers: A protocol


1 Dir Health, ACMS, Delhi, India
2 HOD and Professor, ACMS, Delhi, India
3 Jt Dir Health, Delhi, India
4 Assoc Prof, Department of Community Medicine, AFMC, Pune, Maharashtra, India

Date of Submission22-Sep-2020
Date of Decision14-Oct-2020
Date of Acceptance14-Oct-2020
Date of Web Publication02-Feb-2021

Correspondence Address:
Arun Kumar Yadav
Department of Community Medicine, AFMC, Pune - 411 040, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_529_20

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  Abstract 


Introduction: The objectives of the present survey are to estimate the seroprevalence and sero-conversion of SARS CoV2 among the health-care workers (HCWs) in health-care establishments and to analyze the various characteristics (risk factors) associated with SARS CoV-2 infection with the overall aim to generate evidence for planning and preventive measures in the Armed Forces. Methodology: Eight hospitals have been chosen based on the hospital admission rates of COVID-19 patients and local epidemiological situation of COVID-19 prevalent in the region. A total of 3800 HCWs would be enrolled in the cross-sectional survey. For longitudinal study, 1000 personnel would be followed up at 3 and 6 months. Population proportion to size would be used for enrolment at various stages. A validation study is inbuilt in the study. From each site, a nodal officer would be designated for facilitating. Real-time data monitoring and quality checks would be done. Sero-surveillance would be done using ELISA-based immunoglobulin antibody. Results: The present study would provide the estimates of seroprevalence and rate of seroconversion among the HCWs. The factors associated with seroprevalence and seroconversion would be delineated. Discussion: The protocol lays down the plan of action to implement the multi-centric serosurveillance project. The survey will provide an assessment of seroprevalence of COVID-19 infection among the health-care workers of hospitals of central ministry from the various parts of the country and its trend over a period of time.

Keywords: Health-care workers, protocol, seroconversion, serosurvey


How to cite this article:
Ghosh S, Kotwal A, Pandya K, Yadav AK. Sero-surveillance of SARS-CoV2 infection among health-care workers: A protocol. Med J DY Patil Vidyapeeth 2021;14:123-7

How to cite this URL:
Ghosh S, Kotwal A, Pandya K, Yadav AK. Sero-surveillance of SARS-CoV2 infection among health-care workers: A protocol. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 Apr 13];14:123-7. Available from: https://www.mjdrdypv.org/text.asp?2021/14/2/123/308621




  Introduction Top


The coronavirus pandemic has created substantial panic on a global scale with more than 14.6 million cases and 0.6 million deaths being reported worldwide as on July 20, 2020.[1] No continent has been spared from the effects of the ongoing pandemic.[1] According to the WHO, 80% of COVID-19 cases are mild or asymptomatic, 15% are moderate, and 5% are severe in nature.[2] The asymptomatic and presymptomatic cases can play a significant role in disease transmission in the community.[3] The proportion of asymptomatic to symptomatic cases in various studies has varied between 30% and 50%.[4],[5]

Early identification of cases followed by prompt isolation, proactive contact tracing, and testing are the cornerstones for preventing disease transmission in the community.[6] However, there are a large number of undetected cases because of natural history of disease and subjectivity and characteristics of the tests. Serosurveillance serves as an additional tool to estimate the true prevalence and trend of infection in a community. Due to the inherent profession-associated risk, health-care workers (HCWs) are more susceptible to contracting the infection and accordingly Indian Council of Medical Research (ICMR) vide its guidelines in the context have recommended that serosurveillance studies in this high-risk group may be carried out.[7] The WHO has given a surveillance protocol for SARS-Cov2 infection among health workers.[8]

Health-care workers involved in managing COVID-19 cases or in surveillance and contact tracing activities form a sub-set of population at high risk of contracting the infection. A total of 2.3% of asymptomatic HCWs were found to be positive in laboratory-based surveillance conducted by ICMR.[9] A cross-sectional survey conducted in Netherlands in the early phase of the pandemic revealed a 1% prevalence of COVID-19 among HCWs.[10] Another seroprevalence survey in a Spanish hospital during the initial stage of the pandemic revealed that 40% of those with past or present infection, as identified by a positive antibody test, had not been previously diagnosed with COVID-19.[11] A large survey conducted among HCWs in the USA showed an overall seroprevalence between 3.9% and 5.4% among those who were directly involved in the management of COVID-19 cases.[12]

A large number of HCWs of the hospitals under central ministry have been involved in the various aspects of COVID-19 management since March 2020 which includes the management of quarantine facilities, clinical management of admitted patients in health-care establishments, and contact tracing activities. The prevalence of seropositivity among HCWs would provide valuable insight into the risks associated with contracting the infection provide a better understanding of the lacunae existing in the current practices pertaining to the use of personal protective equipment (PPE), disinfection procedures, and patient management protocols which would in turn help in managing the valuable health workforce in an efficient manner. In addition, follow-up of a cohort of HCWs with serial seroprevalence estimates would help in elucidating the temporality of ongoing high-risk behavioral patterns, duration of persistence of protective antibody, and the efficacy of protective antibodies in preventing reinfections. This would eventually translate into better and more efficient hospital infection control practices through the revision of existing guidelines on the subject.

Proposed protocol

Various study designs may be utilized for conducting sero-epidemiological studies. While cross-sectional studies are the most common, (estimation of initial prevalence), repeated cross-sectional surveys in the same population help in observing the trend in a given geographical area. Longitudinal studies, the other alternative, involves serial sampling of the same participants/population over a period of time, which is best suited to delineate the rate of seroconversion, risk factors for conversion, risk stratification, and trends over time. However, they are time, workforce, and resource intensive. Longitudinal studies may be conducted as a descriptive study of one group or a cohort study by having two well-defined groups of antibody positive and negative individuals with follow-up of these cohorts over a period of time for assessing the rate of seroconversion and persistence of antibodies at various time points.

With repeated cross-sectional studies, although the data are representative of the population during the period of study conduction, the individual temporality over a period of time is lost. Longitudinal studies are more efficient in comparison to repeated cross-sectional surveys as the power to detect statistically significant differences may be undermined in later. The longitudinal study focuses on changes within individuals and inference about population which are not as sensitive to “between subject” variation.[13] The longitudinal survey is preferred in situations where the study population is amenable to follow-up, and there are closed population groups. However, complex designs which combine benefits of both the study designs are also available.[13]

Objectives

The primary objectives of the present survey are to estimate the seroprevalence of SARS CoV2 among the HCWs in health-care establishments and to analyze various characteristics (risk factors) associated with SARS CoV-2 infection. The other objectives are to estimate the incidence of seroconversion among HCWs over a period of 6 months and status of seropositivity among those positive at baseline at 3 and 6 months with the overall aim to generate evidence for planning and preventive measures in the Armed Forces.

The survey has been divided into two parts, initial baseline cross-sectional survey (Phase 1) followed by a longitudinal study among the subset of initial survey with serial testing at 3 and 6 months (Phase 2 and 3).

Sampling strategy

COVID-19 patients are being admitted in designated hospitals across the country in hospitals under central ministry. Eight hospitals have been chosen based on the hospital admission rates of COVID-19 patients and local epidemiological situation of COVID-19 in the region. All HCWs (hospital staff, those working in field in contact tracing and community surveillance) would form the part of study population. Persons who are on long leave/course or likely to be posted out shortly would be excluded from the study.

Sample size

For the first phase of the study, (cross-sectional survey), the requirement would depend upon assumed proportion of seroprevalence, design effect, and desired precision. Sample size is being estimated for the entire population of the HCWs and has been calculated with the following assumptions: Desired level of confidence (1−α) = 95%, expected prevalence of seropositivity among health-care workers (π) =5%, absolute precision (d) =1%, design effect (δ) =2 (standard).

The sample size has been calculated using the following formula: (sample size = Z1−α/22 × δ × π (1−π)/d2). This has yielded a sample of 3667 participants. However, considering possibility of dropouts, a sample size of 3800 would be taken.

For the longitudinal seroconversion study (Phase 2 and 3), sample size would be based on assuming a sero-conversion rate of 5%, 80% power and alpha error as 5%, and difference of 0.05 in marginal proportion, applying continuity correction and design effect of two. Using these parameters, the sample size varies from 566 to 854 pairs for correlation values which vary from 0.4 to 0.05. Taking into consideration likely dropouts and loss to follow-up from the study, it is planned to enrol 1000 pairs.

Sampling method

A complex sampling method would be adopted. Population proportion to size would be used for enrolment from a given site wherein the number of personnel selected from the site would depend on the posted strength of HCWs in the hospital. Within the selected hospital, list of all eligible participants will be made as per the category of HCWs. The list would be categorized into various categories of HCW (Medical Officers, Nursing Officers, Nursing Assistants, Ambulance Assistants etc.,). Study participants would be selected by the random sampling from each category which would be proportional to the population size in each category.

All individuals who have evidence of an antibody response during Phase 1 of the study will be re-evaluated at 3 and 6 months to check for persistence of antibody, while those testing positive during Phase 2 will be re-evaluated at 6 months. From those who test negative for an antibody response during Phase 1 of the study, 1000 participants will be randomly selected in accordance with population proportion to size for different classes of HCWs for Phase 2 of the study. To assess the rates of sero-conversion, the subset of participants who tested negative during Phase 1 will be tested during Phase 2 and those testing negative in Phase 2 will be re-evaluated in Phase 3.

Validation study: A validation study would be inbuilt into the survey whereby the serological tests would be done for 30 positive real-time polymerase chain reaction (RT-PCR) (after at least 2 weeks of a positive RT-PCR) and 30 negative RT-PCR cases (within 72 h of testing negative) at the designated center. In case a particular designated center did not have 30 positive RT-PCR during the period of the study, then the maximum number available would be tested (after at least 2 weeks of a positive RT-PCR). However, minimum 30 negative RT-PCR cases would be tested (within 72 h of testing negative). The validation study will help in revising the estimate later on after the study is completed.

The sampling process and sample size are shown pictorially in [Figure 1].
Figure 1: Diagrammatic presentation of sampling and sample size

Click here to view


Total serology tests required are 6710. However, taking into account a wastage factor of 20%, the final test requirement is 8052 (~8050).

Study procedures

A nodal officer would be designated from each center. The nodal officer would undergo training in sero-epidemiological aspects of the study through videoconferencing for 3 h duration. A questionnaire would be adapted from questionnaire given for serosurveillance by the WHO.[14] The questionnaire would consist of information on the interviewer, demographic details, information on the health-care facility and on the HCWs basic knowledge of infection prevention and control (IPC) and PPE use, activities carried out during interaction with COVID-19 patient, adherence to IPC measures, on the availability and use of PPE and information on accidental exposure to biological material. All essential questions as marked by the WHO would form the part of the questionnaire. Data will be collected using an Open Data Kit without any personal identifiers. Preferably, data would be collected on mobile/tab using the open source platform available like Kobotoolbox, etc., if not possible then data would be compiled in Excel format on a personal computer. Data management would be done centrally. Data collection form would be sent to experts for face and content validity. The changes suggested by them would be incorporated. Data collection form will be pretested in 30 HCWs and changes would be made before finalizing. The Cronbach's Alpha would be calculated for inter-item reliability. Electronic monitoring with parameters like time taken to complete the form, etc., would be analyzed for the quality of data collection. All investigators will be trained on data capturing. An electronic platform would be provided to facilitate real-time query for data collection on Open Data Kit. For quality check of captured data, the form would have logic checks in built and would not be submitted unless all essential fields are filled. Any real-life modifications or error would be E-mailed or conveyed to the data management team centrally which would try to resolve the issue.

ELISA Kit and blood samples

An ELISA-based immunoglobulin (IgG) antibody detection test validated by ICMR would be used. Venous blood samples (approximately 3 mL) will be collected by trained phlebotomists under aseptic conditions. The phlebotomists would be trained in infection, prevention, and control procedures for the collection of samples. The blood would be transported to the hospital laboratory for serum separation and testing for specific SARS-CoV-2-specific IgG antibodies as per the specified optical density cutoff value.

Analysis plan

The cross-sectional survey will give the estimation of the seroprevalence of SARS-COV-2 infection. Contingency tables would be prepared for association between seropositivity and other studied variables. Multiple logistic regression would be done to adjust for confounders, estimation of strength of association, and check for interactions. In the longitudinal part of the study, the seroconversion rate would be calculated. The factors associated with the seroconversion would be delineated by contingency tables. The percentage of people who show persistence of antibodies at 3 months and 6 months would be calculated. Sensitivity analysis would be done based on the inbuilt validation study. Data analysis will be done using R version 3.6.3. P = 0.05 would be taken as statistically significant.

Ethical considerations

Requisite ethical clearance will be obtained from the Institutional Ethical Committee at the institute level/centrally. The participant would be interviewed maintaining their privacy. Patient confidentiality will be maintained throughout the survey by censoring personal identifiers. The data will be analyzed, and final report would be presented in aggregate numbers without any personal identifier. The informed consent form and participant information sheet would be designed.

Quality assurance

It will be ensured at all levels starting from design, methodology, training, supervision, data collection, analysis, and reporting.


  Discussion Top


Sero-surveillance studies among HCWs have been recommended in ICMR Additional Advisory for antibody testing.[7] Many countries have already conducted sero-surveillance among HCWs.[15],[16],[17] There have been studies conducted wherein all health-care workers in a single health-care facility have undergone serology testing.[18] The seroprevalence among HCW in these studies varied from 1.2% to 9%.[14],[15],[16],[17]

ICMR has conducted laboratory-based surveillance for SARS-CoV-2 in India. HCWs were also included as a part of surveillance. The prevalence among asymptomatic HCWs in India was 2.3%.[9] However, all health-care workers were tested according to the prevailing testing policy at that time; hence, bias in the findings cannot be entirely ruled out. The actual prevalence or risk of COVID-19 among HCWs may only be found by through a scientific survey. The survey needs to be monitored and audited. An apex committee at the central level will monitor the study. The nodal officer in each center will be responsible for the conduct of the study at the center. There will be daily monitoring of the project. Weekly progress report of the project will be generated.

The protocol lays down the plan of action to implement the multi-centric serosurveillance project. The survey will provide an assessment of seroprevalence of COVID-19 infection among the health-care workers at hospitals of central ministries from the various parts of the country and its trend over a period of time. It will also help in identifying the various factors associated with higher risk of COVID-19 infection among health-care workers to initiate better preventive measures to reduce their risk as well as to break the chain of further transmission. The survey is also likely to fill some gaps in the natural history of disease. Overall, the survey will help in better planning of preventive measures and tune its advisories based on the scientific evidence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Coronavirus Update (Live): 14,646,894 Cases and 608,987 Deaths from COVID-19 Virus Pandemic Worldometer. Available from: https://www.worldometers.info/coronavirus/. [Last accessed on 2020 Jul 20].  Back to cited text no. 1
    
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Lahner E, Dilaghi E, Prestigiacomo C, Alessio G, Marcellini L, Simmaco M, et al. Prevalence of sars-Cov-2 infection in health workers (HWs) and diagnostic test performance: The experience of a teaching hospital in central Italy. Int J Environ Res Public Health 2020;17:2020;17:4417.  Back to cited text no. 17
    
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Paderno A, Fior M, Berretti G, Schreiber A, Grammatica A, Mattavelli D, et al. SARS-CoV-2 Infection in health care workers: Cross-sectional Analysis of an otolaryngology unit. Otolaryngol Head Neck Surg 2020;163:671-672. doi: 10.1177/0194599820932162. Epub 2020 Jun 2. PMID: 32482123.  Back to cited text no. 18
    


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