|Year : 2021 | Volume
| Issue : 2 | Page : 178-182
Prevaccination seroprevalence of COVID-19 immunoglobulin g antibodies in health-care personnel and general population after first pandemic wave in a himalayan region in North India
Inam Danish Khan1, Ashok Kumar Jindal2, Kavita Sahai3, Indranil Samanta4
1 Department of Clinical Microbiology and Infectious Diseases, Army College of Medical Sciences and Base Hospital Delhi Cantt, New Delhi, India
2 Department of Community Medicine and Commandant Command Hospital (Northern Command), Udhampur, India
3 Addtl DGAFMS (HR), Ministry of Defence, New Delhi, India
4 Department of Community Medicine and OC 121 FHO, Udhampur, India
|Date of Submission||17-May-2021|
|Date of Decision||06-Aug-2021|
|Date of Acceptance||10-Aug-2021|
|Date of Web Publication||07-Oct-2021|
Lt Col (Dr) Inam Danish Khan
Army College of Medical Sciences and Base Hospital, Delhi Cantt, Delhi - 110 010
Source of Support: None, Conflict of Interest: None
Introduction: COVID-19 has been declared as Public Health Emergency of International Concern with extreme risk of sustained global spread. The pandemic is likely to evolve in successive waves until herd immunity threshold (HIT) is achieved. Asymptomatic carriers and contacts are likely to elude case reporting through conventional algorithm of case finding, testing, contact tracing, and outbreak surveillance, thereby leading to underestimation of disease burden. Widespread community-level transmission of COVID-19 renders higher risk to health-care personnel due to higher propensity and duration of multiple exposures compared to general population. Methods: This is a cross-sectional clinicoepidemiological outcome surveillance study on prevaccination seroprevalence of COVID-19 immunoglobulin G (IgG) antibodies against S1 receptor binding domain in health-care personnel and general population. Results: Seroprevalence of COVID-19 IgG in 570 health-care personnel was 224/570 (39.3%), without any skew based on age or gender. 75% were exposed in the hospital while 21.2% were exposed during travel and 3.1% through high-risk contact outside the hospital. Out of 33 COVID-19 positives, 88% underwent hospital isolation including one ICU admission and 12 home isolation. Seroprevalence of COVID-19 IgG in 400 individuals from general population samples was 138/400 (34.5%). Conclusion: Prevaccination seroprevalence of COVID-19 IgG antibodies after the first pandemic wave revealed no significant difference among health-care personnel and general population reflecting upon a possibility of consecutive pandemic waves until community attainment of HIT. Seroepidemiology can be a robust tool essential to ascertain exposure, immune response, immunity status, and predict susceptibility in population cohorts.
Keywords: COVID-19 antibody testing, COVID-19 pandemic, seroepidemiology, seroprevalence, serosurveillance
|How to cite this article:|
Khan ID, Jindal AK, Sahai K, Samanta I. Prevaccination seroprevalence of COVID-19 immunoglobulin g antibodies in health-care personnel and general population after first pandemic wave in a himalayan region in North India. J Mar Med Soc 2021;23:178-82
|How to cite this URL:|
Khan ID, Jindal AK, Sahai K, Samanta I. Prevaccination seroprevalence of COVID-19 immunoglobulin g antibodies in health-care personnel and general population after first pandemic wave in a himalayan region in North India. J Mar Med Soc [serial online] 2021 [cited 2021 Nov 28];23:178-82. Available from: https://www.marinemedicalsociety.in/text.asp?2021/23/2/178/327564
| Introduction|| |
COVID-19 is a highly transmissible respiratory zoonosis transmitted through respiratory droplets, direct contact and aerosols from human or animal reservoirs and intermediary sources such as surfaces, fomites and hands to humans owing to universal susceptibility in the absence of prior exposure. Severe acute respiratory syndrome (SARS) coronavirus-2 causes COVID-19 after an incubation period of 2–14 days, ranging from asymptomatic to lethal infections. A large proportion of SARS coronavirus-2 infections remains asymptomatic and contributes to disease transmission.
The unprecedented evolution of COVID-19 pandemic has crippled clinical, diagnostic, and public-health infrastructure worldwide leading to high morbidity and mortality in the absence of specific antiviral therapy. The world has witnessed four COVID-19 waves with Hong Kong witnessing the fifth wave and Vietnam witnessing the sixth wave. India is witnessing the second wave with the national capital New Delhi is witnessing the fourth wave of infections.
Long after the World Health Organization (WHO) declared COVID-19 pandemic as Public Health Emergency of International Concern with extreme risk of sustained global spread, multiple variants of concern armed with widespread mutations have emerged worldwide enhancing transmissibility and escape from immunity. The COVID-19 pandemic is likely to evolve in successive waves until herd immunity threshold (HIT) or herd immunity level is achieved.
Every wave exposes a large population to COVID-19 which can be assessed by determination of immunoglobulin G (IgG) antibodies against COVID-19. Asymptomatic carriers and contacts are likely to elude case reporting through conventional algorithm of case finding, testing, contact tracing, and outbreak surveillance, thereby leading to underestimation of disease burden. Determination of prevaccination seroprevalence of COVID-19 antibodies is a robust tool essential to ascertain exposure, immune response, immunity status, and predict susceptibility in population cohorts toward consecutive pandemic waves for integrated clinicoepidemiological management of COVID-19 pandemic.
Widespread community-level transmission of COVID-19 renders higher risk to health-care personnel due to higher propensity and duration of multiple exposures compared to general population. The study characterizes prevaccination seroprevalence of COVID-19 antibodies in health-care personnel and general population after the first pandemic wave in a Himalayan region in North India.
| Methods|| |
The cross-sectional clinicoepidemiological outcome surveillance study was carried out over a 4-week period in February 2021 in a Himalayan region in Northern India after approval from Institutional Ethics, Scientific and Biosafety Committee, and written informed consent from all participating individuals. All personal identifiers were anonymized for confidentiality of data.
Two epidemiologically homogenous cohorts comprising 570 health-care personnel and 400 individuals from general population were sampled. Precalculated sample size was 570 for health-care cohort and 400 for general population cohort with a 95% confidence level, hypothesized maximum seroprevalence of 50%, and absolute precision of 5%. Appropriate stratified sampling frame was drawn up for both cohorts. Study subjects were randomly selected by computer-generated random number table from the sampling frame by stratified random sampling technique. All individuals more than 18 years of age were included while individuals having contraindications to venipuncture were excluded. Both cohorts were clinicodemographically evaluated through a predesigned, pretested, and validated interview administered instrument on history of exposure, symptomatology, repeat infections, and hospital/home isolation post-COVID-19 positivity. 3–5 ml of venous blood samples from proportionately representative population with respect to various strata of interest in both cohorts were drawn under strict aseptic and COVID-19 precautions by trained personnel and serum was separated. The study qualitatively evaluated IgG antibodies against S1 receptor binding domain of COVID-19 from prevaccination serum samples through the Indian Council of Medical Research–National Institute of Virology approved Kavach Karwa SARS coronavirus-2 IgG enzyme-linked immunosorbent assay (ELISA) kit (Karwa Enterprises, Delhi, India) having a sensitivity of 93% and a specificity of 100%. Assay was calibrated with negative and positive known samples before analysis. ELISA cut-off was calculated with inbuilt positive and negative controls. Assay results ≥1 were interpreted as positive for COVID-19 antibodies. Serum IgG antibodies were detected against whole-cell antigen of SARS coronavirus-2 coated on wells of microtiter plates after laboratory validation of reproducibility by retesting 5% positive and negative samples.
Clinicodemographic, surveillance, clinical, management, and outcome profile were correlated for descriptive statistics, including frequency, percentages, and 95% confidence intervals (95% CI). Strict confidentiality of data collected and study results was maintained.
| Results|| |
Seroprevalence of COVID-19 IgG in 570 health-care personnel was 224/570 (39.3%, 95% CI: 35.4%–43.3%) comprising 8/41 (19.5%, 95% CI: 10.2%–34%) seropositive doctors, 24/81 (29.6%, 95% CI: 20.8%–40.3%) nurses, 128/334 (38.3%, 95% CI: 33.3%–43.6%) paramedics, and 64/114 (56.1%, 95% CI: 47.9%–63.9%) ancillary staffers, without any skew based on age or gender. 202/570 (35.4%) were sampled for COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) on account of traveler screening (105/202, 52%), health-care personnel screening (51/202, 25%), history of contact (22/202, 11%), symptomatic influenza like illness (14/202, 7%), and postquarantine (10/202, 5%).
33/570 (5.8%) had a history of documented COVID-19 infection and 22/33 (66.7%) exhibited IgG seropositivity. 11/33 (33.3%) were asymptomatic while 22/33 (66.7%) were symptomatic with fever (82%), anosmia (68%), ageusia (68%), cough (64%), headache (59%), weakness (45.4%), blocked ear/nose (23%), breathlessness (32%), nausea/vomiting (14%), and diarrhea (9%). 75% were exposed in the hospital while 21.2% were exposed during travel and 3.1% through high-risk contact outside the hospital. Out of 33 COVID-19 positives, 88% underwent hospital isolation including one ICU admission and 12 home isolation.
Seroprevalence of COVID-19 IgG in 400 individuals from general population samples was 138/400 (34.5%, 95% CI: 30.0%–39.2%) comprising 118/300 (39.3%, 95% CI: 34.0%–44.9%) males and 20/100 (20%, 95% CI: 13.3%–28.9%) females. Positivity was 03/40 (7.5%) in higher income group compared to 18/40 (45%) and 97/220 (44%) in two cohorts of middle-income group. 88/400 (22%) were sampled for COVID-19 RT-PCR on account of traveler screening (80/400, 90.9%), history of contact (1/400, 1.1%), symptomatic influenza like illness (6/400, 6.8%), and postquarantine (1/400, 1.1%).
02/400 (0.5%) individuals having a history of documented COVID-19 in the past demonstrated IgG antibodies. One was asymptomatic and the other was symptomatic and got hospitalized with fever, cough, headache, and breathlessness. One was exposed at workplace and the other during travel [Table 1].
| Discussion|| |
Management of COVID-19 pandemic is a three-tier construct involving both individual, community, and environment under One Health approach. Peak pandemic response is mandated to be focused on first-level clinicodiagnostic management targeted on individual level such as early detection, isolation of COVID-19 patients, and contact tracing. Parallel second level epidemiological and public health interventions of quarantine, identification of outbreaks/clusters, containment zoning, and mass-mitigatory measures such as travel restrictions and lockdown are essential to flatten the COVID-19 curve. Third-level interventions are mandated during periods of limited disease transmission seen between two pandemic waves. Third-level interventions target serosurveillance and seroepidemiology to ascertain disease prevalence, immunity and protection against further exposure, herd immunity, candidature for vaccination, and enhancing health-care and community resilience. This stage addresses socioeconomic determinants of health which guard health-care outcomes during the peak of the pandemic such as limited health-care accessibility and provisioning, missed opportunities for community-level interventions and psychosocial gaps on public knowledge, attitude, practices, and COVID-19 appropriate behavior.
In this study done in January 2021, seroprevalence was 35%–39% without any significant difference based on age, gender or occupation, depicting similar exposure dynamics. Despite 10-fold higher COVID-19 infection among health-care personnel compared to general population, there was no significant difference in seroprevalence among two groups. This may be attributable to subclinical and asymptomatic infections in general population which may evade detection. Comparatively, health-care personnel are more likely to get tested on every high-risk exposure even in subclinical and asymptomatic infection.
Periodic serosurveillance studies have been done worldwide at various points of time during the pandemic with varying results. India's first national COVID-19 serosurveillance in May–June 2020 in 700 villages within 70 districts in 21 states in >18 years aged population found an antibody prevalence of 0.73% (95% CI: 0.34–1.13) while the second national COVID-19 serosurveillance in August–September 2020 in 29082 individuals of age >10 years from same geographical areas was 6.6%–7.1% (95% CI: 5.8%–8.2%) with higher seropositivity in urban slums (16.9%) compared to urban nonslum areas (9%) and rural areas (5.2%), without any skew based on age, gender, or occupation. The third national COVID-19 serosurveillance in the same region and population in December 2020–January 2021 revealed an antibody prevalence of 25.4% in age 10–17 years with higher seropositivity in urban slums (31.7%) compared to urban nonslum areas (26.2%) and rural areas (19.1%).,,
Drawing from national data from 0.73% to 7.1% to 25.4% to 35%–39% in 7 months, the pandemic has doubled many folds, and seroprevalence is fairly consistent with case data. Nevertheless, the exposure dynamics have been variable due to peak during March–August 2020 and trough during September 2020–January 2021 followed by steep second wave leading to 1.5-fold daily infections in March–April 2021. Pandemic doubling time has shortened from 20 days to 10 days to 4 days in the second wave leading to steep rise in infections owing to higher transmission. While there was a 10-fold increase in seroprevalence from June to September 2020, there was only 3.5-fold increase from September to January 2021 owing to the trough between September 2020 and January 2021, which increased by 1.38 fold in February 2021. There is an obvious shift of infections from urban to rural areas. The current seroprevalence of 35% reflects on the possibility of consecutive pandemic waves unless protective immunity reaches HIT, which so far has been a moving target emphasizing augmentation of health-care systems and resources along with nonpharmacological interventions.
Serosurveillance by qualitative ELISA is a robust, cost-effective, simple, and implementable tool which can boost integrated clinicoepidemiological management of the pandemic. First, serosurveillance has a deployable potential on a mass scale in multiple population cohorts such as health-care personnel, immunocompromised population, people with multiple comorbidities, mass gatherings, and marginalized communities. In addition to ascertaining exposure to COVID-19 and differentiating susceptible and nonsusceptible cohorts, it can help detect previous outbreaks/clusters, determine candidature and duration for vaccination, selection for travel requirements, and evolution of the pandemic.
Second, achieving herd immunity is a plausible tool to break the chain of transmission and contain the pandemic worldwide. HIT is deterministic of endemic steady state with no exponential growth or decline and is estimated between 70% and 90% for COVID-19. Mortality rate of 11.9 per 100,000 in India is the lowest among 20 most affected countries and case-fatality ratio of 1.4% is lower than most countries owing to younger population, which is a positive aspect toward reaching herd immunity. However, dynamics of individual exposure, susceptibility, vaccination, immunogenicity of COVID-19, and nonpharmacological interventions can affect the attainment of HIT. Serosurveillance can act as a surrogate marker for ascertaining HIT on a mass scale using a network of existing medium sized diagnostic and public health laboratories.
Third, serosurveillance can help measure antibody response postvaccination and be able to differentiate seroprevalence postnatural infection vis a vis postvaccination by employing different targets. Herd immunity achieved by natural infection is purportedly superior to vaccine-induced herd immunity due to exposure to multiple antigenic stimuli which may not be achievable through most vaccines except whole virion inactivated vaccines.
Considerable knowledge gaps exist on immune response against COVID-19, reinfections, and recovery which preclude detailed interpretation from IgG-based serosurveillance. Natural infection from COVID-19 does not guarantee protection from reinfections which have been reported worldwide, generally after 3–5 months, which may be deemed as duration of protection. The rapid emergence of mutants and immune escape variants further precludes immunity after natural infection and vaccination. COVID-19 immunity includes humoral immunity through antibodies and cell-mediated immunity. IgG antibodies have variable expression in different hosts and can decline soon after antigenic exposure. This explains why only 22/33 of health-care personnel with documented COVID-19 infection by RTPCR in the past were found positive for IgG. Epidemiological static and dynamic modeling worldwide has not been able to incorporate immunological constructs to successfully predict the course of COVID-19 pandemic pre and postvaccination.
The study is limited by qualitative assay parameter instead of quantitative assay, which is appropriate in design as there are no benchmark levels or cut-offs defined for COVID-19 antibodies. Quantitative estimates/cut-offs between 60 and 180 were followed by various institutions for selecting candidates for convalescent plasma therapy, however, it was summarily found to be of limited clinical benefit by various studies. Further, the detected IgG by ELISA constitutes both neutralizing and nonneutralizing antibodies and may not represent immunity/protection against infection. There are differences in expression, detection, sensitivity, and specificity of antibodies against whole-cell antigen, S1 spike glycoprotein antigen, and nucleocapsid antigen Seroprevalence is also affected by persistence of antibodies postexposure to infection. Detectable IgG antibodies are known to persist up to 7 months with an average 100 days after infection, which can preclude conclusive interpretation from serosurveillance studies. Although the used kit is approved by an apex medical research body, there is no consensus on validated serologic assays for serosurveillance and seroepidemiological studies, especially in terms of protective titers, avidity based older infections and power of the testing modality. Limited sample size can be boosted by pooled antibody assays to optimize population level resources. Regional serosurveillance restricts interpretation of infection-case ratio and infection-fatality ratio. Evolutionary aspects of COVID-19 pandemic in the future would entail detection of protective titers of neutralizing COVID-19 IgG antibodies, memory B lymphocyte, and T lymphocyte activity in naturally infected or vaccinated individuals to ascertain immunological perspectives, which are yet to be concluded upon.,
| Conclusion|| |
Prevaccination seroprevalence of COVID-19 IgG antibodies after the first pandemic wave revealed no significant difference among health-care personnel and general population reflecting upon a possibility of consecutive pandemic waves until community attainment of HIT. Seroepidemiology can be a useful tool to ascertain protection conferred postvaccination.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, et al
. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect 2021;54 (1):12-6.
Clapham H, Hay J, Routledge I, Takahashi S, Choisy M, Cummings D et al
. Seroepidemiologic study designs for determining SARS-CoV2 transmission and immunity. Emerg Infect Dis 2020; 26:1978-86. PMID: 32544053, PMCID: PMC7454079, https://pubmed.ncbi.nlm.nih.gov/32544053/
Lai CC, Wang JH, Hsueh PR. Population-based seroprevalence surveys of anti-SARS-CoV-2 antibody: An up-to-date review. Int J Infect Dis 2020;101:314-22.
Murhekar MV, Bhatnagar T, Selvaraju S, Rade K, Saravankumar V, Thangaraj JWV et al
. Prevalence of SARS-Cov-2 infection in India: Findings from the national serosurvey, May-Jun 2020. Ind J Med Res. 2020; 152: 48-60. PMID: 32952144, PMCID: PMC7853249, https://pubmed.ncbi.nlm.nih.gov/32952144/
Murhekar MV, Bhatnagar T, Selvaraju S, Saravankumar V, Thangaraj JWV, Shah N, et al
, SARS-Cov-2 antibody seroprevalence in India, Aug-Sep 2020: findings from second nationwide household serosurvey. The Lancet Global Health. 2021; 9 (3): E257-E266. PMID: 33515512, PMCID: PMC7906675, https://europepmc.org/article/pmc/pmc7906675
Goenka M, Afzalpurkar S, Goenka U, Das SS, Mukherjee M, Jajodia S, et al
. Seroprevalence of Covid-19 amongst Healthcare workers in a tertiary care hospital of a metropolitan city from India. J Assoc Physicians India. 2020; 68 (11): 14-19. PMID: 33187030, https://pubmed.ncbi.nlm.nih.gov/33187030/
Figueiredo-Campos P, Blankenhaus B, Mota C, et al
. Seroprevalence of anti-SARS-CoV-2 antibodies in Covid-19 patients and healthy volunteers up to 6 months post disease onset. Eur J Immunol 2020;50 (12):2025-40.
BBlackberg A, Fernstrom N, Sarbrant E, Rasmussen M, Sunnerhagen T. Antibody kinetics and clinical course of Covid-19: A prospective observational study. PLoS One. 2021; 16 (3): e0248918. PMID: 33750984, PMCID: PMC7984607, https://pubmed.ncbi.nlm.nih.gov/33750984/
Simonaeaux R, Shafer SL. Can herd immunity save us from Covid-19? ASA Monit 2020;84:18-9.
Vabret N. Antibody responses to SARS-CoV-2 short lived. Nat Rev Immunol 2020;20:519.
Ripperger TJ, Uhrlaub JL, Watanabe M, et al
. Orthogonal SARS-CoV-2 serological assays enable serosurveillance of low prevalence communities and reveal durable humoral immunity. Immunity 2020;53 (33.e4):925.
Poustchi H, Darvishian M, Mohammadi Z, et al
. SARS-Cov-2 antibody seroprevalence in the general population and high risk occupational groups across 18 cities in Iran: A population based cross-sectional study. Lancet Infect Dis 2021;21 (4):473-81.