Sero-prevalence of Anti-SARS-CoV-2 Antibody Among the Asymptomatic and Confirmed COVID-19 Positive Population of Chattogram Metropolitan Area

Abstract

Prof. Dr. Sharmin Chowdhury, PhD Supervisor -------------------------------------------------------------- Prof. Dr. Sharmin Chowdhury, PhD Chairman of the Examination Committee One Health Institute Chattogram Veterinary and Animal Sciences University Chattogram-4225, Bangladesh iv Acknowledgements All praises to almighty Allah who gave me the opportunity to be enrolled in the One Health Institute for achieving Master in Public Health. I would like to express my veneration to honorable supervisor Prof. Dr. Sharmin Chowdhury, Professor, Department of Pathology and Parasitology, Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University (CVASU) for her coherent and articulated instructions. It wouldnot be possible to complete such a laborious task without her scholastic guidelines. It was an exquisite experience for me to work under her supervision. I feel much pleasure to convey my gratitude to Prof. Dr. M. A. Hassan Chowdhury, Professor, Department of Medicine, Chittagong Medical College Hospital for his valuable suggestions. Special thanks to him for his encouragement and cordial co-operation throughout thework. I would like to acknowledge the support and encouragement received during MPH program from other teachers, technical and non-technical staffs of the One Health Institute, CVASU. I am also grateful to my family members for their allowance and heartiest support. v Table of Contents Acknowledgements iv List of Tables vii List of Figures viii List of Abbreviations ix Abstract x Chapter 1: Introduction 1 Chapter 2: Review of the Literature 7-26 2.1 COVID-19 pandemic and its causative agent 7 2.2 Symptoms of COVID-19 8 2.3. Pathogenesis and host response 9 2.4. Symptoms and diagnosis of COVID-19 13 2.5. Seroprevalence of SARS-CoV-2 16 2.6. The Bangladesh context of the disease 22 2.7. Seroprevalence in Bangladesh 23 Chapter 3: Materials and Methods 27-34 3.1 Study design 27 3.2 Place of study 27 3.3 Period of study 27 3.4 Study population 27 3.5 Sampling technique 27 vi 3.6 Sample size determination 27 3.7 Selection criteria 28 3.8 Variables 29 3.9 Research instruments 29 3.10 Data collection technique 29 3.11 Study procedure 29 3.12 Baseline blood collection and processing 30 3.13 Serological test examination 30 3.14 Data management 31 3.15 Data analysis 31 3.16 Ethical aspect 32 3.17 Data processing plan 33 3.18 Procedure for Maintaining Confidentiality 34 Chapter 4: Result 35 Chapter 5: Discussion 44 Chapter 6: Conclusion 47 Chapter 7: Limitations 48 Chapter 8: Recommendations 49 References 50 Annexure 59 vii List of Tables Table 4.1 Baseline characteristics of study participants 36 Table 4.2 Prevalence of SARS-CoV-2 IgG antibodies estimation in CMA 37 Table 4.3 Univariable analysis (ttest, one way ANOVA) to evaluate the mean difference of quantity of anti-SARS-CoV-2 antibody in serum samples 39 Table 4.4 Univariable analysis (χ2 test, logistic regression) to evaluate the association of different variables with seroprevalence of anti-SARS-CoV-2 antibody 42 Table 4.5 Output from the final multivariable logistic regression model showing the adjusted effect of potential factors on the seroprevalence of anti-SARS-CoV-2 antibody 43 viii List of Figures Figure 2.1 Mode of spread of COVID-19 (Karia et al., 2020) 9 Figure 2.2 Pathogenesis of COVID-19 (Chams et al., 2020) 10 Figure 2.3 Key components of the adaptive immune response to SARS-CoV-2 (Flanagan et al., 2020) 15 Figure 2.4 Mild versus severe immune response during virus infection (Lebeau et al., 2020) 17 Figure 4.1 Prevalence of anti-SARS-CoV-2 antibody (IgG) in different donor types along with vaccinated percent. 37 Figure 4.2 Evaluation of time effects of vaccines mean difference of quantitative anti-SARS-CoV-2 antibody (IgG) in serum samples 40 ix List of Abbreviations RT-PCR Real Time Polymerase Chain Reaction HCW Health Care Worker ARDS Acute Respiratory Distress Syndrome CRP C-Reactive Protein LDH Lactate Dehydrogenase IL-6 Inter Leukin-6 RBD Receptor Binding Domain EMA European Medicines Agency FDA Food and Drug Administration CRS Cytokine Release Syndrome ACE-2 Angiotensin Converting Enzyme-2 CMA Chattogram Metropolitan Area x Abstract Seroprevalence studies of coronavirus disease 2019 (COVID-19) assess the degree of undetected transmission in the community. Different groups, such as healthcare workers (HCWs), garment workers, and others, are deemed vulnerable due to their workplace hazards and immense responsibility. The present study was conducted to estimate the seroprevalence of anti-SARS-CoV-2 antibody (IgG) and its association with different explanatory variables. Further, the antibody was quantified to assess the increasing or decreasing trend over different intervention periods and according to other factors. This cross-sectional study observed health workers - doctor, nurse, hospital staff, etc. in and outpatients (non-COVID-19) and garments workers of Chattogram metropolitan area (CMA, N=748) from randomly selected six government and private hospitals and two garment factories. Study subjects were included upon written consent, fulfilling specific inclusion criteria. Venous blood was collected following standard aseptic methods. Qualitative and quantitative ELISA was used to identify and quantify antibodies (IgG) in serum samples. Descriptive, univariable, and multivariable statistical analysis was performed. Overall seroprevalence was estimated as 66.99% (95% CI: 63.40%-70.40%). Seroprevalence among HCWs, in and outpatients, and garments workers were 68.99 % (95% CI: 63.8%-73.7%), 81.37 % (95% CI: 74.7%-86.7%), and 50.56 % (95% CI: 43.5%- 57.5%), respectively. Sero-prevalence was 44.47 % (95% CI: 38.6%-50.4%) in the non-vaccinated population while it was significantly (p<0.001) higher in the population receiving the first dose (61.66 %, 95% CI: 54.8%-68.0%) and both (first and second) doses of vaccine (100%, 95% CI: 98.4%-100%). The mean titer of the antibody was estimated as 255.46 DU/ml and 159.08 DU/ml in the population with both doses and one dose of vaccine, respectively, compared to 53.71 DU/ml of the unvaccinated population. A decreasing trend in the titer of antibodies with increasing time after vaccination was observed. Sero-prevalence and mean antibody titer varied according to different factors in this study. The second dose of vaccine significantly increased the sero-prevalence and titer, which decreased to a certain level over time. Although antibody was produced following natural infection, the mean titer was relatively low compared to antibody after vaccination. This study emphasizes the role of the vaccine in antibody production. Based on the findings, interventions like continuing extensive mass vaccination of the leftover unvaccinated population and