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Dynamics of IgG Antibody Responses to SARS-CoV-2 Reveals Insight into Immunity During the Early Pandemic Period in Pakistan

24 Pages Posted: 24 Mar 2022 Publication Status: Under Review

See all articles by Kiran Iqbal Masood

Kiran Iqbal Masood

Aga Khan University - Department of Pathology and Laboratory Medicine

Shama Qaiser

Aga Khan University - Department of Pathology and Laboratory Medicine

Syed Abidi

Aga Khan University - Department of Biological and Biomedical Sciences

Erum Khan

Aga Khan University - Department of Pathology and Laboratory Medicine

Syed Faisal Mahmood

Aga Khan University - Section of Infectious Diseases

Areeba Hussain

Aga Khan University - Department of Pathology and Laboratory Medicine

Zara Ghous

Aga Khan University - Department of Pathology and Laboratory Medicine

Kehkashan Imtiaz

Aga Khan University - Department of Pathology and Laboratory Medicine

Natasha Ali

Aga Khan University - Department of Pathology and Laboratory Medicine

Hassan Hayat

Aga Khan University - Department of Pathology and Laboratory Medicine

Haris Ali Memon

Aga Khan University - Department of Pathology and Laboratory Medicine

Maliha Yameen

Aga Khan University - Department of Pathology and Laboratory Medicine

Shiza Ali

Aga Khan University - Department of Pathology and Laboratory Medicine

Gulzar Lakhani

Aga Khan University - Department of Medicine

Sadaf Baloch

Aga Khan University - Department of Pathology and Laboratory Medicine

Paula Alves

NOVA University of Lisbon - Instituto de Biologia Experimental e Tecnológica (IBET)

Najeeha Talat Iqbal

Aga Khan University - Department of Biological and Biomedical Sciences

Kumail Ahmed

Aga Khan University - Centre of Excellence in Women and Child Health

Junaid Mehmood

Aga Khan University - Centre of Excellence in Women and Child Health

Zulfiqar A Bhutta

University of Toronto - Centre for Global Child Health

Rabia Hussain

Aga Khan University - Department of Pathology and Laboratory Medicine

Martin Rottenberg

Karolinska Institutet - Department of Microbiology, Tumor and Cell Biology (MTC)

J. Pedro Simas

Catholic University of Portugal (UCP) - Católica Biomedical Research

Marc Veldhoen

University of Lisbon - Instituto de Medicina Molecular João Lobo Antunes

Kulsoom Ghias

Aga Khan University - Department of Biological and Biomedical Sciences

Zahra Hasan

Aga Khan University - Department of Pathology and Laboratory Medicine

Multiple version iconThere are 2 versions of this paper

Abstract

Background: COVID-19 related disease morbidity and mortality has varied worldwide. We investigated antibody and T cell responses to SARS-CoV-2 in COVID-19 cases and exposed but healthy individuals further compared with pre-pandemic controls in a high infectious disease burden setting.

Methods: IgG antibodies against Spike and Spike Receptor Binding Domain (RBD) were determined by ELISA in a Health Care cohort (HC; n=304), COVID-19 cases (n=163) and Pre-Pandemic Controls (PPC; n=114). Neutralizing antibody assays and T cell ELISpot assays were also conducted.

Findings: IgG anti Spike proteins and RBD were present in all three groups albeit at varying levels. The highest rate of positivity was observed in COVID-19 cases (87.7% to Spike; 53.9% to RBD); followed by HC (35% to Spike; 21.3% to RBD) and PPC (12.2% to Spike; 10.50% to RBD). Antibody positivity in HC rose from 4.5% in October 2020 to 61% in January 2021. Levels of IgG antibodies to Spike and RBD strongly correlated in COVID-19 and HC but not in PPC. IgG to RBD was associated with neutralizing activity against SARS-CoV-2. Spike reactive T cells were identified in COVID-19 patients (6/18), HC (2/7) and but only one PPC (1/6).

Interpretation: IgG to Spike and RBD in pre-pandemic sera is likely associated with cross-protection induced by other pathogens. The increasing percentage of IgG antibody positivity in HCC over the pandemic period may be due to expansion of cross-reactive B cells as observed in PPC, due either to exposure or asymptomatic subclinical infection with SARS-CoV-2. Neutralizing activity of RBD IgG antibodies and reactive T cells to Spike in PPC suggests the presence of memory B and T cells to cross-reactive epitopes that can expand quickly, jumpstarting protection against SARS-CoV-2.

Funding Information: This work was supported by the Provost’s Academic Priorities Fund, Aga Khan University. Funding support was also received through Swedish Research Council project SRL 4-182/2019. We acknowledge the support for recombinant protein provided by IBET, NOVA University, Portugal. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV).

Conflict of Interests: The authors have no competing interests to declare.

Ethical Approval: This study was approved by the Ethical Review Committee of The Aga Khan University (projects #2020-5152-11688 and 2020-3687-10181).

Keywords: spike, Receptor binding domain, SARS-CoV-2, IgG

Suggested Citation

Masood, Kiran Iqbal and Qaiser, Shama and Abidi, Syed and Khan, Erum and Mahmood, Syed Faisal and Hussain, Areeba and Ghous, Zara and Imtiaz, Kehkashan and Ali, Natasha and Hayat, Hassan and Memon, Haris Ali and Yameen, Maliha and Ali, Shiza and Lakhani, Gulzar and Baloch, Sadaf and Alves, Paula and Iqbal, Najeeha Talat and Ahmed, Kumail and Mehmood, Junaid and Bhutta, Zulfiqar A and Hussain, Rabia and Rottenberg, Martin and Simas, J. Pedro and Veldhoen, Marc and Ghias, Kulsoom and Hasan, Zahra, Dynamics of IgG Antibody Responses to SARS-CoV-2 Reveals Insight into Immunity During the Early Pandemic Period in Pakistan. Available at SSRN: https://ssrn.com/abstract=4065417 or http://dx.doi.org/10.2139/ssrn.4065417

Kiran Iqbal Masood

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Shama Qaiser

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Syed Abidi

Aga Khan University - Department of Biological and Biomedical Sciences ( email )

Karachi
Pakistan

Erum Khan

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Syed Faisal Mahmood

Aga Khan University - Section of Infectious Diseases ( email )

Karachi
India

Areeba Hussain

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Zara Ghous

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Kehkashan Imtiaz

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Natasha Ali

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Hassan Hayat

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Haris Ali Memon

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Maliha Yameen

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Shiza Ali

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Gulzar Lakhani

Aga Khan University - Department of Medicine ( email )

Karachi
Pakistan

Sadaf Baloch

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Paula Alves

NOVA University of Lisbon - Instituto de Biologia Experimental e Tecnológica (IBET) ( email )

Oeiras
Portugal

Najeeha Talat Iqbal

Aga Khan University - Department of Biological and Biomedical Sciences ( email )

Karachi
Pakistan

Kumail Ahmed

Aga Khan University - Centre of Excellence in Women and Child Health ( email )

Pakistan

Junaid Mehmood

Aga Khan University - Centre of Excellence in Women and Child Health ( email )

Pakistan

Zulfiqar A Bhutta

University of Toronto - Centre for Global Child Health ( email )

Toronto
Canada

Rabia Hussain

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

Martin Rottenberg

Karolinska Institutet - Department of Microbiology, Tumor and Cell Biology (MTC) ( email )

Solnavägen 9
Solna, 171 65
Sweden

J. Pedro Simas

Catholic University of Portugal (UCP) - Católica Biomedical Research ( email )

Lisboa
Portugal

Marc Veldhoen

University of Lisbon - Instituto de Medicina Molecular João Lobo Antunes ( email )

Lisbon
Portugal

Kulsoom Ghias

Aga Khan University - Department of Biological and Biomedical Sciences ( email )

Karachi
Pakistan

Zahra Hasan (Contact Author)

Aga Khan University - Department of Pathology and Laboratory Medicine ( email )

Karachi
Pakistan

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