Immune Memory in Mild COVID-19 Patients and Unexposed Donors Reveals Persistent T Cell Responses After SARS-CoV-2 Infection.

Asgar Ansari,Alba Grifoni,Anurag Kalia,Ashok Sharma,Shilpa Sachan,Poonam Coshic,Rakesh Arya,Someshwar Nath Jha,Nimesh Gupta,Daniela Weiskopf,Anupam Lall,Alessandro Sette

doi:10.3389/fimmu.2021.636768

Abstract

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4+ T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4+ T cells and B cells, with a minimal contribution from CD8+ T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.

Highlights

The COVID-19 pandemic has evolved with variable trajectory in diverse geographical locations
Because we observed cross-reactive antibodies to the SARSCoV-2 nucleoprotein in unexposed donors, we examined the IgG reactivity to nucleoproteins from common-cold HCoVOC43 and Human Coronaviruses (HCoVs)-NL63 as a representative betacoronavirus and alphacoronavirus, respectively
COVID-19 patients showed an increase in IgG response against the HCoV-OC43 but not to the other common cold coronavirus tested, HCoV-NL-63, which may have less closely related Nucleoprotein to SARS-CoV-2 [18]

Summary

Introduction

The COVID-19 pandemic has evolved with variable trajectory in diverse geographical locations. Recent reports reveal the existence of cross-reactive CD4+ T cells in ~20-50% of the individuals never been exposed to SARS-CoV-2 [1,2,3,4,5] These cross-reactive CD4+ T cells are largely canonical memory cells and they may be the outcome of previous infections with many of the common cold HCoVs [4]. The cross-reactive immune memory to SARS-CoV-2 is limited to CD4+ T cells and more studies are required to understand the cross-reactivity from HCoVs in case of the humoral immunity [6,7,8] Most of these studies are limited to the antibody analyses and there is no firm knowledge available for the cross-reactivity in the B cell pool. It’s not clear if this decline is gradual and if the similar decline exists in the memory pool of T cells and B cells

Methods

Results

Conclusion