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Many people have a cross-reactive pre-existing cellular immunity to Covid 19 caused by previous exposure to common cold coronaviruses

Tuesday, August 4, 2020 17:49

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This new paper characterises a cellular immune response involving lymphocytes called T cells that are able to react with other cells in the body that have been infected with the Covid 19 virus, and which are expected to have roles in amplifying coronavirus patient immune responses and clearing the body after infection.

This has hugely important ramifications for understanding the disease and possibly for better treatment and prophylaxis

Abstract

Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of pre-existing memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.

Article introduction:

The emergence of SARS-CoV-2 in late 2019 and its subsequent global spread has led to millions of infections and substantial morbidity and mortality (1). Coronavirus disease 2019 (COVID-19), the clinical disease caused by SARS-CoV-2 infection, can range from mild self-limiting disease to acute respiratory distress syndrome and death (2). The mechanisms underlying the spectrum of COVID-19 disease severity states, and the nature of protective immunity against COVID-19 currently remains unclear.

Studies dissecting the human immune response against SARS-CoV-2 have begun to characterize SARS-CoV-2 antigen-specific T cell responses (3–8), and multiple studies have described marked activation of T cell subsets in acute COVID-19 patients (9–13).

Surprisingly, antigen-specific T cell studies performed with five different cohorts reported that 20-50% of people who had not been exposed to SARS-CoV-2 had significant T cell reactivity directed against peptides corresponding to SARS-CoV-2 sequences (3–7).

The studies were from geographically diverse cohorts (USA, Netherlands, Germany, Singapore, and UK), and the general pattern observed was that the T cell reactivity found in unexposed individuals was predominantly mediated by CD4+ T cells. It was speculated that this phenomenon might be due to preexisting memory responses against human “common cold” coronaviruses (HCoVs), such as HCoV-OC43, HCoV-HKU1, HCoV-NL63, or HCoV-229E.

These HCoVs share partial sequence homology with SARS-CoV-2, are widely circulating in the general population, and are typically responsible for mild respiratory symptoms (14–16). However, the hypothesis of crossreactive immunity between SARS-CoV-2 and common cold HCoVs still awaits experimental trials.

This potential preexisting cross-reactive T cell immunity to SARS-CoV-2 has broad implications, as it could explain aspects of differential COVID-19 clinical outcomes, influence epidemiological models of herd immunity (17, 18), or affect the performance of COVID-19 candidate vaccines.

RESEARCH ARTICLE CITATION DETAILS

Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

Jose Mateus1, Alba Grifoni1, Alison Tarke1, John Sidney1, Sydney I. Ramirez 1,3, Jennifer M. Dan 1,3, Zoe C. Burger3, Stephen A. Rawlings 3, Davey M. Smith 3, Elizabeth Phillips2, Simon Mallal2, Marshall Lammers1, Paul Rubiro1, Lorenzo Quiambao1, Aaron Sutherland1, Esther Dawen Yu1, Ricardo daSilva Antunes1, Jason Greenbaum1, April Frazier1, Alena J. Markmann4, Lakshmanane Premkumar5,Aravinda de Silva5, Bjoern Peters1,3, Shane Crotty 1,3, Alessandro Sette 1,3,*,†,
Daniela Weiskopf 1,*,†

Science 04 Aug 2020 :eabd3871 DOI: 10.1126/science.abd3871

Source: http://gmopundit.blogspot.com/2020/08/many-people-have-cross-reactive-pre.html

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