{"id":1932,"date":"2021-08-12T18:48:23","date_gmt":"2021-08-12T18:48:23","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=1932"},"modified":"2021-08-12T18:48:23","modified_gmt":"2021-08-12T18:48:23","slug":"pre-existing-immunity-to-sars-cov-2-the-knowns-and-unknowns","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=1932","title":{"rendered":"Pre-existing immunity to SARS-CoV-2: the knowns and unknowns"},"content":{"rendered":"\n

Authors: Alessandro Sette<\/a>\u00a01<\/a>\u00a02<\/a><\/sup>,\u00a0Shane Crotty<\/a>\u00a03<\/a>\u00a04<\/a><\/sup><\/p>\n\n\n\n

Abstract<\/h2>\n\n\n\n

T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating \u2018common cold\u2019 coronaviruses. It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses.<\/p>\n\n\n\n

As data start to accumulate on the detection and characterization of SARS-CoV-2 T cell responses in humans, a surprising finding has been reported: lymphocytes from 20\u201350% of unexposed donors display significant reactivity to SARS-CoV-2 antigen peptide pools1<\/a>,2<\/a>,3<\/a>,4<\/a><\/sup>.<\/p>\n\n\n\n

In a study by Grifoni et al.1<\/a><\/sup>, reactivity was detected in 50% of donor blood samples obtained in the USA between 2015 and 2018, before SARS-CoV-2 appeared in the human population. T cell reactivity was highest against proteins other than the coronavirus spike protein, but T cell reactivity was also detected against spike. The SARS-CoV-2 T cell reactivity was mostly associated with CD4+<\/sup> T cells, with a smaller contribution by CD8+<\/sup> T cells1<\/a><\/sup>. Similarly, in a study of blood donors in the Netherlands, Weiskopf et al.2<\/a><\/sup> detected CD4+<\/sup> T cell reactivity against SARS-CoV-2 spike peptides in 1 of 10 unexposed subjects and against SARS-CoV-2 non-spike peptides in 2 of 10 unexposed subjects. CD8+<\/sup> T cell reactivity was observed in 1 of 10 unexposed donors. In a third study, from Germany, Braun et al.3<\/a><\/sup> reported positive T cell responses against spike peptides in 34% of SARS-CoV-2 seronegative healthy donors. Finally, a study of individuals in Singapore, by Le Bert et al.4<\/a><\/sup>, reported T cell responses to nucleocapsid protein nsp7 or nsp13 in 50% of subjects with no history of SARS, COVID-19, or contact with patients with SARS or COVID-19. A study by Meckiff using samples from the UK also detected reactivity in unexposed subjects5<\/a><\/sup>. Taken together, five studies report evidence of pre-existing T cells that recognize SARS-CoV-2 in a significant fraction of people from diverse geographical locations.<\/p>\n\n\n\n

These early reports demonstrate that substantial T cell reactivity exists in many unexposed people; nevertheless, data have not yet demonstrated the source of the T cells or whether they are memory T cells. It has been speculated that the SARS-CoV-2-specific T cells in unexposed individuals might originate from memory T cells derived from exposure to \u2018common cold\u2019 coronaviruses (CCCs), such as HCoV-OC43, HCoV-HKU1, HCoV-NL63 and HCoV-229E, which widely circulate in the human population and are responsible for mild self-limiting respiratory symptoms. More than 90% of the human population is seropositive for at least three of the CCCs6<\/a><\/sup>. Thiel and colleagues3<\/a><\/sup> reported that the T cell reactivity was highest against a pool of SARS-CoV-2 spike peptides that had homology to CCCs.<\/p>\n\n\n\n

What are the implications of these observations? The potential for pre-existing crossreactivity against COVID-19 in a fraction of the human population has led to extensive speculation. Pre-existing T cell immunity to SARS-CoV-2 could be relevant because it could influence COVID-19 disease severity. It is plausible that people with a high level of pre-existing memory CD4+<\/sup>\u00a0T cells that recognize SARS-CoV-2 could mount a faster and stronger immune response upon exposure to SARS-CoV-2 and thereby limit disease severity. Memory T follicular helper (TFH<\/sub>) CD4+<\/sup>\u00a0T cells could potentially facilitate an increased and more rapid neutralizing antibody response against SARS-CoV-2. Memory CD4+<\/sup>\u00a0and CD8+<\/sup>\u00a0T cells might also facilitate direct antiviral immunity in the lungs and nasopharynx early after exposure, in keeping with our understanding of antiviral CD4+<\/sup>\u00a0T cells in lungs against the related SARS-CoV7<\/a><\/sup>\u00a0and our general understanding of the value of memory CD8+<\/sup>\u00a0T cells in protection from viral infections. Large studies in which pre-existing immunity is measured and correlated with prospective infection and disease severity could address the possible role of pre-existing T cell memory against SARS-CoV-2.<\/p>\n\n\n\n

For More Information: https:\/\/www.nature.com\/articles\/s41577-020-0389-z<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Authors: Alessandro Sette\u00a01\u00a02,\u00a0Shane Crotty\u00a03\u00a04 Abstract T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that […]<\/p>\n","protected":false},"author":2,"featured_media":1933,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[982,985,987,101,996,296,890,541,964],"tags":[],"class_list":["post-1932","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-b-cell","category-cd4","category-cd8","category-covid-19","category-immune-system-covid-19","category-lymphocyte","category-natural-immunity-immune-system","category-spike-protein","category-t-cell"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/1932","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1932"}],"version-history":[{"count":0,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/1932\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/1933"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1932"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1932"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1932"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}