The trinity of COVID-19: immunity, inflammation and intervention

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new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="XE1BR55Ij63XVGax02GTbG4wJO6cxUNfFoJaVaf0vmaELjkrRA20cAy0U73gMuIN"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="XE1BR55Ij63XVGax02GTbG4wJO6cxUNfFoJaVaf0vmaELjkrRA20cAy0U73gMuIN"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="XE1BR55Ij63XVGax02GTbG4wJO6cxUNfFoJaVaf0vmaELjkrRA20cAy0U73gMuIN"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="XE1BR55Ij63XVGax02GTbG4wJO6cxUNfFoJaVaf0vmaELjkrRA20cAy0U73gMuIN"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> 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Immunology"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Nat+Rev+Immunol%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Nat+Rev+Immunol%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Nat Rev Immunol" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Nat Rev Immunol"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Nat+Rev+Immunol%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Nat Rev Immunol"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Nat Rev Immunol"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Nat Rev Immunol"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2020 Jun;20(6):363-374.</span> </div> <span class="citation-doi"> doi: 10.1038/s41577-020-0311-8. </span> <span class="secondary-date"> Epub 2020 Apr 28. </span> </div> <h1 class="heading-title"> The trinity of COVID-19: immunity, inflammation and intervention </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Tay+MZ&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Matthew Zirui Tay">Matthew Zirui Tay</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Poh+CM&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Chek Meng Poh">Chek Meng Poh</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=R%C3%A9nia+L&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Laurent Rénia">Laurent Rénia</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=MacAry+PA&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Paul A MacAry">Paul A MacAry</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ng+LFP&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Lisa F P Ng">Lisa F P Ng</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg." href="#full-view-affiliation-6" ref="linksrc=author_aff"> 6 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK. lisa_ng@immunol.a-star.edu.sg." href="#full-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/32346093/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore.</li> <li data-affiliation-id="full-view-affiliation-2" id="full-view-affiliation-2" ><sup class="key">2</sup> Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg.</li> <li data-affiliation-id="full-view-affiliation-3" id="full-view-affiliation-3" ><sup class="key">3</sup> Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg.</li> <li data-affiliation-id="full-view-affiliation-4" id="full-view-affiliation-4" ><sup class="key">4</sup> Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg.</li> <li data-affiliation-id="full-view-affiliation-5" id="full-view-affiliation-5" ><sup class="key">5</sup> Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg.</li> <li data-affiliation-id="full-view-affiliation-6" id="full-view-affiliation-6" ><sup class="key">6</sup> Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg.</li> <li data-affiliation-id="full-view-affiliation-7" id="full-view-affiliation-7" ><sup class="key">7</sup> Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK. lisa_ng@immunol.a-star.edu.sg.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">32346093</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC7187672&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7187672/" data-ga-category="full_text" data-ga-action="PMCID" > PMC7187672 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1038/s41577-020-0311-8&id_type=DOI" href="https://doi.org/10.1038/s41577-020-0311-8" data-ga-category="full_text" data-ga-action="DOI" > 10.1038/s41577-020-0311-8 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <div class="publication-type" >Review</div> <h1 class="heading-title"> The trinity of COVID-19: immunity, inflammation and intervention </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Matthew Zirui Tay</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> Nat Rev Immunol<span class="citation-separator">.</span> </span> <span class="date"> <span class="citation-year">2020 Jun</span><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/32346093/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> 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Immunology"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Nat+Rev+Immunol%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Nat+Rev+Immunol%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Nat Rev Immunol" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Nat Rev Immunol"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Nat+Rev+Immunol%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Nat Rev Immunol"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Nat Rev Immunol"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Nat Rev Immunol"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2020 Jun;20(6):363-374.</span> </div> <span class="citation-doi"> doi: 10.1038/s41577-020-0311-8. </span> <span class="secondary-date"> Epub 2020 Apr 28. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Tay+MZ&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Matthew Zirui Tay">Matthew Zirui Tay</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Poh+CM&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Chek Meng Poh">Chek Meng Poh</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=R%C3%A9nia+L&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Laurent Rénia">Laurent Rénia</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=MacAry+PA&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Paul A MacAry">Paul A MacAry</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ng+LFP&cauthor_id=32346093" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Lisa F P Ng">Lisa F P Ng</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK. lisa_ng@immunol.a-star.edu.sg." href="#short-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. renia_laurent@immunol.a-star.edu.sg.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. micpam@nus.edu.sg.</li> <li data-affiliation-id="short-view-affiliation-5" id="short-view-affiliation-5" ><sup class="key">5</sup> Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg.</li> <li data-affiliation-id="short-view-affiliation-6" id="short-view-affiliation-6" ><sup class="key">6</sup> Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg.</li> <li data-affiliation-id="short-view-affiliation-7" id="short-view-affiliation-7" ><sup class="key">7</sup> Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK. lisa_ng@immunol.a-star.edu.sg.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">32346093</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC7187672&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7187672/" data-ga-category="full_text" data-ga-action="PMCID" > PMC7187672 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1038/s41577-020-0311-8&id_type=DOI" href="https://doi.org/10.1038/s41577-020-0311-8" data-ga-category="full_text" data-ga-action="DOI" > 10.1038/s41577-020-0311-8 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/32346093/citations/" data-citation-style="nlm" data-pubmed-format-link="/32346093/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" data-ga-category="literature_resources" data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a> </p> <div class="conflict-of-interest" id="conflict-of-interest"> <h2 class="title"> Conflict of interest statement </h2> <div class="statement"> <p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare no competing interests.</p> </div> </div> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="fig-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/bdd99ff8dbc9/41577_2020_311_Fig1_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="709" data-image-height="843" data-image-alt="Fig. 1" data-pmc-id="PMC7187672" data-figure-id="Fig1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/7ac412cd97fa/41577_2020_311_Fig1_HTML.gif" alt="Fig. 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="709"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="843"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 1. Chronology of events during SARS-CoV-2… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 1. Chronology of events during SARS-CoV-2 infection. </p> </strong> <div class="figure-caption-contents"><p> When severe acute respiratory syndrome coronavirus 2… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 1. Chronology of events during SARS-CoV-2 infection. </strong> <div class="figure-caption-contents">When severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells expressing the surface receptors angiotensin-converting enzyme 2 (ACE2) and TMPRSS2, the active replication and release of the virus cause the host cell to undergo pyroptosis and release damage-associated molecular patterns, including ATP, nucleic acids and ASC oligomers. These are recognized by neighbouring epithelial cells, endothelial cells and alveolar macrophages, triggering the generation of pro-inflammatory cytokines and chemokines (including IL-6, IP-10, macrophage inflammatory protein 1α (MIP1α), MIP1β and MCP1). These proteins attract monocytes, macrophages and T cells to the site of infection, promoting further inflammation (with the addition of IFNγ produced by T cells) and establishing a pro-inflammatory feedback loop. In a defective immune response (left side) this may lead to further accumulation of immune cells in the lungs, causing overproduction of pro-inflammatory cytokines, which eventually damages the lung infrastructure. The resulting cytokine storm circulates to other organs, leading to multi-organ damage. In addition, non-neutralizing antibodies produced by B cells may enhance SARS-CoV-2 infection through antibody-dependent enhancement (ADE), further exacerbating organ damage. Alternatively, in a healthy immune response (right side), the initial inflammation attracts virus-specific T cells to the site of infection, where they can eliminate the infected cells before the virus spreads. Neutralizing antibodies in these individuals can block viral infection, and alveolar macrophages recognize neutralized viruses and apoptotic cells and clear them by phagocytosis. Altogether, these processes lead to clearance of the virus and minimal lung damage, resulting in recovery. G-CSF, granulocyte colony-stimulating factor; TNF, tumour necrosis factor.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="fig-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/6b3ee3d38448/41577_2020_311_Fig2_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="622" data-image-height="438" data-image-alt="Fig. 2" data-pmc-id="PMC7187672" data-figure-id="Fig2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/0fdc56ff3763/41577_2020_311_Fig2_HTML.gif" alt="Fig. 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="622"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="438"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 2. The structure of the trimeric… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 2. The structure of the trimeric spike protein of SARS-CoV-2. </p> </strong> <div class="figure-caption-contents"><p> The receptor-binding domain (RBD)… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 2. The structure of the trimeric spike protein of SARS-CoV-2. </strong> <div class="figure-caption-contents">The receptor-binding domain (RBD) is shown interacting with its receptor, human angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Adapted from Protein Data Bank IDs 6VSB and 6VW1 (ref.150).</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="fig-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/f0faad87283e/41577_2020_311_Fig3_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="685" data-image-height="513" data-image-alt="Fig. 3" data-pmc-id="PMC7187672" data-figure-id="Fig3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/70e2c6c55dc1/41577_2020_311_Fig3_HTML.gif" alt="Fig. 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="685"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="513"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 3. Potential therapeutic approaches against SARS-CoV-2. </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 3. Potential therapeutic approaches against SARS-CoV-2. </p> </strong> <div class="figure-caption-contents"><p> ( <b> 1 </b> ) Antibodies against the spike protein… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 3. Potential therapeutic approaches against SARS-CoV-2. </strong> <div class="figure-caption-contents">(<b>1</b>) Antibodies against the spike protein (raised through vaccination or by adoptive transfer) could block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interacting with the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. (<b>2</b>) Protease inhibitors against the serine protease TMPRSS2 can prevent spike protein cleavage, which is necessary for viral fusion into the host cell. Blocking either ACE2 interaction or viral fusion could prevent the virus from infecting the host cell. (<b>3</b>) Virus-specific memory CD8<sup>+</sup> T cells from a previous vaccination or infection can differentiate into effector cells during rechallenge. When they identify infected cells presenting virus-specific epitopes, they degranulate and kill infected cells before they can produce mature virions. (<b>4</b>) In a novel treatment method that targets the cytokine storm symptoms, the blood of patients with coronavirus disease 2019 (COVID-19) can be passed through customized columns that are specially designed to trap pro-inflammatory cytokines, before the purified blood is passed back into patients.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="fig-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/c16862ca7443/41577_2020_311_Fig4_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="686" data-image-height="647" data-image-alt="Fig. 4" data-pmc-id="PMC7187672" data-figure-id="Fig4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ba/7187672/e09b3f468030/41577_2020_311_Fig4_HTML.gif" alt="Fig. 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="686"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="647"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 4. Sequence alignment and structural comparison… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 4. Sequence alignment and structural comparison of SARS-CoV and SARS-CoV-2 spike proteins. </p> </strong> <div class="figure-caption-contents"><b> a </b> |…</div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 4. Sequence alignment and structural comparison of SARS-CoV and SARS-CoV-2 spike proteins. </strong> <div class="figure-caption-contents"><b>a</b> | Sequence alignment of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, with conserved amino acid residues shown in black and non-conserved residues shown in colours. <b>b</b> | The 3D structure of SARS-CoV-2 (Protein Data Bank ID 6VSB, peach ribbon) is superimposed on the SARS-CoV receptor-binding motif (RBM) complex with the neutralizing antibody (nAb; red ribbon) interfacing with the RBM (Protein Data Bank 2DD8 (ref.), purple ribbon). Peach and purple spheres denote the RBMs of SARS-CoV-2 and SARS-CoV, respectively. Magenta spheres denote non-synonymous alterations in the SARS-CoV-2 spike protein that have been reported.</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/32607866/" ref="article_id=32607866&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="32607866" data-ga-label=""> A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV, and MERS-CoV. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Singh A, Singh RS, Sarma P, Batra G, Joshi R, Kaur H, Sharma AR, Prakash A, Medhi B.</span> <span class="docsum-authors short-authors">Singh A, et al.</span> <span class="docsum-journal-citation full-journal-citation">Virol Sin. 2020 Jun;35(3):290-304. doi: 10.1007/s12250-020-00252-z. 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Med. 2020 doi: 10.1038/s41591-020-0820-9. - <a class="reference-link" href="https://doi.org/10.1038/s41591-020-0820-9" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1038/s41591-020-0820-9" > DOI </a> - <a class="reference-link" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7095063/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="PMC7095063" > PMC </a> - <a class="reference-link" href="/32284615/" ref="linksrc=references_link&ordinalpos=3" data-ga-category="reference" data-ga-action="32284615" > PubMed </a> </li> </ol> </li> </ol> <div class="actions-bar"> <button class="show-all" ref="linksrc=show_all_references_link" aria-controls="top-references-list-1" data-next-page-url="/32346093/references/" data-ga-category="reference" data-ga-action="show_more" > Show all 151 references </button> </div> </div> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 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