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<h3>COVID-19</h3> <div class='row'> <div class='small-10 medium-7 large-5 small-centered columns'> <ul class='tabs row' data-tab> <li class='tab-title small-6 centered active'> <a href='#articles'>105 Articles</a> </li> <li class='tab-title small-6 centered '> <a href='#posts'>0 Posts</a> </li> </ul> </div> </div> <div class='tabs-content'> <div class='content active' id='articles'> <div class='row'> <div class='small-12 columns'> <div role="navigation" aria-label="Pagination" class="pagination-centered" previous_label="<--" next_label="-->"><ul class="pagination"><li class="arrow unavailable"><a class="arrow unavailable">← Previous</a></li> <li class="current"><a class="current">1</a></li> <li><a rel="next" href="/tags/118?content=articles&page=2">2</a></li> <li><a href="/tags/118?content=articles&page=3">3</a></li> <li class="unavailable"><a>…</a></li> <li><a href="/tags/118?content=articles&page=10">10</a></li> <li><a href="/tags/118?content=articles&page=11">11</a></li> <li class="arrow"><a class="arrow" rel="next" href="/tags/118?content=articles&page=2">Next →</a></li></ul></div> </div> </div> <div class='row'> <div class='small-12 columns'> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/181136">Post-transfusion activation of coagulation pathways during severe COVID-19 correlates with COVID-19 convalescent plasma antibody profiles</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/181136">Svenja Weiss, … , Raymond A. Alvarez, Benjamin K. Chen</a> <a class='hide-for-small show-more' data-reveal-id='article45874-more' href='#'> <div class='article-authors'> Svenja Weiss, … , Raymond A. Alvarez, Benjamin K. Chen </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e181136. <a href="https://doi.org/10.1172/JCI181136">https://doi.org/10.1172/JCI181136</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/181136">Text</a> | <a href="/articles/view/181136/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI181136' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/181136/ga' ref='group' title='Graphical abstract'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/181000/181136/small/JCI181136.ga.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45874-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/181136">Post-transfusion activation of coagulation pathways during severe COVID-19 correlates with COVID-19 convalescent plasma antibody profiles</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/181136">Text</a></li> <li><a class="button tiny" href="/articles/view/181136/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Early antibody therapy can prevent severe SARS-CoV-2 infection (COVID-19). However, the effectiveness of COVID-19 convalescent plasma (CCP) therapy in treating severe COVID-19 remains inconclusive. To test a hypothesis that some CCP units are associated with a coagulopathy hazard in severe disease that offsets its benefits, we tracked 304 CCP units administered to 414 hospitalized COVID-19 patients to assess their association with the onset of unfavorable post-transfusion D-dimer trends. CCP recipients with increasing or persistently elevated D-dimer trajectories after transfusion experienced higher mortality than those whose D-dimer levels were persistently low or decreasing after transfusion. Within the CCP donor-recipient network, recipients with increasing or persistently high D-dimer trajectories were skewed toward association with a minority of CCP units. In in vitro assays, CCP from “higher-risk” units had higher cross-reactivity with the spike protein of human seasonal betacoronavirus OC43. “Higher-risk” CCP units also mediated greater Fcγ receptor IIa signaling against cells expressing SARS-CoV-2 spike compared with “lower-risk” units. This study finds that post-transfusion activation of coagulation pathways during severe COVID-19 is associated with specific CCP antibody profiles and supports a potential mechanism of immune complex–activated coagulopathy.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Svenja Weiss, Hung-Mo Lin, Eric Acosta, Natalia L. Komarova, Ping Chen, Dominik Wodarz, Ian Baine, Ralf Duerr, Ania Wajnberg, Adrian Gervais, Paul Bastard, Jean-Laurent Casanova, Suzanne A. Arinsburg, Talia H. Swartz, Judith A. Aberg, Nicole M. Bouvier, Sean T.H. Liu, Raymond A. Alvarez, Benjamin K. Chen</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/175233">Sequential intranasal booster triggers class switching from intramuscularly primed IgG to mucosal IgA against SARS-CoV-2</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/175233">Yifan Lin, … , Zheng Zhang, Hua Peng</a> <a class='hide-for-small show-more' data-reveal-id='article45687-more' href='#'> <div class='article-authors'> Yifan Lin, … , Zheng Zhang, Hua Peng </div> </a> <span class='article-published-at'> Published January 14, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025. <a href="https://doi.org/10.1172/JCI175233">https://doi.org/10.1172/JCI175233</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/175233">Text</a> | <a href="/articles/view/175233/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI175233' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45687-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/175233">Sequential intranasal booster triggers class switching from intramuscularly primed IgG to mucosal IgA against SARS-CoV-2</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/175233">Text</a></li> <li><a class="button tiny" href="/articles/view/175233/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>The persistent emergence of COVID-19 variants and recurrent waves of infection worldwide underscores the urgent need for vaccines that effectively reduce viral transmission and prevent infections. Current intramuscular (IM) COVID-19 vaccines inadequately protect the upper respiratory mucosa. In response, we have developed a nonadjuvanted, interferon-armed SARS-CoV-2 fusion protein vaccine with IM priming and intranasal (IN) boost sequential immunization. Our study showed that this sequential vaccination strategy of the IM+IN significantly enhances both upper respiratory and systemic antiviral immunity in a mouse model, characterized by the rapid increase in systemic and mucosal T and B cell responses, particularly the mucosal IgA antibody response. The IN boost triggered a swift secondary immune response, rapidly inducing antigen-specific IgA+ B cells. Further BCR-seq analysis indicated that these IgA+ B cells primarily arise through direct class switching from pre-existing IgG+ B cells in draining lymph nodes. Notably, our clinical studies reveal that the IN boost after IM vaccination elicited a robust systemic IgA antibody response in humans, as measured in serum. Thus, our cytokine-armed protein vaccine presents a promising strategy for inducing rapid and potent mucosal protection against respiratory viral infections.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Yifan Lin, Xuejiao Liao, Xuezhi Cao, Zhaoyong Zhang, Xiuye Wang, Xiaomeng He, Huiping Liao, Bin Ju, Furong Qi, Hairong Xu, Zhenhua Ren, Yanqun Wang, Zhenxiang Hu, Jiaming Yang, Yang-Xin Fu, Jincun Zhao, Zheng Zhang, Hua Peng</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/188222">CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/188222">Jian Zheng, … , Jun Yan, Stanley Perlman</a> <a class='hide-for-small show-more' data-reveal-id='article45668-more' href='#'> <div class='article-authors'> Jian Zheng, … , Jun Yan, Stanley Perlman </div> </a> <span class='article-published-at'> Published January 7, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025. <a href="https://doi.org/10.1172/JCI188222">https://doi.org/10.1172/JCI188222</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/188222">Text</a> | <a href="/articles/view/188222/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI188222' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45668-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/188222">CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/188222">Text</a></li> <li><a class="button tiny" href="/articles/view/188222/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells. CXCL12 levels were negatively correlated with LDN numbers in longitudinal analyses of patient blood samples. CXCL12 blockade in SARS-CoV-2-infected mice increased blood/lung neutrophil numbers thereby accelerating disease progression without changing lung virus titers. The exaggerated mortality caused by CXCL12 blockade can be reversed by neutrophil depletion. In addition, blocking interactions between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) reduced CXCL12 levels, suggesting a signal transduction from virus-mediated ACE2 ligation to increased CXCL12 secretion. Collectively, these results demonstrate a previously unappreciated role of CXCL12 in diminishing neutrophilia, including low density neutrophilia, and its deleterious effects in SARS-CoV-2 infections. The results also support the involvement of SARS-CoV-2-endothelial cell interactions in viral pathogenesis.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Jian Zheng, Hima Dhakal, Enya Qing, Rejeena Shrestha, Anne E. Geller, Samantha M. Morrissey, Divyasha Saxena, Xiaoling Hu, Hong Li, Haiyan Li, Kevin Wilhelmsen, Linder H. Wendt, Klaus Klumpp, Patrick S. Hume, William J. Janssen, Rachel Brody, Kenneth E. Palmer, Silvia M. Uriarte, Patrick P. Ten Eyck, David K. Meyerholz, Michael L. Merchant, Kenneth McLeish, Tom Gallagher, Jiapeng Huang, Jun Yan, Stanley Perlman</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/174304">SARS-CoV-2 Delta and Omicron variants resist spike cleavage by human airway trypsin-like protease</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/174304">Wenyan Ren, … , Shuaiyao Lu, Xiawei Wei</a> <a class='hide-for-small show-more' data-reveal-id='article45345-more' href='#'> <div class='article-authors'> Wenyan Ren, … , Shuaiyao Lu, Xiawei Wei </div> </a> <span class='article-published-at'> Published September 17, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/18">134(18)</a>:e174304. <a href="https://doi.org/10.1172/JCI174304">https://doi.org/10.1172/JCI174304</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/174304">Text</a> | <a href="/articles/view/174304/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI174304' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/174304/ga' ref='group' title='Graphical abstract'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/174000/174304/small/JCI174304.ga.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45345-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/174304">SARS-CoV-2 Delta and Omicron variants resist spike cleavage by human airway trypsin-like protease</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/174304">Text</a></li> <li><a class="button tiny" href="/articles/view/174304/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin–like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Wenyan Ren, Weiqi Hong, Jingyun Yang, Jun Zou, Li Chen, Yanan Zhou, Hong Lei, Aqu Alu, Haiying Que, Yanqiu Gong, Zhenfei Bi, Cai He, Minyang Fu, Dandan Peng, Yun Yang, Wenhai Yu, Cong Tang, Qing Huang, Mengli Yang, Bai Li, Jingmei Li, Junbin Wang, Xuelei Ma, Hongbo Hu, Wei Cheng, Haohao Dong, Jian Lei, Lu Chen, Xikun Zhou, Jiong Li, Wei Wang, Guangwen Lu, Guobo Shen, Li Yang, Jinliang Yang, Zhenling Wang, Guowen Jia, Zhaoming Su, Bin Shao, Hanpei Miao, Johnson Yiu-Nam Lau, Yuquan Wei, Kang Zhang, Lunzhi Dai, Shuaiyao Lu, Xiawei Wei</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/181244">Randomised controlled trial reveals no benefit to a 3-month delay in COVID-19 mRNA booster vaccine</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/181244">Wen Shi Lee, … , Kevin J. Selva, Stephen J. Kent</a> <a class='hide-for-small show-more' data-reveal-id='article45212-more' href='#'> <div class='article-authors'> Wen Shi Lee, … , Kevin J. Selva, Stephen J. Kent </div> </a> <span class='article-published-at'> Published July 11, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024. <a href="https://doi.org/10.1172/JCI181244">https://doi.org/10.1172/JCI181244</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/181244">Text</a> | <a href="/articles/view/181244/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI181244' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45212-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/181244">Randomised controlled trial reveals no benefit to a 3-month delay in COVID-19 mRNA booster vaccine</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/181244">Text</a></li> <li><a class="button tiny" href="/articles/view/181244/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>BACKGROUND. There is uncertainty around the timing of booster vaccination against COVID-19 in highly vaccinated populations during the present endemic phase of COVID-19. Studies focused on primary vaccination have previously suggested improved immunity after delaying immunisation. METHODS. We conducted a randomised controlled trial (Nov 2022 – Aug 2023) and assigned 52 fully vaccinated adults to an immediate or a 3-month delayed bivalent Spikevax mRNA booster vaccine. Follow-up visits were completed for 48 participants (n = 24 per arm), with saliva and plasma samples collected following each visit. RESULTS. The rise in neutralising antibody responses to ancestral and Omicron strains were almost identical between the immediate and delayed vaccination arms. Analyses of plasma and salivary antibody responses (IgG, IgA), plasma antibody-dependent phagocytic activity, and the decay kinetics of antibody responses were similar between the 2 arms. Symptomatic and asymptomatic SARS-CoV-2 infection occurred in 49% (21/49) participants over the median 11.5 months of follow up and were also similar between the 2 arms. CONCLUSIONS. Our data suggests no benefit from delaying COVID-19 mRNA booster vaccination in pre-immune populations during the present endemic phase of COVID-19 TRIAL REGISTRATION. Australian New Zealand Clinical Trials Registry number 12622000411741. FUNDING. National Health and Medical Research Council, Australia, Program Grant App1149990 and Medical Research Future Fund App2005544.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Wen Shi Lee, Jennifer Audsley, Mai-Chi Trieu, Arnold Reynaldi, L. Carissa Aurelia, Palak H. Mehta, Joanne Patterson, Helen E. Kent, Julie Nguyen, Thakshila Amarasena, Robyn Esterbauer, Ebene R. Haycroft, Pradhipa Ramanathan, Miles P. Davenport, Timothy E. Schlub, Joseph Sasadeusz, Adam K. Wheatley, Amy W. Chung, Jennifer A. Juno, Kevin J. Selva, Stephen J. Kent</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/176640">Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/176640">Jeremy P. Gygi, … , Steven H. Kleinstein, Leying Guan</a> <a class='hide-for-small show-more' data-reveal-id='article44984-more' href='#'> <div class='article-authors'> Jeremy P. Gygi, … , Steven H. Kleinstein, Leying Guan </div> </a> <span class='article-published-at'> Published May 1, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/9">134(9)</a>:e176640. <a href="https://doi.org/10.1172/JCI176640">https://doi.org/10.1172/JCI176640</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/176640">Text</a> | <a href="/articles/view/176640/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI176640' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/176640/ga' ref='group' title='Graphical abstract'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/176000/176640/small/JCI176640.ga.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44984-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/176640">Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/176640">Text</a></li> <li><a class="button tiny" href="/articles/view/176640/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>BACKGROUND Patients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODS We performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTS Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSION Our longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATION ClinicalTrials.gov NCT04378777.FUNDING NIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Jeremy P. Gygi, Cole Maguire, Ravi K. Patel, Pramod Shinde, Anna Konstorum, Casey P. Shannon, Leqi Xu, Annmarie Hoch, Naresh Doni Jayavelu, Elias K. Haddad, IMPACC Network, Elaine F. Reed, Monica Kraft, Grace A. McComsey, Jordan P. Metcalf, Al Ozonoff, Denise Esserman, Charles B. Cairns, Nadine Rouphael, Steven E. Bosinger, Seunghee Kim-Schulze, Florian Krammer, Lindsey B. Rosen, Harm van Bakel, Michael Wilson, Walter L. Eckalbar, Holden T. Maecker, Charles R. Langelier, Hanno Steen, Matthew C. Altman, Ruth R. Montgomery, Ofer Levy, Esther Melamed, Bali Pulendran, Joann Diray-Arce, Kinga K. Smolen, Gabriela K. Fragiadakis, Patrice M. Becker, Rafick P. Sekaly, Lauren I.R. Ehrlich, Slim Fourati, Bjoern Peters, Steven H. Kleinstein, Leying Guan</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/174439">Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/174439">Mengfei Chen, … , Nicholas R. Rowan, Andrew P. Lane</a> <a class='hide-for-small show-more' data-reveal-id='article44878-more' href='#'> <div class='article-authors'> Mengfei Chen, … , Nicholas R. Rowan, Andrew P. Lane </div> </a> <span class='article-published-at'> Published March 14, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024. <a href="https://doi.org/10.1172/JCI174439">https://doi.org/10.1172/JCI174439</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/174439">Text</a> | <a href="/articles/view/174439/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI174439' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44878-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/174439">Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/174439">Text</a></li> <li><a class="button tiny" href="/articles/view/174439/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis related genes. Furthermore, robust basal stem cell activation contributed to neuroepithelial regeneration and restores ACE2 expression post-infection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration post infection. The shifting characteristics of viral infection at the airway portal provides insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Mengfei Chen, Andrew Pekosz, Jason S. Villano, Wenjuan Shen, Ruifeng Zhou, Heather Kulaga, Zhexuan Li, Amy Smith, Asiana Gurung, Sarah E. Beck, Kenneth W. Witwer, Joseph L. Mankowski, Murugappan Ramanathan Jr., Nicholas R. Rowan, Andrew P. Lane</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/173715">High-frequency home self-collection of capillary blood correlates <i>IFI27</i> expression kinetics with SARS-CoV-2 viral clearance</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/173715">Fang Yun Lim, … , Ashleigh B. Theberge, Alpana Waghmare</a> <a class='hide-for-small show-more' data-reveal-id='article44568-more' href='#'> <div class='article-authors'> Fang Yun Lim, … , Ashleigh B. Theberge, Alpana Waghmare </div> </a> <span class='article-published-at'> Published December 1, 2023 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2023;<a id="article_metadata" href="http://www.jci.org/133/23">133(23)</a>:e173715. <a href="https://doi.org/10.1172/JCI173715">https://doi.org/10.1172/JCI173715</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/173715">Text</a> | <a href="/articles/view/173715/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI173715' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/173715/figure/1' ref='group' title='Self-blood collection captures temporal alignment between IFI27 and SARS-CoV-2 VL. (A) Dynamic genes and pathways identified through GAMM and TcGSA, respectively. (B) Spaghetti plots depicting time trends of a dynamic antiviral pathway identified through TcGSA. Colored solid lines represent the scaled median expression of one gene across all participants, and black dotted lines represent the smoothed median of all genes for a given time trend. Colors denote genes in distinct time trend clusters (blue, cluster 1; pink, cluster 2). (C) Pearson’s correlation matrix of genes with ≥0.3 absolute correlation coefficient with SARS-CoV-2 VL in temporally aligned blood and swab samples. (D) Temporal kinetics of SARS-CoV-2 VL and genes showing moderate-to-strong associations with VL in previously vaccinated and unvaccinated COVID-19+ participants. Solid lines represent generalized additive model smoothing across all participants within a group, and colored shades represent the 95% confidence interval. Green, red, and blue colors denote healthy, COVID-19+ unvaccinated, and COVID-19+ vaccinated participants, respectively. Dotted lines represent individual temporal trajectories of gene. (E) Temporal kinetics of IFI27 gene expression, VL, and symptom burden in individual participants.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/173000/173715/small/JCI173715.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44568-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/173715">High-frequency home self-collection of capillary blood correlates <i>IFI27</i> expression kinetics with SARS-CoV-2 viral clearance</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/173715">Text</a></li> <li><a class="button tiny" href="/articles/view/173715/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Fang Yun Lim, Soo-Young Kim, Karisma N. Kulkarni, Rachel L. Blazevic, Louise E. Kimball, Hannah G. Lea, Amanda J. Haack, Maia S. Gower, Terry Stevens-Ayers, Lea M. Starita, Michael Boeckh, Ollivier Hyrien, Joshua T. Schiffer, Ashleigh B. Theberge, Alpana Waghmare</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/172659">Cells that survive acute murine SARS-CoV-2 infection are detected nearly exclusively in the respiratory tract</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/172659">Ruangang Pan, … , David K. Meyerholz, Stanley Perlman</a> <a class='hide-for-small show-more' data-reveal-id='article44543-more' href='#'> <div class='article-authors'> Ruangang Pan, … , David K. Meyerholz, Stanley Perlman </div> </a> <span class='article-published-at'> Published November 15, 2023 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2023;<a id="article_metadata" href="http://www.jci.org/133/22">133(22)</a>:e172659. <a href="https://doi.org/10.1172/JCI172659">https://doi.org/10.1172/JCI172659</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/172659">Text</a> | <a href="/articles/view/172659/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI172659' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/172659/figure/1' ref='group' title='SARS-CoV-2–infected cells survive acute infection and persist in the respiratory tract. (A) Schematic showing construction of recombinant SARS-CoV-2 harboring Venus and Cre in place of the ORF7a gene. (B) Schematic showing Venus and Cre expression. (C) Schematic of lineage tracing using recombinant viruses. Infected cells are Venus+ (green) at early times after infection, while surviving cells are tdTomato+ (red). (D) Infected VeroE6 cells (MOI = 0.01) were analyzed for GFP expression (top) and by bright-field microscopy (bottom) at 48 hours after infection (original magnification, ×20). (E) Mice were infected with the indicated viruses (K18-hACE2/Ai9 mice, 3,000 PFU rSARS-2-WH-V2C; Ai9 mice, 3,000 PFU rSARS-2-MA30-V2C) and monitored for survival (n = 5 mice per group). (F) Pathological changes in lungs of mice infected with rSARS-2-WH-V2C or rSARS-2-MA30-V2C at 4 dpi. Asterisks, hemorrhage; red arrowheads, edema; black arrowheads, perivascular infiltrates. Scale bar: 100 μm. (G) Sections from the indicated organs harvested from rSARS2-MA30-V2C–infected Ai9 mice were analyzed for Venus expression at 2 dpi. Venus+ cells were observed in the intestine (white arrows), nasal cavity, and lung. Scale bar: 50 μm. (H and I) Sections from the nasal cavities and lungs of rSARS2-MA30-V2C–infected Ai9 mice were analyzed for tdTomato expression at 20 (H) and 60 dpi (I). (J) Summary of numbers of tdTomato+ cells in the lungs of rSARS2-MA30-V2C–infected Ai9 mice. Each group contain 5 animals (n > 3 sections per animal were analyzed). (K) Rare tdTomato+ cells were found in the brains and hearts of rSARS2-WH-V2C–infected K18-hACE2/Ai9 mice at 20 dpi. Arrowheads indicate surviving cells. In D, F, and G–K images are representative of 2 independent experiments (5 mice/group, n = 4–10 slides per mouse). Higher magnification images of selected areas are shown in insets (G and H). Scale bars: 50 μm (G–K).'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/172000/172659/small/JCI172659.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44543-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/172659">Cells that survive acute murine SARS-CoV-2 infection are detected nearly exclusively in the respiratory tract</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/172659">Text</a></li> <li><a class="button tiny" href="/articles/view/172659/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Ruangang Pan, David K. Meyerholz, Stanley Perlman</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/149834">Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/149834">Janessa Yan Jun Tan, … , Joern Karhausen, Ashley L. St. John</a> <a class='hide-for-small show-more' data-reveal-id='article44292-more' href='#'> <div class='article-authors'> Janessa Yan Jun Tan, … , Joern Karhausen, Ashley L. St. John </div> </a> <span class='article-published-at'> Published August 10, 2023 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2023. <a href="https://doi.org/10.1172/JCI149834">https://doi.org/10.1172/JCI149834</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/149834">Text</a> | <a href="/articles/view/149834/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI149834' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44292-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/149834">Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/149834">Text</a></li> <li><a class="button tiny" href="/articles/view/149834/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. Using a mouse model of MC-deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed, through detection of MC-specific proteases, including chymase, levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Janessa Yan Jun Tan, Danielle E. Anderson, Abhay P.S. Rathore, Aled O'Neill, Chinmay Kumar Mantri, Wilfried A.A. Saron, Cheryl Q.E. Lee, Wern Cui Chu, Adrian E.Z. Kang, Randy Foo, Shirin Kalimuddin, Jenny G. Low, Lena Ho, Paul Tambyah, Thomas W. Burke, Christopher W. Woods, Kuan Rong Chan, Joern Karhausen, Ashley L. St. John</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> </div> </div> <div class='row'> <div class='small-12 columns'> <div role="navigation" aria-label="Pagination" class="pagination-centered" previous_label="<--" next_label="-->"><ul class="pagination"><li class="arrow unavailable"><a class="arrow unavailable">← Previous</a></li> <li class="current"><a class="current">1</a></li> <li><a rel="next" href="/tags/118?content=articles&page=2">2</a></li> <li><a href="/tags/118?content=articles&page=3">3</a></li> <li class="unavailable"><a>…</a></li> <li><a href="/tags/118?content=articles&page=10">10</a></li> <li><a href="/tags/118?content=articles&page=11">11</a></li> <li class="arrow"><a class="arrow" rel="next" href="/tags/118?content=articles&page=2">Next →</a></li></ul></div> </div> </div> </div> <div class='content ' id='posts'> <p>No posts were found with this tag.</p> </div> </div> </div> <div class='large-2 medium-3 hide-for-small columns' style='padding: 12px 9px 12px 9px;'> <div style='width:100%; text-align: center;'> <div id='jci-interior-skyscraper-right-col'> <span class='secondary label'>Advertisement</span> <script> try { googletag.cmd.push(function () { googletag.display('jci-interior-skyscraper-right-col'); }); } catch(e){} </script> </div> </div> </div> </div> </div> </div> </div> </div> <div id='footer'> <div class='row panel-padding'> <div class='small-6 columns'> <div id='social-links'> <a onclick="trackOutboundLink('/twitter?ref=footer');" href="/twitter"><img title="Twitter" src="/assets/social/twitter-round-blue-78025a92064e3594e44e4ccf5446aefeafba696cd3c8e4a7be1850c7c9f62aba.png" /></a> <a onclick="trackOutboundLink('/facebook?ref=footer');" href="/facebook"><img title="Facebook" src="/assets/social/facebook-round-blue-2787910d46dcbdbee4bd34030fee044e5a77cfda2221af9191d437b2f5fadeb1.png" /></a> <a href="/rss"><img title="RSS" src="/assets/social/rss-round-color-6f5fa8e93dc066ee4923a36ba6a7cb97d53c5b77de78a2c7b2a721adc603f342.png" /></a> </div> <br> Copyright © 2025 <a href="http://www.the-asci.org">American Society for Clinical Investigation</a> <br> ISSN: 0021-9738 (print), 1558-8238 (online) </div> <div class='small-6 columns'> <div class='row'> <div class='small-12 columns'> <h4 class='notices-signup'>Sign up for email alerts</h4> <form action='https://notices.jci.org/subscribers/new' method='get'> <input name='utm_source' type='hidden' value='jci'> <input name='utm_medium' type='hidden' value='web'> <input name='utm_campaign' type='hidden' value='email_signup'> <input name='utm_content' type='hidden' value='footer'> <div class='row'> <div class='small-12 medium-9 columns'> <input name='email_address' placeholder='Your email address' required type='text'> </div> <div class='small-12 medium-3 columns'> <input class='button tiny orange' type='submit' value='Sign up'> </div> </div> </form> </div> </div> </div> </div> </div> </div> <script src="/assets/application-27f18b5fe3b7302e5b3e3c6d7cf9bb3f54759fad32679209f5aef429b89f3aef.js"></script>  <script src="//s7.addthis.com/js/300/addthis_widget.js#pubid=ra-4d8389db4b0bb592" async="async"></script> <script src="//d1bxh8uas1mnw7.cloudfront.net/assets/embed.js" async="async"></script>  </body> </html>