Interplay of Antibody and Cytokine Production Reveals CXCL13 as a Potential Novel Biomarker of Lethal SARS-CoV-2 Infection.
Alexander M. Horspool,Theodore Kieffer,Brynnan P. Russ,Megan A. DeJong,M. Allison Wolf,Jacqueline M. Karakiozis,Brice J. Hickey,Paolo Fagone,Danyel H. Tacker,Justin R. Bevere,Ivan Martinez,Mariette Barbier,Peter L. Perrotta,F. Heath Damron +13 more
- Vol. 6, Iss: 1
TLDR
In this article, the interplay of antibodies with the cytokine response in SARS-CoV-2 patients was investigated. But, the results were limited to the first 10 to 20 days of infection and the majority of patients produced antibodies against all three antigens.Abstract:
The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 to 20 days of infection. The majority of patients produced antibodies against all three antigens (219/255 SARS-CoV-2+ patient specimens, 86%), suggesting a broad response to viral proteins. Antibody levels to SARS-CoV-2 antigens were different based on patient mortality, sex, blood type, and age. Analyses of these findings may help explain variation in immunity between these populations. To better understand the systemic immune response, we analyzed the levels of 20 cytokines by SARS-CoV-2 patients throughout infection. Cytokine analysis of SARS-CoV-2+ patients exhibited increases in proinflammatory markers (interleukin 6 [IL-6], IL-8, IL-18, and gamma interferon [IFN-γ]) and chemotactic markers (IP-10 and eotaxin) relative to healthy individuals. Patients who succumbed to infection produced decreased IL-2, IL-4, IL-12, RANTES, tumor necrosis factor alpha (TNF-α), GRO-α, and MIP-1α relative to patients who survived infection. We also observed that the chemokine CXCL13 was particularly elevated in patients who succumbed to infection. CXCL13 is involved in B cell activation, germinal center development, and antibody maturation, and we observed that CXCL13 levels in blood trended with anti-SARS-CoV-2 antibody levels. Furthermore, patients who succumbed to infection produced high CXCL13 and had a higher ratio of nucleocapsid to RBD antibodies. This study provides insights into SARS-CoV-2 immunity implicating the magnitude and specificity of response in relation to patient outcomes. IMPORTANCE The SARS-CoV-2 pandemic is continuing to impact the global population, and knowledge of the immune response to COVID-19 is still developing. This study assesses the interplay of different parts of the immune system during COVID-19 disease. We demonstrate that COVID-19 patients produce antibodies to three proteins of the COVID-19 virus (SARS-CoV-2) and identify many other immunological proteins that are involved during infection. The data suggest that one of these proteins (CXCL13) may be a novel biomarker for severe COVID-19 that can be readily measured in blood. This information combined with our broad-scale analysis of immune activity during COVID-19 provides new information on the immunological response throughout the course of disease and identifies a novel potential marker for assessing disease severity.read more
Citations
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SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages
Giovanny J. Martínez-Colón,Kalani Ratnasiri,Heping Chen,Sizun Jiang,Elizabeth Zanley,Arjun Rustagi,Renu Verma,Han Chen,Jason R. Andrews,Kirsten D. Mertz,Alexandar Tzankov,Dan E. Azagury,Jack H. Boyd,Garry P. Nolan,Christian M. Schürch,Matthias S. Matter,Catherine A. Blish,Tracey McLaughlin +17 more
TL;DR: It is suggested that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of fat tissue-resident macrophages.
Journal ArticleDOI
Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge
Ting Y. Wong,Katherine S. Lee,Brynnan P. Russ,Alexander M. Horspool,Jason Kang,Michael T. Winters,M. Allison Wolf,Nathaniel A. Rader,Olivia A. Miller,Morgane Shiflett,Jerilyn R. Izac,D.C. Varisco,Emel Sen-Kilic,Casey Cunningham,Melissa Cooper,Holly A. Cyphert,Mariette Barbier,Ivan Martinez,Justin R. Bevere,Robert K. Ernst,F. Heath Damron +20 more
TL;DR: In this paper , a two-dose vaccine (BReC-CoV-2) was developed by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®).
Journal ArticleDOI
Cytokine Profiles Associated With Worse Prognosis in a Hospitalized Peruvian COVID-19 Cohort.
Maria J. Pons,Barbara Ymaña,Ana Mayanga-Herrera,Yolanda Sáenz,Lydia Alvarez-Erviti,Salyoc Tapia-Rojas,Roxana Gamarra,Amanda B. Blanco,Gemma Moncunill,Manuel F. Ugarte-Gil +9 more
TL;DR: In this paper, the expression profiles of cytokines, chemokine and growth factor profiles were identified and validated related to severity and outcomes of SARS-CoV-2 infected patients at hospital entry.
Journal ArticleDOI
Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge
Ting Y. Wong,Katherine S. Lee,Brynnan P. Russ,Alexander M. Horspool,Jason Kang,Michael T. Winters,M. Allison Wolf,Nathaniel A. Rader,Olivia A. Miller,Morgane Shiflett,Jerilyn R. Izac,D.C. Varisco,Emel Sen-Kilic,Casey Cunningham,Melissa Cooper,Holly A. Cyphert,Mariette Barbier,Ivan Martinez,Justin R. Bevere,Robert K. Ernst,F. Heath Damron +20 more
TL;DR: In this article , a two-dose vaccine (BReC-CoV-2) was developed by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®).
Posted ContentDOI
SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern induce lethal disease in K18-hACE2 transgenic mice despite convalescent plasma therapy
Alexander M. Horspool,Chengjin Ye,Ting Y. Wong,Brynnan P. Russ,Katherine S. Lee,Michael T. Winters,Justin R. Bevere,Theodore Kieffer,Ivan Martinez,Julien Sourimant,Alexander L. Greninger,Richard K. Plemper,James Denvir,Holly A. Cyphert,Jordi B. Torrelles,Luis Martinez-Sobrido,Fredrick Heath Damron +16 more
TL;DR: In this article, a comparison of the SARS-CoV-2 USA-WA1/2020 (WA-1) strain with B.1.7 and B.351 in the mouse model is presented.
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