Interplay of antibody and cytokine production reveals CXCL-13 as a potential novel biomarker of lethal SARS-CoV-2 infection [article]

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 (+2 others)
2020 medRxiv   pre-print
The SARS-CoV-2 pandemic is continuing to impact the global population. This study was designed to assess the interplay of antibodies with the systemic cytokine response in SARS-CoV-2 patients. We demonstrate that significant anti-SARS-CoV-2 antibody production to Receptor Binding Domain (RBD), Nucleocapsid (N), and Spike S1 subunit (S1) of SARS-CoV-2 develops over the first 10 to 20 days of infection. The majority of patients produced antibodies against all three antigens (219/255 SARS-CoV-2
more » ... itive patient specimens, 86%) suggesting a broad response to viral proteins. Patient mortality, sex, blood type, and age were all associated with differences in antibody production to SARS-CoV-2 antigens which may help explain variation in immunity between these populations. To better understand the systemic immune response, we analyzed the production of 20 cytokines by SARS-CoV-2 patients over the course of infection. Cytokine analysis of SARS-CoV-2 positive patients exhibited increases in proinflammatory markers (IL-6, IL-8, IL-18) and chemotactic markers (IP-10, SDF-1, MIP-1β, MCP-1, and eotaxin) relative to healthy individuals. Patients who succumbed to infection produced decreased IL-2, IL-4, IL-12, IL-13, RANTES, 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 that 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 production. Furthermore, patients that succumbed to infection produced high CXCL13 and also tended to have high 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.
doi:10.1101/2020.08.24.20180877 fatcat:gewqqdhhhff7fk4v4gpeap6vsi