Asymptomatic SARS-CoV-2 Infection Is Associated With Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19. Author Alessandra Soares-Schanoski, Natalie Sauerwald, Carl Goforth, Sivakumar Periasamy, Dawn Weir, Stephen Lizewski, Rhonda Lizewski, Yongchao Ge, Natalia Kuzmina, Venugopalan Nair, Sindhu Vangeti, Nada Marjanovic, Antonio Cappuccio, Wan Cheng, Sagie Mofsowitz, Clare Miller, Xuechen Yu, Mary-Catherine George, Elena Zaslavsky, Alexander Bukreyev, Olga Troyanskaya, Stuart Sealfon, Andrew Letizia, Irene Ramos Publication Year 2022 Type Journal Article Abstract Young adults infected with SARS-CoV-2 are frequently asymptomatic or develop only mild disease. Because capturing representative mild and asymptomatic cases require active surveillance, they are less characterized than moderate or severe cases of COVID-19. However, a better understanding of SARS-CoV-2 asymptomatic infections might shed light into the immune mechanisms associated with the control of symptoms and protection. To this aim, we have determined the temporal dynamics of the humoral immune response, as well as the serum inflammatory profile, of mild and asymptomatic SARS-CoV-2 infections in a cohort of 172 initially seronegative prospectively studied United States Marine recruits, 149 of whom were subsequently found to be SARS-CoV-2 infected. The participants had blood samples taken, symptoms surveyed and PCR tests for SARS-CoV-2 performed periodically for up to 105 days. We found similar dynamics in the profiles of viral load and in the generation of specific antibody responses in asymptomatic and mild symptomatic participants. A proteomic analysis using an inflammatory panel including 92 analytes revealed a pattern of three temporal waves of inflammatory and immunoregulatory mediators, and a return to baseline for most of the inflammatory markers by 35 days post-infection. We found that 23 analytes were significantly higher in those participants that reported symptoms at the time of the first positive SARS-CoV-2 PCR compared with asymptomatic participants, including mostly chemokines and cytokines associated with inflammatory response or immune activation (i.e., TNF-α, TNF-β, CXCL10, IL-8). Notably, we detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic participants than in participants with symptoms; these are known to be involved in tissue repair and may be related to the control of symptoms. Overall, we found a serum proteomic signature that differentiates asymptomatic and mild symptomatic infections in young adults, including potential targets for developing new therapies and prognostic tests. Keywords Humans, Proteomics, Fibroblast Growth Factors, COVID-19, SARS-CoV-2, Interleukin-17, Matrix Metalloproteinase 10 Journal Front Immunol Volume 13 Pages 821730 Date Published 2022 ISSN Number 1664-3224 DOI 10.3389/fimmu.2022.821730 Alternate Journal Front Immunol PMCID PMC9037090 PMID 35479098 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML