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

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.

Bovine lactoferrin inhibits SARS‐CoV‐2 and SARS‐CoV‐1 by targeting the RdRp complex and alleviates viral infection in the hamster model

“…Among these genes, the expression of circadian rhythm proteins Period 2 and matrix metalloproteinase‐10 (MMP‐10) exhibited the most significant upregulation and downregulation, which was confirmed by RT‐qPCR analysis (Figure 6A,C ). The MMP‐10 expression pattern is conserved between humans and mouse, 40 and its expression is higher in asymptomatic COVID‐19 patients than in patients with reported symptoms, 41 indicating the role of MMP‐10 in anti‐SARS‐CoV‐2 infection. In the biological processes of Gene Ontology enrichment analysis, the growth‐related processes of cells were the most enriched in DEGs, such as the developmental process, multicellular organizational process, and collections structure development.…”

The Variation of Transcriptomic Perturbations is Associated with the Development and Progression of Various Diseases

“…This disease has caused more than 552 million cases and 6.3 million deaths as of July 1, 2022 [ 15 ]. In four transcriptome datasets (GSE152075 [ 16 ], GSE157103 [ 17 ], GSE161731 [ 18 ], and GSE198449 [ 19 ]) for COVID-19 patients, VTP values were significantly greater in COVID-19 patients than in normal controls ( P < 0.01) ( Figure 2(a) ). Notably, in GSE157103, VTP values were significantly greater in intensive care unit (ICU) COVID-19 patients than in non-ICU patients ( P < 0.001) ( Figure 2(a) ).…”

An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart

“…Several studies on COVID-19 deceased patients confirmed regeneration of damaged lung epithelium following infection, while others showed extensive alveolar damage and lung fibrosis ( 16 ). That such regeneration may in part at least be actively imposed early on as a virus washout mechanism is suggested by a study that compared asymptomatic cases to patients with symptoms and detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic infection ( 119 ). These are known to be involved in tissue repair.…”