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Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.

ABSTRACT: The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

SUBMITTER: Bi X

PROVIDER: S-EPMC8712267 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses.MethodsIn this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed.ResultsThe white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells.ConclusionOur results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.

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Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.

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