Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19.
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ABSTRACT:
SUBMITTER: Wilson JC
PROVIDER: S-EPMC8686203 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGallbladder disease is highly related to inflammation, but the inflammatory processes are not well understood. Bile provides a direct substrate in assessing the local inflammatory response that develops in the gallbladder. To assess the reproducibility of measuring inflammatory markers in bile, we designed a methods study of 69 multiplexed immune-related markers measured in bile obtained from gallstone patients.MethodsTo evaluate assay performance, a total of 18 bile samples were tested twice within the same plate for each analyte, and the 18 bile samples were tested on two different days for each analyte. We used the following performance parameters: detectability, coefficient of variation (CV), intraclass correlation coefficient (ICC), and percent agreement (concordance among replicate measures above and below detection limit). Furthermore, we examined the association of analyte levels with gallstone characteristics such as type, numbers, and size.ResultsAll but 3 analytes (Stem Cell Factor, SCF; Thrombopoietin, TPO; sIL-1RI) were detectable in bile. 52 of 69 (75.4%) analytes had detectable levels for at least 50% of the subjects tested. The within-plate CVs were ⩽25% for 53 of 66 (80.3%) detectable analytes, and across-plate CVs were ⩽25% for 32 of 66 (48.5%) detectable analytes. Moreover, 64 of 66 (97.0%) analytes had ICC values of at least 0.8. Lastly, the percent agreement was high between replicates for all of the analytes (median; within plate, 97.2%; across plate, 97.2%). In exploratory analyses, we assessed analyte levels by gallstone characteristics and found that levels for several analytes decreased with increasing size of the largest gallstone per patient.ConclusionsOur data suggest that multiplex assays can be used to reliably measure cytokines and chemokines in bile. In addition, gallstone size was inversely related to the levels of select analytes, which may aid in identifying critical pathways and mechanisms associated with the pathogenesis of gallbladder diseases.
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Project description:Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1? were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.
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Project description:The severity of COVID-19 ranges from mild to critical diseases. However, limited data have been published on the detailed kinetics of viral load and host immune response throughout the disease course depending on disease severity. In this study, we comprehensively analyzed viral load, antibody responses to SARS-CoV-2, and cytokines/chemokines during the disease course, and identified the factors related to severity. Nasopharyngeal (NP) and plasma specimens were obtained from 31 patients with COVID-19 during hospitalization. Viral RNA in NP specimens was quantified by reverse transcription-PCR. Anti-SARS-CoV-2 antibodies and cytokines/chemokines in plasma specimens were analyzed by ELISA and cytometric bead array. The viral load in patients with COVID-19 peaked at the early stage of the disease and continuously decreased. Severe and critical cases showed higher viral load and prolonged viral shedding than asymptomatic and mild cases. Whereas plasma IgG was gradually increased and maintained during hospitalization, plasma IgM peaked at 3 weeks after symptom onset and dissipated. The antibody response in severe and critical cases was slightly delayed but stronger than those in others. High levels of interferon (IFN)-α, IFN-γ-induced protein-10, monokine induced by IFN-γ, and interleukin-6 at 5-10 days from symptom onset were associated with the severity of COVID-19. Our data indicate that high viral load in the respiratory tract and excessive production of cytokines and chemokines between 1 and 2 weeks from the symptom onset were significantly associated with the severity of COVID-19.
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