RESUMO
Convalescent plasma (CP) has emerged as a treatment for COVID-19. However, the composition and mechanism of action are not fully known. Therefore, we undertook a two-phase controlled study in which, first the immunological and metabolomic status of recovered and severe patients were evaluated. Secondly, the 28-day effect of CP on the immune response in severe patients was assessed. Nineteen recovered COVID-19 patients, 18 hospitalized patients with severe disease, and 16 pre-pandemic controls were included. Patients with severe disease were treated with CP transfusion and standard therapy (i.e., plasma recipients, n = 9) or standard therapy alone (n = 9). Clinical and biological assessments were done on day 0 and during follow-up on days 4, 7, 14, and 28. Clinical parameters, viral load, total immunoglobulin (Ig) G and IgA anti-S1-SARS-CoV-2 antibodies, neutralizing antibodies (NAbs), autoantibodies, cytokines, T and B cells, and metabolomic and lipidomic profiles were examined. Total IgG and IgA anti-S1-SARS-CoV-2 antibodies were key factors for CP selection and correlated with NAbs. In severe COVID-19 patients, mostly interleukin (IL)-6 (P = <0.0001), IL-10 (P = <0.0001), IP-10 (P = <0.0001), fatty acyls and glycerophospholipids were higher than in recovered patients. Latent autoimmunity and anti-IFN-α antibodies were observed in both recovered and severe patients. COVID-19 CP induced an early but transient cytokine profile modification and increases IgG anti-S1-SARS-CoV-2 antibodies. At day 28 post-transfusion, a decrease in activated, effector and effector memory CD4+ (P < 0.05) and activated and effector CD8+ (P < 0.01) T cells and naïve B cells (P = 0.001), and an increase in non-classical memory B cells (P=<0.0001) and central memory CD4+ T cells (P = 0.0252) were observed. Moreover, IL-6/IFN-γ (P = 0.0089) and IL-6/IL-10 (P = 0.0180) ratios decreased in plasma recipients compared to those who received standard therapy alone. These results may have therapeutic implications and justify further post-COVID-19 studies.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/terapia , Interleucina-10/sangue , Interleucina-6/sangue , SARS-CoV-2 , Adulto , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , COVID-19/sangue , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Soroterapia para COVID-19RESUMO
In this study, we aimed to apply an untargeted LC/QTOF-MS analysis for the identification of compounds that positively and negatively affect the acceptance of coffee beverages from liquid coffee concentrates (CLCs) before and after storage. The metabolomic results were integrated with physicochemical and sensory parameters, such as color, pH, titratable acidity, and oxygen contents, by a bootstrapped version of partial least squares discriminant analysis (PLS-DA) to select and classify the most relevant variables regarding the rejection or acceptance of CLC beverages. The OPLS-DA models for metabolite selection discriminated between the percent sensory acceptance (the Accepted group) and rejection (the Rejected group). Eighty-two molecular features were considered statistically significant. Our data suggest that coffee sample rejection is associated with chlorogenic acid hydrolysis to produce ferulic and quinic acids, consequently generating methoxybenzaldehydes that impact the perceived acidity and aroma. Furthermore, acceptance was correlated with higher global scores and sweetness, as with lactones such as feruloyl-quinolactone, caffeoyl quinolactone, and 4-caffeoyl-1,5-quinolactone, and significant oxygen levels in the headspace.