We have analyzed BNT162b2 vaccine-induced immune responses in naïve and individuals recovered from COVID-19, both early (fourteen days) and late (almost eight months) after vaccination. Plasma S-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naïve subjects, although the latter group shows reduced levels all-along the analyzed period. Despite the neutralization capacity against SARS-CoV-2 mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cells levels late post-vaccination. When studying cellular responses, naïve individuals exhibit higher SARS-CoV-2-specific cytokines production, CD4 + T cells activation and proliferation than individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost eight months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.

Sepsis is a pathology in which patients suffer from a proinflammatory response and a dysregulated immune response, including T cell exhaustion. A number of therapeutic strategies to treat human sepsis, which are different from antimicrobial and fluid resuscitation treatments, have failed in clinical trials, and solid biomarkers for sepsis are still lacking. Herein, we classified 85 patients with sepsis into two groups according to their blood oxygen saturation (SaO2): group I (SaO2 ≤ 92%, n = 42) and group II (SaO2 > 92%, n = 43). Blood samples were taken before any treatment, and the immune response after ex vivo LPS challenge was analyzed, as well as basal expression of PD-L1 on monocytes and levels of sPD-L1 in sera. The patients were followed up for 1 month. Taking into account reinfection and exitus frequency, a significantly poorer evolution was observed in patients from group I. The analysis of HLA-DR expression on monocytes, T cell proliferation and cytokine profile after ex vivo LPS stimulation confirmed an impaired immune response in group I. In addition, these patients showed both, high levels of PD-L1 on monocytes and sPD-L1 in serum, resulting in a down-regulation of the adaptive response. A blocking assay using an anti-PD-1 antibody reverted the impaired response. Our data indicated that SaO2 levels on admission have emerged as a potential signature for immune status, including PD-L1 expression. An anti-PD-1 therapy could restore the T cell response in hypoxemic sepsis patients with SaO2 ≤ 92% and high PD-L1 levels.

The asterisk * labels those variables included in the Wald backward stepwise regression model. In bold are the areas under the ROC curve (AUC) > 0.5 and the p-values < .05. Abbreviations: AHT, arterial hypertension; DM, history of diabetes mellitus; CVD, history of cardiovascular disease; CKD, history of chronic kidney disease; COPD, history of chronic obstructive pulmonary disease; OncoD, history of oncologic disease; ImmunoD, history of immunologic disease; Resp rate, respiratory rate; SpO 2 , oxygen saturation; FiO 2 , fraction of inspired oxygen; SpO 2 /FiO 2 , peripheral blood oxygen saturation to fraction of inspired oxygen ratio; ANC, absolute neutrophil counts; ALC, absolute lymphocyte counts; AMC, absolute monocyte counts; N/L Ratio, neutrophil to lymphocyte ratio; AST, aspartate transaminase; ALT, alanine transaminase; LDH, lactate dehydrogenase; CRP, c-reactive protein, PCT, procalcitonin; qSOFA, quick sequential organ failure assessment score.

No abstract

Increased cytokine levels, acute phase reactants and immune checkpoint expression changes have been described in patients with Coronavirus Disease 2019 (COVID-19). Here, we have reported a monocyte polarization towards a low HLA-DR and high PD-L1 expression after long exposure to proteins from SARS-CoV-2. Moreover, CD86 expression was also reduced over SARS-CoV-2 proteins exposure. Additionally, T-cells proliferation was significantly reduced after stimulation with these proteins. Eventually, patients with long-term SARS-CoV-2 infection also exhibited a significant blockade of T-cells proliferation.

According to a large number of reported cohorts, sepsis has been observed in nearly all deceased patients with COVID-19. We and others have described sepsis, among other pathologies, to be an endotoxin tolerance (ET)related disease. In this study, we demonstrate that the culture of human blood cells from healthy volunteers in the presence of SARS-CoV-2 proteins induced ET hallmarks, including impairment of proinflammatory cytokine production, low MHC class II (HLA-DR) expression, poor T cell proliferation, and enhancing of both phagocytosis and tissue remodeling. Moreover, we report the presence of SARS-CoV-2 blood circulating proteins in patients with COVID-19 and how these levels correlate with an ET status, the viral RNA presence of SARS-CoV-2 in plasma, as well as with an increase in the proportion of patients with secondary infections.

Despite viral control, basal chronic inflammation and its related comorbidities remain unsolved problems among HIV-infected individuals. Soluble factors derived from myeloid cells have emerged as potent markers associated with HIV-related comorbidities and mortality. In the present report, we explored the relationship between soluble programmed death-ligand 1 (sPD-L1) and HIV-1 infection, antiretroviral therapy (ART), CD4/CD8 ratio, viral load (VL), and sexually transmitted coinfections. A prospective observational study on 49 HIV-1 infected adults. We found sPD-L1 levels were significantly higher in 49 HIV infected subjects than in 30 uninfected adults (1.05 ng/ml vs 0.52 ng/ml; P < .001). In this line, sPD-L1 levels were found to be elevated in 16 HIV infected subjects with undetectable VL compared with the uninfected subjects (0.75 ng/ml vs 0.52 ng/ml; P = .02). Thirteen ART-treated individuals with virological failure exhibited the highest sPDL1 levels, which were significantly higher than both 20 ART naïve infected individuals (1.68 ng/ml vs 0.87 ng/ml; P = .003) and the 16 ART-treated individuals with suppressed viremia (1.68 ng/ml vs 0.79 ng/ml; P = 002). Entire cohort data showed a statistically significant positive correlation between VL and sPD-L1 levels in plasma (r = 0.3; P = 036). Our findings reveal sPDL-1 as a potential biomarker for HIV infection especially interesting in those individuals with virological failure.

Background: Cystic fibrosis (CF) is an endotoxin tolerance (ET)-related disease. Given that increased PD-L1 has been reported in ET, its expression and physiological effects on cystic fibrosis monocytes should be studied. Methods: We analyzed the phenotype and ex vivo response of immune system cells in 32 patients with CF, 19 of them colonized by Pseudomonas aeruginosa. An in vitro model was developed of Pseudomonas aeruginosa colonization using purified lipopolysaccharides (LPS) from one of the most prevalent strains in patients with CF (a CFadapted Pseudomonas aeruginosa ST395 clone). Changes in the immune response, including cytokine production and T-lymphocyte proliferation, as well as expression of PD-L1, were evaluated. Results: PD-L1 was overexpressed in the monocytes of patients with CF compared with healthy volunteers, and levels of this immune checkpoint were associated with Pseudomonas aeruginosa colonization. In addition, patients with Pseudomonas aeruginosa colonization showed a patent ET status, including poor inflammatory response, reduced HLA-DR expression and T-lymphocyte proliferation impairment. PD-L1/PD-1 blocking assays reverted the impaired adaptive response. Ultimately, monocytes from healthy volunteers cultured in the presence of the clinically relevant strain of Pseudomonas aeruginosa or serum collected from patients with CF colonized by Pseudomonas aeruginosa reproduced the previous observed features. Conclusions: Pseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T cell response, and LPS from this pathogen induced the observed phenotype. Our findings open new avenues for the use of anti-PD-1/PD-L1 immunotherapy in patients with CF who are colonized by Pseudomonas aeruginosa.