Association of Antiretroviral Therapy with Platelet Function and Systemic Inflammatory Response in People Living with HIV: A Cross-Sectional Study.

People living with HIV (PLWHIV) present an increased risk of adverse cardiovascular events. We aimed to assess whether antiretroviral therapy (ART) pharmacologically enhances platelet reactivity and platelet activation intensity, and explore the potential association with underlying inflammatory status. This was a cross-sectional cohort study carried out among PLWHIV on diverse ART regimens. Platelet reactivity and activation intensity were assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU), measurements of monocyte-platelet complexes, and P-selectin and GPIIb/IIIa expression increase, following activation with ADP, respectively. Levels of major inflammatory markers and whole blood parameters were also evaluated. In total, 71 PLWHIV, 59 on ART and 22 healthy controls, were included in this study. PRU values were significantly elevated in PLWHIV compared to controls [Mean; 257.85 vs. 196.67, p < 0.0001], but no significant differences were noted between ART-naïve or ART-experienced PLWHIV, or between TAF/TDF and ABC based regimens, similar to systemic inflammatory response. However, within-group analysis showed that PRUs were significantly higher in ABC/PI vs ABC/INSTI or TAF/TDF + PI patients, in line with levels of IL-2. PRU values did not correlate strongly with CD4 counts, viral load, or cytokine values. P-selectin and GPIIb/IIIa expression increased following ADP activation and were significantly more prominent in PLWHIV (p < 0.005). Platelet reactivity and platelet activation intensity were shown to be increased in PLWHIV, but they did not appear to be related to ART initiation, similar to the underlying systemic inflammatory response.

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential.

Although coronavirus disease 2019 (COVID-19) is primarily associated with mild respiratory symptoms, a subset of patients may develop more complicated disease with systemic complications and multiple organ injury. The gastrointestinal tract may be directly infected by SARS-CoV-2 or secondarily affected by viremia and the release of inflammatory mediators that cause viral entry from the respiratory epithelium. Impaired intestinal barrier function in SARS-CoV-2 infection is a key factor leading to excessive microbial and endotoxin translocation, which triggers a strong systemic immune response and leads to the development of viral sepsis syndrome with severe sequelae. Multiple components of the gut immune system are affected, resulting in a diminished or dysfunctional gut immunological barrier. Antiviral peptides, inflammatory mediators, immune cell chemotaxis, and secretory immunoglobulins are important parameters that are negatively affected in SARS-CoV-2 infection. Mucosal CD4+ and CD8+ T cells, Th17 cells, neutrophils, dendritic cells, and macrophages are activated, and the number of regulatory T cells decreases, promoting an overactivated immune response with increased expression of type I and III interferons and other proinflammatory cytokines. The changes in the immunologic barrier could be promoted in part by a dysbiotic gut microbiota, through commensal-derived signals and metabolites. On the other hand, the proinflammatory intestinal environment could further compromise the integrity of the intestinal epithelium by promoting enterocyte apoptosis and disruption of tight junctions. This review summarizes the changes in the gut immunological barrier during SARS-CoV-2 infection and their prognostic potential.

N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study.

BACKGROUND: N-acetyl-cysteine (NAC) has been previously shown to exert beneficial effects in diverse respiratory diseases, through antioxidant and anti-inflammatory actions. Our aim was to evaluate NAC potential impact in hospitalised patients with COVID-19 pneumonia, in terms of progression to severe respiratory failure (SRF) and mortality. PATIENTS AND METHODS: This retrospective, two-centre cohort study included consecutive patients hospitalised with moderate or severe COVID-19 pneumonia. Patients who received standard of care were compared with patients who additionally received NAC 600 mg bid orally for 14 days. Patients' clinical course was recorded regarding (i) the development of SRF (PO2/FiO2 <150) requiring mechanical ventilation support and (ii) mortality at 14 and 28 days. RESULTS: A total of 82 patients were included, 42 in the NAC group and 40 in the control group. Treatment with oral NAC led to significantly lower rates of progression to SRF as compared to the control group (p < .01). Patients in the NAC group presented significantly lower 14- and 28-day mortality as compared to controls (p < .001 and p < .01 respectively). NAC treatment significantly reduced 14- and 28-day mortality in patients with severe disease (p < .001, respectively). NAC improved over time the PO2/FiO2 ratio and decreased the white blood cell, CRP, D-dimers and LDH levels. In the multivariable logistic regression analysis, non-severe illness and NAC administration were independent predictors of 28-days survival. CONCLUSION: Oral NAC administration (1200 mg/d) in patients with COVID-19 pneumonia reduces the risk for mechanical ventilation and mortality. Our findings need to be confirmed by properly designed prospective clinical trials.

Intestinal Barrier Biomarker ZO1 and Endotoxin Are Increased in Blood of Patients With COVID-19-associated Pneumonia.

BACKGROUND/AIM: The present study was undertaken to investigate (i) whether hospitalized patients with COVID-19 pneumonia present intestinal barrier dysfunction with consequent translocation of endotoxin into the systemic circulation and (ii) whether intestinal barrier biomarkers have any prognostic role in terms of progression to severe respiratory failure. PATIENTS AND METHODS: In this prospective study, 22 patients with COVID-19-associated pneumonia and 19 patients with non-COVID-19-related community-acquired pneumonia (CAP group) were studied while 12 healthy persons comprised the control group. Blood samples were collected on admission and analysed for serum levels of endotoxin and zonula occludens-1 (ZO1). Clinical courses regarding progression to severe respiratory failure (SRF) requiring mechanical ventilation were recorded. RESULTS: Patients with COVID-19-associated pneumonia and patients with CAP presented significantly higher serum endotoxin and ZO1 concentrations on admission as compared to healthy controls. There was no difference in endotoxin levels between patients with COVID-19-related pneumonia and patients with CAP. In patients with COVID-19-related pneumonia, serum endotoxin concentrations were positively correlated with C-reactive protein and ferritin values. There were no significant differences in serum endotoxin and ZO1 concentrations between patients with severe and not severe COVID-19-related pneumonia, nor between patients who developed SRF and those who did not Conclusion: Patients with COVID-19-related pneumonia present intestinal barrier dysfunction leading to systemic endotoxemia. Admission values of endotoxin and ZO1 do not have any prognostic role for progression to SRF.