Highlights Inflammatory innate immunity can be described as prognostic factors. A reasonable hypothesis is that the balancing between Th1 and Th2 response can be associated with mortality in patients with moderate to severe COVID-19 infection. IFN-γ was an independent risk factor associated with mortality in patients with SARS-Cov2.

Background and Aims: We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease.Methods: This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines.Results: We demonstrate that BDNF levels predict intensive care (IC) need (p < 0.01). This association was found to be stronger in patients >60y (p = 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p < 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p = 0.023). In older patients, BDNF concentration was lower than that of younger patients (p = 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status.Conclusion: Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.

The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease’s mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1β, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.

The COVID-19 pandemic, promoted by the SARS-CoV-2 respiratory virus, has resulted in widespread global morbidity and mortality. The immune response against this pathogen has shown a thin line between protective effects and pathological reactions resulting from the massive release of cytokines and poor viral clearance. The latter is possibly caused by exhaustion, senescence, or both of TCD8+ cells and reduced activity of natural killer (NK) cells. The imbalance between innate and adaptive responses during the early stages of infection caused by SARS-CoV-2 contributes to the ineffective control of viral spread. The present study evaluated the tissue immunoexpression of the tissue biomarkers (Arginase-1, CCR4, CD3, CD4, CD8, CD20, CD57, CD68, CD138, IL-4, INF-α, INF-γ, iNOS, PD-1, Perforin and Sphingosine-1) to understand the cellular immune response triggered in patients who died of COVID-19. We evaluated twenty-four paraffin-embedded lung tissue samples from patients who died of COVID-19 (COVID-19 group) and compared them with ten lung tissue samples from patients who died of H1N1pdm09 (H1N1 group) with the immunohistochemical markers mentioned above. In addition, polymorphisms in the Perforin gene were genotyped through Real-Time PCR. Significantly increased tissue immunoexpression of Arginase, CD4, CD68, CD138, Perforin, Sphingosine-1, and IL-4 markers were observed in the COVID-19 group. A significantly lower immunoexpression of CD8 and CD57 was also found in this group. It is suggested that patients who died from COVID-19 had a poor cellular response concerning viral clearance and adaptive response going through tissue repair.

BACKGROUND AND AIMS One of the complications described in critically ill patients in intensive care units with severe COVID-19 was acute kidney injury (AKI). The pathophysiology of AKI in patients with COVID-19 is multifactorial. In addition to the direct virulence of SARS-CoV-2 in renal cells, the tissue inflammation and local immune cell infiltration, cytokine storm, secondary infections and nephrotoxicity associated drugs may contribute to AKI [1]. Mounting evidence throughout the pandemic suggests that patients with severe COVID-19 may have a cytokine storm syndrome, one of the possible causes of AKI in these patients [2]. The present prospective cohort study analysed the correlation between circulating cytokine profile and estimated glomerular filtration rate (eGFR) in patients with COVID-19. METHOD After signing the informed consent, patients positive for SARS-CoV-2 infection (n = 74) had blood samples (n = 139) collected at hospital admission until the day of the outcome. ELISA measured the cytokines IL-10, IL-4, L-6, TNF-α and IFN-γ, and the eGFR was calculated by the CKD-EPI Cystatin C equation. Statistics description: Continuous variables were checked for normality and presented as mean ± standard deviation or median and interquartile range. The association between continuous variables is shown in scatterplots, and a predicted response with 95% confidence interval (95% CI) is plotted using fractional polynomials. For linear correlations, we obtained P-values using Pearson's correlation coefficient. RESULTS There is a more significant distribution of eGFR below 90 mL/min in the population studied, associated with older patients. Glomerular filtration rates were negatively correlated with age as expected (–0.60; P &lt; 0.0001). Lower eGFR was correlated with levels of proinflammatory cytokines such as IL-6 (–0.33; P &lt; .0007) and TNF- α (–0.21; P &lt; .03); but without positive correlation with IL-10 (0.04; P &lt; 0.68) or IFN-γ (–0.14; P &lt; .16), even though higher IFN-γ levels have been linked to a worse prognosis in patients with severe COVID-19 [3]. Curiously, a positive correlation was observed between lower eGFR and IL-4 levels. CONCLUSION These results demonstrate that a shift in the immune response profile, cytokines with a Th2 profile such as IL-4, and cytokines with systemic functions such as IL-6 and TNF-α can be related to renal failure. The elucidation of the potential pathophysiological mechanisms of AKI associated with COVID-19 as well as monitoring of cytokine levels can (a) help to identify patients with severe COVID-19 at risk of loss of renal function, (b) provide information on specific therapeutic strategies.