Association of soluble PD-L1 and NLR combination with 1-Year mortality in patients with COVID-19.

PURPOSE: Understanding the relationship between patient immune characteristics, disease severity, and mortality represents a critical step in the fight against COVID-19. Elevated levels of programmed death ligand-1 (PD-L1) and Neutrophil-lymphocyte ratio (NLR) are linked to increased severity of acute COVID-19 in patients. This study aimed to investigate the association of the combination of sPD-L1 and NLR with 1-year Mortality in patients with COVID-19. METHODS: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of sPD-L1 in the blood serum was evaluated by ELISA. The effect of biomarkers on the development of mortality was analyzed with multivariate regression. RESULTS: The risk of mortality within one year HR was 2.46 if the plasma sPD-L1 value of more than 277.13 pg/ml, and for NLR more than 2.46 HR was 2.87. The model of combining sPD-L1 and NLR resulted in an improvement in the predictive accuracy of the Hazard Ratio 7.6 (95 % CI: 3.02-19.11). CONCLUSION: The combination of two immune-mediated markers (sPD-L1 and NLR), which reflect the systemic inflammatory balance of activation and exhaustion, can complement each other and improve the assessment of the risk of death in patients with COVID-19.

Association of sTREM-1 and Neutrophil-to-Lymphocyte Ratio as Prognostic Markers in COVID-19 Short- and Long-Term Mortality.

Aim: Current problem related to COVID-19 is various complications after disease, especially long-term mortality after COVID-19. Routine blood tests presented their effectiveness in the diagnosis, prognosis and mortality of COVID-19. The neutrophil-to-lymphocyte ratio (NLR) is an important marker of systemic inflammation. Soluble Trigger receptor expressed on myeloid cells-1 (sTREM-1) is considered an intrinsic enhancer of inflammatory signals. This study examined the predictive value of these markers in COVID-19 mortality. Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The neutrophil-to-lymphocyte ratio (NLR) was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. The level of sTREM-1 in the blood serum was evaluated by ELISA. Results: Plasma sTREM-1 concentration greater than 59.08 pg/mL and an NLR greater than 2.29 had an increased risk of early mortality (hazard ratio = 8.07; 95% CI: 1.03-62.17 and 9.24; 95% CI: 1.202-71.08, respectively); for long-term mortality of sTREM-1 greater than 47.34 pg/mL (hazard ratio = 7.96; 95% CI: 1.072-59.18) and NLR greater than 2.10 (hazard ratio = 11.52; 95% CI: 1.551-85.52). Conclusion: This study suggests that early levels of sTREM-1 and NLR are associated with the risk of 6-month mortality after experiencing COVID-19.

The Association of Endothelin-1 with Early and Long-Term Mortality in COVID-19.

(1) Background: Endothelial dysfunction is a key mechanism in the pathogenesis of COVID-19. High endothelin-1 during COVID-19 is associated with severe complications and increased mortality rates during hospitalization. This study is aimed to investigate the association of endothelin-1 levels with the risk of 30-day and 12-month all-cause mortality in patients with prior COVID-19. (2) Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of endothelin-1 in the blood serum was evaluated by ELISA. Univariate and multivariate Cox regression was used to determine factors and significance of endothelin-1 associated with the risk of mortality within 30 and 365 days from hospitalization. (3) Results: The median endothelin-1 was higher in the group of patients who passed away within 30 days. The group showed statistically significant differences when compared to healthy volunteers from the control group (p = 0.0001), surviving patients (p = 0.001), and those who passed away within a year (p = 0.002). (4) Conclusions: Endothelin-1 levels are associated with increased mortality risk during the acute period of COVID-19, while plasma endothelin-1 level association with COVID-19 survivor mortality risk does not persist after 12 months.

The impact of Gam-COVID-Vac, an Adv5/Adv26 COVID-19 vaccine, on the biomarkers of endothelial function, coagulation and platelet activation.

COVID-19 vaccines have played a critical role in controlling the COVID-19 pandemic. Although overall considered safe, COVID-19 vaccination has been associated with rare but severe thrombotic events, occurring mainly in the context of adenoviral vectored vaccines. A better understanding of mechanisms underlying vaccine-induced hypercoagulability and prothrombotic state is needed to improve vaccine safety profile. We assessed changes to the biomarkers of endothelial function (endothelin, ET-1), coagulation (thrombomodulin, THBD and plasminogen activator inhibitor, PAI) and platelet activation (platelet activating factor, PAF, and platelet factor 4 IgG antibody, PF4 IgG) within a three-week period after the first (prime) and second (boost) doses of Gam-Covid-Vac, an AdV5/AdV26-vectored COVID-19 vaccine. Blood plasma collected from vaccinees (n = 58) was assayed using ELISA assays. Participants were stratified by prior COVID-19 exposure based on their baseline SARS-CoV-2-specific serology results. We observed a significant post-prime increase in circulating ET-1, with levels sustained after the boost dose compared to baseline. ET-1 elevation following dose 2 was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in post-dose 1 PAI. Vaccination was associated with elevated ET-1 up to day 21 after the second vaccine dose, while no marked alterations to other biomarkers, including PF4 IgG, were seen. A role of persistent endothelial activation following COVID-19 vaccination warrants further investigation.

Mortality Risk Factors of Early Neonatal Sepsis During COVID-19 Pandemic.

Purpose: This study aimed to determine predisposing factors for negative outcome in infants with early neonatal sepsis during COVID-19. Patients and Methods: A prospective cohort study of 172 newborns up to 4 days diagnosed with neonatal sepsis was carried out in Karaganda (Kazakhstan). The microbiological examination was used to identify a causative agent of bloodstream infection. ELISA was performed to determine the total anti-SARS-CoV-2 antibodies. Gestational age, mode of delivery, birth weight, C-reactive protein and procalcitonin levels, comorbidities, type of pathogen, duration of hospitalization and mother's infection diseases were used for statistical analysis. Results: Mortality in infants with neonatal sepsis was 22% (38/172). Anti-SARS-CoV-2 antibodies were detected in 68.3% of the newborns. Culture-negative ELBW infants have a 5.3-fold higher risk of death (p<0.001). Low gestational age and a shorter period of hospitalization were statistically associated with fatality. CRP is generally higher in deceased children (p=0.002). Necrotizing enterocolitis (p<0.001), pneumonia (p=0.009) and anemia (p=0.016) were significantly associated with negative outcome. And, 31.4% of the infants with sepsis had positive blood cultures. The leading cause of sepsis in newborns was CoNS - 57%. Conclusion: During COVID-19 pandemic neonatal sepsis mortality was associated with low birth weight, gestational age, and comorbidities as in non-pandemic time. The relationship between COVID-19 in the mother and neonatal mortality was not found. However, anti-SARS-CoV-2 antibodies were detected in more than half of newborns.

The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis.

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Neonatal sepsis is the main cause of death in newborns, especially preterm infants. The pathogenesis of sepsis is based on a hyper-inflammatory syndrome combined with an immunosuppressive mechanism in sepsis. This study aimed to find critical parameters that are associated with the outcome of newborns with suspected sepsis. Understanding the association might have clinical relevance for immuno-monitoring, outcome prediction, and targeted therapy. Methods: A total of 210 newborn infants no older than 4 days with suspected sepsis at admission in Karaganda (Kazakhstan) were prospectively enrolled. Blood cultures were incubated, and pathogens in positive cultures were determined by MALDI-TOF. An immunological assay for blood cell components was conducted by flow cytometry with antibody cocktails. The diagnostic criteria for neonatal sepsis were identified by qualified neonatologists and included both clinical sepsis and/or positive blood culture. The analyzed infants were grouped into non-septic infants, surviving septic infants, and deceased septic infants. The results showed that deceased septic newborns had a lower level of CD8+ lymphocytes and higher PDL-1 expression in comparison with surviving septic newborns. PDL-1 expression on CD8+ T cells might play an immunosuppressive role during neonatal sepsis and might be used as a laboratory biomarker in the future.