Krebs von den Lungen 6 (KL-6) levels in COVID-19 ICU patients are associated with mortality

Background Krebs von den Lungen 6 (KL-6) is a high-molecular-weight mucin-like glycoprotein, which is also known as MUC1. KL-6 is mainly produced by type 2 pneumocytes and bronchial epithelial cells, and, therefore, elevated circulating KL-6 levels may denote disorders of the alveolar epithelial lining. The objective of this study is to verify if KL-6 serum level might support ICU physicians in predicting mortality, risk stratifying and triaging severe COVID-19 patients. Methods A retrospective cohort study, including all the COVID-19 patients who measured KL-6 serum values at least once during their ICU stay, was performed. The study sample, 122 patients, was divided in two groups, according to the median KL-6 value at ICU admission (median log-transformed KL-6 value: 6.73 U/ml;group A: KL-6 lower than the median and group B: KL-6 higher than the median). Results One-hundred twenty-two ICU patients were included in this study. Mortality was higher in group B than in group A (80 versus 46%;p < 0.001);both linear and logistic multivariate analyses showed ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) significantly and inversely related to KL-6 values. Conclusion At ICU admission, KL-6 serum level was significantly higher in the most hypoxic COVID-19 patients and independently associated with ICU mortality.

Different Immunogenicity of Previous SARS-COV-2 Infection or Comirnaty Vaccine (BNT162B2, BioNTech/Pfizer) in Haemodialysis Patients

BACKGROUND AND AIMS The pandemic emergency deriving from the SARS-CoV-2 infection has made it necessary to find effective strategies to preserve high-risk populations with severe comorbidities like haemodialysis patients. Adequate vaccination coverage is of vital importance, representing the main weapon to counter the spread of the virus. The purpose of our study was to evaluate the antibody response of our dialysis patients vaccinated with the Comirnaty-BioNTech/Pfizer vaccine in comparison with those with previous infection. METHOD We retrospectively analysed 52 patients referried to the Dialysis Unit of University Hospital G. Martino, Messina, from 2020 to 2021. Of these, 41 patients had never contracted SARS-CoV-2 (group A), while 11 patients had contracted the infection (group B). Serum samples were taken before vaccine administration, 3 months and 6 months after administration. A linear mixed model was performed on the measurements to analyse the difference in antibody response, comparing the values ​​of neutralizing IgG and anti-COVID-19 antibodies during time (Fig. 1). RESULTS The results showed a statistically significant higher titre of anti-spike antibodies in patients with a previous infection (P = 0.003), with a stronger association at 6 months after infection. The linear mixed model showed a significant association over time between infection and antispike (ln U/L) in the univariate model, which was confirmed in the multivariate model {adjSlope: 2.9, [95% confidence interval (95% CI) 1.3–4.6];P =.001}. No other variables were related to antispike. CONCLUSION These findings can raise novel questions on the role of natural immunity and antibody titre in the haemodialysis population.

Arteriovenous fistula thrombosis in hemodialysis patients with COVID-19: epiphenomenon or marker of severe clinical disease?

Background: Pandemic condition due to Coronavirus disease (COVID-19) caused a fastest augmentation of hospitalization, impairing the healthcare organization. As a consequence, diagnostic and therapeutic delays have been showed. COVID-19-associated coagulopathy is an endothelial disease related to SARSCoV-2 infection. Our study evaluated the thrombosis of arteriovenous fistula (AVF) as risk marker of mortality. Methods: the analysis included 24 dialysis-dependent patients admitted in a period between March 2020 and June 2021. Patients were divided based on AVF thrombosis: the A group without AVF thrombosis (13 patients), and the B group with AVF thrombosis events (11 patients). Pearson or Spearman' correlation tests were performed to detect possible confounding variable to include in multivariate models. Kaplan Meier and Cox regression analysis were performed to compute mortality analysis. Results: Delta D-dimer (Rho: 0.613, p=0.007), over-infections (Rho 0.456; p= 0,026), C-reactive Protein (CRP) (Rho=0.417, p=0.043), death (Rho=0.492, p=0.027), positive pulmonary imaging (Rho 0.388, p=0.074), and high OLT (0.408, p=0.047) were related to AVF thrombosis, using Pearson or Spearman correlation tests. Kaplan Meier test showed a death average of 19 days in group B compared to a global average of 38 days (p=0.029), and Cox analysis showed an HR of 5.01, 95% CI 1.01-24.99, p=0.049. Furthermore, AVF thrombosis explained about the 68% of the mortality, evaluated through the Harrel's C test. Conclusion: We can speculate that AVF thrombosis in hemodialysis patients with COVID-19 could be an early marker of both pro-coagulative process and severe clinical disease and it could be used to stratify patients and identify the ones that can be considered "frail".

Hypernatraemia and low eGFR at hospitalization in COVID-19 patients: a deadly combination.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on the general population and the burden of pre-existing comorbidities has heavily affected the outcome of the infection. Hyponatraemia has been frequently described. Conversely, hypernatraemia has rarely been described in COVID-19. METHODS: The studied cohort encompasses all COVID-19 patients consecutively admitted to the Messina Hospital, Italy, during the first wave of the epidemic. Since healthcare structures were not overwhelmed at that time, indications for hospitalization were homogeneous throughout the study period. Serum sodium levels, kidney function [estimated glomerular filtration rate (eGFR)], demographic and clinical characteristics were recorded at admission. Correlation between mortality, sodium and eGFR was evaluated by survival curves and univariate and multivariate regression models. RESULTS: Baseline biochemical and clinical data at the time of admission were available for 115 COVID-19-confirmed patients. The median age at admission was 73 years (48% men), with a median Charlson Comorbidity Index of 4. A total of 23.5% of patients presented with a sodium level ≥146 mmol/L, while 7.8% had sodium <135 mmol/L. Hypernatraemic patients were older, with higher comorbidity. Age, hypernatraemia and reduced eGFR were associated with increased mortality in both univariate and multivariate regression models (P < 0.001). The combination of hypernatraemia and reduced renal function at admission had an odds ratio of 47.67 (95% confidence interval 10.08-225.43) of dying compared with patients with an eGFR ≥60 mL/min and sodium <145 mmol/L. CONCLUSIONS: Our study suggests that the association between hypernatraemia and reduced eGFR at referral is a highly relevant prognostic marker for death during hospitalization. The role of this association should be further tested in larger, multicentre cohorts.