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Background: Abnormal serum magnesium (Mg) concentrations are common and associated with worse mortality in kidney-transplant recipients. Many kidney and transplant-related factors affect Mg homeostasis. The concentration of the active form, ionized Mg (iMg), is not measured clinically, and total Mg (tMg) and iMg correlations have conflicted. We hypothesized that iMg and tMg concentrations show poor categorical agreement (i.e., low, normal, and high) in kidney-transplant recipients but that ionized calcium (iCa) correlates with iMg. Methods: We retrospectively evaluated hypomagnesemia in kidney-transplant recipients over a 2-yr period. We prospectively collected blood at 0-28 days post-transplant to measure correlations between iMg and iCa/tMg. iMg and iCa concentrations in the reference ranges of 0.44-0.65 and 1.0-1.3 mmol/L, respectively, were considered normal. Fisher's exact test and unweighted kappa statistics revealed category agreements. Pearson's correlation coefficients and linear regression measured correlations. Results: Among 58 retrospective kidney-transplant recipients, 54 (93%) had tMg<0.66 mmol/L, 28/58 (48%) received Mg supplementation, and 20/28 (71%) had tacrolimus dose adjustments during supplementation. In 13 prospective transplant recipients (N=43 samples), iMg and tMg showed strong category agreement (P =0.0003) and correlation (r=0.71, P <0.001), whereas iMg and iCa did not (P =0.7; r=-0.25, P =0.103, respectively). Conclusions: tMg and iMg exhibited strong correlation following kidney transplantation. However, iCa may not be an accurate surrogate for iMg. Determining the effect of Mg supplementation and the Mg concentration where supplementation is clinically necessary are important next steps. [ABSTRACT FROM AUTHOR]

Introduction: According to a substantial body of research, electrolyte abnormalities are a common manifestation in coronavirus disease 2019 (COVID-19) patients and are associated with adverse outcomes. This study aimed to investigate electrolyte imbalances in COVID-19 patients and assess their relation to mortality. Methods: Adult COVID-19 patients hospitalized in the Security Forces Hospital in Saudi Arabia from June 8th till August 18th, 2020 were enrolled in this retrospective observational study. We examined baseline characteristics, comorbidities, acute organ injuries, medications, and electrolyte levels including sodium, potassium, chloride, calcium, bicarbonate, phosphate, and magnesium on ICU admission, as well as every following day of ICU stay, until death or discharge. Patients were stratified according to survival, and differences in variables between groups were compared using Mann-Whitney's U test or Fisher's exact test. Longitudinal electrolyte profiles were modeled using random intercept linear regression models. Results: A total of 60 COVID-19 patients were enrolled. Compared to survivors, non-survivors had significantly higher sodium and phosphate on admission and death, higher potassium and magnesium at death, and significantly lower calcium at death. Abnormalities in admission levels of chloride and bicarbonate were also more frequently observed in non-survivors. Furthermore, in the deceased group, we observed a daily increase in potassium and phosphate levels, and a daily decrease in sodium and chloride. Finally, calcium increased in non-survivors over time, however, not as significantly as in the survivor group. Conclusion: Admission levels of electrolytes and changes over the course of ICU stay appear to be associated with mortality in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected over 600 million individuals and caused nearly 7 million deaths worldwide (10 January 2023). Patients with renal disease undergoing hemodialysis are among those most adversely affected, with an increased predisposition to SARS-CoV-2 infection and death. This systematic review aimed to pool evidence assessing the humoral response of hemodialysis patients (HDP) post-mRNA SARS-CoV-2 vaccination. A systematic search of the literature was performed through MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers up to 10 January 2023. Cohort and case-control studies were included if they reported an immune response in one group of patients undergoing hemodialysis who received mRNA SARS-CoV-2 vaccination compared with another group of patients receiving the same vaccine but not on hemodialysis. The methodological quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was not deemed appropriate due to the high heterogeneity between studies. From the 120 studies identified, nine (n = 1969 participants) met the inclusion criteria. Most studies (n = 8/9, 88%) were of high or medium methodological quality (≥6/9 stars). The results revealed that HDP developed lower antibody levels across all timepoints post-vaccination when compared with controls. Patients with chronic kidney disease elicited the highest antibody immune response, followed by HDP and, lastly, kidney transplant recipients. Overall, post-vaccination antibody titers were comparatively lower than in the healthy population. Current results imply that robust vaccination strategies are needed to address waning immune responses in vulnerable populations. [ABSTRACT FROM AUTHOR]

Introduction: Severe COVID-19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID-19 and for associations with disease progression and acute kidney injury (AKI). Methods: Patients presenting to the emergency department (ED) with COVID-19 were enrolled in this prospective, observational study. ADAMTS13 activity and VWF:Ag were measured at index ED visit. The primary endpoint was severe AKI de- fined by KDIGO stage 2 + 3 criteria, while the secondary endpoint was peak 30-day COVID-19 severity. Results: A total of 52 adult COVID-19 patients were enrolled. Overall, we observed that 23.1% of the cohort had a relative deficiency in ADAMTS13 activity, while 80.8% had elevated VWF:Ag. The ADAMTS13 activity/VWF:Ag ratio was significantly lower in patients with severe AKI (P = .002) and those who developed the severe form of COVID-19 (P = .020). The ADAMTS13 activity/VWF:Ag ratio was negatively correlated with age (P < .001) and LDH (P < .001), while positively correlated with hemoglobin (P = .041). After controlling for confounders, a one-unit increase in ADAMTS13/VWF:Ag ratio was associated with 20% decreased odds of severe AKI. Conclusion: A low ADAMTS13 activity: VWF:Ag ratio at ED presentation is associated with progression to severe COVID-19 disease and severe AKI, with a pattern suggestive of a secondary microangiopathy. Further interventional studies should be conducted to assess the restoration of ADAMTS13:VWF:Ag ratio in hospitalized patients with COVID-19. [ABSTRACT FROM AUTHOR]

Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Keywords: blood; epidemiology; pathogenesis; SARS coronavirus; virus classification EN blood epidemiology pathogenesis SARS coronavirus virus classification 708 711 4 01/01/21 20210201 NES 210201 In a recent report, Tao et al.1 described that anemia, diagnosed based on hemoglobin measured within the first 24 h after hospital admission, was independently associated with progression to severe coronavirus disease 2019 (COVID-19). Three of the patients with anemia died (17.6%), whereas no patient without anemia died. For example, Tao et al. reported that COPD was present in 10.1% of patients with anemia and 0% without anemia. Blood, epidemiology, pathogenesis, SARS coronavirus, virus classification. [Extracted from the article]

: Biological, Clinical, and Technical Considerations These considerations are important when performing serology studies, with anti-S1/S2 serology tests preferably used to assess true seroprevalence; anti-RBD-specific serology immunoassays may be better suited to reflecting the presence of neutralizing antibodies. We read with interest the report by Geisler et al[1] and commend the authors for their efforts to address the important need to evaluate the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic assays in pediatric populations, especially with respect to serology, given the noted differences in immune responses between children and adults.[2] We do feel, however, that the title of this paper may be misleading. This behavior would make it challenging to define whether anti-RBD antibodies are false negatives or if anti-S1 antibodies are false positives. [Extracted from the article]

Coronavirus disease 2019 is associated with low circulating plasma levels of angiotensin 1 and angiotensin 1,7 Compared to healthy controls, patients with COVID-19 had significantly lower levels of Ang1 (146.8 [IQR: 9.6-219.7] vs. 704.6 pg/ml [IQR: 526.3-1038.0]; I p i < .001) and Ang1,7 (168.1 [IQR: 132.1-267.9] vs. 318.1 pg/ml [IQR: 226.7-370.6]; I p i = .003) (Figures 1A and 1D). GLO:OCQ/01feb21:jmv26479-fig-0001.jpg PHOTO (COLOR): 1 Angiotensin 1,7 (Ang1,7) and angiotensin 1 (Ang1) levels in COVID-19 positive patients and healthy controls. [Extracted from the article]

Background: Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry., Methods: We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems., Results: We identified the human extracellular serine protease inhibitor (serpin) alpha 1 anti-trypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity., Conclusions: Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells., Competing Interests: M.E.R. is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharma, Celgene, Astra Zeneca, Allakos, Arena Pharmaceuticals, Guidepoint, and Suvretta Capital Management and has an equity interest in the first 4 listed and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate. M.E.R. is an inventor of patents owned by Cincinnati Children's Hospital. M.E.R. and N.P.A. are inventors of a patent owned by Cincinnati Children's Hospital with the provisional number of 63/017,027., (Copyright © Pathogens and Immunity 2021.)

Introduction: Glomerular filtration rate (GFR) is routinely estimated with cystatin C. In June 2010, the International Federation of Clinical Chemistry (IFCC) released a certified cystatin C reference material (ERM-DA471/IFCC), and new cystatin C glomerular filtration rate estimation (eGFR) equations were developed with the IFCC standard. Early in 2018, Siemens discontinued their nonstandardized cystatin C reagent kits and replaced them with IFCC-calibrated kits in the US market. The aim of the current study was to assess the effect of IFCC calibration on cystatin C values and corresponding GFR estimations., Methods: Cystatin C concentration was measured in 81 pediatric patients using a plasma sample from their nuclear GFR measurement with 99mTc-diethylenetriaminepentaaccetic acid. Calibration curves were generated using Siemens nonstandardized and IFCC-standardized kits to measure paired cystatin C concentrations in each sample. GFR-estimating equations using pre-IFCC and IFCC cystatin C values were compared using Bland-Altman analyses., Results: The IFCC-standardized assay resulted in a mean increase in the measured cystatin C value of 24%. Estimating equations consistently overestimated GFR prior to IFCC standardization. Following incorporation of the IFCC standard, the Full Age Spectrum equation demonstrated the best overall performance, whereas the Chronic Kidney Disease in Children (CKiD) equation was more accurate in children with decreased GFR., Conclusion: Incorporation of the IFCC standard significantly increased cystatin C values and affected the performance of GFR estimating equations. Clinical laboratories and providers may need to update the equation used for cystatin C-based estimation of GFR following adoption of the IFCC reference standard., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)