[Predictors of severe course of new coronavirus infection (COVID-19): study design].

AIM: To identify predictors of the severe course of a new coronavirus infection. MATERIALS AND METHODS: A retrospective analysis of 120 clinical case histories of patients hospitalized in hospitals in Tyumen with a confirmed diagnosis of COVID-19 within one year (01.08.2020-01.08.2021) was carried out. The patients were divided into two groups: 1st - with a favorable outcome (n=96), 2nd - with an unfavorable (fatal) outcome (n=24). For a more complete analysis, scales for assessing the clinical condition of patients (SHOCK-COVID), severity assessment (NEWS2) were used. Information processing was carried out in the IBM.SPSS.Statistics-19 program (USA). RESULTS: As a result of the study, the median age for the 1st group was significantly lower (58 years) than for patients of the 2nd group (69 years; p=0.029). A certain set of laboratory parameters for group 2 patients deviate significantly from the reference values (C-reactive protein - CRP - 7.6 [4.7; 15.2] mg/dl, D-dimer - 1.89 [1.36; 5.3] mcg/ml, ferritin - 605 [446.7; 792] ng/ml). When analyzed in groups, taking into account the main markers of the severity of the disease, using the V.Yu. Mareev CCAS-COVID (Clinical Condition Assessment Scale) scale, for the 1st group, the sum of the set of parameters was 6 [2; 7] points, which corresponds to the average severity of coronavirus infection, for the 2nd group 13 [9; 16] points - severe course. For patients of the 2nd group, a significant increase in the indicators of an unfavorable prognosis was revealed in comparison with the 1st group. CONCLUSION: Thus, in this study, the level of CRP, ferritin, D-dimer, the percentage of lung tissue damage according to computed tomography results, SaO2 were significantly associated with an unfavorable prognosis.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Iron as a therapeutic target in chronic liver disease.

It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor in the development and progression of liver disease. The recent clarification of ferroptosis as a specific form of regulated hepatocyte death different from apoptosis and the description of ferritinophagy as a specific variation of autophagy prompted detailed investigations on the association of iron and the liver. In this review, we will present a brief discussion of iron absorption and handling by the liver with emphasis on the role of liver macrophages and the significance of the iron regulators hepcidin, transferrin, and ferritin in iron homeostasis. The regulation of ferroptosis by endogenous and exogenous mod-ulators will be examined. Furthermore, the involvement of iron and ferroptosis in various liver diseases including alcoholic and non-alcoholic liver disease, chronic hepatitis B and C, liver fibrosis, and hepatocellular carcinoma (HCC) will be analyzed. Finally, experimental and clinical results following interventions to reduce iron deposition and the promising manipulation of ferroptosis will be presented. Most liver diseases will be benefited by ferroptosis inhibition using exogenous inhibitors with the notable exception of HCC, where induction of ferroptosis is the desired effect. Current evidence mostly stems from in vitro and in vivo experimental studies and the need for well-designed future clinical trials is warranted.

Longitudinal profiles of plasma gelsolin, cytokines and antibody expression predict COVID-19 severity and hospitalization outcomes.

Background: Prognostic markers for COVID-19 disease outcome are currently lacking. Plasma gelsolin (pGSN) is an actin-binding protein and an innate immune marker involved in disease pathogenesis and viral infections. Here, we demonstrate the utility of pGSN as a prognostic marker for COVID-19 disease outcome; a test performance that is significantly improved when combined with cytokines and antibodies compared to other conventional markers such as CRP and ferritin. Methods: Blood samples were longitudinally collected from hospitalized COVID-19 patients as well as COVID-19 negative controls and the levels of pGSN in µg/mL, cytokines and anti- SARS-CoV-2 spike protein antibodies assayed. Mean ± SEM values were correlated with clinical parameters to develop a prognostic platform. Results: pGSN levels were significantly reduced in COVID-19 patients compared to healthy individuals. Additionally, pGSN levels combined with plasma IL-6, IP-10 and M-CSF significantly distinguished COVID-19 patients from healthy individuals. While pGSN and anti-spike IgG titers together strongly predict COVID-19 severity and death, the combination of pGSN and IL-6 was a significant predictor of milder disease and favorable outcomes. Conclusion: Taken together, these findings suggest that multi-parameter analysis of pGSN, cytokines and antibodies could predict COVID-19 hospitalization outcomes with greater certainty compared with conventional clinical laboratory markers such as CRP and ferritin. This research will inform and improve clinical management and health system interventions in response to SARS-CoV-2 infection.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.

In the SARS-CoV-2 Pandora Pandemic: Can the Stance of Premorbid Intestinal Innate Immune System as Measured by Fecal Adnab-9 Binding of p87:Blood Ferritin, Yielding the FERAD Ratio, Predict COVID-19 Susceptibility and Survival in a Prospective Population Database?

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.

COVID-19 severity appears to be reduced in spring/summer.

BACKGROUND: because of different human behaviours, SARS-CoV-2 spread may be lower in spring/summer. On the contrary, it is not clearly known whether the clinical course/severity of hospitalized patients infected by SARS-CoV-2 can be different in the various seasons.. OBJECTIVES: to understand whether there were differences in severity of COVID-19 in patients who had contracted the infection in winter versus those infected in spring/summer. DESIGN: observational retrospective cohort study. SETTING AND PARTICIPANTS: from the administrative database of the SARS-CoV-2 surveillance system and that of hospital discharge, a cohort of patients (8,221, 653 of which were hospitalized) who tested positive to the RT-PCR test for SARS-CoV-2 between 01.12.2020 and 31.07.2021 in the Grosseto province (Tuscany Region, Central Italy) was selected and analysed. MAIN OUTCOME MEASURES: hospitalization rate and length, continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) use, Intensive Care Unite (ICU) admissions, intra-hospital mortality and PaO2/FiO2 values were measured and compared between subjects infected in winter and those who developed COVID-19 in spring/summer. Viral load (cycle threshold, Ct), vitamin D, serum ferritin, IL-6, procalcitonin, D-dimer, and C-reactive protein measured in the two periods were also compared. RESULTS: in the considered months, the hospitalization rate among 8,221 patients with COVID-19 was 8%: 370 (8.5%) individuals were hospitalized in winter and 283 (7,3%; p=0.31) in spring/summer; 62 (16.8%), 88 (23.8%), and 63 (17%) in winter and 28 (9.9%), 40 (14.1%), and 36 (12.7%) in spring/summer were admitted in ICU (p=0.01), used CPAP/NIV (p=0.002) and died (p=0.13), respectively. Hospitalization days were 14.5±11.6 in winter and 10.3±8.84 in spring/summer (p=0.001), while minimum PaO2/FiO2, measured during hospital stays was 123.2±38.6 in spring/summer and 112.6±40.8 in winter (p=0.054). Multivariate analysis (adjusted for all confounding factors) also confirmed reduced risks of having ICU admissions (0.53; 95%CI 0.32;0.88; p=0.01) and of using CPAP/NIV (0.48; 95%CI 0.32;0.75; p=0.001) in spring/summer when compared to winter. Hospitalization days and minimum PaO2/FiO2 were also lower in spring/summer (ß= -3.9; 95%CI -5.5;-2.2; p=0.001) and winter (ß= -17; 95%CI -0.93;35; p=0.06), respectively. The adjusted hazard ratio of mortality in winter, obtained with a Cox model, was higher of about 38% compared to spring/summer. No Ct values (viral load) differences were found either in winter (19.45±6.18) or spring/summer (20.3±6.7; p=0.343). IL-6, ferritin, procalcitonin, D-dimer were similar. Conversely, CRP was lower whereas vitamin D was higher in the warmer seasons. CONCLUSIONS: COVID-19 may be less severe during spring/summer in hospitalized patients. This does not seem to be influenced by different SARS-CoV-2 viral load in the different periods considered. C-reactive protein was found to be lower whereas vitamin D higher in the warmer months. It can be hypothesized that higher levels of vitamin D in spring/summer, compared to winter, may be associated to a positive modulation of COVID-19 induced inflammation with a possible disease severity reduction during spring/summer.

Distinct phenotypes of multisystem inflammatory syndrome in children: a cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe disease with an unpredictable course and a substantial risk of cardiogenic shock. Our objectives were to (a) compare MIS-C phenotypes across the COVID-19 pandemic, (b) identify features associated with intensive care need and treatment with biologic agents. METHODS: Youth aged 0-18 years, fulfilling the World Health Organization case definition of MIS-C, and admitted to the Alberta Children's Hospital during the first four waves of the COVID-19 pandemic (May 2020-December 2021) were included in this cohort study. Demographic, clinical, biochemical, imaging, and treatment data were captured. RESULTS: Fifty-seven MIS-C patients (median age 6 years, range 0-17) were included. Thirty patients (53%) required intensive care. Patients in the third or fourth wave (indicated as phase 2 of the pandemic) presented with higher peak ferritin (µg/l, median (IQR) = 1134 (409-1806) vs. 370 (249-629), P = 0.001), NT-proBNP (ng/l, median (IQR) = 12,217 (3013-27,161) vs. 3213 (1216-8483), P = 0.02) and D-dimer (mg/l, median (IQR) = 4.81 (2.24-5.37) vs. 2.01 (1.27-3.34), P = 0.004) levels, and higher prevalence of liver enzyme abnormalities (n(%) = 17 (68) vs. 11 (34), P = 0.02), hypoalbuminemia (n(%) = 24 (100) vs. 25 (81), P = 0.03) and thrombocytopenia (n(%) 18 (72) vs. 11 (34), P = 0.007) compared to patients in the first two waves (phase 1). These patients had a higher need of non-invasive/mechanical ventilation (n(%) 4 (16) vs. 0 (0), P = 0.03). Unsupervised clustering analyses classified 47% of the patients in the correct wave and 74% in the correct phase of the pandemic. NT-proBNP was the only significant contributor to the need for intensive care in all applied multivariate regression models. Treatment with biologic agents was significantly associated with peak CRP (mg/l (median, IQR = 240.9 (132.9-319.4) vs. 155.8 (101.0-200.7), P = 0.02) and ferritin levels (µg/l, median (IQR) = 1380 (509-1753) vs. 473 (280-296)). CONCLUSIONS: MIS-C patients in a later stage of the pandemic displayed a more severe phenotype, reflecting the impact of distinct SARS-CoV-2 variants. NT-proBNP emerged as the most crucial feature associated with intensive care need, underscoring the importance of monitoring.

Cardiac magnetic resonance T2* mapping in patients with COVID-19 pneumonia is associated with serum ferritin level?

The coronavirus disease of 2019 (COVID-19)-related myocardial injury is an increasingly recognized complication and cardiac magnetic resonance imaging (MRI) has become the most commonly used non-invasive imaging technique for myocardial involvement. This study aims to assess myocardial structure by T2*-mapping which is a non-invasive gold-standard imaging tool for the assessment of cardiac iron deposition in patients with COVID-19 pneumonia without significant cardiac symptoms. Twenty-five patients with COVID-19 pneumonia and 20 healthy subjects were prospectively enrolled.Cardiac volume and function parameters, myocardial native-T1, and T2*-mapping were measured. The association of serum ferritin level and myocardial mapping was analyzed. There was no difference in terms of cardiac volume and function parameters. The T2*-mapping values were lower in patients with COVID-19 compared to controls (35.37 [IQR 31.67-41.20] ms vs. 43.98 [IQR 41.97-46.88] ms; p < 0.0001), while no significant difference was found in terms of native-T1 mapping value(p = 0.701). There was a positive correlation with T2*mapping and native-T1 mapping values (r = 0.522, p = 0.007) and negative correlation with serum ferritin values (r = - 0.653, p = 0.000), while no correlation between cardiac native-T1 mapping and serum ferritin level. Negative correlation between serum ferritin level and T2*-mapping values in COVID-19 patients may provide a non-contrast-enhanced alternative to assess tissue structural changes in patients with COVID-19. T2*-mapping may provide a non-contrast-enhanced alternative to assess tissue alterations in patients with COVID-19. Adding T2*-mapping cardiac MRI in patients with myocardial pathologies would improve the revealing of underlying mechanisms. Further in vivo and ex vivo animal or human studies designed with larger patient cohorts should be planned.

Variation in biochemical parameters in COVID-19 patients admitted at a tertiary care dedicated COVID hospital: A prospective study.

Introduction: COVID-19 infection has a myriad of presentation. Rural India and other developing nations are relatively resource poor, not having access to modern specialized investigations. In this study, we tried to evaluate only biochemical parameters in predicting the severity of the infection. The aim of this study was to find a cost-effective means to predict the clinical course at the time of admission and thereby to reduce mortality and, if possible, morbidity by timely intervention. Materials and Methods: All COVID-19-positive cases admitted at our hospital from March 21 to December 31, 2020, were recruited in this study. The same acted as sham control at recovery. Results: We observed a significant difference in biochemical parameters at the time of admission and discharge, between mild/moderate disease and severe disease. We found slightly deranged liver function tests at admission, which becomes normal at the time of discharge. Urea, C-reactive protein (CRP), procalcitonin, lactate dehydrogenase, and ferritin concentrations in severe/critical patients were significantly higher than that in the mild/moderate group. Receiver operating characteristic curves were plotted to predict the severity on the basis of biochemical parameters independently, of the patients based on these values. Conclusion: We proposed cutoff values of certain biochemical parameters, which will help in judging the severity of the infection at admission. We developed a predictive model with a significant predictive capability for CRP and ferritin values, using normal available biochemical parameters, routinely done in resource-poor centers. Clinicians working in resource-poor situations will be benefitted by having an idea of the severity of the disease. Timely intervention will reduce mortality and severe morbidity.

Résumé Introduction: L'infection au COVID19 a une myriade de présentations. L'Inde rurale et d'autres pays en développement sont relativement pauvres en ressources, non avoir accès aux enquêtes spécialisées modernes. Dans cette étude, nous avons essayé d'évaluer uniquement les paramètres biochimiques pour prédire la gravité de l'infection. Le but de cette étude était de trouver un moyen rentable de prédire l'évolution clinique au moment de l'admission et ainsi de réduire la mortalité et, si possible, la morbidité par une intervention rapide. Matériels et méthodes: Tous les cas positifs au COVID19 admis à notre hospitalisés du 21 mars au 31 décembre 2020, ont été recrutés dans cette étude. La même chose a agi comme un contrôle factice lors de la récupération. Résultats: Nous avons observé une différence significative dans les paramètres biochimiques au moment de l'admission et de la sortie, entre une maladie légère/modérée et une maladie grave. Nous avons trouvé des tests de la fonction hépatique légèrement dérangés à l'admission, qui deviennent normaux au moment de la sortie. Urée, protéine Créactive (CRP, les concentrations de procalcitonine, de lactate déshydrogénase et de ferritine chez les patients sévères/critiques étaient significativement plus élevées que chez les patients légers/modérés groupe. Les courbes caractéristiques de fonctionnement du récepteur ont été tracées pour prédire la gravité sur la base de paramètres biochimiques indépendamment, deles patients en fonction de ces valeurs. Conclusion: Nous avons proposé des valeurs seuils de certains paramètres biochimiques, qui permettront de juger de la gravité de l'infection à l'admission. Nous avons développé un modèle prédictif avec une capacité prédictive significative pour les valeurs de CRP et de ferritine, en utilisant les paramètres biochimiques normaux disponibles, systématiquement effectués dans les centres pauvres en ressources. Les cliniciens travaillant dans des situations où les ressources sont limitées bénéficier d'avoir une idée de la gravité de la maladie. Une intervention rapide réduira la mortalité et la morbidité grave. Mots-clés: COVID19, ferritine, lactate déshydrogénase, urée.

Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles.

The presentation of viral antigens on nanoparticles in multivalent arrays has emerged as a valuable technology for vaccines. On the nanoparticle surface, highly ordered, repetitive arrays of antigens can mimic their geometric arrangement on virion surfaces and elicit stronger humoral responses than soluble viral antigens. More recently, bacterial antigens have been presented on self-assembling protein nanoparticles and have elicited protective antibody and effective T-helper responses, further supporting the nanoparticle platform as a universal approach for stimulating potent immunogenicity. Here, we present the rational design, structural analysis, and immunogenicity of self-assembling ferritin nanoparticles displaying eight copies of the Neisseria meningitidis trimeric adhesin NadA. We engineered constructs consisting of two different NadA fragments, head only and head with stalk, that we fused to ferritin and expressed in Escherichia coli. Both fusion constructs self-assembled into the expected nanoparticles as determined by Cryo electron microscopy. In mice, the two nanoparticles elicited comparable NadA antibody levels that were 10- to 100-fold higher than those elicited by the corresponding NadA trimer subunits. Further, the NadAferritin nanoparticles potently induced complement-mediated serum bactericidal activity. These findings confirm the value of self-assembling nanoparticles for optimizing the immunogenicity of bacterial antigens and support the broad applicability of the approach to vaccine programs, especially for the presentation of trimeric antigens.

Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study.

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.

Presentation and outcomes of chronic kidney disease patients with COVID-19.

INTRODUCTION: COVID-19 is currently a global health issue and an important cause of mortality. Chronic kidney disease (CKD) is one of the risk factors for infection, morbidity and mortality by SARS-CoV-2. In our study, we aimed to evaluate the clinical presentation and outcomes of CKD patients with COVID-19, as well as identify predictors of mortality. METHODS: This was a retrospective study of CKD patients admitted in a tertiary-care Portuguese hospital between March and August of 2020. Variables were submitted to univariate and multivariate analysis to determine factors predictive of in-hospital mortality. RESULTS: 130 CKD patients were analyzed (median age 73.9 years, male 60.0%). Hypertension (81.5%), cardiovascular disease (36.2%), and diabetes (54.6%) were frequent conditions. Cough, dyspnea, fever and respiratory failure were also common. Almost 60% had anemia, 50% hypoalbuminemia, 13.8% hyperlactacidemia and 17% acidemia. Mean serum ferritin was 1531 µg/L, mean CRP 8.3 mg/dL and mean LDH 336.9 U/L. Most patients were treated with lopinavir/ritonavir, hydroxychloroquine or corticosteroids and only 2 with remdesivir. Eighty percent had acute kidney injury and 16.2% required intensive care unit admission. The 34 patients who died were older and more likely to have heart failure. They had higher neutrophils/lymphocytes ratio, ferritin, lactate, and LDH levels. Multivariate analysis identified an association between older age [OR 1.1 (CI 1.01-1.24), p=0.027], higher ferritin [OR 1.0 (CI 1.00-1.00), p=0.009] and higher LDH levels [OR 1.0 (CI 1.00-1.01), p=0.014] and mortality. CONCLUSION: In our cohort of CKD patients with COVID-19, older age, higher ferritin, and higher LDH levels were independent risk factors for mortality.

The impact of transient and persistent acute kidney injury in hospital mortality in COVID-19 patients.

INTRODUCTION: Acute kidney injury (AKI) has been described in Coronavirus Disease 2019 (COVID-19) patients and is considered a marker of disease severity and a negative prognostic factor for survival. In this study, the authors aimed to study the impact of transient and persistent acute kidney injury (pAKI) on in-hospital mortality in COVID-19 patients. METHODS: This was a retrospective observational study of patients hospitalized with COVID-19 in the Department of Medicine of the Centro Hospitalar Universitario Lisboa Norte, Lisbon, Portugal, between March 2020 and August 2020. A multivariate analysis was performed to predict AKI development and in-hospital mortality. RESULTS: Of 544 patients with COVID-19, 330 developed AKI: 166 persistent AKI (pAKI), 164 with transient AKI. AKI patients were older, had more previous comorbidities, had higher need to be medicated with RAAS inhibitors, had higher baseline serum creatine (SCr) (1.60 mg/dL vs 0.87 mg/dL), higher NL ratio, and more severe acidemia on hospital admission, and more frequently required admission in intensive care unit, mechanical ventilation, and vasopressor use. Patients with persistent AKI had higher SCr level (1.71 mg/dL vs 1.25 mg/dL) on hospital admission. In-hospital mortality was 14.0% and it was higher in AKI patients (18.5% vs 7.0%). CKD and serum ferritin were independent predictors of AKI. AKI did not predict mortality, but pAKI was an independent predictor of mortality, as was age and lactate level. CONCLUSION: pAKI was independently associated with in-hospital mortality in COVID-19 patients but its impact on long-term follow-up remains to be determined.

ACE2 and TMPRSS2 SNPs as Determinants of Susceptibility to, and Severity of, a COVID-19 Infection.

Background: Genetic risk factors may be related to the infectivity and severity of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) and host transmembrane serine protease (TMPRSS2) have key role in viral cell entrance and priming. Methods: This case-control study on 147 healthy controls and 299 COVID-19 patients identified potential determinants and risk factors, including gene polymorphism involved in the severity (mild, moderate, severe) of COVID-19 disease defined by CORAD radiological criteria. Results: The ACE2 s2285666 and TMPRSS2 rs12329760 SNPs were significantly linked with COVID-19 disease severity, as were certain co-morbidities (hypertension, heart disease) and laboratory parameters. Both SNPs were amongst the highest predictors of disease severity: TMPRSS2 rs12329760 CT + TT [odds ratio (95% CI) 17.6 (5.1-61.10), ACE2 rs2285666 CT + TT 9.9 (3.2-30.9), both p < 0.001]. There was an increase in the expression of genotype frequencies of ACE2 rs2285666 and TMPRSS2 rs1232976 (TT), (CT + TT), and (T) allele in severe COVID-19 group compared to control and mild groups. Disease severity was also linked to elevated CRP, ferritin and D-dimer, and lower lymphocytes and platelet count (all p < 0.001). Conclusion: ACE2 rs2285666 and TMPRSS2 rs12329760 SNPs, in addition to lymphocyte count, CRP, D-dimers, ferritin, and hypertension, are predictors of COVID-19 disease severity.

Chemistry and biology of ferritin.

Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells forming multimeric assemblies with crystalline iron cores. We discuss the latest findings on ferritin structure and activity and its link to cell metabolism and ferroptosis. The chemistry of iron, including its oxidation states, is important for its biological functions, its reactivity, and the biology of ferritin. Ferritin can be localized in different cellular compartments and secreted by cells with a variety of functions depending on its spatial context. Here, we discuss how cellular ferritin localization is tightly linked to its function in a tissue-specific manner, and how impairment of iron homeostasis is implicated in diseases, including cancer and coronavirus disease 2019. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.

[Frequency of clinical characteristics and factors associated with mortality in patients hospitalized for COVID-19 in Puebla, Mexico]. / Frecuencia de características clínicas y factores asociados con mortalidad en pacientes hospitalizados por COVID-19 en Puebla, México.

BACKGROUND: Mexico has a very high mortality rate from COVID19, risk factors, clinical manifestations of our population are unknown. OBJECTIVE: To know risk factors for mortality from COVID19 in hospitalized patients of the Secretary of Health (SSA) Puebla, and clinical characteristics. MATERIAL AND METHODS: Case-control, observational, retrospective, cross-sectional study in COVID-19 patients. 2 groups: COVID-19 patients who died and those who did not die. RESULTS: 502  patients,  314  men  (62.5%  CI95%  58-66%),  188  women  (37.5%  CI95%  33-42%),  mean  age  54.14  +13.8,  interquartile  range  (IQR)  45-63, age interval 19 and 90 years, hospital stay (DEIH) 1-43 days, mean 9.8+7.8 days, median 8, IQR 4-13 days. Symptoms associated with mortality: dyspnea, chest pain, MR>1. Variables associated with mortality: age = or > 65 years, greater IHD, having > 2 comorbidities (OR 1.453), diabetes (OR 1.759), hypertension (OR 6.29) and chronic kidney failure (CRF) (OR 3.16) , (p<0.05). Ferritin >500ng/ml (OR 5.1799), DHL >400 IU/L (OR 3.313) and D-dimer >2000 m/ml (OR 2.868). CONCLUSIONS: Age > or = 65 years, greater IHD, > 2 comorbidities, diabetes, hypertension or CRF, increased ferritin, D-dimer or DHL, are risk factors for mortality from COVID-19.

OBJECTIVO: Identificar los factores de riesgo y las manifestaciones clínicas asociadas con mortalidad por COVID-19 en pacientes internados en hospitales de la Secretaria de Salud (SSA) del estado de Puebla, México. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo y transversal, llevado a cabo en pacientes con COVID-19, internados en hospitales de la Secretaria de Salud (SSA) del estado de Puebla, México. Los pacientes se dividieron en dos grupos: 1) fallecidos por COVID-19 y 2) supervivientes de COVID-19. RESULTADOS: Se registraron 502 pacientes: 314 hombres (62.5 % IC95% 58-66 %) y 188 mujeres (37.5% IC95% 33-42%), con edad promedio de 54.14 ± 13.8 años (rango intercuartil de 45-63, intervalo de edad de 19 y 90 años); estancia hospitalaria de 1 a 43 días (media 9.8 ± 7.8 días, me-diana 8, rango intercuartil 4-13 días). Los síntomas asociados con mortalidad por COVID-19 fueron: disnea y dolor torácico (RM >1). Las variables asociadas con mortalidad: edad igual o mayor de 65 años, estancia hospitalaria prolongada, coexistencia de dos o más comorbilidades (RM: 1.453), diabetes (RM: 1.759), hipertensión (RM: 6.29) e insuficiencia renal crónica (RM: 3.16; p<0.05); ferritina >500 ng/mL (RM: 5.1799), DHL >400 IU/L (RM: 3.313) y Dimero D >2000 m/ml (RM: 2.868). CONCLUSIONES: Este estudio demuestra que los principales factores de riesgo asociados con mortalidad por COVID-19 son: edad igual o mayor de 65 años, estancia hospitalaria prolongada, coexistencia de dos o más enfermedades, diabetes, hipertensión e insuficiencia renal crónica; además de concentraciones elevadas de ferritina, Dimero D y DHL.

Do Laboratory Biomarkers Predict Survival In Severe Covid-19? A Cross-Sectional Study.

Background: This study aims to compare lymphocyte count, C-reactive protein (CRP), ferritin, Lactate Dehydrogenase (LDH) and D-dimer among survivors and non-survivors of severe COVID-19. Methods: This retrospective cross-sectional analytical study included 69 patients for whom a record of the biomarkers and survival status was available. Baseline and peak values were selected for serum CRP, ferritin, LDH and D-Dimer. Baseline and trough lymphocyte counts were selected. Data were analyzed using SPSS version 21. Mean and standard deviation were used to compare the biomarkers with paired t-test. p-value <0.05 was taken as significant. Results: The mean age of the study population was 55.5±9.1 years and 50 (72.5%) were male. Among survivors, the increase in CRP level was not significant (from 15.80±9.8 mg/dl to 17.87±8.4 mg/dl, p=0.45) while it was significant in non-survivors (from 16.68±10.90 mg/dl to 20.77±12.69 mg/dl, p=0.04). There was no significant rise in LDH levels in survivors (from 829.59±499 U/L to 1018.6±468 U/L, p=0.20) while it increased significantly in non-survivors (from 816.2±443.08 U/L to 1056.61±480.54 U/L, p=0.003). The decrease in lymphocyte count and increase in D-Dimers in both the groups was significant (p=0.001). There was no significant elevation in ferritin in both the groups (p>0.05). Conclusion: In severe COVID-19 patients, serum CRP and LDH can be used for risk stratification and predicting survival. Lymphopenia, increase in serum ferritin and D-dimers may not predict survival.