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      The potential role of neopterin in Covid-19: a new perspective

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          Abstract

          Neopterin (NPT) is a member of pteridines group, synthesized by macrophages when stimulated by interferon gamma (INF-γ). NPT is regarded as a macrophage stimulation indicator, marker of cellular immune activation and T helper 1 (Th1) type 1 immune response. Here, we aimed to provide a view point on the NPT features and role in Covid-19. Serum NPT level is regarded as an independent prognostic factor for Covid-19 severity, with levels starting to increase from the 3rd day of SARS-CoV-2 infection, being associated with severe dyspnea, longer hospitalization period and complications. Also, early raise of NPT reflects monocytes/macrophages activation before antibody immune response, despite the NPT level may also remain high in Covid-19 patients or at the end of incubation period before the onset of clinical symptoms. On the other hand , NPT attenuates the activity of macrophage foam cells and is linked to endothelial inflammation through inhibition of adhesion molecules and monocytes migration. However, NPT also exerts anti-inflammatory and antioxidant effects by suppressing NF-κB signaling and NLRP3 inflammasomes. NPT can be viewed as a protective compensatory mechanism to counterpoise hyper-inflammation, oxidative stress, and associated organ damage.

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Fei Zhou, Ting Yu, Ronghui Du … (2020)
          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            ACUTE KIDNEY INJURY IN PATIENTS HOSPITALIZED WITH COVID-19

            Jamie Hirsch, Jia H. Ng, Daniel Ross … (2020)
            The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis.
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              Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

              Yanchun Peng, Alexander Mentzer, Guihai Liu … (2020)
              The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.
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                Author and article information

                Contributors
                Hayder M. Al-kuraishy: Hayderm36@yahoo.com
                Ali I. Al-Gareeb: Dr.alialgareeb78@yahoo.com
                Khalid J. Alzahrani: Ak.jamaan@tu.edu.sa
                Natália Cruz-Martins:
                ORCID: http://orcid.org/0000-0002-5934-5201
                ncmartins@med.up.pt
                Gaber El-Saber Batiha: gaberbatiha@gmail.com
                Journal
                Journal ID (nlm-ta): Mol Cell Biochem
                Journal ID (iso-abbrev): Mol Cell Biochem
                Title: Molecular and Cellular Biochemistry
                Publisher: Springer US (New York )
                ISSN (Print): 0300-8177
                ISSN (Electronic): 1573-4919
                Publication date (Electronic): 28 July 2021
                Pages: 1-6
                Affiliations
                [1 ]Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
                [2 ]GRID grid.412895.3, ISNI 0000 0004 0419 5255, Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, , Taif University, ; P.O. Box 11099, Taif, 21944 Saudi Arabia
                [3 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Faculty of Medicine, , University of Porto, ; Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
                [4 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Institute for Research and Innovation in Health (i3S), , University of Porto, ; 4200-135 Porto, Portugal
                [5 ]GRID grid.421335.2, ISNI 0000 0000 7818 3776, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, , CESPU, ; Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
                [6 ]GRID grid.449014.c, ISNI 0000 0004 0583 5330, Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, , Damanhour University, ; Damanhour, 22511 AlBeheira Egypt
                Author information
                http://orcid.org/0000-0002-5934-5201
                Article
                Publisher ID: 4232
                DOI: 10.1007/s11010-021-04232-z
                PMC ID: 8317144
                PubMed ID: 34319496
                SO-VID: fd8dafeb-825b-4e25-8b14-5eeae04b183c
                Copyright © © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 1 April 2021
                Date accepted : 19 July 2021
                Categories
                Subject: Article

                ScienceOpen disciplines: Biochemistry
                Keywords: neopterin,sars-cov-2 infection,covid-19 severity
                Data availability:
                ScienceOpen disciplines: Biochemistry
                Keywords: neopterin, sars-cov-2 infection, covid-19 severity

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