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      Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19

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          Abstract

          Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells. In the present manuscript, we explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death. HLA-A, HLA-B, and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with next-generation sequencing. Deceased patients were split into two groups according to age at the time of death: n = 26 adult patients aged below 60 and n = 85 elderly patients over 60. With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual. The resulting RS was significantly higher in the group of deceased adults compared to elderly adults [ p = 0.00348, area under the receiver operating characteristic curve ( AUC ROC = 0.68)]. In particular, presence of HLA-A *01:01 allele was associated with high risk, while HLA-A *02:01 and HLA-A *03:01 mainly contributed to low risk. The analysis of patients with homozygosity strongly highlighted these results: homozygosity by HLA-A *01:01 accompanied early deaths, while only one HLA-A *02:01 homozygote died before 60 years of age. Application of the constructed RS model to an independent Spanish patients cohort ( n = 45) revealed that the score was also associated with the severity of the disease. The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.

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          SciPy 1.0: fundamental algorithms for scientific computing in Python

          SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments.
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            Matplotlib: A 2D Graphics Environment

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              Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

              Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 February 2021
                2021
                23 February 2021
                : 12
                : 641900
                Affiliations
                [1] 1Faculty of Biology and Biotechnology, HSE University , Moscow, Russia
                [2] 2Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University , Moscow, Russia
                [3] 3Faculty of Mechanics and Mathematics, Lomonosov Moscow State University , Moscow, Russia
                [4] 4O.M. Filatov City Clinical Hospital , Moscow, Russia
                [5] 5Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences , Moscow, Russia
                Author notes

                Edited by: Musa R. Khaitov, Institute of Immunology, Russia

                Reviewed by: Israel Nieto Gañán, Ramón y Cajal University Hospital, Spain; Ludvig M. Sollid, University of Oslo, Norway

                *Correspondence: Stepan Nersisyan snersisyan@ 123456hse.ru
                Alexander Tonevitsky atonevitsky@ 123456hse.ru

                This article was submitted to Antigen Presenting Cell Biology, a section of the journal Frontiers in Immunology

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2021.641900
                7959787
                33732261
                04f536da-7610-4210-b1a6-9938850a57dc
                Copyright © 2021 Shkurnikov, Nersisyan, Jankevic, Galatenko, Gordeev, Vechorko and Tonevitsky.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 December 2020
                : 02 February 2021
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 39, Pages: 12, Words: 7189
                Categories
                Immunology
                Original Research

                Immunology
                hla class i,mhc class i,covid-19,sars-cov-2,peptide presentation
                Immunology
                hla class i, mhc class i, covid-19, sars-cov-2, peptide presentation

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