#Prognostic Value of #Leukocytosis and #Lymphopenia for #Coronavirus Disease #Severity (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 8—August 2020 | Dispatch

Prognostic Value of Leukocytosis and Lymphopenia for Coronavirus Disease Severity

Glen Huang1  , Alex J. Kovalic1, and Christopher J. Graber1

Author affiliations: David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA (G. Huang, C.J. Graber); Novant Forsyth Medical Center, Winston Salem, North Carolina, USA (A.J. Kovalic); VA Greater Los Angeles Healthcare System, Los Angeles (C.J. Graber)

 

Abstract

To evaluate lymphopenia as a marker for coronavirus disease severity, we conducted a meta-analysis of 10 studies. Severe illness was associated with lower lymphocyte and higher leukocyte counts. Using these markers for early identification of patients with severe disease may help healthcare providers prioritize the need to obtain therapy.

Keywords: SARS-CoV-2; COVID-19; Immunopathology.

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#Immune #mechanisms of #pulmonary intravascular #coagulopathy in #COVID19 pneumonia (Lancet Resp Med., abstract)

[Source: Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia

Prof Dennis McGonagle, PhD,  Prof James S O’Donnell, PhD, Kassem Sharif, MD, Prof Paul Emery, MD, Charles Bridgewood, PhD

Published: May 07, 2020 | DOI: https://doi.org/10.1016/S2665-9913(20)30121-1

 

Summary

The lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.

Keywords: SARS-CoV-2; COVID-19; Coagulopathy; Immunopathology; Pathology.

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#Tropism, #replication competence, and innate immune responses of the #coronavirus #SARS-CoV-2 in #human #respiratory tract and #conjunctiva: an analysis in ex-vivo and in-vitro cultures (Lancet Resp Med., abstract)

[Source: The Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures

Kenrie P Y Hui, PhD, Man-Chun Cheung, MSc, Ranawaka A P M Perera, PhD, Ka-Chun Ng, BSc, Christine H T Bui, PhD, John C W Ho, PhD, Mandy M T Ng, BSc, Denise I T Kuok, PhD, Kendrick C Shih, MBBS, Prof Sai-Wah Tsao, PhD, Prof Leo L M Poon, DPhil, Prof Malik Peiris, FRCPath, Prof John M Nicholls, FRCPA, Michael C W Chan, PhD

Published: May 07, 2020 | DOI: https://doi.org/10.1016/S2213-2600(20)30193-4

 

Summary

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.

Methods

We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls.

Findings

SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV.

Interpretation

The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens.

Funding

US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

Keywords: SARS-CoV; SARS-CoV-2; MERS-CoV; H5N1; H1N1pdm09; Cytokines; Immunopathology.

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T cell subset counts in peripheral blood can be used as discriminatory #biomarkers for #diagnosis and #severity prediction of #COVID19 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

T cell subset counts in peripheral blood can be used as discriminatory biomarkers for diagnosis and severity prediction of COVID-19

Mei Jiang, Yang Guo, Qing Luo, ZiKun Huang, Rui Zhao, ShuYuan Liu, AiPing Le, JunMing Li, LaGen Wan

The Journal of Infectious Diseases, jiaa252, https://doi.org/10.1093/infdis/jiaa252

Published: 07 May 2020

 

Abstract

This study evaluated the significance of lymphocyte subsets detection in peripheral blood in the diagnosis and prognosis of coronavirus disease 2019 (COVID-19). Our results revealed that CD3+T, CD4+T, CD8+T cells and NK cells were significantly decreased in COVID-19 patients. COVID-19 patients had a relatively slight decrease in CD4+T cells but a severe decrease of CD8+T cells. The significantly elevated CD4/CD8 ratio was observed in COVID-19 patients. T cell subset counts were related to the severity and prognosis of COVID-19. The counts of CD8+T and CD4+T cells can be used as diagnostic markers of COVID-19 and predictors of disease severity.

SARS-CoV2, lymphocyte subsets, diagnosis, prognosis

Issue Section: Brief Report

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© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Immunopathology.

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#SARS-CoV-2 and enhancing #antibodies (J Clin Virol., summary)

[Source: Journal of Clinical Virology, full page: (LINK). Summary, edited.]

Journal of Clinical Virology | Available online 7 May 2020, 104424  | In Press, Journal Pre-proof | Letter to the editor

SARS-CoV-2 and enhancing antibodies

Joachim Denner, Robert Koch Institute, Berlin, Germany

Received 30 April 2020, Available online 7 May 2020.

DOI: https://doi.org/10.1016/j.jcv.2020.104424

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To the Editor, Human coronaviruses (CoV) are common, and some of them are associated with mild respiratory infections including common cold [1]. In contrast, other CoV infections including the severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS) and the recent COVID-19 are characterised by a higher pathogenicity in certain human populations and may be lethal. CoV infections were shown to induce an effective antibody response, however in addition to neutralising antibodies also enhancing antibodies were described, e. g., in the case of SARS-CoV [2] and MERS-CoV [3]. Antibody-dependent enhancement (ADE) occurs when antibodies facilitate viral entry into host cells. ADE has been observed for a variety of viruses, most notable flaviviruses [4].

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Keywords: SARS-CoV-2; COVID-19; ADE; Immunopathology.

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DC/L‐SIGNs of Hope in the #COVID19 #Pandemic (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

DC/L‐SIGNs of Hope in the COVID‐19 Pandemic

Adam Brufsky MD, PhD,  Michael T. Lotze MD, FACS

First published: 06 May 2020 | DOI:  https://doi.org/10.1002/jmv.25980

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.25980

 

Abstract

In a rapidly evolving pandemic such as COVID‐19, theories which help unify disparate pre‐clinical and clinical observations would be useful. The current pandemic and its pleotropic effects can be explained in part by interaction between SARS‐CoV‐2 spike protein S, the ACE2/L‐SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC‐SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells. Infection of the DC by SARS‐CoV‐2 can potentially explain the exuberant distal immunopathology seen in COVID‐19.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Immunopathology.

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#Silencing the #cytokine #storm: the use of intravenous #anakinra in haemophagocytic lymphohistiocytosis or #macrophage activation syndrome (Lancet Rheumatol., summary)

[Source: Lancet Rheumatology, full page: (LINK). Summary, edited.]

Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome

Puja Mehta, MD, Prof Randy Q Cron, MD, James Hartwell, MPharm, Jessica J Manson, MD  †, Rachel S Tattersall, MD †

Published: May 04, 2020 | DOI: https://doi.org/10.1016/S2665-9913(20)30096-5

 

Summary

The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.

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Keywords: SARS-CoV-2; COVID-19; Cytokines; Immunopathology; Anakinra.

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#Bioinformatic #Analysis and #Identification of Single-Stranded #RNA #Sequences Recognized by #TLR7/8 in the #SARS-CoV-2, #SARS-CoV, and #MERS-CoV #Genomes (Microbes Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Microbes Infect. 2020 Apr 30;S1286-4579(20)30076-9. doi: 10.1016/j.micinf.2020.04.009. Online ahead of print.

Bioinformatic Analysis and Identification of Single-Stranded RNA Sequences Recognized by TLR7/8 in the SARS-CoV-2, SARS-CoV, and MERS-CoV Genomes

Mario Adán Moreno-Eutimio 1, Constantino Lopez-Macias 2, Rodolfo Pastelin-Palacios 3

Affiliations: 1 Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, CP, 04510, Mexico. Electronic address: marioadan@inmunoquimica.com. 2 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, CP, 06020, Mexico; Visiting Professor of Immunology. Nuffield Department of Medicine, University of Oxford. UK. 3 Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, CP, 04510, Mexico.

PMID: 32361001 DOI: 10.1016/j.micinf.2020.04.009

 

Abstract

During virus infection, host toll-like receptors (TLRs) can recognize different pathogen-associated molecular patterns and trigger the innate immune response. TLR7/8 can identify the single-stranded RNA (ssRNA) of the virus. This study aimed to search ssRNA sequences recognized by TLR7/8 from the SARS-CoV-2, SARS-CoV, and MERS-CoV whole genomes by a bioinformatic technique. The immunoinformatic approach showed that the SARS-CoV-2 genome has more ssRNA fragments that could be recognized by TLR7/8 than the SARS-CoV genome. These findings suggest innate immune hyperactivation by SARS-CoV-2. This activity is possibly able to provoke a robust proinflammatory response via TLR7/8 recognition and cause acute lung injury.

Keywords: MERS; SARS; SARS-CoV-2; TLR7; TLR8.

Copyright © 2020. Published by Elsevier Masson SAS.

Conflict of interest statement

Declaration of Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: SARS-CoV-2; COVID-19; SARS; SARS-CoV-2; MERS-CoV; Cytokines; Immunopathology.

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Adjunct #immunotherapies for the #management of severely ill #COVID19 patients (Cell Rep Med., abstract)

[Source: Cell Reports Medicine, full page: (LINK). Abstract, edited.]

Adjunct immunotherapies for the management of severely ill COVID-19 patients

Srinivasa Reddy Bonam, Srini V. Kaveri, Anavaj Sakuntabhai, Laurent Gilardin, Jagadeesh Bayry

Open Access | Published: April 29, 2020 | DOI: https://doi.org/10.1016/j.xcrm.2020.100016

 

Highlights

  • Inflammation is the hallmark of SARS-CoV-2 infection
  • Cytokine storm characterizes severely ill COVID-19 cases
  • Immunotherapies represent promising options for the management of severe COVID-19
  • Immunotherapies either neutralize cytokines, SARS-CoV-2 or exert  immunomodulation

 

Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has infected millions with more than 181,000 fatal cases as of 22nd April 2020. Currently, there are no specific COVID-19 therapies. Most patients depend on mechanical ventilation. Current COVID-19 data clearly highlight that cytokine storm and activated immune cell migration to the lungs characterize the early immune response to COVID-19 that causes severe lung damage and development of acute respiratory distress syndrome. In view of uncertainty associated with immunosuppressive treatments such as corticosteroids and their possible secondary effects, including risks of secondary infections, we suggest immunotherapies as an adjunct therapy in severe COVID-19 cases. Such immunotherapies based on inflammatory cytokine neutralization, immunomodulation and passive viral neutralization, not only reduce inflammation, inflammation-associated lung damage, or viral load, but could also prevent intensive care unit hospitalization and dependency on mechanical ventilation both of which are limited resources.

Keywords: SARS-CoV-2; COVID-19; Cytokines; Immunopathology; Immunotherapy.

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Case Report of a #SARS-CoV-2 Infection in a Patient With Ulcerative #Colitis on #Tofacitinib (Inflam Bowel Dis., summary)

[Source: Inflammatory Bowel Diseases, full page: (LINK). Summary, edited.]

Case Report of a SARS-CoV-2 Infection in a Patient With Ulcerative Colitis on Tofacitinib

Jeffrey Jacobs, MD, Kindra Clark-Snustad, DNP, Scott Lee, MD

Inflammatory Bowel Diseases, izaa093, https://doi.org/10.1093/ibd/izaa093

Published: 28 April 2020

Issue Section: Letter to the Editor

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To the Editors, The emergence of a novel coronavirus in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant disease, COVID-19, has led to a global pandemic with severe disease in 14% of those infected and a case fatality rate of 2.3% reported in China.1 This has caused uncertainty among providers and fear among patients with inflammatory bowel disease (IBD) on immunosuppressive medications. Though the risk of infection is thought to be similar to that of non-IBD patients, it remains unknown whether patients with IBD may have a more severe presentation compared with non-IBD patients. Furthermore, in IBD patients with COVID-19, the best management strategy has yet to be determined with regard to immunosuppressive medications, many of which have a long serum half-life and even longer tissue effect that can persist much longer than the course of a typical infection.

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Keywords: SARS-CoV-2; COVID-19; Immunopathology.

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