1. Questions on COVID-19 to be answered
ACE2, COVID-19 Infection, Inflammation and Coagulopathy: Missing Pieces in the Puzzle, Frontiers in Physiology 2020; 11: 574753;
ADAM
ADAM9 is a Novel Product of Polymorphonuclear Neutrophils: Regulation of Expression and Contributions to Extracellular Matrix Protein Degradation During Acute Lung Injury, Journal of Immunology 2014 Sep 1; 193(5): 2469-2482;
The Role of Metalloproteinase ADAM17 in Regulating ICOS Ligand-Mediated Humoral Immune Responses, The Journal of Immunology Vol. 193, Issue 6, 15 September 2014;
B cell ADAM17 controls T cell independent humoral immune responses through regulation of TACI and CD138, Biochemical and Biophysical Research Communications Vol. 552, Issue 2, 5 February 2020;
ACE2/ADAM17/TMPRSS2 Interplay may be the Main Risk Factor for COVID-19, Frontiers Inflammation, 07 October 2020;
ADAM17, the TNF-alpha convertase, ScienceDirect
ALI (Acute Lung Injury) due to COVID-19
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19, Medicine in Drug Discovery 2020 Sep; 7: 100052;
Autophagy
Can endolysosomal deacidification and inhibition of autophagy prevent severe COVID-19?, Life Sciences Vol. 262, 1 December 2020;
Caveolin-1, ARDS and ALI
Caveolin-1: a critical regulator of lung injury, American Journal of Physiology, Lung Cellular and Molecular Physiology 2011 Feb; 300(2);
Inflammation-induced caveolin-1 and BMPRII depletion promotes endothelial dysfunction and TGF-β-driven pulmonary vascular remodeling, Lung Cellular and Molecular Physiology 2017 May 1; 312(5);
Clinical Immunology
Long-term infection of SARS-CoV-2 changed the body's immune status, Clinical Immunology 2020 Sep; 218: 108524;
Contact system involvement
The contact activation system as a potential therapeutic target in patients with COVID-19, Research and Practice in Thrombosis and Haemostasis Vol. 4, Issue 4, May 2020;
Cytokine profile
Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis and comparison with other inflammatory syndromes, Lancet Respiratory Medicine October 16, 2020;
Elevation of liver enzymes in COVID-19
Serum Activity of Liver Enzymes is Associated with Higher Mortality COVID-19: A Systematic Review and Meta-Analysis, Frontiers Gastroenterology, 22 July 2020;
Ethnic profiles
Ethnic differences in alpha-1 antitrypsin deficiency allele frequencies may partially explain national differences in COVID-19 fatality rates, FASEB Journal 2020 Sep 22;
FOXP3 (Forkhead family of transcription responsible for Treg development)
FOXP3- an overview, ScienceDirect;
T-cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis, (CD25+ hyperactivation facilitates coronavirus entry by producing Furin; FOXP3-mediated negative feedbacks are impaired) Frontiers Immunological Tolerance and Regulation, 08 October 2020;
The many functions of FOXP3+ Regulatory T cells in the intestine, Frontiers T cell Biology, 20 October 2020;
Genetic profile
Host/genetic factors associated with COVID-19 call for precision medicine (NETs, NETosis and DAMPS), Precision Clinical Medicine 2020 Vol. 3, Issue 3, September 2020;
Interferons (IFN-)
SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity is Increased by a Naturally Occurring Elongation Variant (anti-IFN I and NLS), Cell Report Vol. 32, Issue 12, 108185, September 22, 2020;
The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I Interferon (IFN) signaling pathway (SARS-CoV-2 inhibits IFN-β activation and the NF-kB pathway, ORF6 and ORF8 suppress innate immune functions), Virus Research Vol. 286, September 2020;
Heightened circulating Interferon-Inducible Chemokines and activated Pro-Cytolytic Th1-cell phenotype features COVID-19 aggravation in the second week, Frontiers Cytokines and Soluble Mediators in Immunity, 20 October 2020;
Interleukins (IL- )
Elevated
IL-33 promotes expression of MMP2 and MMP9 via activating STAT3 in
alveolar macrophages during LPS-induced acute lung injury (ALI), Cellular & Molecular Biology Letters 2018; 23:52;
IL-1 induces thromboxane-A2 (TxA2) in COVID-19 causing inflammation and micro-thrombi: inhibitory effect of the IL-1-Receptor antagonist (IL-1Ra), Journal of Biological Regulators and Homeostatic Agents 2020 Aug 3;34(5);
Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?, Lancet Rheumatology, 9 October 2020;
Macrophages
Targeting macrophages as a therapeutic option for COVID-19 (M1 and M2), Frontiers Inflammation Pharmacology, to be published;
Activated protein C and PAR1-derived peptides are anti-inflammatory by suppressing macrophage NLRP3 inflammasomes, Journal of Thrombosis and Haemostasis, 13 October 2020;
A critical role for suppressor of cytokine signalling 3 in promoting M1 macrophage activation in vitro and in vivo, Immunology 2014 Jan;141(1):96-110;
Protective effect op suppressing STAT3 activity in LPS-induced lung injury, Lung Cellular and Molecular Physiology 2016 Nov 1; 311(5);
Macrophage responses associated with COVID-19: A pharmacological perspective, European Journal of Pharmacology Vol. 887, 15 November 2020;
Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients, EBioMedicine Vol. 57, July 2020;
The lung macrophage in SARS-CoV-2 Infection: A Friend or a Foe?, Frontiers in Immunology 2020; 11: 1312;
MAPK signalling pathways
MAPK signalling pathways as molecular targets for anti-inflammatory therapy- from molecular mechanisms to therapeutic benefits, Biochimica et Biophysica Acta (BBA)- Proteins and Proteomics, Vol. 1754, Issue 1-2, 30 December 2005, p253-262;
Megakaryocytes
Development and characterisation of a novel, megakaryocyte NF-kB reporter cell line for investigating inflammatory responses, Journal of Thrombosis and Haemostasis, 09 October 2020;
Matrix Metalloproteinases (MMPs) and their role in Acute Lung Injury (ALI)
Elevated IL-33 promotes expression of MMP2 and MMP9 via activating STAT3 in alveolar macrophages during LPS-induced acute lung injury (ALI), Cellular & Molecular Biology Letters 2018; 23:52;
Upregulation of matrix metalloproteinase 9 (MMP9)/tissue inhibitor of metalloproteinase 1 (TIMP1) and MMP2/TIMP2 ratios may be involved in lipopolysaccharide-induced acute lung injury (LPS-induced ALI), Journal of International Medical Research 2020 Apr; 48(4);
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19, Medicine in Drug Discovery 2020 Sep; 7: 100052;
Matrix Metalloproteinases in ALI: mediators of injury and drivers of repair, European Respiratory Journal Vol. 38 Issue 4, 2011;
Serum MMP-8 and TIMP-1 in critically ill patients with acute respiratory failure: TIMP-1 is associated with increased 90-day mortality, Anesthesia and analgesia 2014 Apr;118(4):790-8;
Natriuretic peptide in healthy individuals
Subclinical elevated B-type natriuretic peptide (BNP) indicates endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals, Life Sciences Vol. 260, 1 November 2020;
Natural Killer Cells (NK-)
KLRD1 Killer Cell lectin-like receptor (CD94), gene id;
Neutrophil Extracellular Traps (NETs) and NETosis
Host/genetic factors associated with COVID-19 call for precision medicine (NETs, NETosis and DAMPS), Precision Clinical Medicine 2020 Vol. 3, Issue 3, September 2020;
Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment, Mediators of Inflammation 2020;2020;
Devilishly radical NETwork in COVID-19: Oxidative Stress, neutrophil extracellular traps (NET) and T cell suppression, Advances in Biological Regulation 2020 Aug; 77;
Tissue damage from neutrophil-induced oxidative stress in COVID-19, Nature Reviews Immunology 2020 Jul 29: 1-2;
Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19, Cells 2020 Jun; 9(6): 1383;
SARS-CoV-2-triggered NETs mediate COVID-19, Journal of Experimental Medicine 2020 Dec 7; 217(12);
NLRP3 Inflammasome
Severe COVID-19: NLRP3 Inflammasome Dysregulated, Frontiers Immunology 2020; 11: 1580;
PAMPs (Pathogen-Associated Molecular Patterns)
Host/genetic factors associated with COVID-19 call for precision medicine (NETs, NETosis and DAMPS), Precision Clinical Medicine 2020 Vol. 3, Issue 3, September 2020;
Perspective from scientists
Surviving COVID-19: A disease tolerance perspective, Science Advances 2020 May; 6(18);
ROS (Reactive Oxidative Species) and Oxidative Stress (= biophysics)
Reactive Oxidative Species-Modulated Ca2+ release Regulates β2 integrin activation on CD4+CD28null T Cells of Acute Coronary Syndrome Patients, Journal of Immunology Vol. 205, Issue 9, 1 November 2020 (see edit);
Mild SARS-CoV-2 infections in children might be based on evolutionary biology and linked with host Reactive Oxidative Stress and antioxidant capabilities, New Microbes and New Infections Vol. 36, July 2020;
Suppressor of Cytokine Signalling (SOCS)
SOCS Proteins Participate in the Regulation of Innate Immune Response Caused by Viruses (feedback through Janus kinase and STAT), Frontiers in Immunology 2020; 11;
Suppressor of cytokine signalling (SOCS1) is a key determinant of differential macrophage activation and function, Journal of Leukocyte Biology Vol. 90, Issue 5, November 2011, p845-854;
SOCS3 Attenuates GM-CSF/IFN-y-Mediated Inflammation During Spontaneous Spinal Cord Regeneration, Neuroscience Bulletin 2020 Jul; 36(7): 778-792;
T cells
Decreased T cell populations contribute to the increased severity of COVID-19 (CD3+, CD4+ and CD8+ lymphocytes decreased in severe COVID), Clinica Chimica Acta Vol. 508, September 2020, P110-114;
T-cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis, Frontiers Immunological Tolerance and Regulation, 08 October 2020;
Tumor-derived soluble MIC ligands impair expression of NKG2D and T-cell activation, Nature 419, 734-738(2002), 17 October 2002;
COVID-19 and the Path to Immunity (boosting CD8+ and TH1 CD4+ T cells), JAMA 2020;324(13):1279-1281;
Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19, Cell 5 October 2020;
Th cells and Treg cells
Th17 and Treg cells function in SARS-CoV-2 patients compared with healthy controls, Journal of Cellular Physiology, 14 September 2020;
Heightened
circulating Interferon-Inducible Chemokines and activated Pro-Cytolytic
Th1-cell phenotype features COVID-19 aggravation in the second week,
Frontiers Cytokines and Soluble Mediators in Immunity, 20 October 2020;
Therapeutic targets
Treatment of COVID-19 With Conestat Alfa, a Regulator of the Complement, Contact Activation and Kallikrein-Kinin System, Frontiers Molecular Innate Immunity, 14 August 2020;
Nutraceuticals have potential for boosting the type I Interferon (IFN) response to RNA viruses including influenza and coronavirus (downregulation of NOX2 to enhance Toll-like Receptor 7 (TLR7) activity), Progress in Cardiovascular Diseases 2020 May-June; 63(3): 383-385;
Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients, Pharmacology & Therapeutics 2020 Sep; 213: 107587;
Caveolin-1: a critical regulator of lung injury, Lung Cellular and Molecular Physiology 2011 Feb; 300(2);
MMP8 Inactivates Macrophage Inflammatory Protein-1alpha to Reduce ALI in mice, Journal of Immunology 2010 Feb 1; 184(3);
Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?, International Journal of Molecular Science 2020 Jul;21(14):5171;
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19, Medicine in Drug Discovery 2020 Sep; 7: 100052;
IL-1
induces thromboxane-A2 (TxA2) in COVID-19 causing inflammation and
micro-thrombi: inhibitory effect of the IL-1-Receptor antagonist
(IL-1Ra), Journal of Biological Regulators and Homeostatic Agents 2020 Aug 3;34(5);
New putative insights into neprisylin (NEP)-dependent pharmacotherapeutic role of roflumimast in treating COVID-19, Vol. 889, 15 December 2020;
Can endolysosomal deacidification and inhibition of autophagy prevent severe COVID-19?, Life Sciences Vol. 262, 1 December 2020;
