1. Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review
- Author
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Enrique Esteve-Valverde, Jaume Alijotas-Reig, Josep Pardos-Gea, Ariadna Anunciacion-Llunell, Cristina Belizna, Angela Quintana, Arsène Mekinian, Francesc Miró-Mur, and Albert Selva-O'Callaghan
- Subjects
0301 basic medicine ,SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2 ,PTE, Pulmonary thromboembolism ,Angiotensin-Converting Enzyme Inhibitors ,TGF-β, Transforming growth factor-beta ,Cytokine storm ,medicine.disease_cause ,Immunosuppressive ,Pathogenesis ,MERS-CoV, Middle East Respiratory Syndrome Coronavirus ,0302 clinical medicine ,Risk Factors ,HCQ, Hydroxychloroquine ,Immunology and Allergy ,CQ, Chloroquine ,IL, Interleukin ,NHC, National Health Council ,mTOR, Mammalian target of Rapamycin ,Coronavirus ,COVID-19, Coronavirus disease 2019 ,Acute respiratory distress syndrome ,RA, Rheumatoid arthritis ,aPL, Antiphospholipid antibodies ,Immunoglobulins, Intravenous ,APC, Antigen-presenting cells ,CDC, Centres for disease control ,PIC, Pulmonary intravascular coagulation ,Cytokines ,TLR, Toll-Like Receptor ,medicine.symptom ,Coronavirus Infections ,JAK, Janus-Kinase family of enzymes (JAK1, JAK2, JAK3, TYK2) ,medicine.drug ,CyA, Cyclosporine A ,TNF-α, Tumour necrosis factor-alpha ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Immunology ,Inflammation ,Antiviral Agents ,Article ,NK, natural killer cells ,WHO, World Health Organization ,IFNγ, Interferon gamma ,LMWH, Low-molecular weight heparin ,Immunomodulation ,Antimalarials ,Betacoronavirus ,03 medical and health sciences ,GCS, Glucocorticoids ,ACE-2, Angiotensin-converting enzyme-2 ,ADE, Antibody dependent enhancement ,medicine ,Humans ,TCZ, Tocilizumab ,Glucocorticoids ,Pandemics ,Janus Kinases ,TRAASVIR, Thrombotic Risk Associated with Antiphospholipid Syndrome after Viral infection ,030203 arthritis & rheumatology ,SARS-CoV-2 ,AD, Autoimmune diseases ,business.industry ,SLE, Systemic Lupus Erythematosus ,COVID-19 ,Anticoagulants ,Hydroxychloroquine ,medicine.disease ,Tregs, Regulatory T-cells ,HPS, Haemophagocytic syndrome ,Treatment ,Calcineurin ,030104 developmental biology ,ADRS, Acute distress respiratory syndrome ,MHC-II, Major histocompatibility type-II ,IVIG, Intravenous immunoglobulins ,CD, Cluster of differentiation or cluster of designation or classification determinant ,FDA, Food and Drugs Administration ,MDA5, Melanoma differentiation-associated gene 5 ,MAS, Macrophage activation syndrome ,NF-kβ, Nuclear Factor-Kβ ,TRALI, Transfusion-related acute lung injury ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business - Abstract
Severe Acute Respiratory Syndrome related to Coronavirus-2 (SARS-CoV-2), coronavirus disease-2019 (COVID-19) may cause severe illness in 20% of patients. This may be in part due to an uncontrolled immune-response to SARS-CoV-2 infection triggering a systemic hyperinflammatory response, the so-called “cytokine storm”. The reduction of this inflammatory immune-response could be considered as a potential therapeutic target against severe COVID-19. The relationship between inflammation and clot activation must also be considered. Furthermore, we must keep in mind that currently, no specific antiviral treatment is available for SARS-CoV-2. While moderate-severe forms need in-hospital surveillance plus antivirals and/or hydroxychloroquine; in severe and life-threating subsets a high intensity anti-inflammatory and immunomodulatory therapy could be a therapeutic option. However, right data on the effectiveness of different immunomodulating drugs are scarce. Herein, we discuss the pathogenesis and the possible role played by drugs such as: antimalarials, anti-IL6, anti-IL-1, calcineurin and JAK inhibitors, corticosteroids, immunoglobulins, heparins, angiotensin-converting enzyme agonists and statins in severe COVID-19., Higlights • Severe COVID-19 forms may be related to a hyperinflammatory syndrome. • Severe COVID-19 is associated with clot pathway hyperactivity and sometimes, with thromboses. • Immunosuppression may be a complementary therapy in COVID-19 patients. • Antimalarials, heparin, cytokine blockers, JAK-inhibitors, IVIG could be useful for treating severe COVID-19 patients. • In SARS-CoV-2 infections the effectiveness of the hyperimmune plasma remains uncertain.
- Published
- 2020