Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review

https://doi.org/10.1016/j.autrev.2020.102569Get rights and content

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.

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.

Keywords

Acute respiratory distress syndrome
COVID-19
Cytokine storm
Immunosuppressive
SARS-CoV-2
Treatment

Abbreviations

ACE-2
Angiotensin-converting enzyme-2
AD
Autoimmune diseases
ADE
Antibody dependent enhancement
ADRS
Acute distress respiratory syndrome
APC
Antigen-presenting cells
aPL
Antiphospholipid antibodies
CD
Cluster of differentiation or cluster of designation or classification determinant
CDC
Centres for disease control
COVID-19
Coronavirus disease 2019
CQ
Chloroquine
CyA
Cyclosporine A
FDA
Food and Drugs Administration
GCS
Glucocorticoids
HCQ
Hydroxychloroquine
HPS
Haemophagocytic syndrome
IFNγ
Interferon gamma
IL
Interleukin
JAK
Janus-Kinase family of enzymes (JAK1, JAK2, JAK3, TYK2)
IVIG
Intravenous immunoglobulins
MDA5
Melanoma differentiation-associated gene 5
MHC-II
Major histocompatibility type-II
LMWH
Low-molecular weight heparin
MAS
Macrophage activation syndrome
MERS-CoV
Middle East Respiratory Syndrome Coronavirus
mTOR
Mammalian target of Rapamycin
NHC
National Health Council
NK
natural killer cells
NF-kβ
Nuclear Factor-Kβ
PIC
Pulmonary intravascular coagulation
PTE
Pulmonary thromboembolism
RA
Rheumatoid arthritis
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus-2
SLE
Systemic Lupus Erythematosus
TCZ
Tocilizumab
TLR
Toll-Like Receptor
TNF-α
Tumour necrosis factor-alpha
TRAASVIR
Thrombotic Risk Associated with Antiphospholipid Syndrome after Viral infection
TRALI
Transfusion-related acute lung injury
TGF-β
Transforming growth factor-beta
Tregs
Regulatory T-cells
WHO
World Health Organization

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