Predictive monitoring and therapeutic immune biomarkers in the management of clinical complications of COVID-19

https://doi.org/10.1016/j.cytogfr.2020.10.002Get rights and content

Abstract

The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), appears with a wide spectrum of mild-to-critical clinical complications. Many clinical and experimental findings suggest the role of inflammatory mechanisms in the immunopathology of COVID-19. Hence, cellular and molecular mediators of the immune system can be potential targets for predicting, monitoring, and treating the progressive complications of COVID-19. In this review, we assess the latest cellular and molecular data on the immunopathology of COVID-19 according to the pathological evidence (e.g., mucus and surfactants), dysregulations of pro- and anti-inflammatory mediators (e.g., cytokines and chemokines), and impairments of innate and acquired immune system functions (e.g., mononuclear cells, neutrophils and antibodies). Furthermore, we determine the significance of immune biomarkers for predicting, monitoring, and treating the progressive complications of COVID-19. We also discuss the clinical importance of recent immune biomarkers in COVID-19, and at the end of each section, recent clinical trials in immune biomarkers for COVID-19 are mentioned.

Abbreviations

AAK-1
activated protein (AP) 2 associated kinase 1
Ab
antibody
ACE
angiotensin-converting enzyme
ACEI
ACE inhibitor
AEC
alveolar epithelial cells
AICD
activation-induced cell death
Ang
angiotensin
APC
antigen-presenting cell
APTT
activated partial thromboplastin time
ARB
Ang II receptor blocker
ARDS
acute respiratory distress syndrome
AT1R
Ang II receptor type 1
BALF
bronchoalveolar lavage fluid
BEC
bronchial epithelial cell
BTK
Bruton tyrosine kinase
C3 and C5
complement proteins
ChiCTR
chinese clinical trial registry
CCL
chemokine (C-C motif) ligand
CCR
chemokine (C-C motif) ligand receptor
C-GAS-STING
cGAMP binds to stimulator of interferon genes
COVID-19
coronavirus disease-2019
CP
convalescent plasma
CQ
chloroquine
CRP
c-reactive protein
CRS
cytokine release syndrome
CT
computerized tomography
CTL
cytotoxic T lymphocyte
CXCL
chemokine (C-X-C motif) ligand
CXCR
chemokine (C-X-C motif) ligand receptor
DIC
disseminated intravascular coagulation
dsRNA
double-stranded RNA
ESR
erythrocyte sedimentation rate
FcγR
Fc gamma receptor
Fio2
fraction of inspired oxygen
GAK
G-associated kinase
GM-CSF
granulocyte-macrophage colony-stimulating factor
GzmB
granzyme B
HCQ
hydroxychloroquine
HLA
human leukocyte antigen
HLH
hemophagocytic lymphohistiocytosis
HR-2
heptad repeat region-2
ICU
admissions to intensive care units
IFITM
interferon-induced transmembrane protein
IFN
interferon
IL
interleukin
IP-10
interferon (IFN)-γ inducible protein-10
IRF-1
IFN regulatory factor 1
ISG
induction of IFN-stimulated gene
IVIg
intravenous immunoglobulin
JAK
janus kinase
JUN
c-Jun N-terminal kinases
KL-6
Krebs von den Lungen-6
LAG-3
lymphocyte-activation gene 3
LDH
lactate dehydrogenase
LWR
lymphocyte-to-WBCs ratio
LY6E
lymphocyte antigen 6 family member E
mAb
monoclonal antibody
MCP
monocyte chemoattractant protein
MDA-5
melanoma differentiation-associated protein-5
MERS
middle east respiratory syndrome
MIP
macrophage inflammatory proteins
MOF
multiple organ failure
MUC
mucin
nAb
neutralizing antibody
N
nucleocapsid
NCT
clinicaltrials.gov identifier
NFkB
nuclear factor kappa-light-chain-enhancer of activated B cells
NK
natural killer
NKRF
NFkB repressing factor
NLR
neutrophil-to-lymphocyte ratio
NLRP3
nod-like receptor protein 3
NSP
non-structural proteins
NTD
N terminal domain
ORF-1ab
open reading frame 1ab
Pao2
partial pressure of oxygen
PCT
procalcitonin
PD1
programmed cell death protein 1
PKR
protein kinase R
PLR
platelet-to-lymphocyte ratios
PRR
pattern recognition receptors
PT
prothrombin time
RA
rheumatoid arthritis
RAS
regulator of the renin-angiotensin system
RBD
receptor-binding domain
rBP-C33Leu
recombinant surfactant protein C analogue
rhACE2-Fc fusion proteins
recombinant human ACE2-Fc fusion proteins
rhIL-1ra
recombinant human IL-1 receptor
RIG
retinoic acid-inducible gene-I
rIL7
recombinant IL-7
RLR
RIG-I-like receptors
RT-qPCR
real time-quantitative PCR
S1PR
sphingosine-1-phosphate receptors
SAA
serum amyloid A
SARS
severe acute respiratory
SARS-CoV
severe acute respiratory syndrome coronavirus
scFv
single-chain variable fragment
siRNA
small interfering RNA
SP
surfactant
SPo2
arterial oxygen saturation
S-protein
spike-protein
srhACE2
soluble recombinant human (srh)ACE2
ssRNA
single-stranded RNA
TGF
transforming growth factor
Th
helper T cell
TIM-3
T-cell immunoglobulin mucin 3
TLR
toll like receptor
TMPRSS2
transmembrane serine protease 2
TNF-α
tumor necrosis factor
Treg
regulatory T cells
VEGF
vascular endothelial growth factor
WBC
white blood cell

Keywords

COVID-19
Biomarker
Immunopathology
Cytokine storm
Lung
Complications

Cited by (0)

Hamed Fouladseresht received his B.Sc. degree in Cellular and Molecular Biology from Islamic Azad University, Tehran Medical Science in 2010. He completed his M.Sc. degree in Medical Immunology from Kerman University of Medical Sciences in 2014 and obtained his Ph.D. in Medical Immunology from Shiraz University of Medical Sciences in 2019 with a project focused on “HLA-A*02 & -A*24 typing and investigating specific CD8+ T cell (Tc1, Tc2, Tc9 & Tc17) responses to In-silico designed immunodominant epitopes of IE-62 & IE-63 antigens of varicella zoster virus (VZV) in patients with atherosclerosis.”. Dr. Fouladseresht is currently the member of Trauma Research Center in Shiraz University of Medical Sciences. His research interest is focused on developing prognostic and therapeutic indicators for trauma complications.

Mehrnoosh Doroudchi received her Ph.D. from Shiraz University of Medical Sciences in Shiraz, Iran in 1999 and started her career as an Assistant professor in the Department of Immunology. She then joined Prof. Rafick Sekaly’s lab in the Université de Montréal, Montreal, Canada for her Sabbatical where she conducted In-depth research on the effect of escape mutations within the HIV CD8+ epitopes on the function and phenotype of the CD8+ T cells during viremia. On her return in 2009, she established a laboratory dedicated to deciphering the role of viral and bacterial specific memory T cells in Atherosclerosis and heart diseases. Her group in the Department of Immunology of Shiraz University of Medical Sciences has published more than 20 papers on this topic in the past 5 years. Dr. Doroudchi is currently the Head of Immunology Department and the Director of Memory T cell laboratory in the School of Medicine.

Najmeh Rokhtabnak completed her B.Sc. in microbiology at the Islamic Azad University of Jahrom in 2010 and obtained her M.Sc. in microbiology at the Shahid Bahonar University of Kerman in 2014.

Hossein Abdolrahimzadehfard obtained his M.D. degree at Shiraz University of Medical Science in 2006. He completed his post-graduate degree in general surgery at Kashan University of Medical Science in 2014 and obtained his fellowship in trauma and acute care surgery at Shiraz University of Medical Science in 2016. He joined the Department of surgery of Shiraz University of Medical Science as an Assistant Professor in 2016. His main research fields are management of immune responses in severe trauma, and the role of herbal drugs in nosocomial infections.

Amir Roudgari obtained his M.D. at the Shiraz University of Medical Science in 1995. He completed his postgraduate degree in M.P.H. at the University of Shahid Beheshti Medical Science in 2005 and also Infectious Disease at the University of Shahid Beheshti Medical Science in 2007. At present, he works as an infectious diseases specialist in Shiraz University of Medical Science.

Golnar Sabetian obtained her M.D. degree at Shiraz University of Medical Sciences in 1990. Her Anesthesialogy and Critical Care Board certification was in 2001. She completed Critical Care fellowship at Shahid Beheshti University of Medical Sciences in 2008. At present her position is Associate Professor in Anesthesialogy and Critical Care at Shiraz University of Medical Sciences, head of Trauma Intensive Care. She works in Trauma Research Center and her main research fields are: Critical Care, Trauma, Infection, Neuro Critical Care.

Shahram Paydar obtained his M.D. degree at Shiraz University of Medical Science in 2000. He completed his post-graduate degree in general surgery at Shiraz University of Medical Science in 2007 and obtained his fellowship in trauma and surgery at Shiraz University of Medical Science in 2011. He is an Associate Professor of surgery at Shiraz University of Medical Science. Dr. Paydar is currently the founder and vice-chancellor for research of Trauma Research Center in Shiraz University of Medical Sciences in Shiraz, Iran. His research interest is focused on Shock, Trauma Coagulopathy, Medical Education and Endocrine Surgery.

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