Targeting Specific Checkpoints in the Management of SARS-CoV-2 Induced Cytokine Storm

Area of Science:

• Immunology
• Pharmacology
• Virology

Background:

• COVID-19 complications and mortality are linked to cytokine storm syndrome, an overproduction of proinflammatory cytokines.
• An intact immune system is crucial for suppressing SARS-CoV-2 replication, but dysregulation leads to severe outcomes.

Purpose of the Study:

• To identify and report targeted molecular checkpoints for managing SARS-CoV-2-induced cytokine storm.
• To review therapeutic agents effective in mitigating cytokine storm and reducing COVID-19 mortality.

Main Methods:

• Literature search conducted across PubMed, Embase, MEDLINE, and CNKI databases.
• Retrieved and appraised journal articles discussing SARS-CoV-2 infection and cytokine storm.
• Identified specific molecular pathways and drugs targeting them.

Main Results:

• Decreasing Nod-Like Receptor 3 (NLRP3) inflammasome levels with quercetin and anakinra showed efficacy.
• Blocking Janus kinase-2/signal transducer and activator of transcription-1 (JAK2/STAT1) pathways with tocilizumab, baricitinib, and quercetin was beneficial.
• Inhibiting interleukin-6 (IL-6) with dexamethasone, tocilizumab, and sarilumab, and IL-1 with canakinumab and anakinra reduced mortality.
• Bruton tyrosine kinase (BTK) inhibition with zanubrutinib and ibrutinib also proved beneficial.

Conclusions:

• Targeting cytokine storm pathways, including NLRP3, JAK/STAT, IL-6, IL-1, and BTK, enhances lung function and reduces COVID-19 mortality.
• These therapeutic agents decrease circulating proinflammatory cytokines and improve respiratory parameters like PaO2/FiO2 ratio.
• Interfering with the molecular pathogenesis of cytokine storms is a promising strategy for managing severe COVID-19.