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Review
. 2022 Mar 25;12(4):478.
doi: 10.3390/life12040478.

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

Abdullahi Rabiu Abubakar  1 , Rahnuma Ahmad  2 , Adekunle Babajide Rowaiye  3 , Sayeeda Rahman  4 , Katia Iskandar  5 , Siddhartha Dutta  6 , Angus Nnamdi Oli  7 , Sameer Dhingra  8 , Maryam Abba Tor  9 , Ayukafangha Etando  10 , Santosh Kumar  11 , Mohammed Irfan  12 , Marshall Gowere  13 , Kona Chowdhury  14 , Farhana Akter  15 , Dilshad Jahan  16 , Natalie Schellack  13 , Mainul Haque  17
Affiliations
Review

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

Abdullahi Rabiu Abubakar et al. Life (Basel). .

Abstract

COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO2/FiO2 ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.

Keywords: COVID-19; SARS-CoV-2; cytokine storm; hyperinflammation; immune response; interleukins; pathogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genera of coronaviruses and SARS-CoV-2 (genome and proteome).
Figure 2
Figure 2
Molecular pathogenesis of SARS-CoV-2-induced cytokine storm.
Figure 3
Figure 3
Symptoms of SARS-CoV-2 infection.
Figure 4
Figure 4
Molecular structure of SARS-CoV-2.
Figure 5
Figure 5
Progression of cytokine storm in COVID-19. CS—cytokine storm; ARDS—acute respiratory distress syndrome; MODS—multiple organ dysfunction syndromes.
Figure 6
Figure 6
Genes associated with SARS-CoV-2 infection.
Figure 7
Figure 7
SARS-CoV-2 induced thromboinflammation.
See this image and copyright information in PMC

References

    1. WHO Timeline—COVID-19. Cited on 8 November 2021. [(accessed on 30 December 2021)]. Available online: https://www.who.int/news/item/27-04-2020-who-timeline---covid-19.
    1. WHO Coronavirus (COVID-19) Dashboard. Cited on 11 February 2022. [(accessed on 30 December 2021)]. Available online: https://covid19.who.int/
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7. - DOI - PMC - PubMed
    1. Nile S.H., Nile A., Qiu J., Li L., Jia X., Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020;53:66–70. doi: 10.1016/j.cytogfr.2020.05.002. - DOI - PMC - PubMed
    1. Fu L., Wang B., Yuan T., Chen X., Ao Y., Fitzpatrick T., Li P., Zhou Y., Lin Y.-F., Duan Q., et al. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. J. Infect. 2020;80:656–665. doi: 10.1016/j.jinf.2020.03.041. - DOI - PMC - PubMed