Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | SARS-CoV-2 | Review

Innate immunity, cytokine storm, and inflammatory cell death in COVID-19

Authors: Rajendra Karki, Thirumala-Devi Kanneganti

Published in: Journal of Translational Medicine | Issue 1/2022

Login to get access

Abstract

The innate immune system serves as the first line of defense against invading pathogens; however, dysregulated innate immune responses can induce aberrant inflammation that is detrimental to the host. Therefore, careful innate immune regulation is critical during infections. The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in global morbidity and mortality as well as socio-economic stresses. Innate immune sensing of SARS-CoV-2 by multiple host cell pattern recognition receptors leads to the production of various pro-inflammatory cytokines and the induction of inflammatory cell death. These processes can contribute to cytokine storm, tissue damage, and acute respiratory distress syndrome. Here, we discuss the sensing of SARS-CoV-2 to induce innate immune activation and the contribution of this innate immune signaling in the development and severity of COVID-19. In addition, we provide a conceptual framework for innate immunity driving cytokine storm and organ damage in patients with severe COVID-19. A better understanding of the molecular mechanisms regulated by innate immunity is needed for the development of targeted modalities that can improve patient outcomes by mitigating severe disease.
Literature
1.
Tan W, Zhao X, Ma X, Wang W, Niu P, Xu W, et al. A novel coronavirus genome identified in a cluster of pneumonia cases—Wuhan, China 2019–2020. China CDC Wkly. 2020;2(4):61–2.PubMedPubMedCentralCrossRef
2.
3.
4.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395(10223):497–506.PubMedCrossRef
5.
6.
Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, et al. Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis. J Infect. 2020;81(2):e16–25.PubMedPubMedCentralCrossRef
7.
8.
Guo C, Li B, Ma H, Wang X, Cai P, Yu Q, et al. Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm. Nat Commun. 2020;11(1):3924.PubMedPubMedCentralCrossRef
9.
10.
Park A, Iwasaki A. Type I and type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27(6):870–8.PubMedPubMedCentralCrossRef
11.
12.
Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-alpha and IFN-gamma triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021;184(1):149-68.e17.PubMedCrossRef
13.
Karki R, Lee S, Mall R, Pandian N, Wang Y, Sharma BR, et al. ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Sci Immunol. 2022;7(74):eabo6294.PubMedCrossRef
14.
Diamond MS, Kanneganti TD. Innate immunity: the first line of defense against SARS-CoV-2. Nat Immunol. 2022;23(2):165–76.PubMedCrossRef
15.
Liu G, Zhao Y. Toll-like receptors and immune regulation: their direct and indirect modulation on regulatory CD4+ CD25+ T cells. Immunology. 2007;122(2):149–56.PubMedPubMedCentralCrossRef
16.
17.
Thompson CM, Holden TD, Rona G, Laxmanan B, Black RA, Keefe GE, et al. Toll-like receptor 1 polymorphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study. Ann Surg. 2014;259(1):179–85.PubMedCrossRef
18.
Zheng M, Karki R, Williams EP, Yang D, Fitzpatrick E, Vogel P, et al. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol. 2021;22(7):829–38.PubMedPubMedCentralCrossRef
19.
Jung S, Potapov I, Chillara S, Del Sol A. Leveraging systems biology for predicting modulators of inflammation in patients with COVID-19. Sci Adv. 2021;7(6):eabe5735.PubMedCrossRef
20.
van der Sluis RM, Cham LB, Gris-Oliver A, Gammelgaard KR, Pedersen JG, Idorn M, et al. TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS-CoV-2 infection. EMBO J. 2022;41(10): e109622.PubMedPubMedCentralCrossRef
21.
Proud PC, Tsitoura D, Watson RJ, Chua BY, Aram MJ, Bewley KR, et al. Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model. EBioMedicine. 2021;63: 103153.PubMedCrossRef
22.
Lee S, Channappanavar R, Kanneganti TD. Coronaviruses: Innate immunity, inflammasome activation, inflammatory cell death, and cytokines. Trends Immunol. 2020;41(12):1083–99.PubMedPubMedCentralCrossRef
23.
Zhao J, Wohlford-Lenane C, Zhao J, Fleming E, Lane TE, McCray PB Jr, et al. Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections. J Virol. 2012;86(21):11416–24.PubMedPubMedCentralCrossRef
24.
Barnard DL, Day CW, Bailey K, Heiner M, Montgomery R, Lauridsen L, et al. Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice. Antivir Chem Chemother. 2006;17(5):275–84.PubMedCrossRef
25.
Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT, et al. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio. 2015;6(3):e00638-e715.PubMedPubMedCentralCrossRef
26.
Bortolotti D, Gentili V, Rizzo S, Schiuma G, Beltrami S, Strazzabosco G, et al. TLR3 and TLR7 RNA sensor activation during SARS-CoV-2 infection. Microorganisms. 2021;9(9):1820.PubMedPubMedCentralCrossRef
27.
Tamir H, Melamed S, Erez N, Politi B, Yahalom-Ronen Y, Achdout H, et al. Induction of innate immune response by TLR3 agonist protects mice against SARS-CoV-2 infection. Viruses. 2022;14(2):189.PubMedPubMedCentralCrossRef
28.
Menezes MC, Veiga ADM, Martins de Lima T, Kunimi Kubo Ariga S, Vieira Barbeiro H, de Moreira Lucena C, et al. Lower peripheral blood Toll-like receptor 3 expression is associated with an unfavorable outcome in severe COVID-19 patients. Sci Rep. 2011;11(1):15223.CrossRef
29.
Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570.PubMedPubMedCentralCrossRef
30.
Povysil G, Butler-Laporte G, Shang N, Wang C, Khan A, Alaamery M, et al. Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19. J Clin Invest. 2021;131(14):e147834.PubMedPubMedCentralCrossRef
31.
Alseoudy MM, Elgamal M, Abdelghany DA, Borg AM, El-Mesery A, Elzeiny D, et al. Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: a case-control study. Clin Immunol. 2022;235: 108929.PubMedPubMedCentralCrossRef
32.
Choudhury A, Mukherjee S. In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. J Med Virol. 2020;92(10):2105–13.PubMedPubMedCentralCrossRef
33.
Taha SI, Shata AK, Baioumy SA, Fouad SH, Anis SG, Mossad IM, et al. Toll-like receptor 4 polymorphisms (896A/G and 1196C/T) as an indicator of COVID-19 severity in a convenience sample of Egyptian patients. J Inflamm Res. 2021;14:6293–303.PubMedPubMedCentralCrossRef
34.
35.
Petruk G, Puthia M, Petrlova J, Samsudin F, Strömdahl AC, Cerps S, et al. SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity. J Mol Cell Biol. 2020;12(12):916–32.PubMedPubMedCentralCrossRef
36.
37.
Moreno-Eutimio MA, López-Macías C, Pastelin-Palacios R. Bioinformatic analysis and identification of single-stranded RNA sequences recognized by TLR7/8 in the SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. Microbes Infect. 2020;22(4–5):226–9.PubMedPubMedCentralCrossRef
38.
Melchjorsen J, Jensen SB, Malmgaard L, Rasmussen SB, Weber F, Bowie AG, et al. Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner. J Virol. 2005;79(20):12944–51.PubMedPubMedCentralCrossRef
39.
Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Maglorius Renkilaraj MRL, et al. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci Immunol. 2021;6(62):eabl4348.PubMedPubMedCentralCrossRef
40.
Abolhassani H, Vosughimotlagh A, Asano T, Landegren N, Boisson B, Delavari S, et al. X-Linked TLR7 deficiency underlies critical COVID-19 pneumonia in a male patient with ataxia-telangiectasia. J Clin Immunol. 2022;42(1):1–9.PubMedCrossRef
41.
van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, et al. Presence of genetic variants among young men with severe COVID-19. JAMA. 2020;324(7):663–73.PubMedCrossRef
42.
43.
Hurst J, Prinz N, Lorenz M, Bauer S, Chapman J, Lackner KJ, et al. TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic cells. Immunobiology. 2009;214(8):683–91.PubMedCrossRef
44.
Döring Y, Hurst J, Lorenz M, Prinz N, Clemens N, Drechsler MD, et al. Human antiphospholipid antibodies induce TNFalpha in monocytes via Toll-like receptor 8. Immunobiology. 2010;215(3):230–41.PubMedCrossRef
45.
Amezcua-Guerra LM, Rojas-Velasco G, Brianza-Padilla M, Vázquez-Rangel A, Márquez-Velasco R, Baranda-Tovar F, et al. Presence of antiphospholipid antibodies in COVID-19: case series study. Ann Rheum Dis. 2020;80(5): e73.PubMedCrossRef
46.
Borghi MO, Beltagy A, Garrafa E, Curreli D, Cecchini G, Bodio C, et al. Anti-phospholipid antibodies in COVID-19 are different from those detectable in the anti-phospholipid syndrome. Front Immunol. 2020;11: 584241.PubMedPubMedCentralCrossRef
47.
Yin X, Riva L, Pu Y, Martin-Sancho L, Kanamune J, Yamamoto Y, et al. MDA5 governs the innate immune response to SARS-CoV-2 in lung epithelial cells. Cell Rep. 2021;34(2): 108628.PubMedPubMedCentralCrossRef
48.
Yang DM, Geng TT, Harrison AG, Wang PH. Differential roles of RIG-I like receptors in SARS-CoV-2 infection. Mil Med Res. 2021;8(1):49.PubMedPubMedCentral
49.
50.
Horner SM, Liu HM, Park HS, Briley J, Gale M. Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci U S A. 2011;108(35):14590–5.PubMedPubMedCentralCrossRef
51.
Thorne LG, Reuschl AK, Zuliani-Alvarez L, Whelan MVX, Turner J, Noursadeghi M, et al. SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation. EMBO J. 2021;40:e107826.PubMedPubMedCentralCrossRef
52.
Loske J, Röhmel J, Lukassen S, Stricker S, Magalhães VG, Liebig J, et al. Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children. Nat Biotech. 2022;40(3):319–24.CrossRef
53.
Kouwaki T, Nishimura T, Wang G, Oshiumi H. RIG-I-like receptor-mediated recognition of viral genomic RNA of severe acute respiratory syndrome coronavirus-2 and viral escape from the host innate immune responses. Front Immunol. 2021;12: 700926.PubMedPubMedCentralCrossRef
54.
Yamada T, Sato S, Sotoyama Y, Orba Y, Sawa H, Yamauchi H, et al. RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells. Nat Immunol. 2021;22(7):820–8.PubMedCrossRef
55.
Wu XM, Zhang J, Li PW, Hu YW, Cao L, Ouyang S, et al. NOD1 promotes antiviral signaling by binding viral RNA and regulating the interaction of MDA5 and MAVS. J Immunol. 2020;204(8):2216–31.PubMedCrossRef
56.
Christgen S, Kanneganti TD. Inflammasomes and the fine line between defense and disease. Curr Opin Immunol. 2020;62:39–44.PubMedCrossRef
57.
Ma J, Zhu F, Zhao M, Shao F, Yu D, Ma J, et al. SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage. EMBO J. 2021;40(18): e108249.PubMedPubMedCentralCrossRef
58.
Zheng M, Williams EP, Malireddi RKS, Karki R, Banoth B, Burton A, et al. Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection. J Biol Chem. 2020;295(41):14040–52.PubMedPubMedCentralCrossRef
59.
Rodrigues TS, de Sá KSG, Ishimoto AY, Becerra A, Oliveira S, Almeida L, et al. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med. 2021;218(3):e20201707.PubMedCrossRef
60.
Ferreira AC, Soares VC, de Azevedo-Quintanilha IG, Dias S, Fintelman-Rodrigues N, Sacramento CQ, et al. SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes. Cell Death Discov. 2021;7(1):43.PubMedPubMedCentralCrossRef
61.
Campbell GR, To RK, Hanna J, Spector SA. SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the NLRP3 inflammasome in human macrophages through a non-classical pathway. iScience. 2021;24(4):102295.PubMedPubMedCentralCrossRef
62.
Pan P, Shen M, Yu Z, Ge W, Chen K, Tian M, et al. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun. 2021;12(1):4664.PubMedPubMedCentralCrossRef
63.
Xu H, Akinyemi IA, Chitre SA, Loeb JC, Lednicky JA, McIntosh MT, et al. SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway. Virology. 2022;568:13–22.PubMedCrossRef
64.
Theobald SJ, Simonis A, Georgomanolis T, Kreer C, Zehner M, Eisfeld HS, et al. Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol Med. 2021;13: e14150.PubMedPubMedCentralCrossRef
65.
Zeng J, Xie X, Feng XL, Xu L, Han JB, Yu D, et al. Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice. EBioMedicine. 2022;75: 103803.PubMedCrossRef
66.
Eltobgy MM, Zani A, Kenney AD, Estfanous S, Kim E, Badr A, et al. Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and immunothrombosis. Proc Natl Acad Sci U S A. 2022;119(21): e2202012119.PubMedPubMedCentralCrossRef
67.
Zanoni I, Tan Y, Di Gioia M, Broggi A, Ruan J, Shi J, et al. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 2016;352(6290):1232–6.PubMedPubMedCentralCrossRef
68.
Song JW, Lam SM, Fan X, Cao WJ, Wang SY, Tian H, et al. Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis. Cell Metab. 2020;32(2):188-202.e5.PubMedPubMedCentralCrossRef
69.
Akpınar S, Oran M, Doğan M, Çelikkol A, Erdem I, Turgut B. The role of oxidized phospholipids in COVID-19-associated hypercoagulopathy. Eur Rev Med Pharmacol Sci. 2021;25(16):5304–9.PubMed
70.
Junqueira C, Crespo Â, Ranjbar S, de Lacerda LB, Lewandrowski M, Ingber J, et al. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation. Nature. 2022;606(7914):576–84.PubMedCrossRef
71.
72.
Rogers C, Erkes DA, Nardone A, Aplin AE, Fernandes-Alnemri T, Alnemri ES. Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation. Nat Commun. 2019;10(1):1689.PubMedPubMedCentralCrossRef
73.
Franz KM, Neidermyer WJ, Tan YJ, Whelan SPJ, Kagan JC. STING-dependent translation inhibition restricts RNA virus replication. Proc Natl Acad Sci U S A. 2018;115(9):E2058–67.PubMedPubMedCentralCrossRef
74.
Sun B, Sundström KB, Chew JJ, Bist P, Gan ES, Tan HC, et al. Dengue virus activates cGAS through the release of mitochondrial DNA. Sci Rep. 2017;7(1):3594.PubMedPubMedCentralCrossRef
75.
Schoggins JW, MacDuff DA, Imanaka N, Gainey MD, Shrestha B, Eitson JL, et al. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature. 2014;505(7485):691–5.PubMedCrossRef
76.
Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339(6121):786–91.PubMedCrossRef
77.
Domizio JD, Gulen MF, Saidoune F, Thacker VV, Yatim A, Sharma K, et al. The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature. 2022;603(7899):145–51.PubMedPubMedCentralCrossRef
78.
Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507–18.PubMedPubMedCentralCrossRef
79.
Prantner D, Perkins DJ, Lai W, Williams MS, Sharma S, Fitzgerald KA, et al. 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) activates stimulator of interferon gene (STING)-dependent innate immune pathways and is regulated by mitochondrial membrane potential. J Biol Chem. 2012;287(47):39776–88.PubMedPubMedCentralCrossRef
80.
Neufeldt CJ, Cerikan B, Cortese M, Frankish J, Lee JY, Plociennikowska A, et al. SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB. Commun Biol. 2022;5(1):45.PubMedPubMedCentralCrossRef
81.
Li M, Ferretti M, Ying B, Descamps H, Lee E, Dittmar M, et al. Pharmacological activation of STING blocks SARS-CoV-2 infection. Sci Immunol. 2021;6(59):eabi9007.PubMedCrossRef
82.
Humphries F, Shmuel-Galia L, Jiang Z, Wilson R, Landis P, Ng SL, et al. A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection. Sci Immunol. 2021;6(59):eabi9002.PubMedPubMedCentralCrossRef
83.
Liu W, Reyes HM, Yang JF, Li Y, Stewart KM, Basil MC, et al. Activation of STING signaling pathway effectively blocks human coronavirus infection. J Virol. 2021;95(12):e00490-e521.PubMedPubMedCentralCrossRef
84.
Messaoud-Nacer Y, Culerier E, Rose S, Maillet I, Rouxel N, Briault S, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS). Cell Death Dis. 2022;13(3):269.PubMedPubMedCentralCrossRef
85.
86.
87.
Lu Q, Liu J, Zhao S, Gomez Castro MF, Laurent-Rolle M, Dong J, et al. SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2. Immunity. 2021;54(6):1304-19.e9.PubMedPubMedCentralCrossRef
88.
Thépaut M, Luczkowiak J, Vivès C, Labiod N, Bally I, Lasala F, et al. DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist. PLoS Pathog. 2021;17(5): e1009576.PubMedPubMedCentralCrossRef
89.
Amraei R, Yin W, Napoleon MA, Suder EL, Berrigan J, Zhao Q, et al. CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. ACS Cent Sci. 2021;7(7):1156–65.PubMedPubMedCentralCrossRef
90.
Alvarez CP, Lasala F, Carrillo J, Muñiz O, Corbí AL, Delgado R. C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol. 2002;76(13):6841–4.PubMedPubMedCentralCrossRef
91.
92.
Navarro-Sanchez E, Altmeyer R, Amara A, Schwartz O, Fieschi F, Virelizier JL, et al. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep. 2003;4(7):723–8.PubMedPubMedCentralCrossRef
93.
Marzi A, Gramberg T, Simmons G, Möller P, Rennekamp AJ, Krumbiegel M, et al. DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. J Virol. 2004;78(21):12090–5.PubMedPubMedCentralCrossRef
94.
95.
96.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–8.PubMedPubMedCentralCrossRef
97.
Sanders DW, Jumper CC, Ackerman PJ, Bracha D, Donlic A, Kim H, et al. SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation. Elife. 2021;10: e65962.PubMedPubMedCentralCrossRef
98.
Asarnow D, Wang B, Lee WH, Hu Y, Huang CW, Faust B, et al. Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Cell. 2021;184(12):3192-204.e16.PubMedPubMedCentralCrossRef
99.
Stadlmann S, Hein-Kuhnt R, Singer G. Viropathic multinuclear syncytial giant cells in bronchial fluid from a patient with COVID-19. J Clin Pathol. 2020;73(9):607–8.PubMedCrossRef
100.
101.
Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, et al. Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia. Nature. 2021;594(7861):88–93.PubMedPubMedCentralCrossRef
102.
Ma H, Zhu Z, Lin H, Wang S, Zhang P, Li Y, et al. Pyroptosis of syncytia formed by fusion of SARS-CoV-2 spike and ACE2-expressing cells. Cell Discov. 2021;7(1):73.PubMedPubMedCentralCrossRef
103.
Zhang Z, Zheng Y, Niu Z, Zhang B, Wang C, Yao X, et al. SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination. Cell Death Differ. 2021;28(9):2765–77.PubMedPubMedCentralCrossRef
104.
Chakraborty S, Basu A. The COVID-19 pandemic: catching up with the cataclysm. F1000Res. 2020;9:638.CrossRef
105.
106.
Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X, et al. SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther. 2020;5(1):235.PubMedPubMedCentralCrossRef
107.
Li S, Jiang L, Li X, Lin F, Wang Y, Li B, et al. Clinical and pathological investigation of patients with severe COVID-19. JCI insight. 2020;5(12): e138070.PubMedPubMedCentralCrossRef
108.
Malireddi RKS, Karki R, Sundaram B, Kancharana B, Lee S, Samir P, et al. Inflammatory cell death, PANoptosis, mediated by cytokines in diverse cancer lineages inhibits tumor growth. Immunohorizons. 2021;5(7):568–80.PubMedCrossRef
109.
Karki R, Sundaram B, Sharma BR, Lee S, Malireddi RKS, Nguyen LN, et al. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep. 2021;37(3): 109858.PubMedPubMedCentralCrossRef
110.
Malireddi RKS, Gurung P, Kesavardhana S, Samir P, Burton A, Mummareddy H, Vogel P, Pelletier S, Burgula S, Kanneganti TD. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease. J Exp Med. 2020;217(3):e20191644.CrossRef
111.
Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA, McGoldrick DJ, et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature. 2014;516(7530):246–9.PubMedPubMedCentralCrossRef
112.
Karki R, Sharma BR, Lee E, Banoth B, Malireddi RKS, Samir P, et al. Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer. JCI insight. 2020;5(12): e136720.PubMedPubMedCentralCrossRef
113.
Christgen S, Zheng M, Kesavardhana S, Karki R, Malireddi RKS, Banoth B, Place DE, Briard B, Sharma BR, Tuladhar S, Samir P, Burton A, Kanneganti T-D. Identification of the PANoptosome: a molecular platform triggering pyroptosis, apoptosis, and necroptosis (PANoptosis). Front Cell Infect Microbiol. 2020;10:237.PubMedPubMedCentralCrossRef
114.
Kuriakose T, Man SM, Malireddi RK, Karki R, Kesavardhana S, Place DE, et al. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci Immunol. 2016;1(2):aag2045.PubMedPubMedCentralCrossRef
115.
116.
117.
Zheng M, Karki R, Vogel P, Kanneganti TD. Caspase-6 is a key regulator of innate immunity, inflammasome activation and host defense. Cell. 2020;181(3):674-87.e13.PubMedPubMedCentralCrossRef
118.
Lee S, Karki R, Wang Y, Nguyen LN, Kalathur RC, Kanneganti TD. AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature. 2021;597(7876):415–9.PubMedPubMedCentralCrossRef
119.
120.
Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036-45.e9.PubMedPubMedCentralCrossRef
121.
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020;584(7821):463–9.PubMedPubMedCentralCrossRef
122.
Galani IE, Rovina N, Lampropoulou V, Triantafyllia V, Manioudaki M, Pavlos E, et al. Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nat Immunol. 2021;22(1):32–40.PubMedCrossRef
123.
Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, et al. Genetic mechanisms of critical illness in COVID-19. Nature. 2021;591(7848):92–8.PubMedCrossRef
124.
Zhang Q, Matuozzo D, Le Pen J, Lee D, Moens L, Asano T, et al. Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia. J Exp Med. 2022;219(8): e20220131.PubMedPubMedCentralCrossRef
125.
Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585.PubMedPubMedCentralCrossRef
126.
Chang SE, Feng A, Meng W, Apostolidis SA, Mack E, Artandi M, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun. 2021;12(1):5417.PubMedPubMedCentralCrossRef
127.
Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, et al. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021;595(7866):283–8.PubMedCrossRef
128.
Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, et al. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci Immunol. 2021;6(62):eabl4340.PubMedPubMedCentralCrossRef
129.
Zhang Q, Bastard P, Cobat A, Casanova JL. Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature. 2022;603(7902):587–98.PubMedPubMedCentralCrossRef
130.
Burke JM, St Clair LA, Perera R, Parker R. SARS-CoV-2 infection triggers widespread host mRNA decay leading to an mRNA export block. RNA. 2021;27(11):1318–29.PubMedPubMedCentralCrossRef
131.
Liu G, Lee JH, Parker ZM, Acharya D, Chiang JJ, van Gent M, et al. ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol. 2021;6(4):467–78.PubMedPubMedCentralCrossRef
132.
Li JY, Liao CH, Wang Q, Tan YJ, Luo R, Qiu Y, et al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Res. 2020;286: 198074.PubMedPubMedCentralCrossRef
133.
Chen K, Xiao F, Hu D, Ge W, Tian M, Wang W, et al. SARS-CoV-2 nucleocapsid protein interacts with RIG-I and represses RIG-mediated IFN-β production. Viruses. 2020;13(1):47.PubMedPubMedCentralCrossRef
134.
Wu J, Shi Y, Pan X, Wu S, Hou R, Zhang Y, et al. SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Rep. 2021;34(7): 108761.PubMedPubMedCentralCrossRef
135.
Han L, Zhuang MW, Deng J, Zheng Y, Zhang J, Nan ML, et al. SARS-CoV-2 ORF9b antagonizes type I and III interferons by targeting multiple components of the RIG-I/MDA-5-MAVS, TLR3-TRIF, and cGAS-STING signaling pathways. J Med Virol. 2021;93(9):5376–89.PubMedPubMedCentralCrossRef
136.
Znaidia M, Demeret C, van der Werf S, Komarova AV. Characterization of SARS-CoV-2 evasion: interferon pathway and therapeutic options. Viruses. 2022;14(6):1247.PubMedPubMedCentralCrossRef
137.
Miorin L, Kehrer T, Sanchez-Aparicio MT, Zhang K, Cohen P, Patel RS, et al. SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc Natl Acad Sci U S A. 2020;117(45):28344–54.PubMedPubMedCentralCrossRef
138.
Sui L, Zhao Y, Wang W, Wu P, Wang Z, Yu Y, et al. SARS-CoV-2 membrane protein inhibits type I interferon production through ubiquitin-mediated degradation of TBK1. Front Immunol. 2021;12: 662989.PubMedPubMedCentralCrossRef
139.
Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk T, Hirschenberger M, et al. Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science. 2020;369(6508):1249–55.PubMedPubMedCentralCrossRef
140.
Hsu JC, Laurent-Rolle M, Pawlak JB, Wilen CB, Cresswell P. Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein. Proc Natl Acad Sci U S A. 2021;118(24): e2101161118.PubMedPubMedCentralCrossRef
141.
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, et al. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. J Exp Med. 2022;219(1): e20211818.PubMedCrossRef
142.
Bessière P, Wasniewski M, Picard-Meyer E, Servat A, Figueroa T, Foret-Lucas C, et al. Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model. PLoS Pathog. 2021;17(8): e1009427.PubMedPubMedCentralCrossRef
143.
Kalil AC, Mehta AK, Patterson TF, Erdmann N, Gomez CA, Jain MK, et al. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(12):1365–76.PubMedPubMedCentralCrossRef
144.
Wang N, Zhan Y, Zhu L, Hou Z, Liu F, Song P, et al. Retrospective multicenter cohort study shows early interferon therapy is associated with favorable clinical responses in COVID-19 patients. Cell Host Microbe. 2020;28(3):455-64.e2.PubMedPubMedCentralCrossRef
145.
Dinnon KH 3rd, Leist SR, Schäfer A, Edwards CE, Martinez DR, Montgomery SA, et al. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature. 2020;586(7830):560–6.PubMedPubMedCentralCrossRef
146.
Jagannathan P, Andrews JR, Bonilla H, Hedlin H, Jacobson KB, Balasubramanian V, et al. Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat Commun. 2021;12(1):1967.PubMedPubMedCentralCrossRef
147.
WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO solidarity randomised trial and updated meta-analyses. Lancet. 2022;399(10339):1941–53.PubMedCentralCrossRef
148.
Major J, Crotta S, Llorian M, McCabe TM, Gad HH, Priestnall SL, et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science. 2020;369(6504):712–7.PubMedPubMedCentralCrossRef
149.
Banoth B, Tuladhar S, Karki R, Sharma BR, Briard B, Kesavardhana S, et al. ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis). J Biol Chem. 2020;295(52):18276–83.PubMedCrossRef
150.
Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718–24.PubMedPubMedCentralCrossRef
151.
Doherty GM, Lange JR, Langstein HN, Alexander HR, Buresh CM, Norton JA. Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha. J Immunol. 1992;149(5):1666–70.PubMed
152.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120–8.PubMedPubMedCentralCrossRef
153.
Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2. J Clin Invest. 2020;130(11):5967–75.PubMedPubMedCentralCrossRef
154.
Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020;142(5):429–36.PubMedCrossRef
155.
Esmon CT. The interactions between inflammation and coagulation. Br J Haematol. 2005;131(4):417–30.PubMedCrossRef
156.
157.
Kaneko N, Kuo H-H, Boucau J, Farmer JR, Allard-Chamard H, Mahajan VS, et al. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell. 2020;183(1):143-57.e13.PubMedPubMedCentralCrossRef
158.
Ohta A, Sekimoto M, Sato M, Koda T, Nishimura SI, Iwakura Y, et al. Indispensable role for TNF- and IFN- at the effector phase of liver injury mediated by Th1 cells specific to hepatitis B virus surface antigen. J Immunol. 2000;165(2):956–61.PubMedCrossRef
159.
Zhu L, Yang P, Zhao Y, Zhuang Z, Wang Z, Song R, et al. Single-cell sequencing of peripheral mononuclear cells reveals distinct immune response landscapes of COVID-19 and influenza patients. Immunity. 2020;53(3):685-96.e3.PubMedPubMedCentralCrossRef
160.
Simpson DS, Pang J, Weir A, Kong IY, Fritsch M, Rashidi M, et al. Interferon-γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway. Immunity. 2022;55(3):423-41.e9.PubMedPubMedCentralCrossRef
161.
Zhang F, Mears JR, Shakib L, Beynor JI, Shanaj S, Korsunsky I, et al. IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation. Genome Med. 2021;13(1):64.PubMedPubMedCentralCrossRef
162.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2.PubMedPubMedCentralCrossRef
163.
Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell. 2020;182(6):1419-40.e23.PubMedPubMedCentralCrossRef
164.
Silvin A, Chapuis N, Dunsmore G, Goubet AG, Dubuisson A, Derosa L, et al. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell. 2020;182(6):1401-18.e18.PubMedPubMedCentralCrossRef
165.
Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17(1):46–64.PubMedCrossRef
166.
Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26(6):842–4.PubMedCrossRef
167.
Delorey TM, Ziegler CGK, Heimberg G, Normand R, Yang Y, Segerstolpe Å, et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature. 2021;595(7865):107–13.PubMedPubMedCentralCrossRef
168.
Xydakis MS, Albers MW, Holbrook EH, Lyon DM, Shih RY, Frasnelli JA, et al. Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol. 2021;20(9):753–61.PubMedPubMedCentralCrossRef
169.
Livanos AE, Jha D, Cossarini F, Gonzalez-Reiche AS, Tokuyama M, Aydillo T, et al. Intestinal host response to SARS-CoV-2 infection and COVID-19 outcomes in patients with gastrointestinal symptoms. Gastroenterology. 2021;160(7):2435-50.e34.PubMedCrossRef
170.
Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122–7.PubMedCrossRef
171.
Forman R, Shah S, Jeurissen P, Jit M, Mossialos E. COVID-19 vaccine challenges: What have we learned so far and what remains to be done? Health Policy. 2021;125(5):553–67.PubMedPubMedCentralCrossRef
172.
U.S. Food and Drug Administration. Emergency Use Authorization. 2022.
173.
Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.PubMedCrossRef
174.
Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;384(1):20–30.PubMedCrossRef
175.
Lescure FX, Honda H, Fowler RA, Lazar JS, Shi G, Wung P, et al. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(5):522–32.PubMedPubMedCentralCrossRef
176.
Rosas IO, Diaz G, Gottlieb RL, Lobo SM, Robinson P, Hunter BD, et al. Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial. Intensive Care Med. 2021;47(11):1258–70.PubMedPubMedCentralCrossRef
177.
Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. 2021;384(16):1503–16.PubMedCrossRef
178.
Sancho-López A, Caballero-Bermejo AF, Ruiz-Antorán B, Múñez Rubio E, García Gasalla M, Buades J, et al. Efficacy and safety of sarilumab in patients with COVID19 pneumonia: a randomized, phase III clinical trial (SARTRE Study). Infect Dis Ther. 2021;10(4):2735–48.PubMedPubMedCentralCrossRef
179.
Laing AG, Lorenc A, Del Molino Del Barrio I, Das A, Fish M, Monin L, et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med. 2020;26(10):1623–2355.PubMedCrossRef
180.
Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325–31.PubMedPubMedCentralCrossRef
181.
Generali D, Bosio G, Malberti F, Cuzzoli A, Testa S, Romanini L, et al. Canakinumab as treatment for COVID-19-related pneumonia: a prospective case-control study. Int J Infect Dis. 2021;104:433–40.PubMedCrossRef
182.
Caricchio R, Abbate A, Gordeev I, Meng J, Hsue PY, Neogi T, et al. Effect of canakinumab vs placebo on survival without invasive mechanical ventilation in patients hospitalized with severe COVID-19: a randomized clinical trial. JAMA. 2021;326(3):230–9.PubMedPubMedCentralCrossRef
183.
Kyriazopoulou E, Panagopoulos P, Metallidis S, Dalekos GN, Poulakou G, Gatselis N, et al. An open label trial of anakinra to prevent respiratory failure in COVID-19. Elife. 2021;10: e66125.PubMedPubMedCentralCrossRef
184.
Pontali E, Volpi S, Signori A, Antonucci G, Castellaneta M, Buzzi D, et al. Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia. J Allergy Clin Immunol. 2021;147(4):1217–25.PubMedPubMedCentralCrossRef
185.
186.
Lopes MI, Bonjorno LP, Giannini MC, Amaral NB, Menezes PI, Dib SM, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open. 2021;7(1): e001455.PubMedPubMedCentralCrossRef
187.
National Institues of Health. COVID-19 treatment guidelines: colchicine. 2022.
188.
Gianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, Gossec L, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020;79(7):859–66.PubMedCrossRef
189.
Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384(9):795–807.PubMedCrossRef
190.
Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022;23(2):210–6.PubMedCrossRef
191.
Ayoubkhani D, Bermingham C, Pouwels KB, Glickman M, Nafilyan V, Zaccardi F, et al. Trajectory of long covid symptoms after COVID-19 vaccination: community based cohort study. BMJ. 2022;377: e069676.PubMedCrossRef
Metadata
Title
Innate immunity, cytokine storm, and inflammatory cell death in COVID-19
Authors
Rajendra Karki
Thirumala-Devi Kanneganti
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03767-z

Other articles of this Issue 1/2022

Journal of Translational Medicine 1/2022 Go to the issue

Letter to the Editor

Can HPV Selfy be considered as a clinically validated HPV test for use in cervical cancer screening?

Research

Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway

Research

Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank

Research

Pregnancy loss and subsequent risk of prediabetes, diabetes and metabolic syndrome in couples: Tehran lipid and glucose study

Research

Incidental germline findings during molecular profiling of tumor tissues for precision oncology: molecular survey and methodological obstacles

Meeting report

The future of cancer immunotherapy for brain tumors: a collaborative workshop
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits