A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization

Betcy Susan Johnson, Malini Laloraya, Betcy Susan Johnson, Malini Laloraya

Abstract

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.

Keywords: BCG; COVID-19(SARS Cov2); Co-morbidity; Coronavirus; Cytokine; Growth factors.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Venn diagram showing peripheral cytokine profile of SARS CoV, MERS CoV and SARS CoV2 infection. IL-6, IFN-γ and IP-10 showed significantly higher levels in all three highly pathogenic hCoV infections. IL-8, MIG, IL-1, MCP-1 and IL-2 levels were altered in both SARS CoV and SARS CoV2 infected patients. TNF-α and IL-10 levels were increased in SARS CoV2 and MERS. Cytokines and chemokines like IL-1RA, IL-7, IL-9, IL-2R, GCSF, GMCSF, PDGF, CXCL16, MIP2- α, MCP-2, VEGF, bFGF, MIP1-α and MIP1-β cytokines were uniquely elevated in SARS CoV2 infection.
Fig. 2
Fig. 2
Schematic diagram representing higher pro-inflammatory cytokines and chemokines in COVID-19 patients with underlying risk factors, with hyper-cytokinemia associated inflammation culminating in lethal complications in SARS-CoV2 infection.
Fig. 3
Fig. 3
Antiviral immunity provided by BCG vaccine through trained immunity involves the discharge of IL-1β, TNF-α and IL-6 from epigenetically modified monocytes which confer early protection against SARS-Cov2.

References

    1. Masters P.S. The molecular biology of coronaviruses. Adv. Virus Res. 2006;66:193–292.
    1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses2020 The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020;5:536.
    1. Opriessnig T., Huang Y. Coronavirus disease 2019 (COVID–19) outbreak: Could pigs be vectors for human infections? Xenotransplantation. 2020;27
    1. Petrosillo N., Viceconte G., Ergonul O., Ippolito G., Petersen E. COVID-19, SARS and MERS: are they closely related? Clin. Microbiol. Infect. 2020
    1. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–574.
    1. Yi Y., Lagniton P.N.P., Ye S., Li E., Xu R.H. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int. J. Biol. Sci. 2020;16:1753–1766.
    1. Kimura H., Yoshizumi M., Ishii H., Oishi K., Ryo A. Cytokine production and signaling pathways in respiratory virus infection. Front. Microbiol. 2013;4:276.
    1. Mogensen T.H., Paludan S.R. Molecular pathways in virus-induced cytokine production. Microbiol. Mol. Biol. Rev. 2001;65:131–150.
    1. Hofmann P., Sprenger H., Kaufmann A., Bender A., Hasse C., Nain M., Gemsa D. Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response. J. Leukoc. Biol. 1997;61:408–414.
    1. Schultz-Cherry S., Hinshaw V.S. Influenza virus neuraminidase activates latent transforming growth factor beta. J. Virol. 1996;70:8624–8629.
    1. Samuel C.E. Antiviral actions of interferons. Clin. Microbiol. Rev. 2001;14:778–809.
    1. Wang L., Du F., Wang X. TNF-A¦ induces two distinct caspase-8 activation pathways. Cell. 2008;133:693–703.
    1. Subramanian N.A.T.A., Bray M.A. Interleukin 1 releases histamine from human basophils and mast cells in vitro. J. Immunol. 1987;138:271–275.
    1. Chomarat P., Banchereau J., Davoust J., Palucka A.K. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat. Immunol. 2000;1:510–514.
    1. Schett G. Physiological effects of modulating the interleukin-6 axis. Rheumatology. 2018;57:ii43–ii50.
    1. Kimura A., Kishimoto T. IL6: regulator of Treg/Th17 balance. Eur. J. Immunol. 2010;40:1830–1835.
    1. Nakanishi K. Unique action of interleukin-18 on T cells and other immune cells. Front. Immunol. 2018;9:763.
    1. Liu B., Mori I., Hossain M.J., Dong L., Takeda K., Kimura Y. Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity. J. Gen. Virol. 2004;85:423–428.
    1. Channappanavar R., Perlman S. 39 ed. Springer; 2017. Pathogenic Human Coronavirus Infections: Causes and Consequences of Cytokine Storm and Immunopathology; pp. 529–539.
    1. Coperchini F., Chiovato L., Croce L., Magri F., Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020
    1. Peiris J.S.M., Guan Y., Yuen K.Y. Severe acute respiratory syndrome. Nat. Med. 2004;10:S88–S97.
    1. Nicholls J.M., Poon L.L., Lee K.C., Ng W.F., Lai S.T., Leung C.Y., Chu C.M., Hui P.K., Mak K.L., Lim W. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003;361:1773–1778.
    1. Booth C.M., Matukas L.M., Tomlinson G.A., Rachlis A.R., Rose D.B., Dwosh H.A., Walmsley S.L., Mazzulli T., Avendano M., Derkach P. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. Jama. 2003;289:2801–2809.
    1. Kai H., Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitorsΓÇölessons from available evidence and insights into COVID-19. Hypertens. Res. 2020:1–7.
    1. Imai Y., Kuba K., Rao S., Huan Y., Guo F., Guan B., Yang P., Sarao R., Wada T., Leong-Poi H., Crackower M.A., Fukamizu A., Hui C.C., Hein L., Uhlig S., Slutsky A.S., Jiang C., Penninger J.M. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–116.
    1. Kuba K., Imai Y., Penninger J.M. Angiotensin-converting enzyme 2 in lung diseases. Curr. Opin. Pharmacol. 2006;6:271–276.
    1. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., Huan Y., Yang P., Zhang Y., Deng W., Bao L., Zhang B., Liu G., Wang Z., Chappell M., Liu Y., Zheng D., Leibbrandt A., Wada T., Slutsky A.S., Liu D., Qin C., Jiang C., Penninger J.M. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 2005;11:875–879.
    1. Liu J., Zheng X., Tong Q., Li W., Wang B., Sutter K., Trilling M., Lu M., Dittmer U., Yang D. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARSΓÇÉCoV, MERSΓÇÉCoV, and 2019ΓÇÉnCoV. J. Med. Virol. 2020;92:491–494.
    1. Tang N.L.-S., Chan P.K.-S., Wong C.K., To K.F., Wu A.K.-L., Sung Y.M., Hui D.S.-C., Sung J.J.-Y., Lam C.W.-K. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin. Chem. 2005;51:2333–2340.
    1. Jiang Y., Xu J., Zhou C., Wu Z., Zhong S., Liu J., Luo W., Chen T., Qin Q., Deng P. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am. J. Respir. Crit. Care Med. 2005;171:850–857.
    1. Huang K., Su I., Theron M., Wu Y., Lai S., Liu C., Lei H. An interferon γrelated cytokine storm in SARS patients. J. Med. Virol. 2005;75:185–194.
    1. CHIEN J., HSUEH P., CHENG W., YU C., YANG P. Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome. Respirology. 2006;11:715–722.
    1. Wong C.K., Lam C.W.K., Wu A.K.L., Ip W.K., Lee N.L.S., Chan I.H.S., Lit L.C.W., Hui D.S.C., Chan M.H.M., Chung S.S.C. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin. Exp. Immunol. 2004;136:95–103.
    1. Wang C.H., Liu C.Y., Wan Y.L., Chou C.L., Huang K.H., Lin H.C., Lin S.M., Lin T.Y., Chung K.F., Kuo H.P. Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS. Respir. Res. 2005;6:42.
    1. Menachery V.D., Eisfeld A.J., Sch+ñfer A., Josset L., Sims A.C., Proll S., Fan S., Li C., Neumann G., Tilton S.C. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. MBio. 2014;5:e01174.
    1. Channappanavar R., Fehr A.R., Vijay R., Mack M., Zhao J., Meyerholz D.K., Perlman S. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19:181–193.
    1. Bauch C.T., Oraby T. Assessing the pandemic potential of MERS-CoV. Lancet. 2013;382:662–664.
    1. Saad M., Omrani A.S., Baig K., Bahloul A., Elzein F., Matin M.A., Selim M.A., Al Mutairi M., Al Nakhli D., Al Aidaroos A.Y. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int. J. Infect. Dis. 2014;29:301–306.
    1. Song Z., Xu Y., Bao L., Zhang L., Yu P., Qu Y., Zhu H., Zhao W., Han Y., Qin C. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019;11:59.
    1. Widagdo W., Raj V.S., Schipper D., Kolijn K., van Leenders G.J., Bosch B.J., Bensaid A., et al. Differential expression of the Middle East respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels. J. Virol. 2016;90:4838–4842.
    1. Alsaad K.O., Hajeer A.H., Al Balwi M., Al Moaiqel M., Al Oudah N., Al Ajlan A., AlJohani S., Alsolamy S., Gmati G.E., Balkhy H. Histopathology of Middle East respiratory syndrome coronovirus (MERSΓÇÉCoV) infectionΓÇôclinicopathological and ultrastructural study. Histopathology. 2018;72:516–524.
    1. Yeung M.L., Yao Y., Jia L., Chan J.F., Chan K.H., Cheung K.F., Chen H., Poon V.K., Tsang A.K., To K.K. MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2. Nat. Microbiol. 2016;1:1–8.
    1. Chu H., Zhou J., Wong B.H.-Y., Li C., Chan J.F.-W., Cheng Z.S., Yang D., Wang D., Lee A.C.-Y., Li C. Middle East respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J. Infect. Dis. 2016;213:904–914.
    1. Kim E.S., Choe P.G., Park W.B., Oh H.S., Kim E.J., Nam E.Y., Na S.H., Kim M., Song K.H., Bang J.H. Clinical progression and cytokine profiles of Middle East respiratory syndrome coronavirus infection. J. Korean Med. Sci. 2016;31:1717–1725.
    1. Mahallawi W.H., Khabour O.F., Zhang Q., Makhdoum H.M., Suliman B.A. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018;104:8–13.
    1. Zhou J., Chu H., Li C., Wong B.H.-Y., Cheng Z.S., Poon V.K.-M., Sun T., Lau C.C.-Y., Wong K.K.-Y., Chan J.Y.-W. Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis. J. Infect. Dis. 2014;209:1331–1342.
    1. Liu Y., Gayle A.A., Wilder-Smith A., RocklÃv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J. Travel Med. 2020;27 taaa021.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069.
    1. Chen Y., Guo Y., Pan Y., Zhao Z.J. Structure analysis of the receptor binding of 2019-nCoV. Biochem. Biophys. Res. Commun. 2020;525:135–140.
    1. Coutard B., Valle C., de L., Canard X.B., Seidah N.G., Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res. 2020;176 doi: 10.1016/j.antiviral.2020.104742.Epub;%2020Feb 10.: 104742.
    1. Yap J.K.Y., Moriyama M., Iwasaki A. Inflammasomes and Pyroptosis as therapeutic targets for COVID-19. J. Immunol. 2020 ji2000513.
    1. Chen G., Wu D., Guo W., Cao Y., Huang D., Wang H., Wang T., Zhang X., Chen H., Yu H., Zhang X., Zhang M., Wu S., Song J., Chen T., Han M., Li S., Luo X., Zhao J., Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 2020;130:2620–2629.
    1. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., Tian D.S. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin. Infect. Dis. 2020 ciaa248.
    1. Blanco-Melo D., Nilsson-Payant B.E., Liu W.C., Uhl S., Hoagland D., Møller R., Jordan T.X., Oishi K., Panis M., Sachs D., Wang T.T., Schwartz R.E., Lim J.K., Albrecht R.A., tenOever B.R. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181:1036–1045.
    1. Sauty A., Dziejman M., Taha R.A., Iarossi A.S., Neote K., Garcia-Zepeda E.A., Hamid Q., Luster A.D. The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells. J. Immunol. 1999;162:3549–3558.
    1. Glass W.G., Subbarao K., Murphy B., Murphy P.M. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J. Immunol. 2004;173:4030–4039.
    1. Jiang D., Liang J., Hodge J., Lu B., Zhu Z., Yu S., Fan J., Gao Y., Yin Z., Homer R., Gerard C., Noble P.W. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J. Clin. Invest. 2004;114:291–299.
    1. Cheemarla N.R., Brito A.F., Fauver J.R., Alpert T., Vogels C.B., Omer S.B., Ko A., Grubaugh N.D., Landry M.L., Foxman E.F. Host response-based screening to identify undiagnosed cases of COVID-19 and expand testing capacity. medRxiv. 2020
    1. Chu H., Chan J.F., Wang Y., Yuen T.T., Chai Y., Hou Y., Shuai H., Yang D., Hu B., Huang X., Zhang X., Cai J.P., Zhou J., Yuan S., Kok K.H., To K.K., Chan I.H., Zhang A.J., Sit K.Y., Au W.K., Yuen K.Y. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin. Infect. Dis. 2020 ciaa410.
    1. Xiong Y., Liu Y., Cao L., Wang D., Guo M., Jiang A., Guo D., Hu W., Yang J., Tang Z., Wu H., Lin Y., Zhang M., Zhang Q., Shi M., Liu Y., Zhou Y., Lan K., Chen Y. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg. Microbes Infect. 2020;9:761–770.
    1. Liu B., Li M., Zhou Z., Guan X., Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J. Autoimmun. 2020;111 doi: 10.1016/j.jaut.2020.102452. Epub;%2020 Apr 10.: 102452.
    1. Tanaka T., Narazaki M., Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8:959–970.
    1. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8:420–422.
    1. Wang W., Ye L., Ye L., Li B., Gao B., Zeng Y., Kong L., Fang X., Zheng H., Wu Z., She Y. Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res. 2007;128:1–8.
    1. DeDiego M.L., Nieto-Torres J.L., Regla-Nava J.A., Jimenez-GuardeÃo J.M., Fernandez-Delgado R., Fett C., CastaÃo-Rodriguez C., Perlman S., Enjuanes L. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J. Virol. 2014;88:913–924.
    1. Giamarellos-Bourboulis E.J., Netea M.G., Rovina N., Akinosoglou K., Antoniadou A., Antonakos N., Damoraki G., Gkavogianni T., Adami M.E., Katsaounou P., Ntaganou M., Kyriakopoulou M., Dimopoulos G., Koutsodimitropoulos I., Velissaris D., Koufargyris P., Karageorgos A., Katrini K., Lekakis V., Lupse M., Kotsaki A., Renieris G., Theodoulou D., Panou V., Koukaki E., Koulouris N., Gogos C., Koutsoukou A. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27:992–1000.
    1. Vabret N., Britton G.J., Gruber C., Hegde S., Kim J., Kuksin M., Levantovsky R., et al. Immunology of COVID-19: current state of the science. Immunity. 2020;10
    1. Cameron M.J., Ran L., Xu L., Danesh A., Bermejo-Martin J.F., Cameron C.M., Muller M.P., Gold W.L., Richardson S.E., Poutanen S.M., Willey B.M., DeVries M.E., Fang Y., Seneviratne C., Bosinger S.E., Persad D., Wilkinson P., Greller L.D., Somogyi R., Humar A., Keshavjee S., Louie M., Loeb M.B., Brunton J., McGeer A.J., Kelvin D.J. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J. Virol. 2007;81:8692–8706.
    1. Hadjadj J., Yatim N., Barnabei L., Corneau A., Boussier J., Pere H., Charbit B., Bondet V., Chenevier-Gobeaux C., Breillat P. Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients. medRxiv. 2020
    1. Chen H., Liu W., Liu D., Zhao L., Yu J. SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing. medRxiv. 2020
    1. Sallard E., Lescure F.X., Yazdanpanah Y., Mentre F., Peiffer-Smadja N., Florence A.D.E.R., Yazdanpanah Y., Mentre F., Lescure F.X., Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res. 2020
    1. Zhou Q., Chen V., Shannon C.P., Wei X.S., Xiang X., Wang X., Wang Z.H., Tebbutt S.J., Kollmann T.R., Fish E.N. Interferon alpha 2b treatment for COVID-19. Front. Immunol. 2020;11:1061.
    1. Yang J., Zheng Y., Gou X., Pu K., Chen Z., Guo Q., Ji R., Wang H., Wang Y., Zhou Y. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int. J. Infect. Dis. 2020
    1. Alqahtani J.S., Oyelade T., Aldhahir A.M., Alghamdi S.M., Almehmadi M., Alqahtani A.S., Quaderi S., Mandal S., Hurst J.R. Prevalence, severity and mortality associated with COPD and smoking in patients with COVID-19: a rapid systematic review and meta-analysis. PLoS One. 2020;15
    1. Wang B., Li R., Lu Z., Huang Y. Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging (Albany NY). 2020;12:6049–6057.
    1. Di S.A., Caramori G., Ricciardolo F.L., Capelli A., Adcock I.M., Donner C.F. Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overview. Clin. Exp. Allergy. 2004;34:1156–1167.
    1. Moermans C., Heinen V., Nguyen M., Henket M., Sele J., Manise M., Corhay J.L., Louis R. Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease. Cytokine. 2011;56:298–304.
    1. Barnes P.J. The cytokine network in chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol. 2009;41:631–638.
    1. Franciosi L.G., Page C.P., Celli B.R., Cazzola M., Walker M.J., Danhof M., Rabe K.F., Della Pasqua O.E. Markers of disease severity in chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther. 2006;19:189–199.
    1. Barnes P.J., Celli B.R. Systemic manifestations and comorbidities of COPD. Eur. Respir. J. 2009;33:1165–1185.
    1. Selvarajah S., Todd I., Tighe P.J., John M., Bolton C.E., Harrison T., Fairclough L.C. Multiple circulating cytokines are coelevated in chronic obstructive pulmonary disease. Mediators Inflamm. 2016;2016:3604842. doi: 10.1155/2016/3604842. Epub;%2016 Jul 25.: 3604842.
    1. Kumar S. 2020. COVID-19: A Drug Repurposing and Biomarker Identification by Using Comprehensive Gene-disease Associations Through protein-protein Interaction Network Analysis.
    1. Leung J.M., Yang C.X., Tam A., Shaipanich T., Hackett T.L., Singhera G.K., Dorscheid D.R., Sin D.D. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur. Respir. J. 2020;55:2000688–2002020.
    1. Lippi G., Wong J., Henry B.M. Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis. Pol Arch Intern Med. 2020;130:304–309.
    1. Wenzel U., Turner J.E., Krebs C., Kurts C., Harrison D.G., Ehmke H. Immune mechanisms in arterial hypertension. J. Am. Soc. Nephrol. 2016;27:677–686.
    1. Tanase D.M., Gosav E.M., Radu S., Ouatu A., Rezus C., Ciocoiu M., Costea C.F., Floria M. Arterial hypertension and interleukins: potential therapeutic target or future diagnostic marker? Int. J. Hypertens. 2019;2019:3159283. doi: 10.1155/2019/3159283. eCollection;%2019.: 3159283.
    1. Mirhafez S.R., Mohebati M., Feiz D.M., Saberi K.M., Ebrahimi M., Avan A., Eslami S., Pasdar A., Rooki H., Esmaeili H., Ferns G.A., Ghayour-Mobarhan M. An imbalance in serum concentrations of inflammatory and anti-inflammatory cytokines in hypertension. J. Am. Soc. Hypertens. 2014;8:614–623.
    1. Ji Q., Cheng G., Ma N., Huang Y., Lin Y., Zhou Q., Que B., Dong J., Zhou Y., Nie S. Circulating Th1, Th2, and Th17 levels in hypertensive patients. Dis. Markers. 2017;2017:7146290. doi: 10.1155/2017/7146290. Epub;%2017 Jul 5.: 7146290.
    1. Fang L., Karakiulakis G., Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir. Med. 2020;8:e21–2600.
    1. Chen X., Hu W., Ling J., Mo P., Zhang Y., Jiang Q., Ma Z., Cao Q., Deng L., Song S. Hypertension and diabetes delay the viral clearance in COVID-19 patients. medRxiv. 2020
    1. Guzik T.J., Mohiddin S.A., Dimarco A., Patel V., Savvatis K., Marelli-Berg F.M., Madhur M.S., Tomaszewski M., Maffia P., D’Acquisto F., Nicklin S.A., Marian A.J., Nosalski R., Murray E.C., Guzik B., Berry C., Touyz R.M., Kreutz R., Wang D.W., Bhella D., Sagliocco O., Crea F., Thomson E.C., McInnes I.B. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc. Res. 2020 cvaa106.
    1. Rafieian-Kopaei M., Setorki M., Doudi M., Baradaran A., Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int. J. Prev. Med. 2014;5:927–946.
    1. Williams J.W., Huang L.H., Randolph G.J. Cytokine circuits in cardiovascular disease. Immunity. 2019;50:941–954.
    1. Mehra V.C., Ramgolam V.S., Bender J.R. Cytokines and cardiovascular disease. J. Leukoc. Biol. 2005;78:805–818.
    1. Kofler S., Nickel T., Weis M. Role of cytokines in cardiovascular diseases: a focus on endothelial responses to inflammation. Clin. Sci. 2005;108:205–213.
    1. Lindmark E., Diderholm E., Wallentin L., Siegbahn A. Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy. JAMA. 2001;286:2107–2113.
    1. Blankenberg S., Tiret L., Bickel C., Peetz D., Cambien F., Meyer J., Rupprecht H.J. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation. 2002;106:24–30.
    1. Madjid M., Safavi-Naeini P., Solomon S.D., Vardeny O. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol. 2020;10
    1. Ferlita S., Yegiazaryan A., Noori N., Lal G., Nguyen T., To K., Venketaraman V. Type 2 diabetes mellitus and altered immune system leading to susceptibility to pathogens, especially Mycobacterium tuberculosis. J. Clin. Med. 2019;8:2219.
    1. Kumar A., Arora A., Sharma P., Anikhindi S.A., Bansal N., Singla V., Khare S., Srivastava A. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab. Syndr. 2020;14:535–545.
    1. Navarro J.F., Mora C. Role of inflammation in diabetic complications. Nephrol. Dial. Transplant. 2005;20:2601–2604.
    1. Pickup J.C., Crook M.A. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia. 1998;41:1241–1248.
    1. Alexandraki K., Piperi C., Kalofoutis C., Singh J., Alaveras A., Kalofoutis A. Inflammatory process in type 2 diabetes: the role of cytokines. Ann. N. Y. Acad. Sci. 2006;1084:89–117. doi: 10.1196/annals.1372.039.89-117.
    1. Randeria S.N., Thomson G.J.A., Nell T.A., Roberts T., Pretorius E. Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation. Cardiovasc. Diabetol. 2019;18:72–0870.
    1. Hang H., Yuan S., Yang Q., Yuan D., Liu Q. Multiplex bead array assay of plasma cytokines in type 2 diabetes mellitus with diabetic retinopathy. Mol. Vis. 2014;20:1137–1145. eCollection;%2014.: 1137-1145.
    1. Szablewski L. Role of immune system in type 1 diabetes mellitus pathogenesis. Int. Immunopharmacol. 2014;22:182–191.
    1. Fatima N., Faisal S.M., Zubair S., Ajmal M., Siddiqui S.S., Moin S., Owais M. Role of pro-inflammatory cytokines and biochemical markers in the pathogenesis of type 1 diabetes: correlation with age and glycemic condition in diabetic human subjects. PLoS One. 2016;11
    1. Purohit S., Sharma A., Zhi W., Bai S., Hopkins D., Steed L., Bode B., Anderson S.W., Reed J.C., Steed R.D., She J.X. Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria. Front. Immunol. 2018;9:154. doi: 10.3389/fimmu.2018.00154. eCollection;%2018.: 154.
    1. Gouda W., Mageed L., El Dayem S.M.A., Ashour E., Afify M. Evaluation of pro-inflammatory and anti-inflammatory cytokines in type 1 diabetes mellitus. Bulletin of the National Research Centre. 2018;42:14.
    1. Iglesias M., Arun A., Chicco M., Lam B., Talbot C.C., Jr., Ivanova V., Lee W.P.A., Brandacher G., Raimondi G. Type-I interferons inhibit Interleukin-10 signaling and favor type 1 diabetes development in nonobese diabetic mice. Front. Immunol. 2018;9:1565. doi: 10.3389/fimmu.2018.01565. eCollection;%2018.: 1565.
    1. Hussain A., Bhowmik B., do Vale Moreira N.C. COVID-19 and diabetes: knowledge in progress. Diabetes Res. Clin. Pract. 2020;162:108142. . doi: 10.1016/j.diabres.2020.108142. Epub;%2020 Apr 9.: 108142.
    1. Hantoushzadeh S., Shamshirsaz A.A., Aleyasin A., Seferovic M.D., Aski S.K., Arian S.E., Pooransari P., Ghotbizadeh F., Aalipour S., Soleimani Z., Naemi M., Molaei B., Ahangari R., Salehi M., Oskoei A.D., Pirozan P., Darkhaneh R.F., Laki M.G., Farani A.K., Atrak S., Miri M.M., Kouchek M., Shojaei S., Hadavand F., Keikha F., Hosseini M.S., Borna S., Ariana S., Shariat M., Fatemi A., Nouri B., Nekooghadam S.M., Aagaard K. Maternal death due to COVID-19. Am. J. Obstet. Gynecol. 2020:10.
    1. Wedekind L., Belkacemi L. Altered cytokine network in gestational diabetes mellitus affects maternal insulin and placental-fetal development. J. Diabetes Complications. 2016;30:1393–1400.
    1. Kuzmicki M., Telejko B., Zonenberg A., Szamatowicz J., Kretowski A., Nikolajuk A., Laudanski P., Gorska M. Circulating pro- and anti-inflammatory cytokines in Polish women with gestational diabetes. Horm. Metab. Res. 2008;40:556–560.
    1. Zimmermann P., Finn Curtis A.N. Does BCG vaccination protect against nontuberculous mycobacterial infection? A systematic review and meta-analysis. J. Infect. Dis. 2018;218:679–687.
    1. Luca S., Mihaescu T. History of BCG Vaccine. Maedica. 2013;8:53–58.
    1. Fine P.E.M. BCG vaccination against tuberculosis and leprosy. Br. Med. Bull. 1988;44:691–703.
    1. World Health Organization BCG vaccine: WHO position paper, February 2018GÇôrecommendations. Vaccine. 2018;36:3408–3410.
    1. World Health Organization Information sheet observed rate of vaccine reactions Bacille Calmette-Guérin (Bcg) Global Vaccine Saf. Immun. Vaccines Biol. 2012;20
    1. Alhunaidi O., Zlotta A.R. The use of intravesical BCG in urothelial carcinoma of the bladder. Ecancermedicalscience. 2019;13
    1. Aaby P., Roth A., Ravn H., Napirna B.M., Rodrigues A., Lisse I.M., Stensballe L., Diness B.R., Lausch K.R., Lund N. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J. Infec. Dis. 2011;204:245–252.
    1. Higgins J.P., Soares-Weiser K., López-López J.A., Kakourou A., Chaplin K., Christensen H., Martin N.K., Sterne J.A., Reingold A.L. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016:355.
    1. Berendsen M.L., van Gijzel S.W., Smits J., de M.Q., Aaby P., Benn C.S., Netea M.G., van der Ven A.J. BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa. BMJ Glob. Health. 2019;4:e001862.
    1. Stensballe L.G., Nante E., Jensen I.P., Kofoed P.E., Poulsen A., Jensen H., Newport M., Marchant A., Aaby P. Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study. Vaccine. 2005;23:1251–1257.
    1. Hollm-Delgado M.G., Stuart E.A., Black R.E. Acute lower respiratory infection among Bacille Calmette-Guérin (BCG)-vaccinated children. Pediatrics. 2014;133:e73–e81.
    1. Wardhana, Datau E.A., Sultana A., Mandang V.V., Jim E. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med. Indones. 2011;43:185–190.
    1. Netea M.G., van C.R. BCG-induced protection: effects on innate immune memory. Semin. Immunol. 2014;26:512–517.
    1. O'Neill L.A.J., Netea M.G. BCG-induced trained immunity: can it offer protection against COVID-19? Nat. Rev. Immunol. 2020;20:335–337.
    1. Covián C., Fernández-Fierro A., Retamal-Dí­az A., Dí­az F.E., Vasquez A.E., Lay M.K., Riedel C.A., González P.A., Bueno S.M., Kalergis A.M. BCG-induced cross-protection and development of trained immunity: implication for vaccine design. Front Immunol. 2019;10:2806. doi: 10.3389/fimmu.2019.02806.
    1. Kleinnijenhuis J., Quintin J., Preijers F., Joosten L.A., Ifrim D.C., Saeed S., Jacobs C., van L.J., de J.D., Stunnenberg H.G., Xavier R.J., van der Meer J.W., van C.R., Netea M.G. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc. Natl. Acad. Sci. U. S. A. 2012;109:17537–17542.
    1. Arts R.J.W., Moorlag S.J.C.F., Novakovic B., Li Y., Wang S.Y., Oosting M., Kumar V., Xavier R.J., Wijmenga C., Joosten L.A.B., Reusken C.B.E.M., Benn C.S., Aaby P., Koopmans M.P., Stunnenberg H.G., van C.R., Netea M.G. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe. 2018;23:89–100.
    1. Kleinnijenhuis J., Quintin J., Preijers F., Benn C.S., Joosten L.A., Jacobs C., van L.J., Xavier R.J., Aaby P., van der Meer J.W., van C.R., Netea M.G. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J. Innate Immun. 2014;6:152–158.
    1. Moliva J.I., Turner Torrelles J.J.B. Immune responses to bacillus Calmette-Guérin vaccination: why do they fail to protect against Mycobacterium tuberculosis? Front. Immunol. 2017;8:407.
    1. Parra M., Liu X., Derrick S.C., Yang A., Tian J., Kolibab K., Kumar S., Morris S.L. Molecular analysis of non-specific protection against murine malaria induced by BCG vaccination. PLoS One. 2013;8:e66115.
    1. Spencer J.C., Ganguly R., Waldman R.H. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guérin. J. Infect. Dis. 1977;136:171–175.
    1. Floc'h F., Werner G.H. Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-guérin) Ann. Immunol. (Paris) 1976;127:173–186.
    1. Starr S.E., Visintine A.M., Tomeh M.O., Nahmias A.J. Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection. Proc. Soc. Exp. Biol. Med. 1976;152:57–60.
    1. Redelman-Sidi G. Could BCG be used to protect against COVID-19? Nat. Rev. Urol. 2020;17:316–317.
    1. Ozdemir C., Kucuksezer U.C., Tamay Z.U. Is BCG vaccination affecting the spread and severity of COVID -19? Allergy. 2020;10
    1. Gallagher J., Watson C., Ledwidge M. Association of Bacille Calmette-Guérin (BCG), adult pneumococcal and adult seasonal influenza vaccines with Covid-19 adjusted mortality rates in level 4 European countries. medRxiv. 2020
    1. Zwerling A., Behr M.A., Verma A., Brewer T.F., Menzies D., Pai M. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med. 2011;8:e1001012.
    1. Miller A., Reandelar M.J., Fasciglione K., Roumenova V., Li Y., Otazu G.H. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. medRxiv. 2020
    1. Klinger D., Blass I., Rappoport N., Linial M. Significantly improved COVID-19 outcomes in countries with higher BCG vaccination coverage: a multivariable analysis. medRxiv. 2020
    1. Singh S. BCG vaccines may not reduce COVID-19 mortality rates. medRxiv. 2020
    1. Fukui M., Kawaguchi K., Matsuura H. Does TB vaccination reduce COVID-19 infection?: no evidence from a regression discontinuity analysis. No Evidence Regression Discontinuity Anal. 2020 (April 9, 2020)

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться