Current status of potential therapeutic candidates for the COVID-19 crisis

Jiancheng Zhang, Bing Xie, Kenji Hashimoto, Jiancheng Zhang, Bing Xie, Kenji Hashimoto

Abstract

As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.

Keywords: ACE2 blocker; Antimalaria; Antiviral: Chinese traditional medicine; COVID-19; Immunoenhancer; Monoclonal antibody; Vaccine.

Conflict of interest statement

Declaration of Competing Interest 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 Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
SARS-CoV-2 infection-induced impairment of multiple organ function Impairment of multiple organ function by SARS-CoV-2 infection includes acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury, acute liver injury, neurological injury, gastrointestinal injury, immune system injury, and coagulation impairment. Abbreviations: ALT, alanine transaminase; APTT, activated partial thromboplastin time; ARDS, acute respiratory distress syndrome; AST, aspartate aminotransferase; CK-MB, creatine kinase myocardial band; CNS, central nervous system; FDP, fibrinogen degradation products; HLA-DR, human leukocyte antigen DR; INR, international normalized ratio; LDH, lactate dehydrogenase; MYO, myoglobin; NK, natural killer cell; NT-proBNP, N terminal pro-B-type natriuretic peptide; PaO2/FiO2, oxygenation index; PNS, peripheral nervous system; PT, prothrombin time; RAAS, renin-angiotensin-aldosterone system; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TBIL, total bilirubin; Th, helper T cell; TNI, troponin I.
Fig. 2
Fig. 2
The hypothetical replication cycle of SARS-CoV-2 and the possible targets of anti-COVID-19 drugs. SARS-CoV-2 binds to the ACE2 receptor on the surface of cells using the Spike protein, which subsequently triggers endocytosis. On releasing the viral nucleocapsid to the cytoplasm, encapsidated positive-strand genomic RNA [(+)gRNA] serves as a template to translate polypeptide chains, which are cleaved to non-structural proteins including RNA-dependent RNA polymerase. The single negative strand RNA [(-)gRNA] synthesized from (+)gRNA template is employed to replicate more copies of viral RNAs. Subgenomic RNAs (sgRNAs) are synthesized by discontinuous transcription from the (+)gRNA template and then encode viral structural and accessary proteins, which are subsequently assembled with newly synthesized viral RNA to form new virions. The nascent virions are then transported in secretory vesicles to the plasma membrane and released by exocytosis. RhACE2, convalescent plasma and JAK inhibitor baricitinib could dampen the binding of the Spike protein on the surface of the SARS-CoV-2 to ACE2 expressed on the cell surface. Lopinavir/ritonavir and favipiravir inhibit the proteolysis of polypeptide chains. Remdesivir inhibits RNA-dependent RNA polymerase. EIDD-2801 could inhibit SARS-CoV-2 replication. NO and Zinc might inhibit SARS-CoV-2 replication. Vitamin D might induce antimicrobial peptides to reduce SARS-CoV-2 replication. Ivermectin could effectively block SARS-CoV-2 growth. Baricitinib could interrupt the passage of SARS-CoV-2 entering cells through inhibition of AAK1-mediated endocytosis. CQ and HCQ inhibit virus/cell fusion process. LHQW and IFNs could block the process of virus replication (RNAs transcription, protein translation, and post-translational modification). Abbreviations: AAK1, adaptor-associated kinase 1; CQ, chloroquine; ER, endoplasmic reticulum; HCQ, hydroxychloroquine sulfate; IFNs, interferons; iNO, inhaled nitric oxide; JAK, janus kinase; LHQW, Lianhua Qingwen; rhACE2, recombinant human angiotensin-converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Fig. 3
Fig. 3
The hypothetical mechanisms of SARS-CoV-2 infection-induced cytokine storm and antiviral immunity and the possible therapeutic targets of patients with COVID-19 infection. “Cytokine storms” might start with inflammatory cytokine secretion into lung tissue and pulmonary blood vessels from virus-infected alveolar epithelial cells, pulmonary vascular endothelial cells, alveolar macrophages, multinucleated giant cells, and other infiltrated immune cells, which mainly serve to limit the replication and spreading of the virus and to induce downstream immune responses via the blood circulation. Following the recruitment and activation by primary cytokines, systemic immune cells (neutrophils, DCs, Mo-Mφ, NK cells, CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells, etc.) further secrete inflammatory cytokines and promote the cascade of inflammatory processes to eliminate virus and virus-infected cells. Vitamin C might inhibit SARS-CoV-2 and alleviate the illness by decreasing inflammatory cytokines, stimulating IFN production, supporting lymphocyte proliferation, boosting the phagocytic capability of neutrophils, monocytes, and macrophages, protecting lung barrier function and reducing lung vascular injury, increasing IFN secretion from alveolar Mφ, Mo-Mφ, DCs, NK cells, and CD8+ T cells. IFNs could enhance NK cell cytotoxicity, enhance expression of major histocompatibility complex Ⅰ proteins, and promote the production of IFNs and the proliferation of NK cells and Mφ. Bevacizumab could reduce vascular permeability. Vaccines (mRNA1273, Ad5-nCoV, PittCoVacc, and NVX-CoV2373) could induce protective antiviral immune memory, while MSCs could decrease pro-inflammatory cytokines, promote regeneration, secrete multiple paracrine factors and anti-inflammatory cytokines, and enlarge the proportion of Treg cells. iNO could alleviate pulmonary hypertension through its selective pulmonary vasodilation. Corticosteroids, LHQW, Xuebijing, IVIG, tocilizumab, sarilumab, baricitinib, vitamin D, CQ, and HCQ could also reduce inflammation. Heparin blocks the thrombus formation. Abbreviations: AT I, type I alveolar epithelial cell; AT Ⅱ, type Ⅱ alveolar epithelial cell; CQ, chloroquine; DC, dendritic cell; G-CSF, granulocyte-colony stimulating factor; HCQ, hydroxychloroquine sulfate; IFN-γ, interferon gamma; IL, interleukin; iNO, inhaled nitric oxide; IP-10, interferon-inducible protein-10; IVIG, intravenous gamma globulin; LHQW, Lianhua Qingwen; MCP-1, monocyte chemotactic protein 1; MIP-1A, macrophage inflammatory protein-1a; Mo-Mφ, monocyte-macrophage; MSCs, mesenchymal stem cells; NK, natural killer cell; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Th, helper T cell; TNF-α, tumor necrosis factor alpha; Treg, regulatory T cell.

References

    1. Achiron A. Complications of intravenous gammaglobulin in neuromuscular diseases. Neurology. 1997;49:899–900.
    1. Aggarwal S., Pittenger M.F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–1822.
    1. Agostini M.L., Andres E.L., Sims A.C., Graham R.L., Sheahan T.P., Lu X., Smith E.C., Case J.B., Feng J.Y., Jordan R., Ray A.S., Cihlar T., Siegel D., Mackman R.L., Clarke M.O., Baric R.S., Denison M.R. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio. 2018;9:e00221–18.
    1. Agostini M.L., Pruijssers A.J., Chappell J.D., Gribble J., Lu X., Andres E.L., Bluemling G.R., Lockwood M.A., Sheahan T.P., Sims A.C., Natchus M.G., Saindane M., Kolykhalov A.A., Painter G.R., Baric R.S., Denison M.R. Small-molecule antiviral β-d–hydroxycytidine inhibits a proofreading-intact coronavirus with a high genetic barrier to resistance. J. Virol. 2019;93:e01348–19.
    1. Ahn D.G., Shin H.J., Kim M.H., Lee S., Kim H.S., Myoung J., Kim B.T., Kim S.J. Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19) J. Microbiol. Biotechnol. 2020;30:313–324.
    1. Akerström S., Mousavi-Jazi M., Klingström J., Leijon M., Lundkvist A., Mirazimi A. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J. Virol. 2005;79:1966–1969.
    1. Al-Salama Z.T., Scott L.J. Baricitinib: A review in rheumatoid arthritis. Drugs. 2018;78:761–772.
    1. Anderson, D.E., Cui, J., Ye, Q., Huang, B.Y., Zu, W.H., Gong, J., Liu, W.Q., Kim, S.Y., Yan, B.G., Sigmundsson, K., Lim, X.F., Ye, F., Niu, P.H., Zhou, X.M., Tan, W.J., Wang, L.F., Tan, X., 2020. Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy. bioRxiv, 2020.2003.2029.014209.
    1. Andersson J.P., Andersson U.G. Human intravenous immunoglobulin modulates monokine production in vitro. Immunology. 1990;71:372–376.
    1. Andersson U.G., Björk L., Skansén-Saphir U., Andersson J.P. Down-regulation of cytokine production and interleukin-2 receptor expression by pooled human IgG. Immunology. 1993;79:211–216.
    1. Arabi Y.M., Mandourah Y., Al-Hameed F., Sindi A.A., Almekhlafi G.A., Hussein M.A., Jose J., Pinto R., Al-Omari A., Kharaba A., Almotairi A., Al Khatib K., Alraddadi B., Shalhoub S., Abdulmomen A., Qushmaq I., Mady A., Solaiman O., Al-Aithan A.M., Al-Raddadi R., Ragab A., Balkhy H.H., Al Harthy A., Deeb A.M., Al Mutairi H., Al-Dawood A., Merson L., Hayden F.G., Fowler R.A. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am. J. Respir. Crit. Care Med. 2018;197:757–767.
    1. Aranow C. Vitamin D and the immune system. J. Investig. Med. 2011;59:881–886.
    1. Asmussen S., Ito H., Traber D.L., Lee J.W., Cox R.A., Hawkins H.K., McAuley D.F., McKenna D.H., Traber L.D., Zhuo H., Wilson J., Herndon D.N., Prough D.S., Liu K.D., Matthay M.A., Enkhbaatar P. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax. 2014;69:819–825.
    1. Bao Y., Sun Y., Meng S., Shi J., Lu L. 2019-nCoV epidemic: address mental health care to empower society. Lancet. 2020;395:e37–e38.
    1. Barragan P., Podzamczer D. Lopinavir/ritonavir: a protease inhibitor for HIV-1 treatment. Expert Opin. Pharmacother. 2008;9:2363–2375.
    1. Bertorini T.E., Nance A.M., Horner L.H., Greene W., Gelfand M.S., Jaster J.H. Complications of intravenous gammaglobulin in neuromuscular and other diseases. Muscle Nerve. 1996;19:388–391.
    1. BioSpace. April 07, 2020. FDA clears the way for ridgeback biotherapeutics to begin human testing of a promising potential treatment for COVID-19.
    1. Caly L., Druce J.D., Catton M.G., Jans D.A., Wagstaff K.M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;104787
    1. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., Ruan L., Song B., Cai Y., Wei M., Li X., Xia J., Chen N., Xiang J., Yu T., Bai T., Xie X., Zhang L., Li C., Yuan Y., Chen H., Li H., Huang H., Tu S., Gong F., Liu Y., Wei Y., Dong C., Zhou F., Gu X., Xu J., Liu Z., Zhang Y., Li H., Shang L., Wang K., Li K., Zhou X., Dong X., Qu Z., Lu S., Hu X., Ruan S., Luo S., Wu J., Peng L., Cheng F., Pan L., Zou J., Jia C., Wang J., Liu X., Wang S., Wu X., Ge Q., He J., Zhan H., Qiu F., Guo L., Huang C., Jaki T., Hayden F.G., Horby P.W., Zhang D., Wang C. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N. Engl. J. Med. 2020 doi: 10.1056/NEJMoa2001282.
    1. Carr A.C., Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9:1211.
    1. Carr A.C., Rosengrave P.C., Bayer S., Chambers S., Mehrtens J., Shaw G.M. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit. Care. 2017;21:300.
    1. Celularity. April 02, 2020. Celularity announces FDA clearance of IND application for CYNK-001 in coronavirus, first in cellular therapy. .
    1. Chamberlain G., Fox J., Ashton B., Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25:2739–2749.
    1. Chan J.F., Kok K.H., Zhu Z., Chu H., To K.K., Yuan S., Yuen K.Y. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect. 2020;9:221–236.
    1. Channappanavar R., Fehr A.R., Zheng J., Wohlford-Lenane C., Abrahante J.E., Mack M., Sompallae R., McCray P.B., Meyerholz D.K., Perlman S. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J. Clin. Invest. 2019;130:3625–3639.
    1. Chen, C., Huang, J., Cheng, Z., Wu, J., Chen, S., Zhang, Y., Chen, B., Lu, M., Luo, Y., Zhang, J., Yin, P., Wang, X., 2020a. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. medRxiv, 2020.2003.2017.20037432.
    1. Chen G., Gao Y., Jiang Y., Yang F., Li S., Tan D., Ma Q. Efficacy and safety of Xuebijing injection combined with Ulinastatin as adjunctive therapy on sepsis: a systematic review and meta-analysis. Front. Pharmacol. 2018;9:743.
    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 immunologic features in severe and moderate Coronavirus Disease 2019. J. Clin Invest. 2020
    1. Chen L., Liu P., Gao H., Sun B., Chao D., Wang F., Zhu Y., Hedenstierna G., Wang C.G. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin. Infect. Dis. 2004;39:1531–1535.
    1. Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J.a., Yu, T., Zhang, X., Zhang, L., 2020c. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395, 507-513.
    1. Chen R.C., Tang X.P., Tan S.Y., Liang B.L., Wan Z.Y., Fang J.Q., Zhong N. Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience. Chest. 2006;129:1441–1452.
    1. Chimenti L., Luque T., Bonsignore M.R., Ramírez J., Navajas D., Farré R. Pre-treatment with mesenchymal stem cells reduces ventilator-induced lung injury. Eur. Respir. J. 2012;40:939–948.
    1. China's State Council. February 21, 2020. Press conference on scientific and technological innovation to support epidemic prevention and control. .
    1. Chu C.M., Cheng V.C., Hung I.F., Wong M.M., Chan K.H., Chan K.S., Kao R.Y., Poon L.L., Wong C.L., Guan Y., Peiris J.S., Yuen K.Y. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59:252–256.
    1. Cinatl J., Morgenstern B., Bauer G., Chandra P., Rabenau H., Doerr H.W. Treatment of SARS with human interferons. Lancet. 2003;362:293–294.
    1. Coutard B., Valle C., de Lamballerie X., Canard 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
    1. Crackower M.A., Sarao R., Oudit G.Y., Yagil C., Kozieradzki I., Scanga S.E., Oliveira-dos-Santos A.J., da Costa J., Zhang L., Pei Y., Scholey J., Ferrario C.M., Manoukian A.S., Chappell M.C., Backx P.H., Yagil Y., Penninger J.M. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417:822–828.
    1. De Andrea, M., Ravera, R., Gioia, D., Gariglio, M., Landolfo, S., 2002. The interferon system: an overview. Eur. J. Paediatr. Neurol. 6 Suppl A, A41-A46 and A55-A58.
    1. Delang L., Abdelnabi R., Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018;153:85–94.
    1. Deng L., Li C., Zeng Q., Liu X., Li X., Zhang H., Hong Z., Xia J. Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study. J. Infect. 2020 doi: 10.1016/j.jinf.2020.03.002.
    1. Devaney J., Horie S., Masterson C., Elliman S., Barry F., O'Brien T., Curley G.F., O'Toole D., Laffey J.G. Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax. 2015;70:625–635.
    1. Ding Y., He L., Zhang Q., Huang Z., Che X., Hou J., Wang H., Shen H., Qiu L., Li Z., Geng J., Cai J., Han H., Li X., Kang W., Weng D., Liang P., Jiang S. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 2004;203:622–630.
    1. Ding Y., Zeng L., Li R., Chen Q., Zhou B., Chen Q., Cheng P.L., Yutao W., Zheng J., Yang Z., Zhang F. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC Complement. Altern. Med. 2017;17:130.
    1. Dodd R.Y. Emerging pathogens and their implications for the blood supply and transfusion transmitted infections. Br. J. Haematol. 2012;159:135–142.
    1. Dong L., Xia J.W., Gong Y., Chen Z., Yang H.H., Zhang J., He J., Chen X.D. Effect of lianhuaqingwen capsules on airway inflammation in patients with acute exacerbation of chronic obstructive pulmonary disease. Evid. Based Complement Alternat. Med. 2014;2014
    1. Doty R.L. Treatment for smell and taste disorders: a critical review. Handb. Clin. Neurol. 2019;164:455–479.
    1. Duan K., Liu B., Li C., Zhang H., Yu T., Qu J., Zhou M., Chen L., Meng S., Hu Y., Peng C., Yuan M., Huang J., Wang Z., Yu J., Gao X., Wang D., Yu X., Li L., Zhang J., Wu X., Li B., Xu Y., Chen W., Peng Y., Hu Y., Lin L., Liu X., Huang S., Zhou Z., Zhang L., Wang Y., Zhang Z., Deng K., Xia Z., Gong Q., Zhang W., Zheng X., Liu Y., Yang H., Zhou D., Yu D., Hou J., Shi Z., Chen S., Chen Z., Zhang X., Yang X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc. Natl. Acad. Sci. U S A. 2020 doi: 10.1073/pnas.2004168117.
    1. Dvorak H.F., Brown L.F., Detmar M., Dvorak A.M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am. J. Pathol. 1995;146:1029–1039.
    1. Falzarano D., de Wit E., Martellaro C., Callison J., Munster V.J., Feldmann H. Inhibition of novel beta coronavirus replication by a combination of interferon-alpha2b and ribavirin. Sci. Rep. 2013;3:1686.
    1. Fanelli V., Ranieri V.M. Mechanisms and clinical consequences of acute lung injury. Ann. Am. Thorac. Soc. 2015;12(Suppl 1):S3–S8.
    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
    1. FDA, March 24, 2020. Investigational covid-19 convalescent plasma-emergency INDs. .
    1. Fehr J., Hofmann V., Kappeler U. Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin. N. Engl. J. Med. 1982;306:1254–1258.
    1. Ferrara N., Hillan K.J., Gerber H.-P., Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discov. 2004;3:391–400.
    1. Ferrario C.M., Jessup J., Chappell M.C., Averill D.B., Brosnihan K.B., Tallant E.A., Diz D.I., Gallagher P.E. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–2610.
    1. Fisher B.J., Kraskauskas D., Martin E.J., Farkas D., Wegelin J.A., Brophy D., Ward K.R., Voelkel N.F., Fowler A.A., 3rd, Natarajan R. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am. J. Physiol. Lung Cell Mol. Physiol. 2012;303:L20–32.
    1. Fisher B.J., Seropian I.M., Kraskauskas D., Thakkar J.N., Voelkel N.F., Fowler A.A., 3rd, Natarajan R. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit. Care Med. 2011;39:1454–1460.
    1. FitzGerald G.A. Misguided drug advice for COVID-19. Science. 2002;367:1434.
    1. Fowler A.A., 3rd, Syed A.A., Knowlson S., Sculthorpe R., Farthing D., DeWilde C., Farthing C.A., Larus T.L., Martin E., Brophy D.F., Gupta S., Fisher B.J., Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J. Transl. Med. 2014;12:32.
    1. Furuta Y., Gowen B.B., Takahashi K., Shiraki K., Smee D.F., Barnard D.L. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral. Res. 2013;100:446–454.
    1. Furuta Y., Takahashi K., Kuno-Maekawa M., Sangawa H., Uehara S., Kozaki K., Nomura N., Egawa H., Shiraki K. Mechanism of action of T-705 against influenza virus. Antimicrob. Agents Chemother. 2005;49:981–986.
    1. Galipeau J., Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22:824–833.
    1. Gao J., Tian Z., Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci. Trends. 2020;14:72–73.
    1. Gautret, P., Lagier, J.C., Parola, P., Hoang, V.T., Meddeb, L., Mailhe, M., Doudier, B., Coujon, J., Giordanengo, V., Vieira, V.E., Dupont, H.T., Honore, S., Colson, P., Chabriere, E., La Scola, B., Rolain, J.M., Brouqui, P., Raoult D., 2020. Hydrochloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents 10.1016/j.ijantimicag.2020.105949.
    1. Goodbourn S., Didcock L., Randall R.E. Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J. Gen. Virol. 2000;81:2341–2364.
    1. Grant W.B., Lahore H., McDonnell S.L., Baggerly C.A., French C.B., Aliano J.L., Bhattoa H.P. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12:E988.
    1. Grein J., Ohmagari N., Shin D., Diaz G., Asperges E., Castagna A., Feldt T., Green G., Green M.L., Lescure F.-X., Nicastri E., Oda R., Yo K., Quiros-Roldan E., Studemeister A., Redinski J., Ahmed S., Bernett J., Chelliah D., Chen D., Chihara S., Cohen S.H., Cunningham J., D'Arminio Monforte A., Ismail S., Kato H., Lapadula G., L'Her E., Maeno T., Majumder S., Massari M., Mora-Rillo M., Mutoh Y., Nguyen D., Verweij E., Zoufaly A., Osinusi A.O., DeZure A., Zhao Y., Zhong L., Chokkalingam A., Elboudwarej E., Telep L., Timbs L., Henne I., Sellers S., Cao H., Tan S.K., Winterbourne L., Desai P., Mera R., Gaggar A., Myers R.P., Brainard D.M., Childs R., Flanigan T. Compassionate use of remdesivir for patients with severe COVID-19. N. Engl. J. Med. 2020 doi: 10.1056/NEHMoa2007016.
    1. Griffiths M.J.D., Evans T.W. Inhaled nitric oxide therapy in adults. N. Eng. J. Med. 2005;353:2683–2695.
    1. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., Liu L., Shan H., Lei C.L., Hui D., Du B., Li L.J., Zeng G., Yuen K.Y., Chen R.C., Tang C.L., Wang T., Chen P.Y., Xiang J., Li S.Y., Wang J.L., Liang Z.J., Peng Y.X., Wei L., Liu Y., Hu Y.H., Peng P., Wang J.M., Liu J.Y., Chen Z., Li G., Zheng Z.J., Qiu S.Q., Luo J., Ye C.J., Zhu S.Y., Zhong N.S. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020 doi: 10.1056/NEJMoa2002032.
    1. Guo J., Huang Z., Lin L., Lv J. Coronavirus Disease 2019 (COVID-19) and cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on onset and severity of severe acute respiratory syndrome coronavirus 2 infection. J. Am. Heart. Assoc. 2020;9
    1. Gupta N., Krasnodembskaya A., Kapetanaki M., Mouded M., Tan X., Serikov V., Matthay M.A. Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012;67:533–539.
    1. Gupta N., Su X., Popov B., Lee J.W., Serikov V., Matthay M.A. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol. 2007;179:1855–1863.
    1. Haagmans B.L., Kuiken T., Martina B.E., Fouchier R.A., Rimmelzwaan G.F., van Amerongen G., van Riel D., de Jong T., Itamura S., Chan K.H., Tashiro M., Osterhaus A.D. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat. Med. 2004;10:290–293.
    1. Hackett, D.W., Mach 17, 2020. China endorses avigan/favipiravir for COVID-19 disease treatment. .
    1. Hamming I., Timens W., Bulthuis M.L.C., Lely A.T., Navis G.J., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 2004;203:631–637.
    1. Han, H., Xie, L., Liu, R., Yang, J., Liu, F., Wu, K., Chen, L., Hou, W., Feng, Y., Zhu, C., 2020a. Analysis of heart injury laboratory parameters in 273 COVID-19 patients in one hospital in Wuhan, China. J. Med. Virol. doi: 10.1002/jmv.25809.
    1. Han, H., Yang, L., Liu, R., Liu, F., Wu, K.L., Li, J., Liu, X.H., Zhu, C.L., 2020b. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin. Chem. Lab. Med. doi: 10.1515/cclm-2020-0188.
    1. Han K., Ma H., An X., Su Y., Chen J., Lian Z., Zhao J., Zhu B.P., Fontaine R.E., Feng Z., Zeng G. Early use of glucocorticoids was a risk factor for critical disease and death from pH1N1 infection. Clin. Infect. Dis. 2011;53:326–333.
    1. Haschke M., Schuster M., Poglitsch M., Loibner H., Salzberg M., Bruggisser M., Penninger J., Krähenbühl S. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin. Pharmacokinet. 2013;52:783–792.
    1. He X.D., Wang Y., Wu Q., Wang H.X., Chen Z.D., Zheng R.S., Wang Z.S., Wang J.B., Yang Y. Xuebijing protects rats from sepsis challenged with acinetobacter baumannii by promoting annexin A1 expression and inhibiting proinflammatory cytokines secretion. Evid. Based Complement Alternat. Med. 2013;2013
    1. Hemilä, H., Chalker, E., 2013. Vitamin C for preventing and treating the common cold. Cochrane Database Syst. Rev. CD000980. doi: 10.1002/14651858.CD000980.pib4.
    1. Heming N., Sivanandamoorthy S., Meng P., Bounab R., Annane D. Immune effects of corticosteroids in sepsis. Front. Immunol. 2018;9:1736.
    1. Hensley L.E., Fritz L.E., Jahrling P.B., Karp C.L., Huggins J.W., Geisbert T.W. Interferon-beta 1a and SARS coronavirus replication. Emerg. Infect. Dis. 2004;10:317–319.
    1. Heyneman C.A. Zinc deficiency and taste disorders. Ann. Pharmacother. 1996;30:186–187.
    1. Hoffmann J.H.O., Enk A.H. High-dose intravenous immunoglobulin in skin autoimmune disease. Front. Immunol. 2019;10:1090.
    1. Holshue M.L., DeBolt C., Lindquist S., Lofy K.H., Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G., Cohn A., Fox L., Patel A., Gerber S.I., Kim L., Tong S., Lu X., Lindstrom S., Pallansch M.A., Weldon W.C., Biggs H.M., Uyeki T.M., Pillai S.K. First case of 2019 novel coronavirus in the United States. N. Engl. J. Med. 2020;382:929–936.
    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. Hung I.F., To K.K., Lee C.K., Lee K.L., Chan K., Yan W.W., Liu R., Watt C.L., Chan W.M., Lai K.Y., Koo C.K., Buckley T., Chow F.L., Wong K.K., Chan H.S., Ching C.K., Tang B.S., Lau C.C., Li I.W., Liu S.H., Chan K.H., Lin C.K., Yuen K.Y. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin. Infect. Dis. 2011;52:447–456.
    1. Iannello A., Debbeche O., Samarani S., Ahmad A. Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS. J. Leukoc. Biol. 2008;84:1–26.
    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. Inovio. press release at March 03, 2020. Inovio Accelerates Timeline for COVID-19 DNA Vaccine INO-4800. .
    1. Italian ANSA news agency. March 13, 2020. 3 patients get better on arthritis drug. .
    1. Ishiyama Y., Gallagher P.E., Averill D.B., Tallant E.A., Brosnihan K.B., Ferrario C.M. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension. 2004;43:970–976.
    1. Jolles S., Sewell W.A., Misbah S.A. Clinical uses of intravenous immunoglobulin. Clin. Exp. Immunol. 2005;142:1–11.
    1. Kakodkar P., Kaka N., Baig M.N. A comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease 19 (COVID-19) Cureus. 2020;12
    1. Kang L., Li Y., Hu S., Chen M., Yang C., Yang B.X., Wang Y., Hu J., Lai J., Ma X., Chen J., Guan L., Wang G., Ma H., Liu Z. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry. 2020;7
    1. Karram T., Abbasi A., Keidar S., Golomb E., Hochberg I., Winaver J., Hoffman A., Abassi Z. Effects of spironolactone and eprosartan on cardiac remodeling and angiotensin-converting enzyme isoforms in rats with experimental heart failure. Am. J. Physiol. Heart Circ. Physiol. 2005;289:H1351–H1358.
    1. Kaveri S.V., Dietrich G., Hurez V., Kazatchkine M.D. Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases. Clin. Exp. Immunol. 1991;86:192–198.
    1. Keyaerts E., Vijgen L., Chen L., Maes P., Hedenstierna G., Van Ranst M. Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. Int. J. Infect. Dis. 2004;8:223–226.
    1. Keyaerts E., Vijgen L., Maes P., Neyts J., Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem. Biophys. Res. Commun. 2004;323:264–268.
    1. Keyhan S.O., Fallahi H.R., Cheshmi B. Dysosmia and dysgeusia due to the 2019 novel coronavirus; a hypothesis that needs further investigation. Maxillofac Plast. Reconstr. Surg. 2020;42:9.
    1. Khan A., Benthin C., Zeno B., Albertson T.E., Boyd J., Christie J.D., Hall R., Poirier G., Ronco J.J., Tidswell M., Hardes K., Powley W.M., Wright T.J., Siederer S.K., Fairman D.A., Lipson D.A., Bayliffe A.I., Lazaar A.L. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit. Care. 2017;21:234.
    1. Kim E., Erdos G., Huang S., Kenniston T.W., Balmert S.C., Carey C.D., Raj V.S., Epperly M.W., Klimstra W.B., Haagmans B.L., Korkmaz E., Falo L.D., Jr., Gambotto A. Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development. EBioMedicine. 2020;102743 doi: 10.1016/j.ebiom.2020.102743.
    1. Kim U.J., Won E.J., Kee S.J., Jung S.I., Jang H.C. Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for middle east respiratory syndrome. Antivir. Ther. 2016;21:455–459.
    1. Krasnodembskaya A., Samarani G., Song Y., Zhuo H., Su X., Lee J.W., Gupta N., Petrini M., Matthay M.A. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am. J. Physiol. Lung Cell Mol. Physiol. 2012;302:L1003–L1013.
    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. Lane, J.C.E., Weaver, J., Kostka, K., Duarte-Salles, T., Abrahao, M.T.F., Alghoul, H., Alser, O., Alshammari, T.M., Biedermann, P., Burn, E., Casajust, P., Conover, M., Culhane, A.C., Davydov, A., DuVall, S.L., Dymshyts, D., Bertolín, S.F., Fišter, K., Hardin, J., Hester, L., Hripcsak, G., Kent, S., Khosla, S., Kolovos, S., Lambert, C.G., ver der Lei, J., Londhe, A.A., Lynch, K.E., Makadia, R., Margulis, A.V., Matheny, M.E., Mehta, P., Morales, D.R., Morgan-Stewart, H., Mosseveld, M., Newby, D., Nyberg,F., Ostropolets, A., Park, R.W., Prats-Uribe, A., Rao, G.A., Reich, C., Reps, J., Rijnbeek, P., Sathappan, S.M.K., Schuemie, M., Seager, S., Sena, A., Shoaibi, A., Spotnitz, M., Suchard, M.A., Swerdel, J., Torre, C.O., Vizcaya, D., Wen, H., de Wilde, M., You, S.C., Zhang, L., Zhuk, O., Ryan, P., Prieto-Alhambra, D., 2020., Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study. medRxiv .
    1. Le Blanc K., Frassoni F., Ball L., Locatelli F., Roelofs H., Lewis I., Lanino E., Sundberg B., Bernardo M.E., Remberger M., Dini G., Egeler R.M., Bacigalupo A., Fibbe W., Ringdén O. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–1586.
    1. Lechien J.R., Chiesa-Estomba C.M., De Siati D.R., Horoi M., Le Bon S.D., Rodriguez A., Dequanter D., Blecic S., El Afia F., Distinguin L., Chekkoury-Idrissi Y., Hans S., Delgado I.L., Calvo-Henriquez C., Lavigne P., Falanga C., Barillari M.R., Cammaroto G., Khalife M., Leich P., Souchay C., Rossi C., Journe F., Hsieh J., Edjlali M., Carlier R., Ris L., Lovato A., De Filippis C., Coppee F., Fakhry N., Ayad T., Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur. Arch. Otorhinolaryngol. 2020 doi: 10.1007/s00405-020-05965-1.
    1. Lee D.A. Cellular therapy: Adoptive immunotherapy with expanded natural killer cells. Immunol. Rev. 2019;290:85–99.
    1. Lei, C., Fu, W., Qian, K., Li, T., Zhang, S., Ding, M., Hu, S., 2020. Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig. bioRxiv, 2020.2002.2001.929976.
    1. Leng Z., Zhu R., Hou W., Feng Y., Yang Y., Han Q., Shan G., Meng F., Du D., Wang S., Fan J., Wang W., Deng L., Shi H., Li H., Hu Z., Zhang F., Gao J., Liu H., Li X., Zhao Y., Yin K., He X., Gao Z., Wang Y., Yang B., Jin R., Stambler I., Lim L.W., Su H., Moskalev A., Cano A., Chakrabarti S., Min K.J., Ellison-Hughes G., Caruso C., Jin K., Zhao R.C. Transplantation of ACE2(-) mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis. 2020;11:216–228.
    1. Lew T.W.K., Kwek T.-K., Tai D., Earnest A., Loo S., Singh K., Kwan K.M., Chan Y., Yim C.F., Bek S.L., Kor A.C., Yap W.S., Chelliah Y.R., Lai Y.C., Goh S.-K. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290:374–380.
    1. Li H., Yang S.G., Gu L., Zhang Y., Yan X.X., Liang Z.A., Zhang W., Jia H.Y., Chen W., Liu M., Yu K.J., Xue C.X., Hu K., Zou Q., Li L.J., Cao B., Wang C. Effect of low-to-moderate-dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia. Influenza Other Respir. Viruses. 2017;11:345–354.
    1. Li J., Li D., Liu X., Tang S., Wei F. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats. J. Inflamm. (Lond) 2012;9:33.
    1. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454.
    1. Li Z., Wu M., Yao J., Guo J., Liao X., Song S., Li J., Duan G., Zhou Y., Wu X., Zhou Z., Wang T., Hu M., Chen X., Fu Y., Lei C., Dong H., Xu C., Hu Y., Han M., Zhou Y., Jia H., Chen X., Yan J. Caution on kidney dysfunctions of COVID-19 patients. medRxiv. 2020 2020.2002.2008.20021212.
    1. Li Z., Ge J., Yang M., Feng J., Qiao M., Jiang R., Bi J., Zhan G., Xu X., Wang L., Zhou Q., Zhou C., Pan Y., Liu S., Zhang H., Yang J., Zhu B., Hu Y., Hashimoto K., Jia Y., Wang H., Wang R., Liu C., Yang C. Vicarious traumatization in the general public, members, and non-members of medical teams aiding in COVID-19 control. Brain Behav. Immun. 2020 doi: 10.1016/j.bbi.2020.03.007.
    1. Lim H.S., Im J.S., Cho J.Y., Bae K.S., Klein T.A., Yeom J.S., Kim T.S., Choi J.S., Jang I.J., Park J.W. Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrob. Agents Chemother. 2009;53:1468–1475.
    1. Lin L., Jiang X., Zhang Z., Huang S., Zhang Z., Fang Z., Gu Z., Gao L., Shi H., Mai L., Liu Y., Lin X., Lai R., Yan Z., Li X., Shan H. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020 doi: 10.1136/gutjnl-2020-321013.
    1. Liu J., Cao R., Xu M., Wang X., Zhang H., Hu H., Li Y., Hu Z., Zhong W., Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.
    1. Liu, J., Liu, Y., Xiang, P., Pu, L., Xiong, H., Li, C., Zhang, M., Tan, J., Xu, Y., Song, R., Song, M., Wang, L., Zhang, W., Han, B., Yang, L., Wang, X., Zhou, G., Zhang, T., Li, B., Wang, Y., Chen, Z., Wang, X., 2020b. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. medRxiv, 2020.2002.2010.20021584.
    1. Liu K., Fang Y.Y., Deng Y., Liu W., Wang M.F., Ma J.P., Xiao W., Wang Y.N., Zhong M.H., Li C.H., Li G.C., Liu H.G. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin. Med. J. (Engl). 2020 doi: 10.1097/CM9.0000000000000744.
    1. Liu Y., Yang Y., Zhang C., Huang F., Wang F., Yuan J., Wang Z., Li J., Li J., Feng C., Zhang Z., Wang L., Peng L., Chen L., Qin Y., Zhao D., Tan S., Yin L., Xu J., Zhou C., Jiang C., Liu L. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci. China Life Sci. 2020;63:364–374.
    1. Liu Y.J. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 2005;23:275–306.
    1. Loutfy M.R., Blatt L.M., Siminovitch K.A., Ward S., Wolff B., Lho H., Pham D.H., Deif H., LaMere E.A., Chang M., Kain K.C., Farcas G.A., Ferguson P., Latchford M., Levy G., Dennis J.W., Lai E.K., Fish E.N. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA. 2003;290:3222–3228.
    1. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., Zhou H., Hu Z., Zhou W., Zhao L., Chen J., Meng Y., Wang J., Lin Y., Yuan J., Xie Z., Ma J., Liu W.J., Wang D., Xu W., Holmes E.C., Gao G.F., Wu G., Chen W., Shi W., Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–574.
    1. Luke T., Wu H., Zhao J., Channappanavar R., Coleman C.M., Jiao J.A., Matsushita H., Liu Y., Postnikova E.N., Ork B.L., Glenn G., Flyer D., Defang G., Raviprakash K., Kochel T., Wang J., Nie W., Smith G., Hensley L.E., Olinger G.G., Kuhn J.H., Holbrook M.R., Johnson R.F., Perlman S., Sullivan E., Frieman M.B. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci. Transl. Med. 2016;8:326ra321.
    1. Lutz H.U., Stammler P., Jelezarova E., Nater M., Späth P.J. High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn-IgG complexes. Blood. 1996;88:184–193.
    1. Lv F.-J., Tuan R.S., Cheung K.M.C., Leung V.Y.L. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014;32:1408–1419.
    1. Mair-Jenkins J., Saavedra-Campos M., Baillie J.K., Cleary P., Khaw F.M., Lim W.S., Makki S., Rooney K.D., Nguyen-Van-Tam J.S., Beck C.R. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J. Infect. Dis. 2015;211:80–90.
    1. Mak, E. March 18, 2020. China approves first homegrown COVID-19 vaccine to enter clinical trials. .
    1. Mao, L., Wang, M., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Li, Y., Jin, H., Hu, B., 2020. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv, 2020.2002.2022.20026500.
    1. Marchalonis J.J., Kaymaz H., Dedeoglu F., Schluter S.F., Yocum D.E., Edmundson A.B. Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain. Proc. Natl. Acad. Sci. USA. 1992;89:3325–3329.
    1. May J.M., Harrison F.E. Role of vitamin C in the function of the vascular endothelium. Antioxid. Redox. Signal. 2013;19:2068–2083.
    1. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034.
    1. Mei S.H.J., Haitsma J.J., Dos Santos C.C., Deng Y., Lai P.F.H., Slutsky A.S., Liles W.C., Stewart D.J. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am. J. Respir. Crit. Care Med. 2010;182:1047–1057.
    1. Microft-West, C., Su, D., Elli, S., Guimond, S., Miller, G., Turnbull, J., Yates, E., Guerrini, M., Fernig, D., Lima, M., Skidmore, M., 2020. The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 receptor domain undergoes conformational change upon heparin binding. bioRxiv doi:10.1101/2020.02.29.971093.
    1. Minagawa H., Takenaka A., Mohri S., Mori R. Protective effect of recombinant murine interferon beta against mouse hepatitis virus infection. Antiviral Res. 1987;8:85–95.
    1. Moderna. Press release at March 16, 2020a. Moderna announces first participant dosed in NIH-led phase 1 study of mRNA vaccine (mRNA-1273) against novel coronavirus. .
    1. Moderna. Press release at April 16, 2020b. Moderna announces award from U.S. government agency BARDA for up to $483 million to accelerate development of mRNA vaccine (mRNA-1273) against novel coronavirus. .
    1. Mohammed B.M., Fisher B.J., Kraskauskas D., Farkas D., Brophy D.F., Fowler A.A., 3rd, Natarajan R. Vitamin C: a novel regulator of neutrophil extracellular trap formation. Nutrients. 2013;5:3131–3151.
    1. Munster V.J., Koopmans M., van Doremalen N., van Riel D., de Wit E. A novel coronavirus emerging in China - key questions for impact assessment. N. Engl. J. Med. 2020;382:692–694.
    1. Nakano K., Suzuki S. Stress-induced change in tissue levels of ascorbic acid and histamine in rats. J. Nutr. 1984;114:1602–1608.
    1. National Health and Family Planning Commission of China (NHPFC). March 04, 2020. Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th edition). .
    1. National Institutes of Health (NIH). March 16, 2020. NIH clinical trial of investigational vaccine for COVID-19 begins. . .
    1. Nishimoto N., Kishimoto T., Yoshizaki K. Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann. Rhum. Dis. 2000;59(Suppl 1):i21–i27.
    1. Novavax, Press Release April 08, 2020. Novavax identifies coronavirus vaccine candidate: accelerates initiation of first-in-human trial to mid-May. .
    1. O'Shea J.J., Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36:542–550.
    1. Oestereich L., Lüdtke A., Wurr S., Rieger T., Muñoz-Fontela C., Günther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014;105:17–21.
    1. Oudemans-van Straaten H.M., Spoelstra-de Man A.M., de Waard M.C. Vitamin C revisited. Crit. Care. 2014;18:460.
    1. Painter G.R., Bowen R.A., Bluemling G.R., DeBergh J., Edpuganti V., Gruddanti P.R., Guthrie D.B., Hager M., Kuiper D.L., Lockwood M.A., Mitchell D.G., Natchus M.G., Sticher Z.M., Kolykhalov A.A. The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection. Antiviral Res. 2019;171
    1. Pan X.W., Xu D., Zhang H., Zhou W., Wang L.H., Cui X.G. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Med. 2020 doi: 10.1007/s00134-020-06026-1.
    1. Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 2018;18:134–147.
    1. Parkin J., Cohen B. An overview of the immune system. Lancet. 2001;357:1777–1789.
    1. Pepke-Zaba J., Higenbottam T.W., Dinh-Xuan A.T., Stone D., Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet. 1991;338:1173–1174.
    1. Pfefferbaum B., North C.S. Mental Health and the Covid-19 pandemic. N. Eng. J. Med. 2020 doi: 10.1056/NEJMp2008017.
    1. Prasad A.S. Zinc in human health: effect of zinc on immune cells. Mol. Med. 2008;14:353–357.
    1. Prevosto C., Zancolli M., Canevali P., Zocchi M.R., Poggi A. Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica. 2007;92:881–888.
    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 doi: 10.1093/cid/ciaa248.
    1. Raimondo M.G., Biggioggero M., Crotti C., Becciolini A., Favalli E.G. Profile of sarilumab and its potential in the treatment of rheumatoid arthritis. Drug Des. Devel. Ther. 2017;11:1593–1603.
    1. Regeneron. March 16, 2020. REGENERON AND SANOFI BEGIN GLOBAL KEVZARA® (SARILUMAB) CLINICAL TRIAL PROGRAM IN PATIENTS WITH SEVERE COVID-19. .
    1. Ren J.L., Zhang A.H., Wang X.J. Traditional Chinese medicine for COVID-19 treatment. Pharmacol. Res. 2020;155
    1. Reynard O., Nguyen X.N., Alazard-Dany N., Barateau V., Cimarelli A., Volchkov V.E. Identification of a new ribonucleoside inhibitor of Ebola Virus replication. Viruses. 2015;7:6233–6240.
    1. Rhen T., Cidlowski J.A. Antiinflammatory action of glucocorticoids–new mechanisms for old drugs. N. Engl. J. Med. 2005;353:1711–1723.
    1. Richardson P., Griffin I., Tucker C., Smith D., Oechsle O., Phelan A., Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395:e30–e31.
    1. Roback J.D., Guarner J. Convalescent plasma to treat COVID-19: possibilities and challenges. JAMA. 2020 doi: 10.1001/jama.2020.4940.
    1. Routley, N. April 01, 2020. Every vaccine and treatment in development for COVID-19, so far. .
    1. Ruan, Q., Yang, K., Wang, W., Jiang, L., Song, J., 2020. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. doi: 10.1007/s00134-020-05991-x.
    1. Runfeng L., Yunlong H., Jicheng H., Weiqi P., Qinhai M., Yongxia S., Chufang L., Jin Z., Zhenhua J., Haiming J., Kui Z., Shuxiang H., Jun D., Xiaobo L., Xiaotao H., Lin W., Nanshan Z., Zifeng Y. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2) Pharmacol. Res. 2020 doi: 10.1016/j.phrs.2020.104761. 104761.
    1. Sainz B., Jr., Mossel E.C., Peters C.J., Garry R.F. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) Virology. 2004;329:11–17.
    1. Sakkas L.I. Spotlight on tocilizumab and its potential in the treatment of systemic sclerosis. Drug Des. Devel. Ther. 2016;10:2723–2728.
    1. Saura M., Zaragoza C., McMillan A., Quick R.A., Hohenadl C., Lowenstein J.M., Lowenstein C.J. An antiviral mechanism of nitric oxide: inhibition of a viral protease. Immunity. 1999;10:21–28.
    1. Savarino A., Boelaert J.R., Cassone A., Majori G., Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect. Dis. 2003;3:722–727.
    1. Savarino A., Di Trani L., Donatelli I., Cauda R., Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect. Dis. 2006;6:67–69.
    1. Schmidt H.H., Walter U. NO at work. Cell. 1994;78:919–925.
    1. Schoeman D., Fielding B.C. Coronavirus envelope protein: current knowledge. Virol J. 2019;16:69.
    1. ScienceDaily. April 02, 2020. COVID-19 vaccine candidate shows promise, research shows. .
    1. Sen G.C. Viruses and interferons. Annu Rev Microbiol. 2001;55:255–281.
    1. Sheahan T.P., Sims A.C., Graham R.L., Menachery V.D., Gralinski L.E., Case J.B., Leist S.R., Pyrc K., Feng J.Y., Trantcheva I., Bannister R., Park Y., Babusis D., Clarke M.O., Mackman R.L., Spahn J.E., Palmiotti C.A., Siegel D., Ray A.S., Cihlar T., Jordan R., Denison M.R., Baric R.S. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med. 2017;9:eaal3653.
    1. Sheahan, T.P., Sims, A.C., Zhou, S., Graham, R.L., Pruijssers, A.J., Agostini, M.L., Leist, S.R., Schäfer, A., Dinnon, K.H., Stevens, L.J., Chappell, J.D., Lu, X., Hughes, T.M., George, A.S., Hill, C.S., Montgomery, S.A., Brown, A.J., Bluemling, G.R., Natchus, M.G., Saindane, M., Kolykhalov, A.A., Painter, G., Harcourt, J., Tamin, A., Thornburg, N.J., Swanstrom, R., Denison, M.R., Baric, R.S., 2020. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med. 2020 Apr 6. doi: 10.1126/scitranslmed.abb5883.
    1. Shi Y., Wang J., Yang Y., Wang Z., Wang G., Hashimoto K., Zhang K., Liu H. Knowledge and attitudes of medical staff in Chinese psychiatric hospitals regarding COVID-19. Brain Behav. Immun. Health. 2020;4
    1. Shi Y., Wang N., Zou Q.M. Progress and challenge of vaccine development against 2019 novel coronavirus (2019-nCoV) Zhonghua Yu Fang Yi Xue Za Zhi. 2020;54:E029.
    1. Shimabukuro-Vornhagen A., Gödel P., Subklewe M., Stemmler H.J., Schlößer H.A., Schlaak M., Kochanek M., Böll B., von Bergwelt-Baildon M.S. Cytokine release syndrome. J. Immunother. Cancer. 2018;6:56.
    1. Siegel D., Hui H.C., Doerffler E., Clarke M.O., Chun K., Zhang L., Neville S., Carra E., Lew W., Ross B., Wang Q., Wolfe L., Jordan R., Soloveva V., Knox J., Perry J., Perron M., Stray K.M., Barauskas O., Feng J.Y., Xu Y., Lee G., Rheingold A.L., Ray A.S., Bannister R., Strickley R., Swaminathan S., Lee W.A., Bavari S., Cihlar T., Lo M.K., Warren T.K., Mackman R.L. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. J. Med. Chem. 2017;60:1648–1661.
    1. Siemieniuk R.A.C., Meade M.O., Alonso-Coello P., Briel M., Evaniew N., Prasad M., Alexander P.E., Fei Y., Vandvik P.O., Loeb M., Guyatt G.H. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann. Intern. Med. 2015;163:519–528.
    1. Sissoko D., Laouenan C., Folkesson E., M'Lebing A.B., Beavogui A.H., Baize S., Camara A.M., Maes P., Shepherd S., Danel C., Carazo S., Conde M.N., Gala J.L., Colin G., Savini H., Bore J.A., Le Marcis F., Koundouno F.R., Petitjean F., Lamah M.C., Diederich S., Tounkara A., Poelart G., Berbain E., Dindart J.M., Duraffour S., Lefevre A., Leno T., Peyrouset O., Irenge L., Bangoura N., Palich R., Hinzmann J., Kraus A., Barry T.S., Berette S., Bongono A., Camara M.S., Chanfreau Munoz V., Doumbouya L., Souley H., Kighoma P.M., Koundouno F.R., Réné L., Loua C.M., Massala V., Moumouni K., Provost C., Samake N., Sekou C., Soumah A., Arnould I., Komano M.S., Gustin L., Berutto C., Camara D., Camara F.S., Colpaert J., Delamou L., Jansson L., Kourouma E., Loua M., Malme K., Manfrin E., Maomou A., Milinouno A., Ombelet S., Sidiboun A.Y., Verreckt I., Yombouno P., Bocquin A., Carbonnelle C., Carmoi T., Frange P., Mely S., Nguyen V.K., Pannetier D., Taburet A.M., Treluyer J.M., Kolie J., Moh R., Gonzalez M.C., Kuisma E., Liedigk B., Ngabo D., Rudolf M., Thom R., Kerber R., Gabriel M., Di Caro A., Wölfel R., Badir J., Bentahir M., Deccache Y., Dumont C., Durant J.F., El Bakkouri K., Gasasira Uwamahoro M., Smits B., Toufik N., Van Cauwenberghe S., Ezzedine K., D'Ortenzio E., Pizarro L., Etienne A., Guedj J., Fizet A., de Sainte Barte, Fare E., Murgue B., Tran-Minh T., Rapp C., Piguet P., Poncin M., Draguez B., Allaford Duverger T., Barbe S., Baret G., Defourny I., Carroll M., Raoul H., Augier A., Eholie S.P., Yazdanpanah Y., Levy-Marchal C., Antierrens A., Van Herp M., Günther S., de Lamballerie X., Keïta S., Mentre F., Anglaret X., Malvy D. Experimental treatment with favipiravir for Ebola Virus disease (the JIKI Trial): A historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016;13
    1. Smither S.J., Eastaugh L.S., Steward J.A., Nelson M., Lenk R.P., Lever M.S. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014;104:153–155.
    1. Sperber S.J., Hayden F.G. Comparative susceptibility of respiratory viruses to recombinant interferons-alpha 2b and -beta. J. Interferon Res. 1989;9:285–293.
    1. Stockman L.J., Bellamy R., Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3
    1. Strabelli, T.M.V., Uip, D.E., 2020. COVID-19 and the Heart. Arq. Bras. Cardiol. doi: 10.36660/abc.20200209.
    1. Ströher U., DiCaro A., Li Y., Strong J.E., Aoki F., Plummer F., Jones S.M., Feldmann H. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha. J. Infect. Dis. 2004;189:1164–1167.
    1. Su S., Wong G., Shi W., Liu J., Lai A.C.K., Zhou J., Liu W., Bi Y., Gao G.F. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24:490–502.
    1. Sun J., Xue Q., Guo L., Cui L., Wang J. Xuebijing protects against lipopolysaccharide-induced lung injury in rabbits. Exp. Lung Res. 2010;36:211–218.
    1. Tan E.L., Ooi E.E., Lin C.Y., Tan H.C., Ling A.E., Lim B., Stanton L.W. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg. Infect. Dis. 2004;10:581–586.
    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb. Haemost. 2020;18:844–847.
    1. Tang N., Bai H., Chen X., Gong J., Li D., Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J. Thromb. Haemost. 2020 doi: 10.1111/jth.14817.
    1. te Velthuis A.J.W., van den Worm S.E.V., Sims A.C., Baric R.S., Snijder E.J., van Hemert M.J. Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6
    1. Thickett D.R., Armstrong L., Christie S.J., Millar A.B. Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 2001;164:1601–1605.
    1. Third People's Hospital of Shenzhen. February 14, 2020. Familavir is more effective than Lopinavir/ritonavir in the treatment of COVID-19 (in Chinese). .
    1. Thompson B.T. Glucocorticoids and acute lung injury. Crit. Care Med. 2003;31:S253–S257.
    1. Toots M., Yoon J.-J., Cox R.M., Hart M., Sticher Z.M., Makhsous N., Plesker R., Barrena A.H., Reddy P.G., Mitchell D.G., Shean R.C., Bluemling G.R., Kolykhalov A.A., Greninger A.L., Natchus M.G., Painter G.R., Plemper R.K. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci. Transl. Med. 2019;11:eaax5866.
    1. van den Borne B.E., Dijkmans B.A., de Rooij H.H., le Cessie S., Verweij C.L. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J. Rheumatol. 1997;24:55–60.
    1. Monteil V., Kwon H., Prado P., Hagelkrüys A., Wimmer R.A., Stahl M., Leopoldi A., Garreta E., Del Pozo C.H., Prosper F., Romero J.P., Wirnsberger G., Zhang H., Slutsky A.S., Conder R., Montserrat N., Mirazimi A., Penninger J.M. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020 doi: 10.1016/j.cell.2020.04.004.
    1. Vivier E., Tomasello E., Baratin M., Walzer T., Ugolini S. Functions of natural killer cells. Nat. Immunol. 2008;9:503–510.
    1. Wajanaponsan N., Cheng S.-F. Acute renal failure resulting from intravenous immunoglobulin therapy. Hawaii Med. J. 2004;63:266–267.
    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., 2020a. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel coronavirus-infected pneumonia in Wuhan, China. JAMA doi: 10.1001/jama.2020.1585.
    1. Wang F., Nie J., Wang H., Zhao Q., Xiong Y., Deng L., Song S., Ma Z., Mo P., Zhang Y. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J. Infect. Dis. 2020 doi: 10.1093/infdis/jiaa150.
    1. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M., Shi Z., Hu Z., Zhong W., Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30:269–271.
    1. Wang P., Song Y., Liu Z., Wang H., Zheng W., Liu S., Feng Z., Zhai J., Yao C., Ren M., Bai C., Shang H. Xuebijing injection in the treatment of severe pneumonia: study protocol for a randomized controlled trial. Trials. 2016;17:142.
    1. Weiss S.J. Tissue destruction by neutrophils. N. Engl. J. Med. 1989;320:365–376.
    1. World Health Organization(WHO). December 31, 2003. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. .
    1. World Health Organization(WHO). March 12, 2020a. Coronavirus disease 2019 (COVID-19) situation report – 52. .
    1. World Health Organization(WHO). March 30, 2020b. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). .
    1. Wilson J.X. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid. Redox. Signal. 2013;19:2129–2140.
    1. Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O., Graham B.S., McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–1263.
    1. Wu, Y., Xu, X., Chen, Z., Duan, J., Hashimoto, K., Yang, L., Liu, C., Yang, C., 2020.Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav. Immun. doi: 10.1016/j.bbi.2020.03.031.
    1. Xie H., Zhao J., Lian N., Lin S., Xie Q., Zhuo H. Clinical characteristics of Non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A Retrospective study. Liver Int. 2020 doi: 10.1111/liv.14449.
    1. Xu D.M., Ma X.H., Ai Y.H. Effect of Xuebijing injection pretreatment on expression of pulmonary surfactant-associated protein A in rat alveolar type II epithelial cells induced by lipopolysaccharide. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2009;21:690–691.
    1. Xu J., Woods C.R., Mora A.L., Joodi R., Brigham K.L., Iyer S., Rojas M. Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Am. J. Physiol. Lung Cell Mol. Physiol. 2007;293:L131–L141.
    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. Yagi T., Asakawa A., Ueda H., Ikeda S., Miyawaki S., Inui A. The role of zinc in the treatment of taste disorders. Recent Pat. Food Nutr. Agric. 2013;5:44–51.
    1. Yan Y., Zou Z., Sun Y., Li X., Xu K.F., Wei Y., Jin N., Jiang C. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res. 2013;23:300–302.
    1. Yang, X., Yu, Y., Xu, J., Shu, H., Xia, J.a., Liu, H., Wu, Y., Zhang, L., Yu, Z., Fang, M., Yu, T., Wang, Y., Pan, S., Zou, X., Yuan, S., Shang, Y., 2020. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. doi: 10.1016/S2213-2600(20)30079-5.
    1. Yao X.H., Li T.Y., He Z.C., Ping Y.F., Liu H.W., Yu S.C., Mou H.M., Wang L.H., Zhang H.R., Fu W.J., Luo T., Liu F., Chen C., Xiao H.L., Guo H.T., Lin S., Xiang D.F., Shi Y., Li Q.R., Huang X., Cui Y., Li X.Z., Tang W., Pan P.F., Huang X.Q., Ding Y.Q., Bian X.W. A pathological report of three COVID-19 cases by minimally invasive autopsies. Zhonghua Bing Li Xue Za Zhi. 2020;49:E009.
    1. Yin S., Huang M., Li D., Tang N. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J. Thromb. Thrombolysis. 2020 doi: 10.1007/s11239-020-02105-8.
    1. Zhang S.W., Sun C.D., Wen Y., Yin C.H. Effect of treatment with Xuebijing injection on serum inflammatory mediators and Th1/2 of spleen in rats with sepsis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006;18:673–676.
    1. Zhao, Y., Zhao, Z., Wang, Y., Zhou, Y., Ma, Y., Zuo, W., 2020. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv, 2020.2001.2026.919985.
    1. Zhang Y., Zheng L., Liu L., Zhao M., Xiao J., Zhao Q. Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single center in Wuhan city, China. Liver Int. 2020 doi: 10.1111/liv.14455.
    1. Zhang K., Zhou X., Liu H., Hashimoto K. Treatment concerns for psychiatric symptoms in COVID-19-infected patients with or without psychiatric disorders. Br. J. Psychiatry. 2020 doi: 10.1192/bjp.2020.84.
    1. Zheng G., Huang L., Tong H., Shu Q., Hu Y., Ge M., Deng K., Zhang L., Zou B., Cheng B., Xu J. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study. Respir. Res. 2014;15:39.
    1. Zheng, M., Gao, Y., Wang, G., Song, G., Liu, S., Sun, D., Xu, Y., Tian, Z., 2020. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol. Immunol. doi: 10.1038/s4123-020-0402.
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.
    1. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., Chen H.D., Chen J., Luo Y., Guo H., Jiang R.D., Liu M.Q., Chen Y., Shen X.R., Wang X., Zheng X.S., Zhao K., Chen Q.J., Deng F., Liu L.L., Yan B., Zhan F.X., Wang Y.Y., Xiao G.F., Shi Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273.
    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R., Niu P., Zhan F., Ma X., Wang D., Xu W., Wu G., Gao G.F., Tan W. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733.

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