A Review of SARS-CoV-2 and the Ongoing Clinical Trials

Yung-Fang Tu, Chian-Shiu Chien, Aliaksandr A Yarmishyn, Yi-Ying Lin, Yung-Hung Luo, Yi-Tsung Lin, Wei-Yi Lai, De-Ming Yang, Shih-Jie Chou, Yi-Ping Yang, Mong-Lien Wang, Shih-Hwa Chiou, Yung-Fang Tu, Chian-Shiu Chien, Aliaksandr A Yarmishyn, Yi-Ying Lin, Yung-Hung Luo, Yi-Tsung Lin, Wei-Yi Lai, De-Ming Yang, Shih-Jie Chou, Yi-Ping Yang, Mong-Lien Wang, Shih-Hwa Chiou

Abstract

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

Keywords: ACE2; COVID-19; SARS-CoV-2; clinical trials; immunotherapy; pneumonia; replicase; vaccine.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of symptomatic, radiological and laboratory characteristics of COVID-19.
Figure 2
Figure 2
Overview of the repurposed therapeutic drugs undergoing clinical trial against COVID-19 in the context of host pathways and virus replication mechanisms.

References

    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323:1061. doi: 10.1001/jama.2020.1585.
    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.S., et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New Engl. J. Med. 2020 doi: 10.1056/NEJMoa2002032.
    1. Chan J.F.-W., Yuan S., Kok K.-H., To K.K.-W., Chu H., Yang J., Xing F., Liu J., Yip C.C.-Y., Poon R.W.-S., et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet. 2020;395:514–523. doi: 10.1016/S0140-6736(20)30154-9.
    1. Paraskevis D., Kostaki E., Magiorkinis G., Panayiotakopoulos G., Sourvinos G., Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect. Genet. Evol. 2020;79:104212. doi: 10.1016/j.meegid.2020.104212.
    1. Hindson J. COVID-19: Faecal–oral transmission? Nat. Rev. Gastroenterol. Hepatol. 2020:1. doi: 10.1038/s41575-020-0295-7.
    1. Xu Y., Li X., Zhu B., Liang H., Fang C., Gong Y., Guo Q., Sun X., Zhao D., Shen J., et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat. Med. 2020:1–4. doi: 10.1038/s41591-020-0817-4.
    1. Mao L., Wang M., Chen S., He Q., Chang J., Hong C., Zhou Y., Wang D., Miao X., Hu Y., et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study. Ssrn Electron. J. 2020 doi: 10.2139/ssrn.3544840.
    1. Zu Z.Y., Di Jiang M., Xu P.P., Chen W., Ni Q., Lua G., Zhang L.J. Coronavirus Disease 2019 (COVID-19): A Perspective from China. Radiology. 2020:200490. doi: 10.1148/radiol.2020200490.
    1. Malainou C., Herold S. Influenza. Internist. 2019;60:1127–1135. doi: 10.1007/s00108-019-00670-6.
    1. De Wit E., Van Doremalen N., Falzarano D., Munster V. SARS and MERS: Recent insights into emerging coronaviruses. Nat. Rev. Genet. 2016;14:523–534. doi: 10.1038/nrmicro.2016.81.
    1. Hui D.S., Zumla A. Severe Acute Respiratory Syndrome. Infect. Dis. Clin. North Am. 2019;33:869–889. doi: 10.1016/j.idc.2019.07.001.
    1. Chan J.F.-W., Lau S.K., To K.K.-W., Cheng V.C.C., Woo P.C., Yuen K.-Y. Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease. Clin. Microbiol. Rev. 2015;28:465–522. doi: 10.1128/CMR.00102-14.
    1. Chan J.F.-W., Li K.S., To K.K.-W., Cheng V.C., Chen H., Yuen K.-Y. Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J. Infect. 2012;65:477–489. doi: 10.1016/j.jinf.2012.10.002.
    1. Kanne J.P. Chest CT Findings in 2019 Novel Coronavirus (2019-nCoV) Infections from Wuhan, China: Key Points for the Radiologist. Radiology. 2020;295:16–17. doi: 10.1148/radiol.2020200241.
    1. Kim H. Outbreak of novel coronavirus (COVID-19): What is the role of radiologists? Eur. Radiol. 2020:1–2. doi: 10.1007/s00330-020-06748-2.
    1. Lee K.S. Pneumonia Associated with 2019 Novel Coronavirus: Can Computed Tomographic Findings Help Predict the Prognosis of the Disease? Korean J. Radiol. 2020;21:257–258. doi: 10.3348/kjr.2020.0096.
    1. Pan F., Ye T., Sun P., Gui S., Liang B., Li L., Zheng D., Wang J., Hesketh R.L., Yang L., et al. Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia. Radiolpgy. 2020:200370. doi: 10.1148/radiol.2020200370.
    1. Chung M., Bernheim A., Mei X., Zhang N., Huang M., Zeng X., Cui J., Xu W., Yang Y., Fayad Z.A., et al. CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) Radiology. 2020;295:202–207. doi: 10.1148/radiol.2020200230.
    1. Song F., Shi N., Shan F., Zhang Z., Shen J., Lu H., Ling Y., Jiang Y., Shi Y. Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020;295:210–217. doi: 10.1148/radiol.2020200274.
    1. Pan Y., Guan H., Zhou S., Wang Y., Li Q., Zhu T., Hu Q., Xia L. Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): A study of 63 patients in Wuhan, China. Eur. Radiol. 2020:1–4. doi: 10.1007/s00330-020-06731-x.
    1. Shi H., Han X., Jiang N., Cao Y., Alwalid O., Gu J., Fan Y., Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: A descriptive study. Lancet Infect. Dis. 2020;20:425–434. doi: 10.1016/S1473-3099(20)30086-4.
    1. Lan L., Xu D., Ye G., Xia C., Wang S., Li Y., Xu H. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. 2020 doi: 10.1001/jama.2020.2783.
    1. Lam T.T.-Y., Shum M.H.-H., Zhu H.-C., Tong Y.-G., Ni X.-B., Liao Y.-S., Wei W., Cheung W.Y.-M., Li W.-J., Li L.-F., et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature. 2020:1–6. doi: 10.1038/s41586-020-2169-0.
    1. Yu I.T., Li Y., Wong T.-W., Tam W.W.S., Chan A., Lee J.H., Leung D., Ho T. Evidence of Airborne Transmission of the Severe Acute Respiratory Syndrome Virus. New Engl. J. Med. 2004;350:1731–1739. doi: 10.1056/NEJMoa032867.
    1. Van Doremalen N., Bushmaker T., Morris D.H., Holbrook M.G., Gamble A., Williamson B.N., Tamin A., Harcourt J.L., Thornburg N.J., Gerber S.I., et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. New Engl. J. Med. 2020 doi: 10.1056/NEJMc2004973.
    1. Lauer S.A., Grantz K.H., Bi Q., Jones F.K., Zheng Q., Meredith H.R., Azman A.S., Reich N.G., Lessler J. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann. Intern. Med. 2020 doi: 10.7326/M20-0504.
    1. Zhang T., Wu Q., Zhang Z. Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak. Curr. Boil. 2020;30:1346–1351. doi: 10.1016/j.cub.2020.03.022.
    1. Müller N.L., Ooi G.C., Khong P.-L., Nicolaou S. Severe Acute Respiratory Syndrome: Radiographic and CT Findings. Am. J. Roentgenol. 2003;181:3–8. doi: 10.2214/ajr.181.1.1810003.
    1. Paul N., Roberts H., Butany J., Chung T., Gold W., Mehta S., Konen E., Rao A., Provost Y., Hong H.H., et al. Radiologic Pattern of Disease in Patients with Severe Acute Respiratory Syndrome: The Toronto Experience. Radiographics. 2004;24:553–563. doi: 10.1148/rg.242035193.
    1. Lee E.Y.P., Ng M.-Y., Khong P.-L. COVID-19 pneumonia: What has CT taught us? Lancet Infect. Dis. 2020;20:384–385. doi: 10.1016/S1473-3099(20)30134-1.
    1. Das K.M., Lee E.Y., Langer R.D., Larsson S.G. Middle East Respiratory Syndrome Coronavirus: What Does a Radiologist Need to Know? Am. J. Roentgenol. 2016;206:1193–1201. doi: 10.2214/AJR.15.15363.
    1. Gu J., Han B., Wang J. COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission. Gastroenterology. 2020 doi: 10.1053/j.gastro.2020.02.054.
    1. Pan Y., Zhang D., Yang P., Poon L.L.M., Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect. Dis. 2020;20:411–412. doi: 10.1016/S1473-3099(20)30113-4.
    1. Pyrc K., Dijkman R., Deng L., Jebbink M.F., Ross H.A., Berkhout B., Van Der Hoek L. Mosaic Structure of Human Coronavirus NL63, One Thousand Years of Evolution. J. Mol. Boil. 2006;364:964–973. doi: 10.1016/j.jmb.2006.09.074.
    1. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.-H., Nitsche A., et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 doi: 10.1016/j.cell.2020.02.052.
    1. Cao Y., Li L., Feng Z., Wan S., Huang P., Sun X., Wen F., Huang X., Ning G., Wang W. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020;6:1–4. doi: 10.1038/s41421-020-0147-1.
    1. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., Huan Y., Yang P., Zhang Y., Deng W., et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat. Med. 2005;11:875–879. doi: 10.1038/nm1267.
    1. Guo L., Ren L., Yang S., Xiao M., Chang D., Yang F., Cruz C.S.D., Wang Y., Wu C., Xiao Y., et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19) Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa310.
    1. Hicks P., Cooper D.J. The Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit. care Resusc. J. Australas. Acad. Crit. Care Med. 2008;10:304–377.
    1. Siegel D., Hui H.C., Doerffler E., Clarke M.O., Chun K., Zhang L., Neville S., Carra E., Lew W., Ross B., et al. 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. doi: 10.1021/acs.jmedchem.6b01594.
    1. Mulangu S., Dodd L.E., Davey R.T., Jr., Tshiani Mbaya O., Proschan M., Mukadi D., Lusakibanza Manzo M., Nzolo D., Tshomba Oloma A., Ibanda A., et al. A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med. 2019;381:2293–2303. doi: 10.1056/NEJMoa1910993.
    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., et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med. 2017;9:eaal3653. doi: 10.1126/scitranslmed.aal3653.
    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., et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018;9 doi: 10.1128/mBio.00221-18.
    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. doi: 10.1038/s41422-020-0282-0.
    1. Holshue M.L., DeBolt C., Lindquist S., Lofy K.H., Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., et al. First Case of 2019 Novel Coronavirus in the United States. New Engl. J. Med. 2020;382:929–936. doi: 10.1056/NEJMoa2001191.
    1. Furuta Y., Komeno T., Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad. Ser. B. 2017;93:449–463. doi: 10.2183/pjab.93.027.
    1. Wagstaff K.M., Sivakumaran H., Heaton S.M., Harrich D., Jans D.A. Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem. J. 2012;443:851–856. doi: 10.1042/BJ20120150.
    1. Yang S.N.Y., Atkinson S.C., Wang C., Lee A., Bogoyevitch M.A., Borg N.A., Jans D.A. The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer. Antivir. Res. 2020:104760. doi: 10.1016/j.antiviral.2020.104760.
    1. Caly L., Wagstaff K., Jans D.A. Nuclear trafficking of proteins from RNA viruses: Potential target for antivirals? Antivir. Res. 2012;95:202–206. doi: 10.1016/j.antiviral.2012.06.008.
    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. Antivir. Res. 2020:104787. doi: 10.1016/j.antiviral.2020.104787.
    1. Chu C.-M., Cheng V.C.C., Hung I.F.N., Wong M.M.L., Chan K., Kao R.Y., Poon L.L.M., Wong C.L.P., Guan Y., Peiris J.S.M., et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax. 2004;59:252–256. doi: 10.1136/thorax.2003.012658.
    1. De Wilde A.H., Jochmans D., Posthuma C.C., Zevenhoven-Dobbe J.C., Van Nieuwkoop S., Bestebroer T.M., Hoogen B.G.V.D., Neyts J., Snijder E.J. Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture. Antimicrob. Agents Chemother. 2014;58:4875–4884. doi: 10.1128/AAC.03011-14.
    1. Chan J.F., Yao Y., Yeung M.L., Deng W., Bao L., Jia L., Li F., Xiao C., Gao H., Yu P., et al. Treatment with Lopinavir/Ritonavir or Interferon-beta1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J. Infect. Dis. 2015;212:1904–1913. doi: 10.1093/infdis/jiv392.
    1. Chan K.S., Lai S.T., Chu C.M., Tsui E., Tam C.Y., Wong M.M.L., Tse M.W., Que T.L., Peiris J.S.M., Sung J., et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: A multicentre retrospective matched cohort study. Hong Kong Med. J. 2003;9:399–406.
    1. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., Ruan L., Song B., Cai Y., Wei M., et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New Engl. J. Med. 2020 doi: 10.1056/NEJMoa2001282.
    1. Vanessa Monteil H.K., Patricia P., Astrid H., Reiner A., Wimmer M.S., Alexandra L., Elena G., Carmen H.P., Felipe P., Romero J.P., et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell Press. 2020 doi: 10.1016/j.cell.2020.04.004.
    1. Khan A., Benthin C., Zeno B., Albertson T.E., Boyd J., Christie J.D., Hall R., Poirier G., Ronco J.J., Tidswell M., et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit. Care. 2017;21:234. doi: 10.1186/s13054-017-1823-x.
    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. doi: 10.1016/S1473-3099(03)00806-5.
    1. Vincent M.J., Bergeron É., Benjannet S., Erickson B.R., Rollin P., Ksiazek T.G., Seidah N.G., Nichol S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J. 2005;2:69. doi: 10.1186/1743-422X-2-69.
    1. Gautret P., Lagier J.-C., Parola P., Hoang V.T., Meddeb L., Mailhe M., Doudier B., Courjon J., Giordanengo V., Vieira V.E., et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents. 2020:105949. doi: 10.1016/j.ijantimicag.2020.105949.
    1. Molina J.M., Delaugerre C., Goff J.L., Mela-Lima B., Ponscarme D., Goldwirt L., de Castro N. No benefit of hydroxychloroquine and azithromycin in people hospitalised with COVID-19. Med. Mal. Infect. 2020 doi: 10.1016/j.medmal.2020.03.006.
    1. Kadam R.U., Wilson I.A. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc. Natl. Acad. Sci. USA. 2016;114:206–214. doi: 10.1073/pnas.1617020114.
    1. Chen C., Huang J., Cheng Z., Wu J., Chen S., Zhang Y., Chen B., Lu M., Luo Y., Zhang J., et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. medRxiv. 2020 doi: 10.1101/2020.03.17.20037432.
    1. Chen J., Lau Y.F., Lamirande E.W., Paddock C.D., Bartlett J.H., Zaki S.R., Subbarao K. Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection. J. Virol. 2009;84:1289–1301. doi: 10.1128/JVI.01281-09.
    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. doi: 10.1016/S0140-6736(03)13973-6.
    1. Sheahan T.P., Sims A.C., Leist S.R., Schäfer A., Won J., Brown A.J., Montgomery S.A., Hogg A., Babusis D., Clarke M.O., et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun. 2020;11:1–14. doi: 10.1038/s41467-019-13940-6.
    1. Lee J.-W., Gupta N., Serikov V., Matthay M.A. Potential application of mesenchymal stem cells in acute lung injury. Expert Opin. Boil. 2009;9:1259–1270. doi: 10.1517/14712590903213651.
    1. Li Y., Xu J., Shi W., Chen C., Shao Y., Zhu L., Lu W., Han X. Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice. Stem Cell Res. 2016;7:159. doi: 10.1186/s13287-016-0395-z.
    1. Jolles S., Sewell W.A.C., Misbah S.A. Clinical uses of intravenous immunoglobulin. Clin. Exp. Immunol. 2005;142:1–11. doi: 10.1111/j.1365-2249.2005.02834.x.
    1. Zhou G., Zhao Q. Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2. Int. J. Boil. Sci. 2020;16:1718–1723. doi: 10.7150/ijbs.45123.
    1. Love J.C., Gupta N.T., Ogunniyi A.O., Zimnisky R.M., Qian F., Yao Y., Wang X., Stern J.N., Chari R., Briggs A.W., et al. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integr. Boil. 2015;7:1587–1597.
    1. Guo R.-F., Ward P.A. Role of c5a in inflammatory responses. Annu. Rev. Immunol. 2005;23:821–852. doi: 10.1146/annurev.immunol.23.021704.115835.
    1. Voiriot G., Razazi K., Amsellem V., Van Nhieu J.T., Abid S., Adnot S., Dessap A.M., Maitre B. Interleukin-6 displays lung anti-inflammatory properties and exerts protective hemodynamic effects in a double-hit murine acute lung injury. Respir. Res. 2017;18:64. doi: 10.1186/s12931-017-0553-6.
    1. Herold T., Jurinovic V., Arnreich C., Hellmuth J.C., Bergwelt-Baildon M., Klein M., Weinberger T. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. medRxiv. 2020 doi: 10.1101/2020.04.01.20047381.
    1. Rose-John S., Waetzig G.H., Scheller J., Grotzinger J., Seegert D. The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin. Ther. Targets. 2007;11:613–624. doi: 10.1517/14728222.11.5.613.
    1. Rose-John S. IL-6 Trans-Signaling via the Soluble IL-6 Receptor: Importance for the Pro-Inflammatory Activities of IL-6. Int. J. Boil. Sci. 2012;8:1237–1247. doi: 10.7150/ijbs.4989.
    1. Shirley M., Deeks E.D. Sarilumab: A Review in Moderate to Severe Rheumatoid Arthritis. Drugs. 2018;78:929–940.
    1. Vargesson N. Thalidomide-induced teratogenesis: History and mechanisms. Birth Defects Res. Part C: Embryo Today Rev. 2015;105:140–156. doi: 10.1002/bdrc.21096.
    1. Zhu H., Shi X., Ju D., Huang H., Wei W., Dong X. Anti-Inflammatory Effect of Thalidomide on H1N1 Influenza Virus-Induced Pulmonary Injury in Mice. Inflamm. 2014;37:2091–2098. doi: 10.1007/s10753-014-9943-9.
    1. Pelletier D., Hafler D.A. Fingolimod for Multiple Sclerosis. New Engl. J. Med. 2012;366:339–347. doi: 10.1056/NEJMct1101691.
    1. Thickett D., 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. doi: 10.1164/ajrccm.164.9.2011071.
    1. Chappell K., Watterson D., Young P. Rapid response pipeline for stabilized subunit vaccines; Proceedings of the Vaccine Technology VII; Mont Tremblant, QC, Canada. 17–22 June 2018.
    1. Al-Halifa S., Gauthier L., Arpin D., Bourgault S., Archambault D. Nanoparticle-Based Vaccines Against Respiratory Viruses. Front. Immunol. 2019;10:22. doi: 10.3389/fimmu.2019.00022.
    1. Zhou Y., Hou Y., Shen J., Huang Y., Martin W., Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6:14–18. doi: 10.1038/s41421-020-0153-3.

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