DOI QR코드

DOI QR Code

Molecular Perspectives of SARS-CoV-2: Pathology, Immune Evasion, and Therapeutic Interventions

  • Shah, Masaud (Department of Physiology, Ajou University School of Medicine) ;
  • Woo, Hyun Goo (Department of Physiology, Ajou University School of Medicine)
  • 투고 : 2021.02.01
  • 심사 : 2021.03.25
  • 발행 : 2021.06.30

초록

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus-host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.

키워드

과제정보

This study was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) (NRF-2019R1A5A2026045 and 2017M3C9A6047620), Republic of Korea.

참고문헌

  1. Acharya, D., Liu, G., and Gack, M.U. (2020). Dysregulation of type I interferon responses in COVID-19. Nat. Rev. Immunol. 20, 397-398. https://doi.org/10.1038/s41577-020-0346-x
  2. 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., et al. (2018). Corticosteroid therapy for critically ill patients with Middle East Respiratory Syndrome. Am. J. Respir. Crit. Care Med. 197, 757-767. https://doi.org/10.1164/rccm.201706-1172OC
  3. Beigel, J.H., Tomashek, K.M., Dodd, L.E., Mehta, A.K., Zingman, B.S., Kalil, A.C., Hohmann, E., Chu, H.Y., Luetkemeyer, A., Kline, S., et al. (2020). Remdesivir for the treatment of Covid-19 - final report. N. Engl. J. Med. 383, 1813-1826. https://doi.org/10.1056/NEJMoa2007764
  4. Blanco-Melo, D., Nilsson-Payant, B.E., Liu, W.C., Uhl, S., Hoagland, D., Moller, R., Jordan, T.X., Oishi, K., Panis, M., Sachs, D., et al. (2020). Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036-1045.e9. https://doi.org/10.1016/j.cell.2020.04.026
  5. Bonanad, C., Garcia-Blas, S., Tarazona-Santabalbina, F., Sanchis, J., Bertomeu-Gonzalez, V., Facila, L., Ariza, A., Nunez, J., and Cordero, A. (2020). The effect of age on mortality in patients with COVID-19: a meta-analysis with 611,583 subjects. J. Am. Med. Dir. Assoc. 21, 915-918. https://doi.org/10.1016/j.jamda.2020.05.045
  6. Bosi, E., Bosi, C., Rovere Querini, P., Mancini, N., Calori, G., Ruggeri, A., Canzonieri, C., Callegaro, L., Clementi, M., De Cobelli, F., et al. (2020). Interferon beta-1a (IFNbeta-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial. Trials 21, 939. https://doi.org/10.1186/s13063-020-04864-4
  7. Brookman, S., Cook, J., Zucherman, M., Broughton, S., Harman, K., and Gupta, A. (2021). Effect of the new SARS-CoV-2 variant B.1.1.7 on children and young people. Lancet Child Adolesc. Health 5, e9-e10. https://doi.org/10.1016/S2352-4642(21)00030-4
  8. Cantuti-Castelvetri, L., Ojha, R., Pedro, L.D., Djannatian, M., Franz, J., Kuivanen, S., van der Meer, F., Kallio, K., Kaya, T., Anastasina, M., et al. (2020). Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370, 856-860. https://doi.org/10.1126/science.abd2985
  9. Cao, L., Goreshnik, I., Coventry, B., Case, J.B., Miller, L., Kozodoy, L., Chen, R.E., Carter, L., Walls, A.C., Park, Y.J., et al. (2020). De novo design of picomolar SARS-CoV-2 miniprotein inhibitors. Science 370, 426-431. https://doi.org/10.1126/science.abd9909
  10. Cavalli, G., De Luca, G., Campochiaro, C., Della-Torre, E., Ripa, M., Canetti, D., Oltolini, C., Castiglioni, B., Tassan Din, C., Boffini, N., et al. (2020). Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2, e325-e331. https://doi.org/10.1016/s2665-9913(20)30127-2
  11. Cavalli, G. and Dinarello, C.A. (2018). Anakinra therapy for non-cancer inflammatory diseases. Front. Pharmacol. 9, 1157. https://doi.org/10.3389/fphar.2018.01157
  12. Chen, Z. and John Wherry, E. (2020). T cell responses in patients with COVID-19. Nat. Rev. Immunol. 20, 529-536. https://doi.org/10.1038/s41577-020-0402-6
  13. Conceicao, C., Thakur, N., Human, S., Kelly, J.T., Logan, L., Bialy, D., Bhat, S., Stevenson-Leggett, P., Zagrajek, A.K., Hollinghurst, P., et al. (2020). The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins. PLoS Biol. 18, e3001016. https://doi.org/10.1371/journal.pbio.3001016
  14. Cox, R.J. and Brokstad, K.A. (2020). Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat. Rev. Immunol. 20, 581-582. https://doi.org/10.1038/s41577-020-00436-4
  15. Dubovsky, J.A., Flynn, R., Du, J., Harrington, B.K., Zhong, Y., Kaffenberger, B., Yang, C., Towns, W.H., Lehman, A., Johnson, A.J., et al. (2014). Ibrutinib treatment ameliorates murine chronic graft-versus-host disease. J. Clin. Invest. 124, 4867-4876. https://doi.org/10.1172/JCI75328
  16. Fajgenbaum, D.C. and June, C.H. (2020). Cytokine storm. N. Engl. J. Med. 383, 2255-2273. https://doi.org/10.1056/NEJMra2026131
  17. Gordon, D.E., Jang, G.M., Bouhaddou, M., Xu, J., Obernier, K., White, K.M., O'Meara, M.J., Rezelj, V.V., Guo, J.Z., Swaney, D.L., et al. (2020). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583, 459-468. https://doi.org/10.1038/s41586-020-2286-9
  18. Grasselli, G., Tonetti, T., Protti, A., Langer, T., Girardis, M., Bellani, G., Laffey, J., Carrafiello, G., Carsana, L., Rizzuto, C., et al. (2020). Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir. Med. 8, 1201-1208. https://doi.org/10.1016/s2213-2600(20)30370-2
  19. Hadjadj, J., Yatim, N., Barnabei, L., Corneau, A., Boussier, J., Smith, N., Pere, H., Charbit, B., Bondet, V., Chenevier-Gobeaux, C., et al. (2020). Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369, 718-724. https://doi.org/10.1126/science.abc6027
  20. Hamre, D. and Procknow, J.J. (1966). A new virus isolated from the human respiratory tract. Proc. Soc. Exp. Biol. Med. 121, 190-193. https://doi.org/10.3181/00379727-121-30734
  21. Hoffmann, M., Kleine-Weber, H., Schroeder, S., Kruger, N., Herrler, T., Erichsen, S., Schiergens, T.S., Herrler, G., Wu, N.H., Nitsche, A., et al. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052
  22. Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497-506. https://doi.org/10.1016/s0140-6736(20)30183-5
  23. Huet, T., Beaussier, H., Voisin, O., Jouveshomme, S., Dauriat, G., Lazareth, I., Sacco, E., Naccache, J.M., Bezie, Y., Laplanche, S., et al. (2020). Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2, e393-e400. https://doi.org/10.1016/S2665-9913(20)30164-8
  24. Hung, I.F., Lung, K.C., Tso, E.Y., Liu, R., Chung, T.W., Chu, M.Y., Ng, Y.Y., Lo, J., Chan, J., Tam, A.R., et al. (2020). Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 395, 1695-1704. https://doi.org/10.1016/s0140-6736(20)31042-4
  25. Israelow, B., Song, E., Mao, T., Lu, P., Meir, A., Liu, F., Alfajaro, M.M., Wei, J., Dong, H., Homer, R.J., et al. (2020). Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. SSRN, https://doi.org/10.2139/ssrn.3628297
  26. Jackson, L.A., Anderson, E.J., Rouphael, N.G., Roberts, P.C., Makhene, M., Coler, R.N., McCullough, M.P., Chappell, J.D., Denison, M.R., Stevens, L.J., et al. (2020). An mRNA vaccine against SARS-CoV-2 - preliminary report. N. Engl. J. Med. 383, 1920-1931. https://doi.org/10.1056/NEJMoa2022483
  27. Jiang, S., Zhang, X., Yang, Y., Hotez, P.J., and Du, L. (2020). Neutralizing antibodies for the treatment of COVID-19. Nat. Biomed. Eng. 4, 1134-1139. https://doi.org/10.1038/s41551-020-00660-2
  28. Kang, C.K., Seong, M.W., Choi, S.J., Kim, T.S., Choe, P.G., Song, S.H., Kim, N.J., Park, W.B., and Oh, M.D. (2020). In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses. Korean J. Intern. Med. 35, 782-787. https://doi.org/10.3904/kjim.2020.157
  29. Ke, Z., Oton, J., Qu, K., Cortese, M., Zila, V., McKeane, L., Nakane, T., Zivanov, J., Neufeldt, C.J., Cerikan, B., et al. (2020). Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature 588, 498-502. https://doi.org/10.1038/s41586-020-2665-2
  30. Kim, C., Ryu, D.K., Lee, J., Kim, Y.I., Seo, J.M., Kim, Y.G., Jeong, J.H., Kim, M., Kim, J.I., Kim, P., et al. (2021). A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein. Nat. Commun. 12, 288. https://doi.org/10.1038/s41467-020-20602-5
  31. Kim, D., Lee, J.Y., Yang, J.S., Kim, J.W., Kim, V.N., and Chang, H. (2020). The architecture of SARS-CoV-2 transcriptome. Cell 181, 914-921.e10. https://doi.org/10.1016/j.cell.2020.04.011
  32. Klein, S., Cortese, M., Winter, S.L., Wachsmuth-Melm, M., Neufeldt, C.J., Cerikan, B., Stanifer, M.L., Boulant, S., Bartenschlager, R., and Chlanda, P. (2020). SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat. Commun. 11, 5885. https://doi.org/10.1038/s41467-020-19619-7
  33. Konno, Y., Kimura, I., Uriu, K., Fukushi, M., Irie, T., Koyanagi, Y., Sauter, D., Gifford, R.J., USFQ-COVID19 Consortium, Nakagawa, S., et al. (2020). SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is increased by a naturally occurring elongation variant. Cell Rep. 32, 108185. https://doi.org/10.1016/j.celrep.2020.108185
  34. Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E.E., Bhattacharya, T., Foley, B., et al. (2020). Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182, 812-827.e19. https://doi.org/10.1016/j.cell.2020.06.043
  35. Krammer, F. (2020). SARS-CoV-2 vaccines in development. Nature 586, 516-527. https://doi.org/10.1038/s41586-020-2798-3
  36. Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., et al. (2005). A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 11, 875-879. https://doi.org/10.1038/nm1267
  37. Kuo, T.Y., Lin, M.Y., Coffman, R.L., Campbell, J.D., Traquina, P., Lin, Y.J., Liu, L.T., Cheng, J., Wu, Y.C., Wu, C.C., et al. (2020). Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Sci. Rep. 10, 20085. https://doi.org/10.1038/s41598-020-77077-z
  38. Le, R.Q., Li, L., Yuan, W., Shord, S.S., Nie, L., Habtemariam, B.A., Przepiorka, D., Farrell, A.T., and Pazdur, R. (2018). FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist 23, 943-947. https://doi.org/10.1634/theoncologist.2018-0028
  39. Lee, J.S., Park, S., Jeong, H.W., Ahn, J.Y., Choi, S.J., Lee, H., Choi, B., Nam, S.K., Sa, M., Kwon, J.S., et al. (2020). Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci. Immunol. 5, eabd1554. https://doi.org/10.1126/sciimmunol.abd1554
  40. Lee, N., Allen Chan, K.C., Hui, D.S., Ng, E.K., Wu, A., Chiu, R.W., Wong, V.W., Chan, P.K., Wong, K.T., Wong, E., et al. (2004). Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J. Clin. Virol. 31, 304-309. https://doi.org/10.1016/j.jcv.2004.07.006
  41. Lei, X., Dong, X., Ma, R., Wang, W., Xiao, X., Tian, Z., Wang, C., Wang, Y., Li, L., Ren, L., et al. (2020). Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11, 3810. https://doi.org/10.1038/s41467-020-17665-9
  42. Letko, M., Marzi, A., and Munster, V. (2020). Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 5, 562-569. https://doi.org/10.1038/s41564-020-0688-y
  43. Linsky, T.W., Vergara, R., Codina, N., Nelson, J.W., Walker, M.J., Su, W., Barnes, C.O., Hsiang, T.Y., Esser-Nobis, K., Yu, K., et al. (2020). De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2. Science 370, 1208-1214. https://doi.org/10.1126/science.abe0075
  44. Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H., Li, Y., Hu, Z., Zhong, W., and Wang, M. (2020a). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 6, 16. https://doi.org/10.1038/s41421-020-0156-0
  45. Liu, Y., Pan, Y., Hu, Z., Wu, M., Wang, C., Feng, Z., Mao, C., Tan, Y., Liu, Y., Chen, L., et al. (2020b). Thymosin alpha 1 reduces the mortality of severe coronavirus disease 2019 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin. Infect. Dis. 71, 2150-2157. https://doi.org/10.1093/cid/ciaa630
  46. Ma, C., Sacco, M.D., Hurst, B., Townsend, J.A., Hu, Y., Szeto, T., Zhang, X., Tarbet, B., Marty, M.T., Chen, Y., et al. (2020). Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res. 30, 678-692. https://doi.org/10.1038/s41422-020-0356-z
  47. McCarthy, K.R., Rennick, L.J., Nambulli, S., Robinson-McCarthy, L.R., Bain, W.G., Haidar, G., and Duprex, W.P. (2021). Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science 371, 1139-1142. https://doi.org/10.1126/science.abf6950
  48. McIntosh, K., Dees, J.H., Becker, W.B., Kapikian, A.Z., and Chanock, R.M. (1967). Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease. Proc. Natl. Acad. Sci. U. S. A. 57, 933-940. https://doi.org/10.1073/pnas.57.4.933
  49. Merad, M. and Martin, J.C. (2020). Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355-362. https://doi.org/10.1038/s41577-020-0331-4
  50. Moustaqil, M., Ollivier, E., Chiu, H.P., Van Tol, S., Rudolffi-Soto, P., Stevens, C., Bhumkar, A., Hunter, D.J.B., Freiberg, A.N., Jacques, D., et al. (2021). SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species. Emerg. Microbes Infect. 10, 178-195. https://doi.org/10.1080/22221751.2020.1870414
  51. Narayan, A., Garg, P., Arora, U., Ray, A., and Wig, N. (2021). Pathophysiology of COVID-19-associated acute respiratory distress syndrome. Lancet Respir. Med. 9, e3. https://doi.org/10.1016/S2213-2600(20)30509-9
  52. Pal Singh, S., Dammeijer, F., and Hendriks, R.W. (2018). Role of Bruton's tyrosine kinase in B cells and malignancies. Mol. Cancer 17, 57. https://doi.org/10.1186/s12943-018-0779-z
  53. Park, M.D. (2020). Immune evasion via SARS-CoV-2 ORF8 protein? Nat. Rev. Immunol. 20, 408. https://doi.org/10.1038/s41577-020-0360-z
  54. Prompetchara, E., Ketloy, C., and Palaga, T. (2020). Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac. J. Allergy Immunol. 38, 1-9.
  55. RECOVERY Collaborative Group; Horby, P., Lim, W.S., Emberson, J.R., Mafham, M., Bell, J.L., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., Elmahi, E., et al. (2021). Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384, 693-704. https://doi.org/10.1056/NEJMoa2021436
  56. Roschewski, M., Lionakis, M.S., Sharman, J.P., Roswarski, J., Goy, A., Monticelli, M.A., Roshon, M., Wrzesinski, S.H., Desai, J.V., Zarakas, M.A., et al. (2020). Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci. Immunol. 5, eabd0110. https://doi.org/10.1126/sciimmunol.abd0110
  57. Rosenberg, E.S., Dufort, E.M., Udo, T., Wilberschied, L.A., Kumar, J., Tesoriero, J., Weinberg, P., Kirkwood, J., Muse, A., DeHovitz, J., et al. (2020). Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. JAMA 323, 2493-2502. https://doi.org/10.1001/jama.2020.8630
  58. Sacco, M.D., Ma, C., Lagarias, P., Gao, A., Townsend, J.A., Meng, X., Dube, P., Zhang, X., Hu, Y., Kitamura, N., et al. (2020). Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against M(pro) and cathepsin L. Sci. Adv. 6, eabe0751. https://doi.org/10.1126/sciadv.abe0751
  59. Sanders, J.M., Monogue, M.L., Jodlowski, T.Z., and Cutrell, J.B. (2020). Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 323, 1824-1836.
  60. Schalk, A.F. and Hawn, M.C. (1931). An apparently new respiratory disease of baby chicks. J. Am. Vet. Med. Assoc. 78, 413-423.
  61. Sciascia, S., Apra, F., Baffa, A., Baldovino, S., Boaro, D., Boero, R., Bonora, S., Calcagno, A., Cecchi, I., Cinnirella, G., et al. (2020). Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin. Exp. Rheumatol. 38, 529-532.
  62. Scutigliani, E.M. and Kikkert, M. (2017). Interaction of the innate immune system with positive-strand RNA virus replication organelles. Cytokine Growth Factor Rev. 37, 17-27. https://doi.org/10.1016/j.cytogfr.2017.05.007
  63. Shah, M., Ahmad, B., Choi, S., and Woo, H.G. (2020). Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization. Comput. Struct. Biotechnol. J. 18, 3402-3414. https://doi.org/10.1016/j.csbj.2020.11.002
  64. Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., and Li, F. (2020). Cell entry mechanisms of SARS-CoV-2. Proc. Natl. Acad. Sci. U. S. A. 117, 11727-11734. https://doi.org/10.1073/pnas.2003138117
  65. Sharma, S., Orlowski, G., and Song, W. (2009). Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells. J. Immunol. 182, 329-339. https://doi.org/10.4049/jimmunol.182.1.329
  66. Skipper, C.P., Pastick, K.A., Engen, N.W., Bangdiwala, A.S., Abassi, M., Lofgren, S.M., Williams, D.A., Okafor, E.C., Pullen, M.F., Nicol, M.R., et al. (2020). Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Ann. Intern. Med. 173, 623-631. https://doi.org/10.7326/M20-4207
  67. Snijder, E.J., Limpens, R., de Wilde, A.H., de Jong, A.W.M., Zevenhoven-Dobbe, J.C., Maier, H.J., Faas, F., Koster, A.J., and Barcena, M. (2020). A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis. PLoS Biol. 18, e3000715. https://doi.org/10.1371/journal.pbio.3000715
  68. Song, X., Hu, W., Yu, H., Zhao, L., Zhao, Y., Zhao, X., Xue, H.H., and Zhao, Y. (2020). Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytometry A 2020 Dec 6 [Epub]. https://doi.org/10.1002/cyto.a.24285
  69. Spinner, C.D., Gottlieb, R.L., Criner, G.J., Arribas Lopez, J.R., Cattelan, A.M., Soriano Viladomiu, A., Ogbuagu, O., Malhotra, P., Mullane, K.M., Castagna, A., et al. (2020). Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA 324, 1048-1057. https://doi.org/10.1001/jama.2020.16349
  70. Starr, T.N., Greaney, A.J., Addetia, A., Hannon, W.W., Choudhary, M.C., Dingens, A.S., Li, J.Z., and Bloom, J.D. (2021). Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 71, 850-854.
  71. Tai, W., Zhang, X., He, Y., Jiang, S., and Du, L. (2020). Identification of SARS-CoV RBD-targeting monoclonal antibodies with cross-reactive or neutralizing activity against SARS-CoV-2. Antiviral Res. 179, 104820. https://doi.org/10.1016/j.antiviral.2020.104820
  72. Tanaka, T., Narazaki, M., and Kishimoto, T. (2016). Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy 8, 959-970. https://doi.org/10.2217/imt-2016-0020
  73. Tay, M.Z., Poh, C.M., Renia, L., MacAry, P.A., and Ng, L.F.P. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 20, 363-374. https://doi.org/10.1038/s41577-020-0311-8
  74. van der Hoek, L., Pyrc, K., Jebbink, M.F., Vermeulen-Oost, W., Berkhout, R.J., Wolthers, K.C., Wertheim-van Dillen, P.M., Kaandorp, J., Spaargaren, J., and Berkhout, B. (2004). Identification of a new human coronavirus. Nat. Med. 10, 368-373. https://doi.org/10.1038/nm1024
  75. Wang, B., Li, D., Liu, T., Wang, H., Luo, F., and Liu, Y. (2020a). Subcutaneous injection of IFN alpha-2b for COVID-19: an observational study. BMC Infect. Dis. 20, 723. https://doi.org/10.1186/s12879-020-05425-5
  76. Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Shi, Z., Hu, Z., Zhong, W., and Xiao, G. (2020b). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30, 269-271. https://doi.org/10.1038/s41422-020-0282-0
  77. Wang, N., Zhan, Y., Zhu, L., Hou, Z., Liu, F., Song, P., Qiu, F., Wang, X., Zou, X., Wan, D., et al. (2020c). Retrospective multicenter cohort study shows early interferon therapy is associated with favorable clinical responses in COVID-19 patients. Cell Host Microbe 28, 455-464.e2. https://doi.org/10.1016/j.chom.2020.07.005
  78. Wang, Y., Zhang, D., Du, G., Du, R., Zhao, J., Jin, Y., Fu, S., Gao, L., Cheng, Z., Lu, Q., et al. (2020d). Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 395, 1569-1578. https://doi.org/10.1016/s0140-6736(20)31022-9
  79. Weinreich, D.M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., Musser, B.J., Soo, Y., Rofail, D., Im, J., et al. (2021). REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N. Engl. J. Med. 384, 238-251. https://doi.org/10.1056/NEJMoa2035002
  80. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne, J.A.C., Murthy, S., Diaz, J.V., Slutsky, A.S., Villar, J., Angus, D.C., Annane, D., Azevedo, L.C.P., Berwanger, O., Cavalcanti, A.B., et al. (2020). Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 324, 1330-1341. https://doi.org/10.1001/jama.2020.17023
  81. Wilk, A.J., Rustagi, A., Zhao, N.Q., Roque, J., Martinez-Colon, G.J., McKechnie, J.L., Ivison, G.T., Ranganath, T., Vergara, R., Hollis, T., et al. (2020). A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat. Med. 26, 1070-1076. https://doi.org/10.1038/s41591-020-0944-y
  82. Williamson, B.N., Feldmann, F., Schwarz, B., Meade-White, K., Porter, D.P., Schulz, J., van Doremalen, N., Leighton, I., Yinda, C.K., Perez-Perez, L., et al. (2020). Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature 585, 273-276. https://doi.org/10.1038/s41586-020-2423-5
  83. Xia, H., Cao, Z., Xie, X., Zhang, X., Chen, J.Y., Wang, H., Menachery, V.D., Rajsbaum, R., and Shi, P.Y. (2020a). Evasion of type I interferon by SARS-CoV-2. Cell Rep. 33, 108234. https://doi.org/10.1016/j.celrep.2020.108234
  84. Xia, S., Liu, M., Wang, C., Xu, W., Lan, Q., Feng, S., Qi, F., Bao, L., Du, L., Liu, S., et al. (2020b). Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 30, 343-355. https://doi.org/10.1038/s41422-020-0305-x
  85. Xia, S., Yan, L., Xu, W., Agrawal, A.S., Algaissi, A., Tseng, C.K., Wang, Q., Du, L., Tan, W., Wilson, I.A., et al. (2019). A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike. Sci. Adv. 5, eaav4580. https://doi.org/10.1126/sciadv.aav4580
  86. Yan, L., Zhang, Y., Ge, J., Zheng, L., Gao, Y., Wang, T., Jia, Z., Wang, H., Huang, Y., Li, M., et al. (2020). Architecture of a SARS-CoV-2 mini replication and transcription complex. Nat. Commun. 11, 5874. https://doi.org/10.1038/s41467-020-19770-1
  87. Yang, Z., Zhang, X., Wang, F., Wang, P., Kuang, E., and Li X. (2020). Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2. BioRxiv, https://doi.org/10.1101/2020.08.12.247767
  88. Yap, J.K.Y., Moriyama, M., and Iwasaki, A. (2020). Inflammasomes and pyroptosis as therapeutic targets for COVID-19. J. Immunol. 205, 307-312. https://doi.org/10.4049/jimmunol.2000513
  89. Zeng, Z., Xu, L., Xie, X.Y., Yan, H.L., Xie, B.J., Xu, W.Z., Liu, X.A., Kang, G.J., Jiang, W.L., and Yuan, J.P. (2020). Pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion. Histopathology 77, 823-831. https://doi.org/10.1111/his.14138
  90. Zhou, Y., Fu, B., Zheng, X., Wang, D., Zhao, C., Qi, Y., Sun, R., Tian, Z., Xu, X., and Wei, H. (2020). Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl. Sci. Rev. 7, 998-1002. https://doi.org/10.1093/nsr/nwaa041
  91. Zhou, Z., Wang, X., Fu, Y., Zhang, X., and Liu, C. (2021). Letter to the editor: neutralizing antibodies for the treatment of COVID-19. Acta Pharm. Sin. B 11, 304-307. https://doi.org/10.1016/j.apsb.2020.10.025

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  1. Cellular and Molecular Effects of SARS-CoV-2 Linking Lung Infection to the Brain vol.12, 2021, https://doi.org/10.3389/fimmu.2021.730088