References
Al-Qahtani, A. A., Lyroni, K., Aznaourova, M., Tseliou, M., Al-Anazi, M.
R., Al-Ahdal, M. N., . . . Tsatsanis, C. (2017). Middle east respiratory
syndrome corona virus spike glycoprotein suppresses macrophage responses
via DPP4-mediated induction of IRAK-M and PPARγ. Oncotarget,
8 (6), 9053-9066. doi:10.18632/oncotarget.14754
Amanat, F., Stadlbauer, D., Strohmeier, S., Nguyen, T. H. O.,
Chromikova, V., McMahon, M., . . . Krammer, F. (2020). A serological
assay to detect SARS-CoV-2 seroconversion in humans. Nat Med,
26 (7), 1033-1036. doi:10.1038/s41591-020-0913-5
Anwar, M. A., Basith, S., & Choi, S. (2013). Negative regulatory
approaches to the attenuation of Toll-like receptor signaling. Exp
Mol Med, 45 (2), e11. doi:10.1038/emm.2013.28
Barnard, D. L., Day, C. W., Bailey, K., Heiner, M., Montgomery, R.,
Lauridsen, L., . . . Sidwell, R. W. (2006). Evaluation of
immunomodulators, interferons and known in vitro SARS-coV inhibitors for
inhibition of SARS-coV replication in BALB/c mice. Antivir Chem
Chemother, 17 (5), 275-284. doi:10.1177/095632020601700505
Barnes, B. J., Adrover, J. M., Baxter-Stoltzfus, A., Borczuk, A.,
Cools-Lartigue, J., Crawford, J. M., . . . Knight, J. S. (2020).
Targeting potential drivers of COVID-19: Neutrophil extracellular traps.Journal of Experimental Medicine, 217 (6).
Blanco-Melo, D., Nilsson-Payant, B. E., Liu, W. C., Uhl, S., Hoagland,
D., Møller, R., . . . tenOever, B. R. (2020). Imbalanced Host Response
to SARS-CoV-2 Drives Development of COVID-19. Cell, 181 (5),
1036-1045.e1039. doi:10.1016/j.cell.2020.04.026
Bouvet, M., Debarnot, C., Imbert, I., Selisko, B., Snijder, E. J.,
Canard, B., & Decroly, E. (2010). In vitro reconstitution of
SARS-coronavirus mRNA cap methylation. PLoS Pathog, 6 (4),
e1000863. doi:10.1371/journal.ppat.1000863
Braun, J., Loyal, L., Frentsch, M., Wendisch, D., Georg, P., Kurth, F.,
. . . Thiel, A. (2020). SARS-CoV-2-reactive T cells in healthy donors
and patients with COVID-19. Nature . doi:10.1038/s41586-020-2598-9
Cameron, M. J., Kelvin, A. A., Leon, A. J., Cameron, C. M., Ran, L., Xu,
L., . . . Kelvin, D. J. (2012). Lack of innate interferon responses
during SARS coronavirus infection in a vaccination and reinfection
ferret model. PLoS One, 7 (9), e45842.
doi:10.1371/journal.pone.0045842
Camp, J. V., & Jonsson, C. B. (2017). A role for neutrophils in viral
respiratory disease. Frontiers in immunology, 8 , 550.
Canton, J., Fehr, A. R., Fernandez-Delgado, R., Gutierrez-Alvarez, F.
J., Sanchez-Aparicio, M. T., García-Sastre, A., . . . Sola, I. (2018).
MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune
response during infection. PLoS Pathog, 14 (1), e1006838.
doi:10.1371/journal.ppat.1006838
Cao, W. C., Liu, W., Zhang, P. H., Zhang, F., & Richardus, J. H.
(2007). Disappearance of antibodies to SARS-associated coronavirus after
recovery. N Engl J Med, 357 (11), 1162-1163.
doi:10.1056/NEJMc070348
Chan, R. W., Chan, M. C., Agnihothram, S., Chan, L. L., Kuok, D. I.,
Fong, J. H., . . . Peiris, J. S. (2013). Tropism of and innate immune
responses to the novel human betacoronavirus lineage C virus in human ex
vivo respiratory organ cultures. J Virol, 87 (12), 6604-6614.
doi:10.1128/jvi.00009-13
Channappanavar, R., Fehr, A. R., Vijay, R., Mack, M., Zhao, J.,
Meyerholz, D. K., & Perlman, S. (2016). Dysregulated Type I Interferon
and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in
SARS-CoV-Infected Mice. Cell Host Microbe, 19 (2), 181-193.
doi:10.1016/j.chom.2016.01.007
Channappanavar, R., & Perlman, S. (2017). Pathogenic human coronavirus
infections: causes and consequences of cytokine storm and
immunopathology. Semin Immunopathol, 39 (5), 529-539.
doi:10.1007/s00281-017-0629-x
Channappanavar, R., Zhao, J., & Perlman, S. (2014). T cell-mediated
immune response to respiratory coronaviruses. Immunol Res,
59 (1-3), 118-128. doi:10.1007/s12026-014-8534-z
Chen, J., Lau, Y. F., Lamirande, E. W., Paddock, C. D., Bartlett, J. H.,
Zaki, S. R., & Subbarao, K. (2010). 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. Journal of virology, 84 (3), 1289-1301.
Chen, L., Liu, H. G., Liu, W., Liu, J., Liu, K., Shang, J., . . . Wei,
S. (2020). [Analysis of clinical features of 29 patients with 2019
novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi,
43 (3), 203-208. doi:10.3760/cma.j.issn.1001-0939.2020.03.013
Cheung, C. Y., Poon, L. L., Ng, I. H., Luk, W., Sia, S.-F., Wu, M. H., .
. . Guan, Y. (2005). Cytokine responses in severe acute respiratory
syndrome coronavirus-infected macrophages in vitro: possible relevance
to pathogenesis. Journal of virology, 79 (12), 7819-7826.
Cheung, C. Y., Poon, L. L., Ng, I. H., Luk, W., Sia, S. F., Wu, M. H., .
. . Peiris, J. S. (2005). Cytokine responses in severe acute respiratory
syndrome coronavirus-infected macrophages in vitro: possible relevance
to pathogenesis. J Virol, 79 (12), 7819-7826.
doi:10.1128/jvi.79.12.7819-7826.2005
Chien, J. Y., Hsueh, P. R., Cheng, W. C., Yu, C. J., & Yang, P. C.
(2006). Temporal changes in cytokine/chemokine profiles and pulmonary
involvement in severe acute respiratory syndrome. Respirology,
11 (6), 715-722. doi:10.1111/j.1440-1843.2006.00942.x
Chu, H., Chan, J. F.-W., Wang, Y., Yuen, T. T.-T., Chai, Y., Hou, Y., .
. . Yuen, K.-Y. (2020). Comparative Replication and Immune Activation
Profiles of SARS-CoV-2 and SARS-CoV in Human Lungs: An Ex Vivo Study
With Implications for the Pathogenesis of COVID-19. Clinical
Infectious Diseases, 71 (6), 1400-1409. doi:10.1093/cid/ciaa410
Chu, H., Zhou, J., Wong, B. H., Li, C., Cheng, Z. S., Lin, X., . . .
Yuen, K. Y. (2014). Productive replication of Middle East respiratory
syndrome coronavirus in monocyte-derived dendritic cells modulates
innate immune response. Virology, 454-455 , 197-205.
doi:10.1016/j.virol.2014.02.018
Coronavirus disease 2019 (COVID-19) Situation Report – 57. (2020).
Cui, J., Li, F., & Shi, Z. L. (2019). Origin and evolution of
pathogenic coronaviruses. Nat Rev Microbiol, 17 (3), 181-192.
doi:10.1038/s41579-018-0118-9
Dahl, H., Linde, A., & Strannegård, O. (2004). In vitro inhibition of
SARS virus replication by human interferons. Scand J Infect Dis,
36 (11-12), 829-831. doi:10.1080/00365540410021144
Davidson, S., Maini, M. K., & Wack, A. (2015). Disease-promoting
effects of type I interferons in viral, bacterial, and coinfections.J Interferon Cytokine Res, 35 (4), 252-264.
doi:10.1089/jir.2014.0227
de Wilde, A. H., Raj, V. S., Oudshoorn, D., Bestebroer, T. M., van
Nieuwkoop, S., Limpens, R., . . . van den Hoogen, B. G. (2013).
MERS-coronavirus replication induces severe in vitro cytopathology and
is strongly inhibited by cyclosporin A or interferon-α treatment.J Gen Virol, 94 (Pt 8), 1749-1760. doi:10.1099/vir.0.052910-0
de Wit, E., van Doremalen, N., Falzarano, D., & Munster, V. J. (2016).
SARS and MERS: recent insights into emerging coronaviruses. Nat
Rev Microbiol, 14 (8), 523-534. doi:10.1038/nrmicro.2016.81
Deng, X., Hackbart, M., Mettelman, R. C., O’Brien, A., Mielech, A. M.,
Yi, G., . . . Baker, S. C. (2017). Coronavirus nonstructural protein 15
mediates evasion of dsRNA sensors and limits apoptosis in macrophages.Proc Natl Acad Sci U S A, 114 (21), E4251-e4260.
doi:10.1073/pnas.1618310114
Dong, P., Ju, X., Yan, Y., Zhang, S., Cai, M., Wang, H., . . . He, W.
(2018). γδ T Cells Provide Protective Function in Highly Pathogenic
Avian H5N1 Influenza A Virus Infection. Front Immunol, 9 , 2812.
doi:10.3389/fimmu.2018.02812
Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B.-J., & Jiang, S. (2009).
The spike protein of SARS-CoV — a target for vaccine and therapeutic
development. Nature Reviews Microbiology, 7 (3), 226-236.
doi:10.1038/nrmicro2090
Du, L., Ma, C., & Jiang, S. (2013). Antibodies induced by
receptor-binding domain in spike protein of SARS-CoV do not
cross-neutralize the novel human coronavirus hCoV-EMC. J Infect,
67 (4), 348-350. doi:10.1016/j.jinf.2013.05.002
Eosinophils and Respiratory Viruses. (2019). Viral Immunology,
32 (5), 198-207. doi:10.1089/vim.2018.0150
Fan, Y., Zhao, K., Shi, Z. L., & Zhou, P. (2019). Bat Coronaviruses in
China. Viruses, 11 (3). doi:10.3390/v11030210
Faure, E., Poissy, J., Goffard, A., Fournier, C., Kipnis, E., Titecat,
M., . . . Guery, B. (2014). Distinct immune response in two
MERS-CoV-infected patients: can we go from bench to bedside? PLoS
One, 9 (2), e88716. doi:10.1371/journal.pone.0088716
Fehr, A. R., Channappanavar, R., & Perlman, S. (2017). Middle East
Respiratory Syndrome: Emergence of a Pathogenic Human Coronavirus.Annu Rev Med, 68 , 387-399. doi:10.1146/annurev-med-051215-031152
Frieman, M., Ratia, K., Johnston, R. E., Mesecar, A. D., & Baric, R. S.
(2009). Severe acute respiratory syndrome coronavirus papain-like
protease ubiquitin-like domain and catalytic domain regulate antagonism
of IRF3 and NF-kappaB signaling. J Virol, 83 (13), 6689-6705.
doi:10.1128/jvi.02220-08
Frieman, M., Yount, B., Heise, M., Kopecky-Bromberg, S. A., Palese, P.,
& Baric, R. S. (2007). Severe acute respiratory syndrome coronavirus
ORF6 antagonizes STAT1 function by sequestering nuclear import factors
on the rough endoplasmic reticulum/Golgi membrane. J Virol,
81 (18), 9812-9824. doi:10.1128/jvi.01012-07
Frieman, M. B., Chen, J., Morrison, T. E., Whitmore, A., Funkhouser, W.,
Ward, J. M., . . . Baric, R. S. (2010). SARS-CoV pathogenesis is
regulated by a STAT1 dependent but a type I, II and III interferon
receptor independent mechanism. PLoS Pathog, 6 (4), e1000849.
doi:10.1371/journal.ppat.1000849
Galani, V., Tatsaki, E., Bai, M., Kitsoulis, P., Lekka, M., Nakos, G.,
& Kanavaros, P. (2010). The role of apoptosis in the pathophysiology of
Acute Respiratory Distress Syndrome (ARDS): an up-to-date cell-specific
review. Pathol Res Pract, 206 (3), 145-150.
doi:10.1016/j.prp.2009.12.002
Giamarellos-Bourboulis, E. J., Netea, M. G., Rovina, N., Akinosoglou,
K., Antoniadou, A., Antonakos, N., . . . Koutsoukou, A. (2020). Complex
Immune Dysregulation in COVID-19 Patients with Severe Respiratory
Failure. Cell Host Microbe, 27 (6), 992-1000.e1003.
doi:10.1016/j.chom.2020.04.009
Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White,
K. M., . . . Krogan, N. J. (2020). A SARS-CoV-2 protein interaction map
reveals targets for drug repurposing. Nature, 583 (7816), 459-468.
doi:10.1038/s41586-020-2286-9
Griffith, J. W., Sokol, C. L., & Luster, A. D. (2014). Chemokines and
chemokine receptors: positioning cells for host defense and immunity.Annu Rev Immunol, 32 , 659-702.
doi:10.1146/annurev-immunol-032713-120145
Guilliams, M., Lambrecht, B. N., & Hammad, H. (2013). Division of labor
between lung dendritic cells and macrophages in the defense against
pulmonary infections. Mucosal Immunology, 6 (3), 464-473.
doi:10.1038/mi.2013.14
Guo, C., Li, B., Ma, H., Wang, X., Cai, P., Yu, Q., . . . Qu, K. (2020).
Single-cell analysis of severe COVID-19 patients reveals a
monocyte-driven inflammatory storm attenuated by Tocilizumab.bioRxiv , 2020.2004.2008.029769. doi:10.1101/2020.04.08.029769
Haagmans, B. L., Kuiken, T., Martina, B. E., Fouchier, R. A.,
Rimmelzwaan, G. F., van Amerongen, G., . . . Osterhaus, A. D. (2004).
Pegylated interferon-alpha protects type 1 pneumocytes against SARS
coronavirus infection in macaques. Nat Med, 10 (3), 290-293.
doi:10.1038/nm1001
Hackbart, M., Deng, X., & Baker, S. C. (2020). Coronavirus
endoribonuclease targets viral polyuridine sequences to evade activating
host sensors. Proc Natl Acad Sci U S A, 117 (14), 8094-8103.
doi:10.1073/pnas.1921485117
Hadjadj, J., Yatim, N., Barnabei, L., Corneau, A., Boussier, J., Smith,
N., . . . Terrier, B. (2020). Impaired type I interferon activity and
inflammatory responses in severe COVID-19 patients. Science,
369 (6504), 718-724. doi:10.1126/science.abc6027
Haveri, A., Smura, T., Kuivanen, S., Österlund, P., Hepojoki, J.,
Ikonen, N., . . . Kantele, A. (2020). Serological and molecular findings
during SARS-CoV-2 infection: the first case study in Finland, January to
February 2020. Eurosurveillance, 25 (11), 2000266.
Hsueh, P. R., Huang, L. M., Chen, P. J., Kao, C. L., & Yang, P. C.
(2004). Chronological evolution of IgM, IgA, IgG and neutralisation
antibodies after infection with SARS-associated coronavirus.Clinical Microbiology and Infection, 10 (12), 1062-1066.
doi:https://doi.org/10.1111/j.1469-0691.2004.01009.x
Huang, A. T., Garcia-Carreras, B., Hitchings, M. D. T., Yang, B.,
Katzelnick, L. C., Rattigan, S. M., . . . Cummings, D. A. T. (2020). A
systematic review of antibody mediated immunity to coronaviruses:
kinetics, correlates of protection, and association with severity.Nature Communications, 11 (1), 4704.
doi:10.1038/s41467-020-18450-4
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., . . . Cao, B.
(2020). Clinical features of patients infected with 2019 novel
coronavirus in Wuhan, China. Lancet, 395 (10223), 497-506.
doi:10.1016/s0140-6736(20)30183-5
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., . . . Cao, B.
(2020). Clinical features of patients infected with 2019 novel
coronavirus in Wuhan, China. The Lancet, 395 (10223), 497-506.
doi:https://doi.org/10.1016/S0140-6736(20)30183-5
Huang, I. C., Bailey, C. C., Weyer, J. L., Radoshitzky, S. R., Becker,
M. M., Chiang, J. J., . . . Farzan, M. (2011). Distinct patterns of
IFITM-mediated restriction of filoviruses, SARS coronavirus, and
influenza A virus. PLoS Pathog, 7 (1), e1001258.
doi:10.1371/journal.ppat.1001258
Hui, D. S., E, I. A., Madani, T. A., Ntoumi, F., Kock, R., Dar, O., . .
. Petersen, E. (2020). The continuing 2019-nCoV epidemic threat of novel
coronaviruses to global health - The latest 2019 novel coronavirus
outbreak in Wuhan, China. Int J Infect Dis, 91 , 264-266.
doi:10.1016/j.ijid.2020.01.009
Hui, E. K. (2006). Reasons for the increase in emerging and re-emerging
viral infectious diseases. Microbes Infect, 8 (3), 905-916.
doi:10.1016/j.micinf.2005.06.032
Ivanov, K. A., Thiel, V., Dobbe, J. C., van der Meer, Y., Snijder, E.
J., & Ziebuhr, J. (2004). Multiple Enzymatic Activities Associated with
Severe Acute Respiratory Syndrome Coronavirus Helicase. J Virol,
78 (11), 5619-5632. doi:10.1128/jvi.78.11.5619-5632.2004
Ivanov, K. A., Thiel, V., Dobbe, J. C., van der Meer, Y., Snijder, E.
J., & Ziebuhr, J. (2004). Multiple enzymatic activities associated with
severe acute respiratory syndrome coronavirus helicase. J Virol,
78 (11), 5619-5632. doi:10.1128/jvi.78.11.5619-5632.2004
Jiang, S., Du, L., & Shi, Z. (2020). An emerging coronavirus causing
pneumonia outbreak in Wuhan, China: calling for developing therapeutic
and prophylactic strategies. Emerg Microbes Infect, 9 (1),
275-277. doi:10.1080/22221751.2020.1723441
Jin, W., & Dong, C. (2013). IL-17 cytokines in immunity and
inflammation. Emerg Microbes Infect, 2 (9), e60.
doi:10.1038/emi.2013.58
Josset, L., Menachery, V. D., Gralinski, L. E., Agnihothram, S., Sova,
P., Carter, V. S., . . . Katze, M. G. (2013). Cell host response to
infection with novel human coronavirus EMC predicts potential antivirals
and important differences with SARS coronavirus. mBio, 4 (3),
e00165-00113. doi:10.1128/mBio.00165-13
Ju, B., Zhang, Q., Ge, J., Wang, R., Sun, J., Ge, X., . . . Zhang, L.
(2020). Human neutralizing antibodies elicited by SARS-CoV-2 infection.Nature, 584 (7819), 115-119. doi:10.1038/s41586-020-2380-z
Kamphuis, E., Junt, T., Waibler, Z., Forster, R., & Kalinke, U. (2006).
Type I interferons directly regulate lymphocyte recirculation and cause
transient blood lymphopenia. Blood, 108 (10), 3253-3261.
doi:10.1182/blood-2006-06-027599
Kato, H., Takahasi, K., & Fujita, T. (2011). RIG-I-like receptors:
cytoplasmic sensors for non-self RNA. Immunol Rev, 243 (1), 91-98.
doi:10.1111/j.1600-065X.2011.01052.x
Kindler, E., Thiel, V., & Weber, F. (2016). Interaction of SARS and
MERS Coronaviruses with the Antiviral Interferon Response. Adv
Virus Res, 96 , 219-243. doi:10.1016/bs.aivir.2016.08.006
Klasse, P. J. (2014). Neutralization of Virus Infectivity by Antibodies:
Old Problems in New Perspectives. Adv Biol, 2014 .
doi:10.1155/2014/157895
Knoops, K., Kikkert, M., Worm, S. H., Zevenhoven-Dobbe, J. C., van der
Meer, Y., Koster, A. J., . . . Snijder, E. J. (2008). SARS-coronavirus
replication is supported by a reticulovesicular network of modified
endoplasmic reticulum. PLoS Biol, 6 (9), e226.
doi:10.1371/journal.pbio.0060226
Kopecky-Bromberg, S. A., Martínez-Sobrido, L., Frieman, M., Baric, R.
A., & Palese, P. (2007). Severe acute respiratory syndrome coronavirus
open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function
as interferon antagonists. J Virol, 81 (2), 548-557.
doi:10.1128/jvi.01782-06
Krishnan, J., Selvarajoo, K., Tsuchiya, M., Lee, G., & Choi, S. (2007).
Toll-like receptor signal transduction. Exp Mol Med, 39 (4),
421-438. doi:10.1038/emm.2007.47
Kumaki, Y., Ennis, J., Rahbar, R., Turner, J. D., Wandersee, M. K.,
Smith, A. J., . . . Barnard, D. L. (2011). Single-dose intranasal
administration with mDEF201 (adenovirus vectored mouse interferon-alpha)
confers protection from mortality in a lethal SARS-CoV BALB/c mouse
model. Antiviral Res, 89 (1), 75-82.
doi:10.1016/j.antiviral.2010.11.007
Lau, S. K. P., Lau, C. C. Y., Chan, K. H., Li, C. P. Y., Chen, H., Jin,
D. Y., . . . Yuen, K. Y. (2013). Delayed induction of proinflammatory
cytokines and suppression of innate antiviral response by the novel
Middle East respiratory syndrome coronavirus: implications for
pathogenesis and treatment. J Gen Virol, 94 (Pt 12), 2679-2690.
doi:10.1099/vir.0.055533-0
Law, H. K., Cheung, C. Y., Ng, H. Y., Sia, S. F., Chan, Y. O., Luk, W.,
. . . Lau, Y. L. (2005). Chemokine up-regulation in
SARS-coronavirus-infected, monocyte-derived human dendritic cells.Blood, 106 (7), 2366-2374. doi:10.1182/blood-2004-10-4166
Law, H. K., Cheung, C. Y., Sia, S. F., Chan, Y. O., Peiris, J. S., &
Lau, Y. L. (2009). Toll-like receptors, chemokine receptors and death
receptor ligands responses in SARS coronavirus infected human monocyte
derived dendritic cells. BMC Immunol, 10 , 35.
doi:10.1186/1471-2172-10-35
Lee, J., Lee, S. H., Shin, N., Jeong, M., Kim, M. S., Kim, M. J., . . .
Choi, I. (2009). Tumor necrosis factor-α enhances IL-15-induced natural
killer cell differentiation. Biochem Biophys Res Commun, 386 (4),
718-723. doi:https://doi.org/10.1016/j.bbrc.2009.06.120
Li, C. K., Wu, H., Yan, H., Ma, S., Wang, L., Zhang, M., . . . Xu, X. N.
(2008). T cell responses to whole SARS coronavirus in humans. J
Immunol, 181 (8), 5490-5500. doi:10.4049/jimmunol.181.8.5490
Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., . . . Feng, Z.
(2020). Early Transmission Dynamics in Wuhan, China, of Novel
Coronavirus-Infected Pneumonia. N Engl J Med, 382 (13), 1199-1207.
doi:10.1056/NEJMoa2001316
Li, T., Qiu, Z., Han, Y., Wang, Z., Fan, H., Lu, W., . . . Wang, A.
(2003). Rapid loss of both CD4+ and CD8+ T lymphocyte subsets during the
acute phase of severe acute respiratory syndrome. Chin Med J
(Engl), 116 (7), 985-987.
Li, T., Qiu, Z., Zhang, L., Han, Y., He, W., Liu, Z., . . . Wang, A.
(2004). Significant changes of peripheral T lymphocyte subsets in
patients with severe acute respiratory syndrome. J Infect Dis,
189 (4), 648-651. doi:10.1086/381535
Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., . . . Zhang, Z.
(2020). Single-cell landscape of bronchoalveolar immune cells in
patients with COVID-19. Nat Med, 26 (6), 842-844.
doi:10.1038/s41591-020-0901-9
Lin, L., Lu, L., Cao, W., & Li, T. (2020). Hypothesis for potential
pathogenesis of SARS-CoV-2 infection-a review of immune changes in
patients with viral pneumonia. Emerg Microbes Infect, 9 (1),
727-732. doi:10.1080/22221751.2020.1746199
Liu, J., Zheng, X., Tong, Q., Li, W., Wang, B., Sutter, K., . . . Yang,
D. (2020). Overlapping and discrete aspects of the pathology and
pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV,
MERS-CoV, and 2019-nCoV. J Med Virol, 92 (5), 491-494.
doi:10.1002/jmv.25709
Liu, W. J., Zhao, M., Liu, K., Xu, K., Wong, G., Tan, W., & Gao, G. F.
(2017). T-cell immunity of SARS-CoV: Implications for vaccine
development against MERS-CoV. Antiviral Res, 137 , 82-92.
doi:10.1016/j.antiviral.2016.11.006
Liu, Y., Yang, Y., Zhang, C., Huang, F., Wang, F., Yuan, J., . . . Liu,
L. (2020). Clinical and biochemical indexes from 2019-nCoV infected
patients linked to viral loads and lung injury. Sci China Life
Sci, 63 (3), 364-374. doi:10.1007/s11427-020-1643-8
Liu, Z. Y., Li, T. S., Wang, Z., Xu, Z. J., Wang, H. L., Yu, Y., . . .
Ni, A. P. (2003). [Clinical features and therapy of 106 cases of
severe acute respiratory syndrome]. Zhonghua Nei Ke Za Zhi,
42 (6), 373-377.
Lokugamage, K. G., Hage, A., de Vries, M., Valero-Jimenez, A. M.,
Schindewolf, C., Dittmann, M., . . . Menachery, V. D. (2020). Type I
interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV.bioRxiv , 2020.2003.2007.982264. doi:10.1101/2020.03.07.982264
Long, Q. X., Tang, X. J., Shi, Q. L., Li, Q., Deng, H. J., Yuan, J., . .
. Huang, A. L. (2020). Clinical and immunological assessment of
asymptomatic SARS-CoV-2 infections. Nat Med, 26 (8), 1200-1204.
doi:10.1038/s41591-020-0965-6
Lu, X., Pan, J., Tao, J., & Guo, D. (2011). SARS-CoV nucleocapsid
protein antagonizes IFN-β response by targeting initial step of IFN-β
induction pathway, and its C-terminal region is critical for the
antagonism. Virus Genes, 42 (1), 37-45.
doi:10.1007/s11262-010-0544-x
Lui, P. Y., Wong, L. Y., Fung, C. L., Siu, K. L., Yeung, M. L., Yuen, K.
S., . . . Jin, D. Y. (2016). Middle East respiratory syndrome
coronavirus M protein suppresses type I interferon expression through
the inhibition of TBK1-dependent phosphorylation of IRF3. Emerg
Microbes Infect, 5 (4), e39. doi:10.1038/emi.2016.33
Mahallawi, W. H., Khabour, O. F., Zhang, Q., Makhdoum, H. M., &
Suliman, B. A. (2018). MERS-CoV infection in humans is associated with a
pro-inflammatory Th1 and Th17 cytokine profile. Cytokine, 104 ,
8-13. doi:10.1016/j.cyto.2018.01.025
Manni, M. L., Robinson, K. M., & Alcorn, J. F. (2014). A tale of two
cytokines: IL-17 and IL-22 in asthma and infection. Expert Rev
Respir Med, 8 (1), 25-42. doi:10.1586/17476348.2014.854167
Mantlo, E., Bukreyeva, N., Maruyama, J., Paessler, S., & Huang, C.
(2020). Antiviral activities of type I interferons to SARS-CoV-2
infection. Antiviral Res, 179 , 104811.
doi:https://doi.org/10.1016/j.antiviral.2020.104811
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., &
Manson, J. J. (2020). COVID-19: consider cytokine storm syndromes and
immunosuppression. The Lancet, 395 (10229), 1033-1034.
doi:https://doi.org/10.1016/S0140-6736(20)30628-0
Minakshi, R., Padhan, K., Rani, M., Khan, N., Ahmad, F., & Jameel, S.
(2009). The SARS Coronavirus 3a protein causes endoplasmic reticulum
stress and induces ligand-independent downregulation of the type 1
interferon receptor. PLoS One, 4 (12), e8342.
doi:10.1371/journal.pone.0008342
Mubarak, A., Alturaiki, W., & Hemida, M. G. (2019). Middle East
Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological
Response, and Vaccine Development. J Immunol Res, 2019 , 6491738.
doi:10.1155/2019/6491738
Newton, A. H., Cardani, A., & Braciale, T. J. (2016). The host immune
response in respiratory virus infection: balancing virus clearance and
immunopathology. Semin Immunopathol, 38 (4), 471-482.
doi:10.1007/s00281-016-0558-0
Ng, O.-W., Chia, A., Tan, A. T., Jadi, R. S., Leong, H. N., Bertoletti,
A., & Tan, Y.-J. (2016). Memory T cell responses targeting the SARS
coronavirus persist up to 11 years post-infection. Vaccine,
34 (17), 2008-2014.
doi:https://doi.org/10.1016/j.vaccine.2016.02.063
Okba, N. M. A., Müller, M. A., Li, W., Wang, C., GeurtsvanKessel, C. H.,
Corman, V. M., . . . Haagmans, B. L. (2020). Severe Acute Respiratory
Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus
Disease Patients. Emerg Infect Dis, 26 (7), 1478-1488.
doi:10.3201/eid2607.200841
Page, C., Goicochea, L., Matthews, K., Zhang, Y., Klover, P., Holtzman,
M. J., . . . Frieman, M. (2012). Induction of alternatively activated
macrophages enhances pathogenesis during severe acute respiratory
syndrome coronavirus infection. J Virol, 86 (24), 13334-13349.
doi:10.1128/jvi.01689-12
Panesar, N. S. Glucocorticoid treatment of patients with SARS:
implications for mechanisms of immunopathology : Nat Rev Immunol.
2006;6(4):334. doi: 10.1038/nri1835-c1.
Panesar, N. S. (2003). Lymphopenia in SARS. Lancet, 361 (9373),
1985. doi:10.1016/s0140-6736(03)13557-x
Panesar, N. S. (2008). What caused lymphopenia in SARS and how reliable
is the lymphokine status in glucocorticoid-treated patients? Med
Hypotheses, 71 (2), 298-301. doi:10.1016/j.mehy.2008.03.019
Perlman, S. (2020). Another Decade, Another Coronavirus. N Engl J
Med, 382 (8), 760-762. doi:10.1056/NEJMe2001126
Priyanka, Choudhary, O. P., & Singh, I. (2020). Protective immunity
against COVID-19: Unravelling the evidences for humoral vs. cellular
components. Travel Med Infect Dis, 39 , 101911.
doi:10.1016/j.tmaid.2020.101911
Prokunina-Olsson, L., Alphonse, N., Dickenson, R. E., Durbin, J. E.,
Glenn, J. S., Hartmann, R., . . . Odendall, C. (2020). COVID-19 and
emerging viral infections: The case for interferon lambda. Journal
of Experimental Medicine, 217 (5).
Prompetchara, E., Ketloy, C., & 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), 1-9.
doi:10.12932/ap-200220-0772
Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., . . . Tian,
D.-S. (2020). Dysregulation of Immune Response in Patients With
Coronavirus 2019 (COVID-19) in Wuhan, China. Clinical Infectious
Diseases, 71 (15), 762-768. doi:10.1093/cid/ciaa248
Rehman, S. U., Shafique, L., Ihsan, A., & Liu, Q. (2020). Evolutionary
Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2.Pathogens, 9 (3). doi:10.3390/pathogens9030240
Ren, L. L., Wang, Y. M., Wu, Z. Q., Xiang, Z. C., Guo, L., Xu, T., . . .
Wang, J. W. (2020). Identification of a novel coronavirus causing severe
pneumonia in human: a descriptive study. Chin Med J (Engl),
133 (9), 1015-1024. doi:10.1097/cm9.0000000000000722
Rogers, M. C., & Williams, J. V. (2018). Quis Custodiet Ipsos Custodes?
Regulation of Cell-Mediated Immune Responses Following Viral Lung
Infections. Annu Rev Virol, 5 (1), 363-383.
doi:10.1146/annurev-virology-092917-043515
Sainz, B., Jr., Mossel, E. C., Peters, C. J., & Garry, R. F. (2004).
Interferon-beta and interferon-gamma synergistically inhibit the
replication of severe acute respiratory syndrome-associated coronavirus
(SARS-CoV). Virology, 329 (1), 11-17.
doi:10.1016/j.virol.2004.08.011
Sariol, A., & Perlman, S. (2020). Lessons for COVID-19 Immunity from
Other Coronavirus Infections. Immunity, 53 (2), 248-263.
doi:10.1016/j.immuni.2020.07.005
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013).
Age-dependent dysregulation of innate immunity. Nat Rev Immunol,
13 (12), 875-887. doi:10.1038/nri3547
Siu, K. L., Chan, C. P., Kok, K. H., Chiu-Yat Woo, P., & Jin, D. Y.
(2014). Suppression of innate antiviral response by severe acute
respiratory syndrome coronavirus M protein is mediated through the first
transmembrane domain. Cell Mol Immunol, 11 (2), 141-149.
doi:10.1038/cmi.2013.61
Siu, K. L., Kok, K. H., Ng, M. H., Poon, V. K., Yuen, K. Y., Zheng, B.
J., & Jin, D. Y. (2009). Severe acute respiratory syndrome coronavirus
M protein inhibits type I interferon production by impeding the
formation of TRAF3.TANK.TBK1/IKKepsilon complex. J Biol Chem,
284 (24), 16202-16209. doi:10.1074/jbc.M109.008227
Smits, S. L., de Lang, A., van den Brand, J. M., Leijten, L. M., van, I.
W. F., Eijkemans, M. J., . . . Haagmans, B. L. (2010). Exacerbated
innate host response to SARS-CoV in aged non-human primates. PLoS
Pathog, 6 (2), e1000756. doi:10.1371/journal.ppat.1000756
Song, C.-Y., Xu, J., He, J.-Q., & Lu, Y.-Q. (2020). COVID-19 early
warning score: a multi-parameter screening tool to identify highly
suspected patients. In: medRxiv.
Stanifer, M. L., Kee, C., Cortese, M., Triana, S., Mukenhirn, M.,
Kraeusslich, H.-G., . . . Boulant, S. (2020). Critical role of type III
interferon in controlling SARS-CoV-2 infection, replication and spread
in primary human intestinal epithelial cells. bioRxiv ,
2020.2004.2024.059667. doi:10.1101/2020.04.24.059667
Ströher, U., DiCaro, A., Li, Y., Strong, J. E., Aoki, F., Plummer, F., .
. . Feldmann, H. (2004). Severe acute respiratory syndrome-related
coronavirus is inhibited by interferon- alpha. J Infect Dis,
189 (7), 1164-1167. doi:10.1086/382597
Tanaka, T., Narazaki, M., & Kishimoto, T. (2016). Immunotherapeutic
implications of IL-6 blockade for cytokine storm. Immunotherapy,
8 (8), 959-970. doi:10.2217/imt-2016-0020
Tang, N., Li, D., Wang, X., & Sun, Z. (2020). Abnormal coagulation
parameters are associated with poor prognosis in patients with novel
coronavirus pneumonia. J Thromb Haemost, 18 (4), 844-847.
doi:10.1111/jth.14768
Thevarajan, I., Nguyen, T. H. O., Koutsakos, M., Druce, J., Caly, L.,
van de Sandt, C. E., . . . Kedzierska, K. (2020). Breadth of concomitant
immune responses prior to patient recovery: a case report of non-severe
COVID-19. Nat Med, 26 (4), 453-455. doi:10.1038/s41591-020-0819-2
To, K. K., Tsang, O. T., Leung, W. S., Tam, A. R., Wu, T. C., Lung, D.
C., . . . Yuen, K. Y. (2020). Temporal profiles of viral load in
posterior oropharyngeal saliva samples and serum antibody responses
during infection by SARS-CoV-2: an observational cohort study.Lancet Infect Dis, 20 (5), 565-574.
doi:10.1016/s1473-3099(20)30196-1
Totura, A. L., & Baric, R. S. (2012). SARS coronavirus pathogenesis:
host innate immune responses and viral antagonism of interferon.Curr Opin Virol, 2 (3), 264-275. doi:10.1016/j.coviro.2012.04.004
Travaglini, K. J., Nabhan, A. N., Penland, L., Sinha, R., Gillich, A.,
Sit, R. V., . . . Krasnow, M. A. (2020). A molecular cell atlas of the
human lung from single cell RNA sequencing. bioRxiv , 742320.
doi:10.1101/742320
Tseng, C. T., Perrone, L. A., Zhu, H., Makino, S., & Peters, C. J.
(2005). Severe acute respiratory syndrome and the innate immune
responses: modulation of effector cell function without productive
infection. J Immunol, 174 (12), 7977-7985.
doi:10.4049/jimmunol.174.12.7977
Vivier, E., Artis, D., Colonna, M., Diefenbach, A., Di Santo, J. P.,
Eberl, G., . . . Spits, H. (2018). Innate Lymphoid Cells: 10 Years On.Cell, 174 (5), 1054-1066.
doi:https://doi.org/10.1016/j.cell.2018.07.017
Von Holle, T. A., & Moody, M. A. (2019). Influenza and
Antibody-Dependent Cellular Cytotoxicity. Front Immunol, 10 ,
1457. doi:10.3389/fimmu.2019.01457
Walter, J. M., Helmin, K. A., Abdala-Valencia, H., Wunderink, R. G., &
Singer, B. D. (2018). Multidimensional assessment of alveolar T cells in
critically ill patients. JCI insight, 3 (17).
Wang, C., Horby, P. W., Hayden, F. G., & Gao, G. F. (2020). A novel
coronavirus outbreak of global health concern. Lancet,
395 (10223), 470-473. doi:10.1016/s0140-6736(20)30185-9
Wang, C. H., Liu, C. Y., Wan, Y. L., Chou, C. L., Huang, K. H., Lin, H.
C., . . . Kuo, H. P. (2005). Persistence of lung inflammation and lung
cytokines with high-resolution CT abnormalities during recovery from
SARS. Respir Res, 6 (1), 42. doi:10.1186/1465-9921-6-42
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., . . . Peng, Z.
(2020). Clinical Characteristics of 138 Hospitalized Patients With 2019
Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama,
323 (11), 1061-1069. doi:10.1001/jama.2020.1585
Wang, F., Nie, J., Wang, H., Zhao, Q., Xiong, Y., Deng, L., . . . Zhang,
Y. (2020). Characteristics of Peripheral Lymphocyte Subset Alteration in
COVID-19 Pneumonia. J Infect Dis, 221 (11), 1762-1769.
doi:10.1093/infdis/jiaa150
Wathelet, M. G., Orr, M., Frieman, M. B., & Baric, R. S. (2007). Severe
acute respiratory syndrome coronavirus evades antiviral signaling: role
of nsp1 and rational design of an attenuated strain. J Virol,
81 (21), 11620-11633. doi:10.1128/jvi.00702-07
Weiskopf, D., Schmitz, K. S., Raadsen, M. P., Grifoni, A., Okba, N. M.
A., Endeman, H., . . . de Vries, R. D. (2020). Phenotype and kinetics of
SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory
distress syndrome. Sci Immunol, 5 (48).
doi:10.1126/sciimmunol.abd2071
Wilk, A. J., Rustagi, A., Zhao, N. Q., Roque, J., Martínez-Colón, G. J.,
McKechnie, J. L., . . . Blish, C. A. (2020). A single-cell atlas of the
peripheral immune response in patients with severe COVID-19. Nat
Med, 26 (7), 1070-1076. doi:10.1038/s41591-020-0944-y
Wong, C. K., Lam, C. W., Wu, A. K., Ip, W. K., Lee, N. L., Chan, I. H.,
. . . Sung, J. J. (2004). Plasma inflammatory cytokines and chemokines
in severe acute respiratory syndrome. Clin Exp Immunol, 136 (1),
95-103. doi:10.1111/j.1365-2249.2004.02415.x
Woo, P. C., Lau, S. K., Wong, B. H., Chan, K. H., Chu, C. M., Tsoi, H.
W., . . . Yuen, K. Y. (2004). Longitudinal profile of immunoglobulin G
(IgG), IgM, and IgA antibodies against the severe acute respiratory
syndrome (SARS) coronavirus nucleocapsid protein in patients with
pneumonia due to the SARS coronavirus. Clin Diagn Lab Immunol,
11 (4), 665-668. doi:10.1128/cdli.11.4.665-668.2004
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L.,
Abiona, O., . . . McLellan, J. S. (2020). Cryo-EM structure of the
2019-nCoV spike in the prefusion conformation. Science,
367 (6483), 1260-1263. doi:10.1126/science.abb2507
Wu, F., Liu, M., Wang, A., Lu, L., Wang, Q., Gu, C., . . . Huang, J.
(2020). Evaluating the Association of Clinical Characteristics With
Neutralizing Antibody Levels in Patients Who Have Recovered From Mild
COVID-19 in Shanghai, China. JAMA Intern Med, 180 (10), 1356-1362.
doi:10.1001/jamainternmed.2020.4616
Xie, J., Fan, H. W., Li, T. S., Qiu, Z. F., & Han, Y. (2006).
[Dynamic changes of T lymphocyte subsets in the long-term follow-up of
severe acute respiratory syndrome patients]. Zhongguo Yi Xue Ke
Xue Yuan Xue Bao, 28 (2), 253-255.
Xu, X., & Gao, X. (2004). Immunological responses against
SARS-coronavirus infection in humans. Cell Mol Immunol, 1 (2),
119-122.
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., . . . Wang,
F. S. (2020). Pathological findings of COVID-19 associated with acute
respiratory distress syndrome. Lancet Respir Med, 8 (4), 420-422.
doi:10.1016/s2213-2600(20)30076-x
Yang, C. Y., Chen, C. S., Yiang, G. T., Cheng, Y. L., Yong, S. B., Wu,
M. Y., & Li, C. J. (2018). New Insights into the Immune Molecular
Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome.Int J Mol Sci, 19 (2). doi:10.3390/ijms19020588
Yang, Y., Zhang, L., Geng, H., Deng, Y., Huang, B., Guo, Y., . . . Tan,
W. (2013). The structural and accessory proteins M, ORF 4a, ORF 4b, and
ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are
potent interferon antagonists. Protein Cell, 4 (12), 951-961.
doi:10.1007/s13238-013-3096-8
Ying, T., Li, W., & Dimitrov, D. S. (2016). Discovery of T-Cell
Infection and Apoptosis by Middle East Respiratory Syndrome Coronavirus.J Infect Dis, 213 (6), 877-879. doi:10.1093/infdis/jiv381
Yu, L., Tong, Y., Shen, G., Fu, A., Lai, Y., Zhou, X., . . . Yu, Z.
(2020). Immunodepletion with Hypoxemia: A Potential High Risk Subtype of
Coronavirus Disease 2019. medRxiv .
Zhang, Y., Li, J., Zhan, Y., Wu, L., Yu, X., Zhang, W., . . . Lou, J.
(2004). Analysis of serum cytokines in patients with severe acute
respiratory syndrome. Infect Immun, 72 (8), 4410-4415.
doi:10.1128/iai.72.8.4410-4415.2004
Zhao, J., Li, K., Wohlford-Lenane, C., Agnihothram, S. S., Fett, C.,
Zhao, J., . . . Perlman, S. (2014). Rapid generation of a mouse model
for Middle East respiratory syndrome. Proc Natl Acad Sci U S A,
111 (13), 4970-4975. doi:10.1073/pnas.1323279111
Zhao, X., Sehgal, M., Hou, Z., Cheng, J., Shu, S., Wu, S., . . . Chang,
J. (2018). Identification of residues controlling restriction versus
enhancing activities of IFITM proteins on entry of human coronaviruses.J Virol, 92 (6).
Zheng, M., Gao, Y., Wang, G., Song, G., Liu, S., Sun, D., . . . Tian, Z.
(2020). Functional exhaustion of antiviral lymphocytes in COVID-19
patients. Cell Mol Immunol, 17 (5), 533-535.
doi:10.1038/s41423-020-0402-2
Zhou, G., & Zhao, Q. (2020). Perspectives on therapeutic neutralizing
antibodies against the Novel Coronavirus SARS-CoV-2. Int J Biol
Sci, 16 (10), 1718-1723. doi:10.7150/ijbs.45123
Zhou, J., Chu, H., Li, C., Wong, B. H., Cheng, Z. S., Poon, V. K., . . .
Yuen, K. Y. (2014). Active replication of Middle East respiratory
syndrome coronavirus and aberrant induction of inflammatory cytokines
and chemokines in human macrophages: implications for pathogenesis.J Infect Dis, 209 (9), 1331-1342. doi:10.1093/infdis/jit504
Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., . . .
Shi, Z. L. (2020). A pneumonia outbreak associated with a new
coronavirus of probable bat origin. Nature, 579 (7798), 270-273.
doi:10.1038/s41586-020-2012-7
Zhou, Y., Fu, B., Zheng, X., Wang, D., Zhao, C., qi, Y., . . . Wei, H.
(2020a). Aberrant pathogenic
GM-CSF<sup>+</sup> T cells
and inflammatory
CD14<sup>+</sup>CD16<sup>+</sup>
monocytes in severe pulmonary syndrome patients of a new coronavirus.bioRxiv , 2020.2002.2012.945576. doi:10.1101/2020.02.12.945576
Zhou, Y., Fu, B., Zheng, X., Wang, D., Zhao, C., Qi, Y., . . . Wei, H.
(2020b). Pathogenic T-cells and inflammatory monocytes incite
inflammatory storms in severe COVID-19 patients. National Science
Review, 7 (6), 998-1002. doi:10.1093/nsr/nwaa041
Zhou, Y., Yang, Y., Huang, J., Jiang, S., & Du, L. (2019). Advances in
MERS-CoV vaccines and therapeutics based on the receptor-binding domain.Viruses, 11 (1), 60.
Zhu, Z., Chakraborti, S., He, Y., Roberts, A., Sheahan, T., Xiao, X., .
. . Dimitrov, D. S. (2007). Potent cross-reactive neutralization of SARS
coronavirus isolates by human monoclonal antibodies. Proceedings
of the National Academy of Sciences, 104 (29), 12123-12128.
doi:10.1073/pnas.0701000104
Zielecki, F., Weber, M., Eickmann, M., Spiegelberg, L., Zaki, A. M.,
Matrosovich, M., . . . Weber, F. (2013). Human cell tropism and innate
immune system interactions of human respiratory coronavirus EMC compared
to those of severe acute respiratory syndrome coronavirus. J
Virol, 87 (9), 5300-5304. doi:10.1128/jvi.03496-12
Zornetzer, G. A., Frieman, M. B., Rosenzweig, E., Korth, M. J., Page,
C., Baric, R. S., & Katze, M. G. (2010). Transcriptomic analysis
reveals a mechanism for a prefibrotic phenotype in STAT1 knockout mice
during severe acute respiratory syndrome coronavirus infection. J
Virol, 84 (21), 11297-11309. doi:10.1128/jvi.01130-10
Figure 1. The illustration of escalating phases of COVID-19
disease progression, with associated signs and symptoms from the onset
to recovery or death. Infection with SARS-CoV-2 (COVID-19) can be
classified into three stages of increasing severity: early infection,
pulmonary phase, and hyperinflammation phase. The first phase is related
to the onset of the disease and is generally characterized by the
development of influenza-like symptoms from mild to moderate. Some
individuals recover and some progress to the second phase. In phase 2,
it is possible to detect pneumonia-like symptoms evidenced as lung
opacities. Phase 3 is characterized by hyperinflammation and sepsis of
lungs and patient often requires intensive care unit (ICU) and most of
them unfortunately cannot overcome the infection and eventually die.
Figure 2. Manifestations of COVID-19 in body. Spike protein on
the virion binds to ACE2, a cell-surface protein. TMPRSS2, an enzyme,
helps the virion enter. The virion releases its RNA. Some RNA is
translated into proteins by the cell’s machinery and some of these
proteins form a replication complex to make more RNA. Then, RNAs are
assembled into a new virion in the Golgi and released. Infection with
SARS-CoV-2 leads to activation of innate immunity and DCs, which will
drive the induction of virus-specific T cell and B cell responses.
Hyperinflammation by innate and adaptive leads to cytokine storm
thorough inflammatory cytokine secretion. COVID-19 manifestations
including pulmonary involvement, ARDS, encephalitis, renal injury, and
intestinal flora disturbance pneumonia and, are well recognized.
CTL, cytotoxic T lymphocyte; TFH, T follicular helper cell; TH, T helper
cell; Treg, regulatory T cell; DCs, dendritic cell.
Figure 3. The time kinetics between viral load, symptoms, and
host immunoglobulins (IgM, IgG) in COVID-19. The onset of symptoms is
usually 5 days after infection. Seroconversion may usually be detectable
between 5–7 days and 14 days after the onset of symptoms. Viral RNA is
inversely correlated with neutralizing antibody titers. Higher titers
have been observed in critically ill patients. The humoral response in
SARS-CoV-1 is relatively short lived, altogether, suggesting that
immunity with SARS-CoV-2 may reduce 1–2 years after primary infection.