Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns

Suliman Khan, Jianbo Liu, Mengzhou Xue, Suliman Khan, Jianbo Liu, Mengzhou Xue

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal-oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.

Keywords: challenges; coronavirus outbreak; infectiousness; medical consequences; prevention.

Copyright © 2020 Khan, Liu and Xue.

Figures

Figure 1
Figure 1
The most common entry to host cells mechanisms of human viruses. (A) SARS-CoV entry. Key points are, virion attachment to receptor; virion internalization by endocytosis; lowering the pH (5.5) of the endocytic vacuole leading to drastic reconfiguration of the viral attachment protein; insertion into the vacuolar membrane; fusion of vacuolar membranes and the viral; viral nucleocapsid release into the cytosol. (B) Poliovirus entry. virion binding to cell surface receptors, endocytosed and ultimately delivered to endosomes (low pH); conformational changes in viral capsid due to low pH environment result in exposure of hydrophobic domains that insert into the endosomal membrane, producing a pore for viral genome exit and entry into cytoplasm. (C) HIV entry. Virion attaches to various attachment factor on cell surface, such as DC-SIGN. The attachment of viral envelope glycoprotein to CD4 alters the structure of envelope glycoprotein, which then induces the second receptor binding domain exposure resulting in the engagement of CCR5 or CXCR4 coreceptors, that in turn causes the viral fusion with the cell membrane.
Figure 2
Figure 2
The SARS-CoV-2 transmission from bats via unknown intermediate to humans causes infectiousness known as COVID-19 disease. The binding of S protein to ACE2 receptor initiates the life cycle which is then followed by conformational changes in the S protein, which further facilitates the fusion of viral envelope and host cell membrane. Following the fusion through endosomal pathway, SARS-CoV-2 then releases RNA into the host cell, which is translated into pp1a and pp1ab. Next, viral proteinases cleave the translated proteins into small products, meanwhile a series of sub-genomic mRNAs are produced by polymerase enzyme through discontinuous transcription, which are then translated into specific viral proteins. These viral proteins and genome RNA are assembled to form virions in Golgi and endoplasmic reticulum, which are later transported out of the cell via vesicles. This figure was designed by updating and modifying the information from our previously published paper (29).

References

    1. Situation Report – 128 Coronavirus Disease COVID-2019. World Health Organization (2020). Available online at: (accessed April 28, 2020).
    1. Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med. (2020) 18:164. 10.1186/s12967-020-02339-3
    1. Khan S, Nabi G, Han G, Siddique R, Lian S, Shi H, et al. . Novel coronavirus: how the things are in Wuhan. Clin Microbiol Infect. (2020) 26:399–400. 10.1016/j.cmi.2020.02.005
    1. Xiang Y-T, Yang Y, Li W, Zhang L, Zhang Q, Cheung T, et al. . Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. Lancet Psychiatry. (2020) 0366:2019–20. 10.1016/S2215-0366(20)30046-8
    1. Khan S, Siddique R, Li H, Ali A, Adnan M, Bashir N, et al. . Impact of coronavirus outbreak on psychological health. J Glob Health. (2020) 10:1–6. 10.7189/jogh.10.010331
    1. Khan S, Ali A, Siddique R, Nabi G. Novel coronavirus is putting the whole world on alert. J Hosp Infect. (2020) 104:252–3. 10.1016/j.jhin.2020.01.019
    1. Khan S, Siddique R, Ali A, Xue M, Nabi G. Novel coronavirus, poor quarantine, and the risk of pandemic. J Hosp Infect. (2020) 104:449–50. 10.1016/j.jhin.2020.02.002
    1. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. (2020) 6736:1–10. 10.1016/S0140-67362030251-8
    1. Ji W, Wang W, Zhao X, Zai J, Li X. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol. (2020) 92:433–40. 10.1002/jmv.25682
    1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. (2020) 323:1061–9. 10.1001/jama.2020.1585
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. . Articles clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. (2020) 6736:1–10. 10.1016/S0140-67362030183-5
    1. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. . The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. (2020) 172:577–82. 10.7326/M20-0504
    1. Chan JFW, Yuan S, Kok KH, To KKW, Chu H, Yang J, 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) 395:514–23. 10.1016/S0140-67362030154-9
    1. Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect. (2020) 50:332–4. 10.1016/j.medmal.2020.03.007
    1. Zhao Z, Zhang F, Xu M, Huang K, Zhong W, Cai W, et al. . Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J Med Microbiol. (2003) 52:715–20. 10.1099/jmm.0.05320-0
    1. Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen KY. Coronaviruses-drug discovery and therapeutic options. Nat Rev Drug Discov. (2016) 15:327–47. 10.1038/nrd.2015.37
    1. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. (2019) 17:181–92. 10.1038/s41579-018-0118-9
    1. de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, Enjuanes L, et al. . Commentary: Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J Virol. (2013) 87:7790–2. 10.1128/JVI.01244-13
    1. Bawazir A, Al-Mazroo E, Jradi H, Ahmed A, Badri M. MERS-CoV infection: mind the public knowledge gap. J Infect Public Health. (2018) 11:89–93. 10.1016/j.jiph.2017.05.003
    1. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. . Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. (2020) 11:222. 10.1038/s41467-019-13940-6
    1. Killerby ME, Biggs HM, Midgley CM, Gerber SI, Watson JT. Middle east respiratory syndrome coronavirus transmission. Emerg Infect Dis. (2020) 26:191–8. 10.3201/eid2602.190697
    1. Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. (2020) 382:1–7. 10.1056/NEJMoa2001017
    1. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. (2020) 579:270–3. 10.1038/s41586-020-2012-7
    1. Phan LT, Nguyen TV, Luong QC, Nguyen TV, Nguyen HT, Le HQ, et al. . Importation and human-to-human transmission of a novel coronavirus in vietnam. N Engl J Med. (2020) 382:872–4. 10.1056/NEJMc2001272
    1. Taylor D, Lindsay AC, Halcox JP. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. (2010) 382:1564–7. 10.1056/NEJMc2004973
    1. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. . Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med. (2020) 382:970–1. 10.1056/NEJMc2001468
    1. Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al. . A new coronavirus associated with human respiratory disease in China. Nature. (2020) 579:265–9. 10.1038/s41586-020-2008-3
    1. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation and treatment coronavirus (COVID-19). In: StatPearls. Napoli: StatPearls Publishing.
    1. Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. J Adv Res. (2020) 24:91–8. 10.1016/j.jare.2020.03.005
    1. Dong N, Yang X, Ye L, Chen K, Chan EW-C, Chen S. Genomic and protein structure modelling analysis depicts the origin and pathogenicity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China. F1000Research. (2020) 9:121 10.12688/f1000research.22357.1
    1. Qian Z, Travanty EA, Oko L, Edeen K, Berglund A, Wang J, et al. . Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. (2013) 48:742–8. 10.1165/rcmb.2012-0339OC
    1. Raj VS, Mou H, Smits SL, Dekkers DHW, Müller MA, Dijkman R, et al. . Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. (2013) 495:251–4. 10.1038/nature12005
    1. Boulant S, Stanifer M, Lozach P-Y. Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis. Viruses. (2015) 7:2794–815. 10.3390/v7062747
    1. White JM, Whittaker GR. Fusion of enveloped viruses in endosomes. Traffic. (2016) 17:593–614. 10.1111/tra.12389
    1. Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci USA. (2009) 106:5871–6. 10.1073/pnas.0809524106
    1. Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol. (2016) 3:237–61. 10.1146/annurev-virology-110615-042301
    1. Gui M, Song W, Zhou H, Xu J, Chen S, Xiang Y, et al. . Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. (2017) 27:119–29. 10.1038/cr.2016.152
    1. Angeletti S, Benvenuto D, Bianchi M, Giovanetti M, Pascarella S, Ciccozzi M. COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis. J Med Virol. (2020). 10.1002/jmv.25719. [Epub ahead of print].
    1. Lei J, Kusov Y, Hilgenfeld R. Nsp3 of coronaviruses: structures and functions of a large multi-domain protein. Antiviral Res. (2018) 149:58–74. 10.1016/j.antiviral.2017.11.001
    1. Tang X, Wu C, Li X, Song Y, Yao X, Wu X, et al. On the origin and continuing evolution of SARS-CoV-2. Natl Sci Rev. (2020) nwaa036. 10.1093/nsr/nwaa036
    1. Liu P, Jiang J-Z, Wan X-F, Hua Y, Li L, Zhou J, et al. . Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? PLOS Pathog. (2020) 16:e1008421. 10.1371/journal.ppat.1008421
    1. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med. (2020) 26:450–2. 10.1038/s41591-020-0820-9
    1. Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, et al. . Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options. J Clin Microbiol. (2020) 58:e00187-20. 10.1128/JCM.00187-20
    1. Sutton TC, Subbarao K. Development of animal models against emerging coronaviruses: from SARS to MERS coronavirus. Virology. (2015) 479–80:247–58. 10.1016/j.virol.2015.02.030
    1. CDC Coronavirus Disease (COVID-19). Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings. Available online at: (accessed April 13, 2020).
    1. WHO Coronavirus Disease (COVID-19). Advice for the Public. (2020). Available online at:
    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. (2020) 323:1239–42. 10.1001/jama.2020.2648
    1. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. (2020). 10.1002/jmv.25728. [Epub ahead of print].
    1. Luo J, Rizvi H, Egger JV, Preeshagul IR, Wolchok JD, Hellmann MD. Impact of PD-1 blockade on severity of COVID-19 in patients with lung cancers. Cancer Discov. (2020) CD-20-0596. 10.1158/-20-0596
    1. Härter G, Spinner CD, Roider J, Bickel M, Krznaric I, Grunwald S, et al. . COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. Infection. (2020). 10.1007/s15010-020-01438-z. [Epub ahead of print].
    1. CDC People Who Are at Higher Risk for Severe Illness (Older Adults). (2020) Available online at: (accessed April 20, 2020).
    1. Khan S, Jun L, Nawsherwan Siddique R, Li Y, Han G, et al. . Association of COVID-19 infection with pregnancy outcomes in healthcare workers and general women. Clin Microbiol Infect. (2020) 26:788–90. 10.1016/j.cmi.2020.03.034
    1. Dong L, Tian J, He S, Zhu C, Wang J, Liu C, et al. . Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA. (2020) 323:1846–8. 10.1001/jama.2020.4621
    1. Patel A, Jernigan DB, Team 2019-nCoV CDC response. Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020. MMWR Morb Mortal Wkly Rep. (2020) 69:140–6. 10.15585/mmwr.mm6908e1
    1. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. (2020) 6736:1–7. 10.1016/S0140-67362030360-3
    1. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. (2020) 382:929–36. 10.1056/NEJMoa2001191
    1. Triggle CR, Bansal D, Farag EABA, Ding H, Sultan AA. COVID-19: learning from lessons to guide treatment and prevention interventions. mSphere. (2020) 5:e00317–20. 10.1128/mSphere.00317-20
    1. Khan S, Siddique R, Li Z, Xue M, Liu J. COVID-19 pandemic; prevention, treatment, and mental health. Hum Vaccin Immunother. (2020). 10.1080/21645515.2020.1759976
    1. Wohlford-Lenane CL, Meyerholz DK, Perlman S, Zhou H, Tran D, Selsted ME, et al. Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease. J Virol. (2009) 83:11385–90. 10.1128/JVI.01363-09
    1. Wiley JA, Richert LE, Swain SD, Harmsen A, Barnard DL, Randall TD, et al. . Inducible bronchus-associated lymphoid tissue elicited by a protein cage nanoparticle enhances protection in mice against diverse respiratory viruses. PLoS ONE. (2009) 4:e0007142. 10.1371/journal.pone.0007142

Source: PubMed

3
Subskrybuj