COVID-19 pathophysiology: A review

Koichi Yuki, Miho Fujiogi, Sophia Koutsogiannaki, Koichi Yuki, Miho Fujiogi, Sophia Koutsogiannaki

Abstract

In December 2019, a novel coronavirus, now named as SARS-CoV-2, caused a series of acute atypical respiratory diseases in Wuhan, Hubei Province, China. The disease caused by this virus was termed COVID-19. The virus is transmittable between humans and has caused pandemic worldwide. The number of death tolls continues to rise and a large number of countries have been forced to do social distancing and lockdown. Lack of targeted therapy continues to be a problem. Epidemiological studies showed that elder patients were more susceptible to severe diseases, while children tend to have milder symptoms. Here we reviewed the current knowledge about this disease and considered the potential explanation of the different symptomatology between children and adults.

Conflict of interest statement

Declaration of Competing Interest None.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
ACE expression on mouse immune cells. ACE2 expression was examined in Immgen (http://rstats.immgen.org/Skyline/skyline.html). BM, bone marrow; Sp, Spleen; PC, peritoneal cavity; Th, thymus; LN, lymph node; SI, small intestine; Lu, lung; CNS, central nervous system; SLN, subcutaneous lymph node.
Fig. 2
Fig. 2
Age-dependent ACE2 expression profiles in the mouse lung. Using Lung Gene Expression Analysis Web Portal (https://research.cchmc.org/pbge/lunggens/mainportal.html), the expression of ACE2 was examined. This data was obtained from microarray experiments of three mice strains A/J mice, C57BL/6J mice and C3H/HeJ mice at different ages [72]. X axis showed age and mouse strain, and y axis showed ACE2 expression level. M.

References

    1. Ksiazek T.G., Erdman D., Goldsmith C.S., Zaki S.R., Peret T., Emery S., Tong S., Urbani C., Comer J.A., Lim W., Rollin P.E., Dowell S.F., Ling A.E., Humphrey C.D., Shieh W.J., Guarner J., Paddock C.D., Rota P., Fields B., DeRisi J., Yang J.Y., Cox N., Hughes J.M., LeDuc J.W., Bellini W.J., Anderson L.J., SW Group A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348:1953–1966.
    1. Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y., Ren R., Leung K.S.M., Lau E.H.Y., Wong J.Y., Xing X., Xiang N., Wu Y., Li C., Chen Q., Li D., Liu T., Zhao J., Liu M., Tu W., Chen C., Jin L., Yang R., Wang Q., Zhou S., Wang R., Liu H., Luo Y., Liu Y., Shao G., Li H., Tao Z., Yang Y., Deng Z., Liu B., Ma Z., Zhang Y., Shi G., Lam T.T.Y., Wu J.T., Gao G.F., Cowling B.J., Yang B., Leung G.M., Feng Z. Early transmission dynamics in Wuhan, China, of Novel Coronavirus-infected pneumonia. N Engl J Med. 2020;382:1199–1207.
    1. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., Xu Y., Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 doi: 10.1038/s41423-020-0402-2.
    1. Zhang J., Litvinova M., Wang W., Wang Y., Deng X., Chen X., Li M., Zheng W., Yi L., Chen X., Wu Q., Liang Y., Wang X., Yang J., Sun K., Longini I.M., Jr., Halloran M.E., Wu P., Cowling B.J., Merler S., Viboud C., Vespignani A., Ajelli M., Yu H. Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30230-9.
    1. JHUoMCr center Journal. 2020
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. 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.
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.
    1. Lu X., Zhang L., Du H., Zhang J., Li Y.Y., Qu J., Zhang W., Wang Y., Bao S., Li Y., Wu C., Liu H., Liu D., Shao J., Peng X., Yang Y., Liu Z., Xiang Y., Zhang F., Silva R.M., Pinkerton K.E., Shen K., Xiao H., Xu S., Wong G.W.K., T Chinese Pediatric Novel Coronavirus Study SARS-CoV-2 infection in children. N Engl J Med. 2020 doi: 10.1056/NEJMc2005073.
    1. Qiu H., Wu J., Hong L., Luo Y., Song Q., Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30198-5.
    1. Cao B. A trial of Lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020 doi: 10.1056/NEJMoa2001282.
    1. Gautret P., Lagier J.C., Parola P., Hoang V.T., Meddeb L., Mailhe M., Doudier B., Courjon J., Giordanengo V., Vieira V.E., Dupont H.T., Honore S., Colson P., Chabriere E., La Scola B., Rolain J.M., Brouqui P., Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;105949
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
    1. Wu Z., McGoogan J.M. 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 doi: 10.1001/jama.2020.2648.
    1. Onder G., Rezza G., Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 doi: 10.1001/jama.2020.4683.
    1. Du Y., Tu L., Zhu P., Mu M., Wang R., Yang P., Wang X., Hu C., Ping R., Hu P., Li T., Cao F., Chang C., Hu Q., Jin Y., Xu G. Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational Study. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202003-0543OC.
    1. Gao Y., Li T., Han M., Li X., Wu D., Xu Y., Zhu Y., Liu Y., Wang X., Wang L. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020 doi: 10.1002/jmv.25770.
    1. Livingston E., Bucher K. Coronavirus disease 2019 (COVID-19) in Italy. Journal. 2020 doi: 10.1001/jama.2020.4344.
    1. Tcfc Information. Journal.
    1. Dong Y., Mo X., Hu Y., Qi X., Jiang F., Jiang Z., Tong S. Epidemiological characteristics of 2143 Pediatric patients with 2019 coronavirus disease in China. Journal. 2020 doi: 10.1542/peds.2020-0702.
    1. Brodin P. Why is COVID-19 so mild in children? Journal. 2020 doi: 10.1111/apa.15271.
    1. CfDCa Prevention. Journal.
    1. Wenham C., Smith J., Morgan R., Gender and C-W Group COVID-19: the gendered impacts of the outbreak. Journal. 2020;395:846–848.
    1. Jin J., Bai P., He W., Wu F., Liu W.F., Han D.M., Liu S., Yang J.K. Gender differences in patients with COVID-19: focus on severity and mortality. Journal. 2020
    1. Hall K.S., Samari G., Garbers S., Casey S.E., Diallo D.D., Orcutt M., Moresky R.T., Martinez M.E., McGovern T. Centring sexual and reproductive health and justice in the global COVID-19 response. Journal. 2020;395:1175–1177.
    1. Moran K.R., Del Valle S.Y. A meta-analysis of the association between gender and protective behaviors in response to respiratory epidemics and pandemics. Journal. 2016;11
    1. Channappanavar R., Zhao J., Perlman S. T cell-mediated immune response to respiratory coronaviruses. Journal. 2014;59:118–128.
    1. Rabi F.A., Al Zoubi M.S., Kasasbeh G.A., Salameh D.M., Al-Nasser A.D. SARS-CoV-2 and Coronavirus disease 2019: what we know so far. Journal. 2020;9
    1. Bosch B.J., van der Zee R., de Haan C.A., Rottier P.J. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. Journal. 2003;77:8801–8811.
    1. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Journal. 2003;426:450–454.
    1. Chen Y., Guo Y., Pan Y., Zhao Z.J. Structure analysis of the receptor binding of 2019-nCoV. Journal. 2020 doi: 10.1016/j.bbrc.2020.02.071.
    1. Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Journal. 2020 doi: 10.1016/j.cell.2020.02.058.
    1. Letko M., Marzi A., Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Journal. 2020;5:562–569.
    1. Zou X., Chen K., Zou J., Han P., Hao J., Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Journal. 2020 doi: 10.1007/s11684-020-0754-0.
    1. Belouzard S., Chu V.C., Whittaker G.R. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Journal. 2009;106:5871–5876.
    1. Millet J.K., Whittaker G.R. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Journal. 2014;111:15214–15219.
    1. Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T., Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Journal. 2020;11:1620.
    1. Belouzard S., Millet J.K., Licitra B.N., Whittaker G.R. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Journal. 2012;4:1011–1033.
    1. Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Muller M.A., Drosten C., Pohlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Journal. 2020 doi: 10.1016/j.cell.2020.02.052.
    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.C., Du B., Li L.J., Zeng G., Yuen K.Y., Chen R.C., Tang C.L., Wang T., Chen P.Y., Xiang J., Li S.Y., Wang J.L., Liang Z.J., Peng Y.X., Wei L., Liu Y., Hu Y.H., Peng P., Wang J.M., Liu J.Y., Chen Z., Li G., Zheng Z.J., Qiu S.Q., Luo J., Ye C.J., Zhu S.Y., Zhong N.S., C China Medical Treatment Expert Group for Clinical characteristics of coronavirus disease 2019 in China. Journal. 2020 doi: 10.1056/NEJMoa2002032.
    1. Hamming I., Timens W., Bulthuis M.L., Lely A.T., Navis G., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. Journal. 2004;203:631–637.
    1. Jia H.P., Look D.C., Shi L., Hickey M., Pewe L., Netland J., Farzan M., Wohlford-Lenane C., Perlman S., McCray P.B., Jr. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. Journal. 2005;79:14614–14621.
    1. Yoshikawa T., Hill T., Li K., Peters C.J., Tseng C.T. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. Journal. 2009;83:3039–3048.
    1. Fujimoto I., Pan J., Takizawa T., Nakanishi Y. Virus clearance through apoptosis-dependent phagocytosis of influenza A virus-infected cells by macrophages. Journal. 2000;74:3399–3403.
    1. Jeffers S.A., Tusell S.M., Gillim-Ross L., Hemmila E.M., Achenbach J.E., Babcock G.J., Thomas W.D., Jr., Thackray L.B., Young M.D., Mason R.J., Ambrosino D.M., Wentworth D.E., Demartini J.C., Holmes K.V. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Journal. 2004;101:15748–15753.
    1. Marzi A., Gramberg T., Simmons G., Moller P., Rennekamp A.J., Krumbiegel M., Geier M., Eisemann J., Turza N., Saunier B., Steinkasserer A., Becker S., Bates P., Hofmann H., Pohlmann S. DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. Journal. 2004;78:12090–12095.
    1. Yang Z.Y., Huang Y., Ganesh L., Leung K., Kong W.P., Schwartz O., Subbarao K., Nabel G.J. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. Journal. 2004;78:5642–5650.
    1. Zhou Y., Fu B., Zheng X., Wnag D., Zhao C., Qi Y., Sun R., Tian Z., Xu X., Wei H. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Journal. 2020
    1. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., Tian D.S. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Journal. 2020 doi: 10.1093/cid/ciaa248.
    1. Huang H., Wang S., Jiang T., Fan R., Zhang Z., Mu J., Li K., Wang Y., Jin L., Lin F., Xia J., Sun L., Xu B., Ji C., Chen J., Chang J., Tu B., Song B., Zhang C., Wang F.S., Xu R. High levels of circulating GM-CSF(+)CD4(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study. Journal. 2019;16:602–610.
    1. Croxford A.L., Lanzinger M., Hartmann F.J., Schreiner B., Mair F., Pelczar P., Clausen B.E., Jung S., Greter M., Becher B. The cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses autoimmunity. Journal. 2015;43:502–514.
    1. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Journal. 2020;8:420–422.
    1. Tian S., Hu W., Niu L., Liu H., Xu H., Xiao S.Y. Pulmonary pathology of Early-phase 2019 Novel Coronavirus (COVID-19) pneumonia in two patients with lung cancer. Journal. 2020 doi: 10.1016/j.jtho.2020.02.010.
    1. Young R.E., Thompson R.D., Larbi K.Y., La M., Roberts C.E., Shapiro S.D., Perretti M., Nourshargh S. Neutrophil elastase (NE)-deficient mice demonstrate a nonredundant role for NE in neutrophil migration, generation of proinflammatory mediators, and phagocytosis in response to zymosan particles in vivo. Journal. 2004;172:4493–4502.
    1. Liu S., Su X., Pan P., Zhang L., Hu Y., Tan H., Wu D., Liu B., Li H., Li H., Li Y., Dai M., Li Y., Hu C., Tsung A. Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury. Journal. 2016;6:37252.
    1. Koutsogiannaki S., Shimaoka M., Yuki K. The use of volatile anesthetics as sedatives for acute respiratory distress syndrome. Journal. 2019;6:27–38.
    1. Fang M., Siciliano N.A., Hersperger A.R., Roscoe F., Hu A., Ma X., Shamsedeen A.R., Eisenlohr L.C., Sigal L.J. Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection. Journal. 2012;109:9983–9988.
    1. Small B.A., Dressel S.A., Lawrence C.W., Drake D.R., 3rd, Stoler M.H., Enelow R.I., Braciale T.J. CD8(+) T cell-mediated injury in vivo progresses in the absence of effector T cells. Journal. 2001;194:1835–1846.
    1. Wang M., Hao H., Leeper N.J., Zhu L., Early Career C. Thrombotic regulation from the endothelial cell perspectives. Journal. 2018;38:e90–e95.
    1. Lovren F., Pan Y., Quan A., Teoh H., Wang G., Shukla P.C., Levitt K.S., Oudit G.Y., Al-Omran M., Stewart D.J., Slutsky A.S., Peterson M.D., Backx P.H., Penninger J.M., Verma S. Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Journal. 2008;295:H1377–H1384.
    1. Sluimer J.C., Gasc J.M., Hamming I., van Goor H., Michaud A., van den Akker L.H., Jutten B., Cleutjens J., Bijnens A.P., Corvol P., Daemen M.J., Heeneman S. Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions. Journal. 2008;215:273–279.
    1. Zeng H., Pappas C., Belser J.A., Houser K.V., Zhong W., Wadford D.A., Stevens T., Balczon R., Katz J.M., Tumpey T.M. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. Journal. 2012;86:667–678.
    1. Liu Y., Yan L.M., Wan L., Xiang T.X., Le A., Liu J.M., Peiris M., Poon L.L.M., Zhang W. Viral dynamics in mild and severe cases of COVID-19. Journal. 2020 doi: 10.1016/S1473-3099(20)30232-2.
    1. Patel S.K., Velkoska E., Burrell L.M. Emerging markers in cardiovascular disease: where does angiotensin-converting enzyme 2 fit in? Journal. 2013;40:551–559.
    1. Saule P., Trauet J., Dutriez V., Lekeux V., Dessaint J.P., Labalette M. Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Journal. 2006;127:274–281.
    1. Li M., Yao D., Zeng X., Kasakovski D., Zhang Y., Chen S., Zha X., Li Y., Xu L. Age related human T cell subset evolution and senescence. Journal. 2019;16:24.
    1. Connors T.J., Ravindranath T.M., Bickham K.L., Gordon C.L., Zhang F., Levin B., Baird J.S., Farber D.L. Airway CD8(+) T cells are associated with lung injury during infant viral respiratory tract infection. Journal. 2016;54:822–830.
    1. Smits S.L., de Lang A., van den Brand J.M., Leijten L.M., Eijkemans M.J., van Amerongen G., Kuiken T., Andeweg A.C., Osterhaus A.D., Haagmans B.L. Exacerbated innate host response to SARS-CoV in aged non-human primates. Journal. 2010;6
    1. Roberts A., Deming D., Paddock C.D., Cheng A., Yount B., Vogel L., Herman B.D., Sheahan T., Heise M., Genrich G.L., Zaki S.R., Baric R., Subbarao K. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. Journal. 2007;3
    1. Wong H.R., Freishtat R.J., Monaco M., Odoms K., Shanley T.P. Leukocyte subset-derived genomewide expression profiles in pediatric septic shock. Journal. 2010;11:349–355.
    1. Nickbakhsh S., Mair C., Matthews L., Reeve R., Johnson P.C.D., Thorburn F., von Wissmann B., Reynolds A., McMenamin J., Gunson R.N., Murcia P.R. Virus-virus interactions impact the population dynamics of influenza and the common cold. Journal. 2019 doi: 10.1073/pnas.1911083116.
    1. Beauchemin K.J., Wells J.M., Kho A.T., Philip V.M., Kamir D., Kohane I.S., Graber J.H., Bult C.J. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development. Journal. 2016;4

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit