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COVID-19 pathophysiology: A review

by Liqiang Zhou 1  and  Shuxing Xing 1,*
1
Department of Orthopedics, Chengdu Fifth People's Hospital, Chengdu, 611130, China
*
Author to whom correspondence should be addressed.
Received: 24 January 2024 / Accepted: 23 February 2024 / Published Online: 25 February 2024

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.


Copyright: © 2024 by Zhou and Xing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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ACS Style
Zhou, L.; Xing, S. COVID-19 pathophysiology: A review. International Journal of Clinical Medical Research, 2024, 2, 21. https://doi.org/https://doi.org/10.61466/ijcmr2020001
AMA Style
Zhou L, Xing S. COVID-19 pathophysiology: A review. International Journal of Clinical Medical Research; 2024, 2(2):21. https://doi.org/https://doi.org/10.61466/ijcmr2020001
Chicago/Turabian Style
Zhou, Liqiang; Xing, Shuxing 2024. "COVID-19 pathophysiology: A review" International Journal of Clinical Medical Research 2, no.2:21. https://doi.org/https://doi.org/10.61466/ijcmr2020001

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References

  1. T.G. Ksiazek, D. Erdman, C.S. Goldsmith, S.R. Zaki, T. Peret, S. Emery, S. Tong, C. Urbani, J.A. Comer, W. Lim, P.E. Rollin, S.F. Dowell, A.E. Ling, C.D. Humphrey, W.J. Shieh, J. Guarner, C.D. Paddock, P. Rota, B. Fields, J. DeRisi, J.Y. Yang, N. Cox, J.M. Hughes, J.W. LeDuc, W.J. Bellini, L.J. Anderson, SW Group, A novel coronavirus associated with severe acute respiratory syndrome, N Engl J Med. 348 (2003) 1953–1966.
  2. Q. Li, X. Guan, P. Wu, X. Wang, L. Zhou, Y. Tong, R. Ren, K.S.M. Leung, E.H.Y. Lau, J.Y. Wong, X. Xing, N. Xiang, Y. Wu, C. Li, Q. Chen, D. Li, T. Liu, J. Zhao, M. Liu, W. Tu, C. Chen, L. Jin, R. Yang, Q. Wang, S. Zhou, R. Wang, H. Liu, Y. Luo, Y. Liu, G. Shao, H. Li, Z. Tao, Y. Yang, Z. Deng, B. Liu, Z. Ma, Y. Zhang, G. Shi, T.T.Y. Lam, J.T. Wu, G.F. Gao, B.J. Cowling, B. Yang, G.M. Leung, Z. Feng, Early transmission dynamics in Wuhan, China, of Novel Coronavirus-infected pneumonia, N Engl J Me
  3. M. Zheng, Y. Gao, G. Wang, G. Song, S. Liu, D. Sun, Y. Xu, Z. Tian, Functional exhaustion of antiviral lymphocytes in COVID-19 patients, Cell Mol Immunol. (2020).
  4. J. Zhang, M. Litvinova, W. Wang, Y. Wang, X. Deng, X. Chen, M. Li, W. Zheng, L. Yi, X. Chen, Q. Wu, Y. Liang, X. Wang, J. Yang, K. Sun, I.M. Longini Jr., M.E. Halloran, P. Wu, B.J. Cowling, S. Merler, C. Viboud, A. Vespignani, M. Ajelli, H. Yu, Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study, Lancet Infect Dis. (2020),
  5. JHUoMCr center, Journal (2020).
  6. C. Huang, Y. Wang, X. Li, L. Ren, J. Zhao, Y. Hu, L. Zhang, G. Fan, J. Xu, X. Gu, Z. Cheng, T. Yu, J. Xia, Y. Wei, W. Wu, X. Xie, W. Yin, H. Li, M. Liu, Y. Xiao, H. Gao, L. Guo, J. Xie, G. Wang, R. Jiang, Z. Gao, Q. Jin, J. Wang, B. Cao, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet 395 (2020) 497–506.
  7. H. Shi, X. Han, N. Jiang, Y. Cao, O. Alwalid, J. Gu, Y. Fan, C. Zheng, Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study, Lancet Infect Dis. 20 (2020) 425–434.
  8. F. Zhou, T. Yu, R. Du, G. Fan, Y. Liu, Z. Liu, J. Xiang, Y. Wang, B. Song, X. Gu, L. Guan, Y. Wei, H. Li, X. Wu, J. Xu, S. Tu, Y. Zhang, H. Chen, B. Cao, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet 395 (2020) 1054–1062.
  9. X. Lu, L. Zhang, H. Du, J. Zhang, Y.Y. Li, J. Qu, W. Zhang, Y. Wang, S. Bao, Y. Li, C. Wu, H. Liu, D. Liu, J. Shao, X. Peng, Y. Yang, Z. Liu, Y. Xiang, F. Zhang, R.M. Silva, K.E. Pinkerton, K. Shen, H. Xiao, S. Xu, G.W.K. Wong, T Chinese Pediatric Novel Coronavirus Study, SARS-CoV-2 infection in children, N Engl J Med. (2020).
  10. H. Qiu, J. Wu, L. Hong, Y. Luo, Q. Song, D. Chen, Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study, Lancet Infect Dis. (2020).
  11. B. Cao, et al., A trial of Lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med. (2020).
  12. P. Gautret, J.C. Lagier, P. Parola, V.T. Hoang, L. Meddeb, M. Mailhe, B. Doudier, J. Courjon, V. Giordanengo, V.E. Vieira, H.T. Dupont, S. Honore, P. Colson, E. Chabriere, B. La Scola, J.M. Rolain, P. Brouqui, D. Raoult, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents 105949 (2020).
  13. N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, Y. Qiu, J. Wang, Y. Liu, Y. Wei, J. Xia, T. Yu, X. Zhang, L. Zhang, Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet 395 (2020) 507–513.
  14. Z. Wu, J.M. McGoogan, 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).
  15. G. Onder, G. Rezza, S. Brusaferro, Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy, JAMA (2020).
  16. Y. Du, L. Tu, P. Zhu, M. Mu, R. Wang, P. Yang, X. Wang, C. Hu, R. Ping, P. Hu, T. Li, F. Cao, C. Chang, Q. Hu, Y. Jin, G. Xu, Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational Study, Am J Respir Crit Care Med. (2020).
  17. Y. Gao, T. Li, M. Han, X. Li, D. Wu, Y. Xu, Y. Zhu, Y. Liu, X. Wang, L. Wang, Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19, J Med Virol. (2020).
  18. E. Livingston, K. Bucher, Coronavirus disease 2019 (COVID-19) in Italy, Journal. (2020).
  19. Tcfc Information. Journal.
  20. Y. Dong, X. Mo, Y. Hu, X. Qi, F. Jiang, Z. Jiang, S. Tong, Epidemiological characteristics of 2143 Pediatric patients with 2019 coronavirus disease in China, Journal. (2020).
  21. P. Brodin, Why is COVID-19 so mild in children? Journal (2020).
  22. CfDCa Prevention. Journal.
  23. C. Wenham, J. Smith, R. Morgan, Gender and C-W Group, COVID-19: the gendered impacts of the outbreak, Journal 395 (2020) 846–848.
  24. J. Jin, P. Bai, W. He, F. Wu, W.F. Liu, D.M. Han, S. Liu, J.K. Yang, Gender differences in patients with COVID-19: focus on severity and mortality, Journal. (2020).
  25. K.S. Hall, G. Samari, S. Garbers, S.E. Casey, D.D. Diallo, M. Orcutt, R.T. Moresky, M.E. Martinez, T. McGovern, Centring sexual and reproductive health and justice in the global COVID-19 response, Journal 395 (2020) 1175–1177.
  26. K.R. Moran, S.Y. Del Valle, A meta-analysis of the association between gender and protective behaviors in response to respiratory epidemics and pandemics, Journal 11 (2016) e0164541.
  27. R. Channappanavar, J. Zhao, S. Perlman, T cell-mediated immune response to respiratory coronaviruses, Journal 59 (2014) 118–128. 28. F.A. Rabi, M.S. Al Zoubi, G.A. Kasasbeh, D.M. Salameh, A.D. Al-Nasser, SARS-CoV-2 and Coronavirus disease 2019: what we know so far, Journal 9 (2020).
  28. B.J. Bosch, R. van der Zee, C.A. de Haan, P.J. Rottier, The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex, Journal 77 (2003) 8801–8811.
  29. W. Li, M.J. Moore, N. Vasilieva, J. Sui, S.K. Wong, M.A. Berne, M. Somasundaran, J.L. Sullivan, K. Luzuriaga, T.C. Greenough, H. Choe, M. Farzan, Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus, Journal 426 (2003) 450–454.
  30. Y. Chen, Y. Guo, Y. Pan, Z.J. Zhao, Structure analysis of the receptor binding of 2019-nCoV, Journal. (2020).
  31. A.C. Walls, Y.J. Park, M.A. Tortorici, A. Wall, A.T. McGuire, D. Veesler, Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein, Journal. (2020).
  32. M. Letko, A. Marzi, V. Munster, Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses, Journal 5 (2020) 562–569.
  33. X. Zou, K. Chen, J. Zou, P. Han, J. Hao, Z. Han, 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).
  34. S. Belouzard, V.C. Chu, G.R. Whittaker, Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites, Journal 106 (2009) 5871–5876.
  35. J.K. Millet, G.R. Whittaker, Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein, Journal 111 (2014) 15214–15219.
  36. X. Ou, Y. Liu, X. Lei, P. Li, D. Mi, L. Ren, L. Guo, R. Guo, T. Chen, J. Hu, Z. Xiang, Z. Mu, X. Chen, J. Chen, K. Hu, Q. Jin, J. Wang, Z. Qian, Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Journal 11 (2020) 1620. 38. S. Belouzard, J.K. Millet, B.N. Licitra, G.R. Whittaker, Mechanisms of coronavirus cell entry mediated by the viral spike protein, Journal 4 (2012) 1011–1033.
  37. M. Hoffmann, H. Kleine-Weber, S. Schroeder, N. Kruger, T. Herrler, S. Erichsen, T.S. Schiergens, G. Herrler, N.H. Wu, A. Nitsche, M.A. Muller, C. Drosten, S. Pohlmann, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Journal. (2020).
  38. W.J. Guan, Z.Y. Ni, Y. Hu, W.H. Liang, C.Q. Ou, J.X. He, L. Liu, H. Shan, C.L. Lei, D.S.C. Hui, B. Du, L.J. Li, G. Zeng, K.Y. Yuen, R.C. Chen, C.L. Tang, T. Wang, P.Y. Chen, J. Xiang, S.Y. Li, J.L. Wang, Z.J. Liang, Y.X. Peng, L. Wei, Y. Liu, Y.H. Hu, P. Peng, J.M. Wang, J.Y. Liu, Z. Chen, G. Li, Z.J. Zheng, S.Q. Qiu, J. Luo, C.J. Ye, S.Y. Zhu, N.S. Zhong, C China Medical Treatment Expert Group for, Clinical characteristics of coronavirus disease 2019 in China, Journal. (2020).
  39. I. Hamming, W. Timens, M.L. Bulthuis, A.T. Lely, G. Navis, H. van Goor, Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, Journal 203 (2004) 631–637.
  40. H.P. Jia, D.C. Look, L. Shi, M. Hickey, L. Pewe, J. Netland, M. Farzan, C. Wohlford-Lenane, S. Perlman, P.B. McCray Jr., ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia, Journal 79 (2005) 14614–14621.
  41. T. Yoshikawa, T. Hill, K. Li, C.J. Peters, C.T. Tseng, 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 83 (2009) 3039–3048.
  42. I. Fujimoto, J. Pan, T. Takizawa, Y. Nakanishi, Virus clearance through apoptosisdependent phagocytosis of influenza A virus-infected cells by macrophages, Journal 74 (2000) 3399–3403.
  43. S.A. Jeffers, S.M. Tusell, L. Gillim-Ross, E.M. Hemmila, J.E. Achenbach, G.J. Babcock, W.D. Thomas Jr., L.B. Thackray, M.D. Young, R.J. Mason, D.M. Ambrosino, D.E. Wentworth, J.C. Demartini, K.V. Holmes, CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus, Journal 101 (2004) 15748–15753.
  44. A. Marzi, T. Gramberg, G. Simmons, P. Moller, A.J. Rennekamp, M. Krumbiegel, M. Geier, J. Eisemann, N. Turza, B. Saunier, A. Steinkasserer, S. Becker, P. Bates, H. Hofmann, S. Pohlmann, DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus, Journal 78 (2004) 12090–12095.
  45. Z.Y. Yang, Y. Huang, L. Ganesh, K. Leung, W.P. Kong, O. Schwartz, K. Subbarao, G.J. Nabel, 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 78 (2004) 5642–5650.
  46. Y. Zhou, B. Fu, X. Zheng, D. Wnag, C. Zhao, Y. Qi, R. Sun, Z. Tian, X. Xu, H. Wei, Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients, Journal. (2020).
  47. C. Qin, L. Zhou, Z. Hu, S. Zhang, S. Yang, Y. Tao, C. Xie, K. Ma, K. Shang, W. Wang, D.S. Tian, Dysregulation of immune response in patients with COVID-19 in Wuhan, China, Journal (2020).
  48. H. Huang, S. Wang, T. Jiang, R. Fan, Z. Zhang, J. Mu, K. Li, Y. Wang, L. Jin, F. Lin, J. Xia, L. Sun, B. Xu, C. Ji, J. Chen, J. Chang, B. Tu, B. Song, C. Zhang, F.S. Wang R. Xu, High levels of circulating GM-CSF(+)CD4(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study, Journal 16 (2019) 602–610.
  49. A.L. Croxford, M. Lanzinger, F.J. Hartmann, B. Schreiner, F. Mair, P. Pelczar, B.E. Clausen, S. Jung, M. Greter, B. Becher, The cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses autoimmunity, Journal 43 (2015) 502–514.
  50. Z. Xu, L. Shi, Y. Wang, J. Zhang, L. Huang, C. Zhang, S. Liu, P. Zhao, H. Liu, L. Zhu, Y. Tai, C. Bai, T. Gao, J. Song, P. Xia, J. Dong, J. Zhao, F.S. Wang, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, Journal 8 (2020) 420–422.
  51. S. Tian, W. Hu, L. Niu, H. Liu, H. Xu, S.Y. Xiao, Pulmonary pathology of Early-phase 2019 Novel Coronavirus (COVID-19) pneumonia in two patients with lung cancer, Journal. (2020).
  52. R.E. Young, R.D. Thompson, K.Y. Larbi, M. La, C.E. Roberts, S.D. Shapiro, M. Perretti, S. Nourshargh, 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 172 (2004) 4493–4502.
  53. S. Liu, X. Su, P. Pan, L. Zhang, Y. Hu, H. Tan, D. Wu, B. Liu, H. Li, H. Li, Y. Li, M. Dai, Y. Li, C. Hu, A. Tsung, Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury, Journal 6 (2016) 37252.
  54. S. Koutsogiannaki, M. Shimaoka, K. Yuki, The use of volatile anesthetics as sedatives for acute respiratory distress syndrome, Journal 6 (2019) 27–38.
  55. M. Fang, N.A. Siciliano, A.R. Hersperger, F. Roscoe, A. Hu, X. Ma, A.R. Shamsedeen, L.C. Eisenlohr, L.J. Sigal, Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection, Journal 109 (2012) 9983–9988. 58. B.A. Small, S.A. Dressel, C.W. Lawrence, D.R. Drake 3rd, M.H. Stoler, R.I. Enelow, T.J. Braciale, CD8(+) T cell-mediated injury in vivo progresses in the absence of effector T cells, Journal 194 (2001) 1835–1846.
  56. M. Wang, H. Hao, N.J. Leeper, L. Zhu, C. Early Career, Thrombotic regulation from the endothelial cell perspectives, Journal 38 (2018) e90–e95.
  57. F. Lovren, Y. Pan, A. Quan, H. Teoh, G. Wang, P.C. Shukla, K.S. Levitt, G.Y. Oudit, M. Al-Omran, D.J. Stewart, A.S. Slutsky, M.D. Peterson, P.H. Backx, J.M. Penninger, S. Verma, Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis, Journal 295 (2008) H1377–H1384.
  58. J.C. Sluimer, J.M. Gasc, I. Hamming, H. van Goor, A. Michaud, L.H. van den Akker, B. Jutten, J. Cleutjens, A.P. Bijnens, P. Corvol, M.J. Daemen, S. Heeneman, Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions, Journal 215 (2008) 273–279.
  59. H. Zeng, C. Pappas, J.A. Belser, K.V. Houser, W. Zhong, D.A. Wadford, T. Stevens, R. Balczon, J.M. Katz, T.M. Tumpey, 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 86 (2012) 667–678.
  60. Y. Liu, L.M. Yan, L. Wan, T.X. Xiang, A. Le, J.M. Liu, M. Peiris, L.L.M. Poon, W. Zhang, Viral dynamics in mild and severe cases of COVID-19, Journal. (2020).
  61. S.K. Patel, E. Velkoska, L.M. Burrell, Emerging markers in cardiovascular disease: where does angiotensin-converting enzyme 2 fit in? Journal 40 (2013) 551–559.
  62. P. Saule, J. Trauet, V. Dutriez, V. Lekeux, J.P. Dessaint, M. Labalette, 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 127 (2006) 274–281.
  63. M. Li, D. Yao, X. Zeng, D. Kasakovski, Y. Zhang, S. Chen, X. Zha, Y. Li, L. Xu, Age related human T cell subset evolution and senescence, Journal 16 (2019) 24.
  64. T.J. Connors, T.M. Ravindranath, K.L. Bickham, C.L. Gordon, F. Zhang, B. Levin, J.S. Baird, D.L. Farber, Airway CD8(+) T cells are associated with lung injury during infant viral respiratory tract infection, Journal 54 (2016) 822–830.
  65. S.L. Smits, A. de Lang, J.M. van den Brand, L.M. Leijten, M.J. Eijkemans, G. van Amerongen, T. Kuiken, A.C. Andeweg, A.D. Osterhaus, B.L. Haagmans, Exacerbated innate host response to SARS-CoV in aged non-human primates, Journal 6 (2010) e1000756.
  66. A. Roberts, D. Deming, C.D. Paddock, A. Cheng, B. Yount, L. Vogel, B.D. Herman, T. Sheahan, M. Heise, G.L. Genrich, S.R. Zaki, R. Baric, K. Subbarao, A mouseadapted SARS-coronavirus causes disease and mortality in BALB/c mice, Journal 3 (2007) e5.
  67. H.R. Wong, R.J. Freishtat, M. Monaco, K. Odoms, T.P. Shanley, Leukocyte subsetderived genomewide expression profiles in pediatric septic shock, Journal 11 (2010) 349–355.
  68. S. Nickbakhsh, C. Mair, L. Matthews, R. Reeve, P.C.D. Johnson, F. Thorburn, B. von Wissmann, A. Reynolds, J. McMenamin, R.N. Gunson, P.R. Murcia, Virus-virus interactions impact the population dynamics of influenza and the common cold, Journal. (2019).
  69. K.J. Beauchemin, J.M. Wells, A.T. Kho, V.M. Philip, D. Kamir, I.S. Kohane, J.H. Graber, C.J. Bult, Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development, Journal 4 (2016) e2318.