مجله زیست شناسی ایران
ایمونوپاتوژنز، تشخیص و درمان کووید-19
نویسندگان
1 تهران، دانشگاه علوم پزشکی تهران، بیمارستان شریعتی، مرکز تحقیقات روماتولوژی
2 تهران، دانشگاه علوم پزشکی تهران، مرکز تحقیقات التهاب
چکیده
ویروس SARS-CoV-2 عضوی از خانواده‌ی کروناویروس‌ها است که در اواخر سال ۲۰۱۹ در کشور چین باعث پدید آمدن اپیدمی بیماری تنفسی کووید-19 و در نهایت همه‌گیری جهانی این بیماری شد. ژنگان (genome) این ویروس شباهت ۷۹ درصدی به ویروس SARS-CoV دارد و برای ورود به سلول، مشابه ویروس SARS-CoV از رسپتور ACE2 استفاده می‌کند. شایع‌ترین علائم این بیماری شامل تب، سرفه و درگیری ریوی است که گاهی با علائم دستگاه گوارش نیز همراه است. کاهش تعداد و عملکرد لنفوسیت‌ها و افزایش شدید فعالیت التهابی لوکوسیت‌ها از عوارض ایمنی شناسی این بیماری است. اگر پاسخ‌های سیستم ایمنی در برابر ویروس کافی و مناسب نباشد بیماری وارد حالت حاد و شدید خود می‌شود. در این حالت فعالیت سلول‌های ایمنی سبب افزایش بیش از حد میزان سایتوکاین‌ها در خون و القای طوفان سایتوکاینی شده و سبب آسیب‌های سیستمی قلبی، ریوی و کلیوی و در نهایت مرگ می‌شود. همچنین آسیب ریوی سبب فیبروزی شدن بافت ریه، سخت شدن تنفس، کاهش سطح اکسیژن خون شریانی می‌شود. تا کنون هیچ داروی اختصاصی برای درمان بیماران کووید-19 شناسایی نشده است اما داروها و روش‌هایی که در کنترل و بهبود بیماری SARS مانند کلروکین، هیدروکسی کلروکین و پلاسما تراپی موثر بوده‌اند از جمله مواردی هستند که نیاز به بررسی بیشتری دارند. در این مقاله مروری به بررسی روند ایمونوپاتوژنز بیماری کووید-19 و درمان‌های ممکن اثربخش در بهبود این بیماری می‌پردازیم.
کلیدواژه‌ها
عنوان مقاله [English]
Coronavirus disease 2019 (COVID-19) Immunopathogenesis, Diagnosis, and Treatment
نویسندگان [English]
- Mobina Jalalvand 1
- Maryam Akhtari 1
- Elham Farhadi 1
- Mahdi Mahmoudi 1 2
چکیده [English]
SARS-CoV-2 is a member of the coronaviruses family that causes the outbreak of coronavirus disease 2019 (COVID-19) in China in late 2019 which has exploded to a global pandemic. The reference genome of the SARS-CoV-2 is considered to be very closely related to SARS-CoV and the virus uses the ACE-2 receptor for cellular entry similar to SARS-CoV. The most common symptoms of COVID-19 are fever, cough, and respiratory symptoms. Although gastrointestinal involvements are also presented in some patients. Reduced number and functional exhaustion of lymphocytes and increased inflammatory responses of leukocytes are the most immunological characteristics of the disease. If the infection was not eliminated by the proper and strong immune responses, the disease enters the severe stage when cytokine storm and elevated inflammatory responses induced pulmonary fibrosis, shortness of breath, reduced O2 saturation, and systemic injuries resulted in patient’s death. There are no specific therapies, however, several agents such as Chloroquine, Hydroxychloroquine, and convalescent plasma are being used for COVID-19 treatment. In the current study, we summarized recent findings on COVID-19 pathogenesis and drug therapy.
کلیدواژه‌ها [English]
- Covid-19
- Immunopathogenesis
- Coronavirus
- Inflammation
1- Coronavirus latest: WHO describes outbreak as pandemic. Nature, 2020.
2- Chen, N., et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020. 395(10223): p. 507-513.
3- Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) Available from: https://coronavirus.jhu.edu/map.html.
4- Cherry, J.D., The chronology of the 2002-2003 SARS mini pandemic. Paediatr Respir Rev, 2004. 5(4): p. 262-9.
5- Wang, L.F. and B.T. Eaton, Bats, civets and the emergence of SARS. Curr Top Microbiol Immunol, 2007. 315: p. 325-44.
6- world health organization. 2015; Available from: https://www.who.int/csr/don/23-february-2015-mers-saudi-arabia/en/.
7- Banerjee, A., et al., Bats and Coronaviruses. Viruses, 2019. 11(1).
8- Reusken, C.B., et al., Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis, 2013. 13(10): p. 859-66.
9- Liu, J., et al., 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, 2020. 92(5): p. 491-494.
10- Fehr, A.R. and S. Perlman, Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol, 2015. 1282: p. 1-23.
11- Masters, P.S., The molecular biology of coronaviruses. Adv Virus Res, 2006. 66: p. 193-292.
12- Lu, R., et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020. 395(10224): p. 565-574.
13- Rota, P.A., et al., Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science, 2003. 300(5624): p. 1394-9.
14- Snijder, E.J., et al., Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol, 2003. 331(5): p. 991-1004.
15- Li, X., et al., Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis, 2020.
16- Belouzard, S., et al., Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 2012. 4(6): p. 1011-33.
17- Li, Q., et al., Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med, 2020.
18- Backer, J.A., D. Klinkenberg, and J. Wallinga, Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro Surveill, 2020. 25(5).
19- Mehta, P., et al., COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet Journal, 2020.
20- Ramos-Casals, M., et al., Adult haemophagocytic syndrome. Lancet, 2014. 383(9927): p. 1503-1516.
21- Wang, Z., et al., Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clinical Infectious Diseases, 2020.
22- Zhao, Y. and C. Xu, Structure and Function of Angiotensin Converting Enzyme and Its Inhibitors. Chinese Journal of Biotechnology, 2008. 24(2): p. 171-176.
23- Qu, X.X., et al., Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy. J Biol Chem, 2005. 280(33): p. 29588-95.
24- Wang, H., et al., SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res, 2008. 18(2): p. 290-301.
25- Chen, Y., et al., Structure analysis of the receptor binding of 2019-nCoV. Biochemical and Biophysical Research Communications, 2020.
26- Raj, V.S., et al., Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 2013. 495(7440): p. 251-254.
27- Lin, M., et al., Association of HLA class I with severe acute respiratory syndrome coronavirus infection. BMC Med Genet, 2003. 4: p. 9.
28- Hajeer, A.H., et al., Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection. Ann Thorac Med, 2016. 11(3): p. 211-3.
29- Liu, Q., Y.H. Zhou, and Z.Q. Yang, The cytokine storm of severe influenza and development of immunomodulatory therapy. (2042-0226 (Electronic)).
30- Barton, G.M., A calculated response: control of inflammation by the innate immune system. J Clin Invest, 2008. 118(2): p. 413-20.
31- Jensen, S. and A.R. Thomsen, Sensing of RNA Viruses: a Review of Innate Immune Receptors Involved in Recognizing RNA Virus Invasion. Journal of Virology, 2012. 86(6): p. 2900-2910.
32- Li, G., X. Chen, and A. Xu, Profile of Specific Antibodies to the SARS-Associated Coronavirus. New England Journal of Medicine, 2003. 349(5): p. 508-509.
33- Shi, Y., et al., COVID-19 infection: the perspectives on immune responses. Cell Death & Differentiation, 2020.
34- Zheng, H.-Y., et al., Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cellular & Molecular Immunology, 2020.
35- Diao, B., et al., Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). medRxiv, 2020: p. 2020.02.18.20024364.
36- Huang, K.J., et al., An interferon-gamma-related cytokine storm in SARS patients. J Med Virol, 2005. 75(2): p. 185-94.
37- Xu, Z., et al., Pathological findings of COVID-19 associated with acute respiratory distress syndrome. LID - S2213-2600(20)30076-X [pii] LID - 10.1016/S2213-2600(20)30076-X [doi] FAU - Xu, Zhe. (2213-2619 (Electronic)).
38- Nicholls, J.M., et al., Lung pathology of fatal severe acute respiratory syndrome. Lancet, 2003. 361(9371): p. 1773-8.
39- Hindson, J., COVID-19: faecal–oral transmission? Nature Reviews Gastroenterology & Hepatology, 2020.
40- Huang, C., et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020. 395(10223): p. 497-506.
41- Wang, Z., et al., Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis, 2020.
42- Wu, C., et al., Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med, 2020.
43- Qu, R., et al., Platelet-to-lymphocyte ratio is associated with prognosis in patients with Corona Virus Disease-19. J Med Virol, 2020.
44- Zhou, F., et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020.
45- Kindler, E., V. Thiel, and F. Weber, Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response. Adv Virus Res, 2016. 96: p. 219-243.
46- Kikkert, M., Innate Immune Evasion by Human Respiratory RNA Viruses. J Innate Immun, 2020. 12(1): p. 4-20.
47- Prompetchara, E., C. Ketloy, and T. Palaga, Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol, 2020. 38(1): p. 1-9.
48- Minakshi, R., et al., The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS One, 2009. 4(12): p. e8342.
49- Kamitani, W., et al., A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. Nat Struct Mol Biol, 2009. 16(11): p. 1134-40.
50- Frieman, M. and R. Baric, Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Microbiology and molecular biology reviews : MMBR, 2008. 72(4): p. 672-685.
51- Wang, W., et al., Detection of SARS-CoV-2 in Different Types of Clinical Specimens. Jama, 2020.
52- Loeffelholz, M.J. and Y.W. Tang, Laboratory Diagnosis of Emerging Human Coronavirus Infections - The State of the Art. Emerg Microbes Infect, 2020: p. 1-26.
53- Liu, R., et al., Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020. Clin Chim Acta, 2020. 505: p. 172-175.
54- Zhao, J., et al., Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clinical Infectious Diseases, 2020.
55- Haveri, A., et al., Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020. Euro Surveill, 2020. 25(11).
56- Lai, C.C., et al., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents, 2020: p. 105924.
57- Zu, Z.Y., et al., Coronavirus Disease 2019 (COVID-19): A Perspective from China. Radiology, 2020: p. 200490.
58- Ai, T., et al., Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology, 2020: p. 200642.
59- Fang, Y., et al., Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology, 2020: p. 200432.
60- Chandwani, A. and J. Shuter, Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag, 2008. 4(5): p. 1023-33.
61- Yao, T.T., et al., A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J Med Virol, 2020.
62- Liu, X. and X.-J. Wang, Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines. bioRxiv, 2020: p. 2020.01.29.924100.
63- Cao, B., et al., A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine, 2020.
64- Brown, A.J., et al., Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res, 2019. 169: p. 104541.
65- de Wit, E., et al., Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proceedings of the National Academy of Sciences, 2020. 117(12): p. 6771-6776.
66- Agostini, M.L., et al., Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio, 2018. 9(2): p. e00221-18.
67- ClinicalTrials.gov Available from: https://www.clinicaltrials.gov/ct2/results?cond=Coronavirus&term=&type=&rslt=&age_v=&gndr=&intr=remdesivir&titles=&outc=&spons=&lead=&id=&cntry=&state=&city=&dist=&locn=&rsub=&strd_s=&strd_e=&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&rfpd_s=&rfpd_e=&lupd_s=&lupd_e=&sort=.
68- Savarino, A., et al., New insights into the antiviral effects of chloroquine. Lancet Infect Dis, 2006. 6(2): p. 67-9.
69- Keyaerts, E., et al., In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun, 2004. 323(1): p. 264-8.
70- Savarino, A., et al., Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis, 2003. 3(11): p. 722-7.
71- Vincent, M.J., et al., Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J, 2005. 2: p. 69.
72- Golden, E.B., et al., Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors. Neurosurg Focus, 2015. 38(3): p. E12.
73- Yao, X., et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis, 2020.
74- Gautret, P., et al., Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial. medRxiv, 2020: p. 2020.03.16.20037135.
75- Randall, R.E. and S. Goodbourn, Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol, 2008. 89(Pt 1): p. 1-47.
76- Hensley, L.E., et al., Interferon-beta 1a and SARS coronavirus replication. Emerg Infect Dis, 2004. 10(2): p. 317-9.
77- Liu, C., et al., Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. ACS Central Science, 2020. 6(3): p. 315-331.
78- Reuters. 2020; Available from: https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-roche-drug-in-battle-against-coronavirus-complications-idUSKBN20R0LF.
79- Tim Smith, P., BCPS; Jennifer Bushek, PharmD; Tony Prosser, PharmD, COVID-19 Drug Therapy – Potential Options. Clinical Drug Information | Clinical Solutions, 2020.
80- Beigelman, A., et al., Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis. Respiratory Research, 2010. 11(1): p. 90.
81- Kanoh, S. and B.K. Rubin, Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev, 2010. 23(3): p. 590-615.
82- Gautret, P., et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, 2020: p. 105949.
83- Soo, Y.O., et al., Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect, 2004. 10(7): p. 676-8.
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دوره 4، شماره 7 - شماره پیاپی 7
اردیبهشت 1399صفحه 251-259
- تاریخ دریافت: 22 دی 1398
- تاریخ بازنگری: 10 تیر 1399
- تاریخ پذیرش: 10 تیر 1399