COVID-19 — нова вірусна інфекція: патогенез, діагностика, лікування

Автор(и)

  • О.M. Rekalova ДУ «Національний інститут фтизіатрії і пульмонології імені Ф.Г. Яновського НАМН України», Київ, Ukraine

DOI:

https://doi.org/10.30978/TB2020-2-7

Ключові слова:

коронавірус, COVID-19, патогенез, діагностика, лікування

Анотація

Під час пандемії нової коронавірусної інфекції SARS­CoV­2 з’являється багато нових даних щодо особливостей інфекції та ведення хворих на COVID­19. У роботі представлено огляд даних, оприлюднених у літературних джерелах на початок травня 2020 р., стосовно патогенезу захворювання, клінічного перебігу, діагностики, а також світовий досвід лікування таких хворих. Більшість даних є попередніми, які представлено у відомих виданнях у відкритому доступі, зокрема досвід зарубіжних лікарів — китайських, російських, американських, британських та інших. Багато з них опубліковано в Інтернеті до офіційного видання. Описано основні уявлення про механізми проникнення вірусу в організм людини (через рецептори АПФ2, CD147, гемоглобін), патогенез захворювання (з розвитком «цитокінового шторму», ознаками руйнування лімфоцитів, зниженням кількості CD4+ та CD8+ Т­лімфоцитів у крові), ознаки тяжкого перебігу інфекції, основні клінічні характеристики COVID­19, пов’язані з патогенезом (гострий респіраторний дистрес­синдром, синдром позалегеневого системного гіперзапалення з клінічною картиною васкуліту з гіперкоагуляцією та пошкодженням багатьох органів). Коротко описано основні підходи до діагностики, недоліки діагностичних методів (з чутливістю ПЛР­методів 50—79 %, строки використання тестів на імуноглобуліни). Також охарактеризовано основні медикаментозні методи терапії, які використовують і розробляють. Представлено коротке описання актуальних противірусних (препарати на основі хлорохіну, лопінавір/ритонавір, фавіпіравір, ремдезивір, інтерферони, переливання плазми), протизапальних (моноклональні антитіла, кортикостероїди) засобів, їхні можливі побічні ефекти, ефективність та перспективи використання.

Біографія автора

О.M. Rekalova, ДУ «Національний інститут фтизіатрії і пульмонології імені Ф.Г. Яновського НАМН України», Київ

Рекалова Олена Михайлівна
д. мед. н., зав. лабораторії клінічної імунології
03038, м. Київ, вул. Миколи Амосова, 10

Посилання

Vremennyye metodicheskiye rekomendatsii «Profilaktika diagnostika i lecheniye novoy koronavirusnoy infektsii COVID-19» (in Rus). [Temporary guidelines "Prevention diagnosis and treatment of new coronavirus infection COVID-19."] Versiya 6 [Version 6] : https://static-1.rosminzdrav.ru/system/attachments/attaches/000/050/116/original/28042020_%D0%9CR_COVID-19_v6.pdf

Gumeniuk M.I, Gumeniuk G.L, Opimakh S.H. Efektyvnist dekametoksynu proty skladnykh virusiv, nezalezhno vid yikh antyhennoyi budovy: perspektyvy vykorystannya pry suchasnykh virusnykh zakhvoryuvannyakh dykhalnykh shlyakhiv [Efficacy of decamethoxine against complex viruses, regardless of their antigenic structure: prospects for use in modern viral diseases of the respiratory tract[. Aktualna infektolohiya [Topical infectology]. 2020;1(8):36—44. doi 10.22141/2312-413kh.8.12020.196168 (inUkr).

Ministerstvo okhorony zdorovya Ukrayiny, Nakaz vid 02 kvitnya 2020 N 762 (u redaktsiyi nakazu Ministerstva okhorony zdorov'ya Ukrayiny vid 10 kvitnya 2020 roku N 852): Protokol nadannya medychnoyi dopomohy dlya likuvannya koronavirusnoyi khvoroby (COVID-19) [Ministry of Health of Ukraine, Order from April 2, 2020 N 762 (as amended by the order of the Ministry of Health of Ukraine from April 10, 2020 N. 852): Protocol for the provision of medical care for the treatment of coronavirus disease (COVID-19)]. https://dec.gov.ua/mtd/koronavirusna-hvoroba-2019-covid-19/.

Ministerstvo okhorony zdorovya Ukrayiny, Nakaz vid 28 bereznya 2020 N 722 (u redaktsiyi nakazu Ministerstva okhorony zdorov'ya Ukrayiny vid 09 kvitnya 2020 N 827 ta vid 23.04.2020 № 953): Standarty medychnoyi dopomohy «Koronavirusna khvoroba (COVID-19)» [Ministry of Health of Ukraine, Order from March 28, 2020 N 722 (as amended by the order of the Ministry of Health of Ukraine from April 09, 2020 № 827 827 and from 23.04.2020 № 953): Standards of medical care “Coronavirus disease (COVID-19)”]. https://dec.gov.ua/mtd/koronavirusna-hvoroba-2019-covid-19/

Rekomendatsiyi shchodo provedennya klinichnykh vyprobuvan u zvyazku z poshyrennyam koronavirusnoyi infektsiyi. Spravochnyk po profylaktyke y lechenyyu COVID-19 (Pervaya klynycheskaya bolnytsa, Medytsynskyy fakultet unyversyteta Chzhtszyan) [Recommendations for conducting clinical trials in connection with the spread of coronavirus infection. COVID-19 Prevention and Treatment Handbook (First Clinical Hospital, Zhejiang University School of Medicine)]:69. https://dec.gov.ua/announcement/do-uvagy-zayavnykiv-ta-doslidnykiv/.

Feshchenko YuI, Belosludtseva KO, Holubovska OA, et al. Adaptovana klinichna nastanova,zasnovana na dokazakh «nehospitalna pnevmoniya u doroslykh osib: etiolohiya, patohenez, klasyfikatsiya, diahnostyka, antymikrobna terapiya ta profilaktyka» [Adapted evidence-based clinical guideline “nosocomial pneumonia in adults: etiology, pathogenesis, classification, diagnosis, antimicrobial therapy and prevention”]. (Ukr). Kyiv, National Academy of Medical Sciences of Ukraine. 2019:94.

Chuchalin AG, Avdeyev SN, Chernyayev AL, Osipova GL, Samsonova MV. Federalnyye klinicheskiye rekomendatsii Rossiyskogo respiratornogo obshchestva po diagnostike i lecheniyu tyazhelykh form grippa [Federal guidelines on diagnosis and management of severe influenza on behalf of Russian Respiratory Society. Pulmonologiya]. Pulmonologiya. 2014;(5):11-19. doi:10.18093/0869-0189-2014-0-5-11-19.

ACR Recommendations for the use of Chest Radiography and Computed Tomography (CT) for Suspected COVID-19 Infection. https://www.acr.org/Advocacy-and-Economics/ACR-Position-Statements/Recommendations-for-Chest-Radiography-and-CT-for-Suspected-COVID19-Infection (Accessed on April 01, 2020).

Adnet F, Schwok SA. Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection (ENACOVID). https://clinicaltrials.gov/ct2/show/NCT04325633.

Alanio A, Delliere S, Fodil S, et al. High Prevalence of Putative Invasive Pulmonary Aspergillosis in Critically Ill COVID-19 Patients (April 14, 2020). SSRN. https://ssrn.com/abstract=3575581 or http://dx.doi.org/10.2139/ssrn.3575581 SSRN. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3575581#.XpW1fnwqf8Y.twitter.

Bhimraj A, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. IDSA. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/.

Bian H, et al. Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial //medRxiv. 2020. doi:10.1101/2020.03.21.20040691.

Bozkurt B, Kovacs R, Harrington B. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. ACC News Story. 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19.

Braun J, et al. Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors. medRxiv. 2020. doi:10.1101/2020.04.17.20061440.

Brodin P. Why is COVID-19 so mild in children? Acta Paediatr. 2020;109:1082-1083. doi:10.1111/apa.15271.

Chow N, Gierke R, Fleming-Dutra K, et al. Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 - United States, February 12 - March 28, 2020. MMWR. 2020;69(13):382-386. doi:10.15585/mmwr.mm6913e2.

Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282.

Cao W, Liu X, Bai T, et al. High-Dose Intravenous Immuno­globulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019. Open Forum Infect Dis 2020;7(3):102. doi:10.1093/ofid/ofaa102.

Casa CG, Catala A, Hernandez GC, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020. doi:10.1111/bjd.19163.

Castagnoli R, Votto M, Licari A, et al. Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. 2020. doi:10.1001/jamapediatrics.2020.1467.

Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-2629. doi: 10.1172/JCI137244.

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-513. doi:10.1016/S0140-6736(20)30211-7.

Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:14. doi:10.1136/bmj.m1091.

Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterol. 2020. pii:S0016-5085(20)30448-0. doi:10.1053/j.gastro.2020.03. 065.

Corman VM, Lienau J, Witzenrath M. Coronaviruses as the cause of respiratory infections. Internist (Berl.). 2019;60:1136-1145.

Coronavirus (COVID-19) Update: FDA Authorizes First Test for Patient At-Home Sample Collection. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-test-patient-home-sample-collection.

Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J. 2020;41(19):1858. doi:10.1093/eurheartj/ehaa254.

De Clercq E. New nucleoside analogues for the treatment of hemorrhagic fever virus infections. Chem Asian J. 2019;14:3962-3968. doi:10.1002/asia.201900841.

De Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14:523-534. doi:10.1038/nrmicro.2016.81.

Deville JG, Song E, Ouellette CP. Coronavirus disease 2019(COVID-19): Considerations in children. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-considerations-in-children.

Fang Y, Zhang H, Xie J, et al. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology. 2020:200432. doi:10.1148/radiol.2020200432.

Fehr AR, Channappanavar R, Perlman S. Middle East Respiratory Syndrome: Emergence of a Pathogenic Human Coronavirus. Annu Rev Med. 2017;68:387-399.

Gandhi RT, Lynch JB, Del Rio C. Mild or Moderate Covid-19. N Engl J Med. 2020. doi:10.1056/NEJMcp2009249.

Gautret P, Lagier JC, Parola P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis. 2020;34:101663. doi:10.1016/j.tmaid.2020.101663.

Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020. pii:ciaa330. doi:10.1093/cid/ciaa330.

Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol. 2013;11(12):836-848. doi:10.1038/nrmicro3143.

Guan WJ, Ni ZY, Hu Y, et al. China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032.

Guo L, Ren L, Yang S, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020. pii:ciaa310. doi:10.1093/cid/ciaa310.

Guo X, Thomas P. New fronts emerge in the influenza cytokine storm. Semin Immunopathol. 2017;39(5):541-550. doi:10.1007/s00281-017-0636-y.

Han X, Cao Y, Jiang N, et al. Novel Coronavirus Pneumonia (COVID-19) Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section CT Features During Recovery. Clin Infect Dis. 2020. pii:ciaa271. doi:10.1093/cid/ciaa271.

Haschke M, Schuster M, Poglitsch M, et al. Pharmacokinetics and Pharmacodynamics of Recombinant Human Angiotensin-Converting Enzyme 2 in Healthy Human Subjects. Clin Pharmacokinet. 2013;52:783-792. doi:10.1007/s40262-013-0072-7.

He X, Lau E.HY, Wu P, et al. Temporal dynamics in viral shedding and transmissibIlity of COVID-19. Nat Med. 2020;26(5):672-675. doi:10.1038/s41591-020-0869-5.

Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280. doi:10.1016/j.cell.2020.02.052.

Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929-936. doi:10.1056/NEJMoa2001191.

Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020;63(5):706-711. doi:10.1007/s11427-020-1661-4.

Huang С, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. doi:10.1016/S0140-6736(20)30183-5.

Kalil A.C. Treating COVID-19-off-label drug use, com­passionate use, and randomized clinical trials during pandemics. JAMA. 2020. doi:10.1001/jama.2020.4742.

Kawase M, Shirato K, van der Hoek L, et al. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol. 2012;86:6537-6654.

Khan A, Benthin C, Zeno B, et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care. 2017;21(1):234. doi:10.1186/s13054-017-1823-x.

Kincaid E. COVID-19 Daily: HCQ Hospital Protocols, ED Physician Death. Medscape. April 24, 2020. https://www.medscape.com/viewarticle/929383.

Klok FA, Kruip MJHA, van derMeer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020. pii:S0049-3848(20)30120-1. doi:10.1016/j.thromres.2020.04.013.

Lai CC, Liu YH, Wang CY, et al. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect. 2020. pii:S1684-1182(20)30040-2. doi:10.1016/j.jmii.2020.02.012.

Lau SK, et al. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc Natl Acad Sci USA. 2005;102:14040-14045.

Lavezzo E, Franchin E, Ciavarella C, et al. Suppression of COVID-19 outbreak in the municipality of Vo, Italy. medRxiv. 2020. doi:10.1101/2020.04.17.20053157.

Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382:1199-1207. doi:10.1056/NEJMoa2001316.

Li X, Geng M, Peng Y, et al. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-108. doi:10.1016/j.jpha.2020.03.001.

Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450-454. doi:10.1038/nature02145.

Lippi G, Mattiuzzi C. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019. Hematol Transfus Cell Ther. 2020. pii:S2531-1379(20)30029-8. doi:10.1016/j.htct.2020.03.001.

Liu Y, Yan LM, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis. 2020. pii:S1473-3099(20)30232-2. doi:10.1016/S1473-3099(20)30232-2.

Lu X, Zhang L, Du H, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020;382:1663-1665. doi:10.1056/NEJMc2005073.

Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 2020;109(6):1088-1095. doi:10.1111/apa.15270.

McIntosh K. Coronavirus disease 2019(COVID-19): Epidemiology, virology, clinical features, diagnosis, and prevention. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-epidemiology-virology-clinical-features-diagnosis-and-prevention.

Miller A, Reandelar MJ, Fasciglione K, et al. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. medRxiv. 2020. doi:10.1101/2020.03.24.20042937.

Miyasaka M. Is BCG vaccination causally related to reduced COVID-19 mortality? EMBO Mol Med. 2020. doi:10.15252/emmm.202012661.

Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019(COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020;25(10). doi:10.2807/1560-7917.ES.2020.25.10.2000180.

Muramatsu T. Basigin (CD147), a multifunctional trans­mem­brane glycoprotein with various binding partners. J Bio­chemist. 2016;159(5):481-490. doi:10.1093/jb/mvv127.

Shereen MA, Khan S, Kazmi A, et al. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020;24:91-98. doi:10.1016/j.jare.2020.03.005.

Shimabukuro-Vornhagen A, Gödel P, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6:56.

Swenson K. New D.C. hospital numbers suggest kids do face some risk of coronavirus hospitalization. Washington Post. 2020. https://www.washingtonpost.com/local/new-dc-hospital-numbers-suggest-kids-do-face-some-risk-of-coronavirus-hospitalization/2020/04/25/5e78c268-86fe-11ea-878a-86477a724bdb_story.html.

ter Meulen J, Bakker AB, van den Brink EN, et al. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet. 2004;363(9427):2139-2141.

Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020. doi:10.1056/NEJMc2009191.

CDC COVID-19 Response Team. Severe Outcomes Among Patients with Coronavirus Disease 2019(COVID-19) - United States, February 12-March 16, 2020. Morb Mortal Wkly Rep. 2020;69(12):343-346. doi:10.15585/mmwr.mm6912e2.

United States National Institutes of Health. Coronavirus Disease 2019(COVID-19). Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov.

Wang C, et al. A novel coronavirus outbreak of global health concern. Lancet. 2020;395:470-473. doi:10.1016/S0140-6736(20)30185-9.

Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. doi:10.1001/jama.2020.1585.

Wang K, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv. 2020. doi: 10.1101/2020.03.14.988345.

Wang M, Cao R, Zhang L, et al.Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. doi:10.1038/s41422-020-0282-0.

Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381-385.

Wenzhong L, Hualan L. COVID-19: attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. ChemRxiv. 2020. doi:10.26434/chemrxiv.11938173.v7.

Wong HYF, Lam HYS, Fong AH, et al. Frequency and distribution of chest radiographic findings in COVID-19 positive patients. Radiology. 2020:201160. doi:10.1148/radiol.2020201160.

Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020. doi:10.1038/s41586-020-2196-x.

World Health Organization. Advice on the use of point-of-care immunodiagnostic tests for COVID-19. 2020. https://www.who.int/news-room/commentaries/detail/advice-on-the-use-of-point-of-care-immunodiagnostic-tests-for-covid-19.

World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 — 11 May 2020. 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-may-2020.

World Health Organization. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. 2020. https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases- 20200117.

Wu C, Chen X, Cai Y, 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. doi:10.1001/jamainternmed. 2020.0994.

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019(COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020. doi:10.1001/jama.2020.2648.

Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020. pii:202005615. doi:10.1073/pnas.2005615117.

Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Resp Med. 2020. doi:10.1016/S2213-2600(20)30076-X.

Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-481. doi:10.1016/S2213-2600(20)30079-5.

Yonker LM, Shen K, Kinane TB. Lessons unfolding from pediatric cases of COVID-19 disease caused by SARS-CoV-2 infection. Pediatr Pulmonol. 2020;55:1085-1086. doi:10.1002/ppul.24748.

Yu F, Yan L, Wang N, et al. Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients. Clin Infect Dis. 2020. pii:ciaa345. doi:10.1093/cid/ciaa345.

Yurchenko V, Constant S, Bukrinsky M. Dealing with the family: CD147 interactions with cyclophilins. Immunology. 2006;117(3):301-309. doi:10.1111/j.1365-2567. 2005. 02316.x.

Zhang H, Baker A. Recombinant human ACE2: acing out angiotensin II in ARDS therapy. Crit Care. 2017;21:305. doi:10.1186/s13054-017-1882-z.

Zhang H, Penninger JM, Li Y, et al. Angiotensin-converting enzyme 2(ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586-590. doi:10.1007/s00134-020-05985-9.

Zhang T, Wu Q, Zhang Z. Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak. Curr Biol. 2020;30(7):1346-1351. doi:10.1016/j.cub.2020.03.022.

Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019(COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol. 202;214:108393. doi:10.1016/j.clim.2020.108393.

Zhao J, Yuan Q, Wang H, et al. Antibody Respons es to SARS-CoV-2 in Patients of Novel Coronavirus Disease 2019. SSRN Electron J. 2020;1:22. doi:10.2139/ssrn.3546052.

Zheng J. SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat. Int J Biol Sci. 2020;16(10):1678-1685. doi:10.7150/ijbs.45053.

Zhou F, Yu T, Du R, et al. 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. doi:10.1016/S2666-5247(20)30009-4.

Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. doi:10.1038/s41586-020-2012-7.

Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targe­ting coronavirus and filovirus entry. Antiviral Res. 2015;116:76-84.

Zhu N, et al. A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med. 2020;382:727-733. doi:10.1056/NEJMoa2001017.

Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020;382:1177-1179. doi:10.1056/NEJMc2001737.

##submission.downloads##

Опубліковано

2020-05-30

Номер

Розділ

Передова стаття