Coronavirus Disease 2019: An Overview of the Complications and Management
PDF

Keywords

Coronavirus disease 2019
Viral infection
Coronavirus
Severe acute respiratory syndrome coronavirus-2
Vaccine
Antiviral agents

DOI

10.36922/itps.v4i1.1037

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Since the first report of COVID-19 emerging in Wuhan, China, authorities in 216 countries and territories have reported about 47.3 million COVID-19 cases and 1.2 million deaths. The WHO guidelines for the management of COVID-19 are very limited to recommendations for managing symptoms and advice on careful management of pediatric patients, pregnant women, and patients with underlying comorbidities. There is no approved treatment for COVID-19 and guidelines vary between countries. In this review, first, a brief overview is provided on the basic knowledge about the virus, clinical features of the disease, and different diagnostic methods. Then, the relationship between COVID-19, various body systems, and other complications is discussed. Finallly, different management strategies are discussed, including those drawn on computational chemistry analyses, pre-clinical investigations, and clinical trials which involve pharmacological and non-pharmacological interventions. In conclusion, despite the recent approval of different vaccine candidates, more virological characteristics of SARS-CoV-2 are required to be explored, which may result in the discovery of more potential therapeutic targets leading to safer and more effective treatment to COVID-19.

References

Yang, F.; Shi, S.; Zhu, J.; Shi, J.; Dai, K.; Chen, X. Analysis of 92 Deceased Patients with COVID-19. J. Med. Virol., 2020, 11, 2511–5.

Zhu, J.; Ji, P.; Pang, J.; Zhong, Z.; Li, H.; He, C.; Zhang, J.; Zhao, C. Clinical Characteristics of 3,062 COVID-19 Patients: A Meta-analysis. J. Med. Virol., 2020, 92, 1902–14.

Zhu, F.C.; Guan, X.H.; Li, Y.H.; Huang, J.Y.; Jiang, T.; Hou, L.H.; Li, J.X.; Yang, B.F.; Wang, L.; Wang, W.J.; Wu, S.P.; Wang, Z.; Wu, X.H.; Xu, J.J.; Zhang, Z.; Jia, S.Y.; Wang, B.S.; Hu, Y.; Liu, J.J.; Zhang, J.; Qian, X.A.; Li, Q.; Pan, H.X.; Jiang, H.D.; Deng, P.; Gou, J.B.; Wang, X.W.; Wang, X.H.; Chen, W. Immunogenicity and Safety of a Recombinant Adenovirus Type- 5-vectored COVID-19 Vaccine in Healthy Adults Aged 18 Years or Older: A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial. Lancet, 2020, 396(10249), 479–88.

Chen, Y.; Liu, Q.; Guo, D. Emerging Coronaviruses: Genome Structure, Replication, and Pathogenesis. J. Med. Virol. 2020, 92(4), 418–23.

Fan, C.; Li, K.; Ding, Y.; Lu, W.; Wang, J. ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection. medRxiv, 2020.

Wan, S.; Xiang, Y.; Fang, W.; Zheng, Y.; Li, B.; Hu, Y.; Lang, C.; Huang, D.; Sun, Q.; Xiong, Y.; Huang, X.; Lv, J.; Luo, Y.; Shen, L.; Yang, H.; Huang, G.; Yang, R. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J. Med. Virol., 2020, 92(7), 797–806.

Wong, C.K.; Lam, C.W.; Wu, A.K.; Ip, W.K.; Lee, N.L.; Chan, I.H.; Lit, L.C.; Hui, D.S.; Chan, M.H.; Chung, S.S.; Sung, J.J. Plasma Inflammatory Cytokines and Chemokines in Severe Acute Respiratory Syndrome. Clin. Exp. Immunol., 2004, 136(1), 95–103.

Zhang, H.; Kang, Z.; Gong, H.; Xu, D.; Wang, J.; Li, Z.; Cui, X.; Xiao, J.; Meng, T.; Zhou, W.; Liu, J.; Xu, H. The Digestive System is a Potential Route of 2019-nCov Infection: A Bioinformatics Analysis Based on Single-Cell Transcriptomes. bioRxiv, 2020.

Guan, W.J.; Liang, W.H.; Zhao, Y.; Liang, H.R.; Chen, Z.S.; Li, Y.M.; Liu, X.Q.; Chen, R.C.; Tang, C.L.; Wang, T.; Ou, C.Q.; Li, L.; Chen, P.Y.; Sang, L.; Wang, W.; Li, J.F.; Li, C.C.; Ou, L.M.; Cheng, B.; Xiong, S.; Ni, Z.Y.; Xiang, J.; Hu, Y.; Liu, L.; Shan, H.; Lei, C.L.; 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.; Cheng, L.L.; Ye, F.; Li, S.Y.; Zheng, J.P.; Zhang, N.F.; Zhong, N.S.; He, J.X.; China Medical Treatment Expert Group for COVIS-19. Comorbidity and its Impact on 1590 Patients with Covid-19 in China: A Nationwide Analysis. Eur. Respir. J., 2020, 55(5), 2000547.

General Office of the National Health and Health Commission. Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 8). Available from: http://www.nhc.gov. cn/yzygj/s7653p/202008/0a7bdf12bd4b46e5bd28ca7f9a7f5e5a. shtml. [Last accessed on 2020 Oct 01].

Xue, H.; Jin, Z. The Appropriate Position of Radiology in COVID-19 Diagnosis and Treatment-Current Status and Opinion from China. Chin. J. Acad. Radiol, 2020, 2020, 1-3.

Pata, D.; Valentini, P.; De Rose, C.; De Santis, R.; Morello, R.; Buonsenso, D. Chest Computed Tomography and Lung Ultrasound Findings in COVID-19 Pneumonia: A Pocket Review for Non-radiologists. Front. Med. (Lausanne), 2020, 7, 375.

Lijia, S.; Lihong, S.; Huabin, W.; Xiaoping, X.; Xiaodong, L.; Yixuan, Z.; Pin, H.; Yina, X.; Xiaoyun, S.; Junqi, W. Serological Chemiluminescence Immunoassay for the Diagnosis of SARS-CoV-2 Infection. J. Clin. Lab. Anal., 2020, 34(10), e23466.

Huang, Z.; Jiang, Y.; Chen, J.; Zhou, Y. Inhibitors of the Renin-angiotensin System: The Potential Role in the Pathogenesis of COVID-19. Cardiol. J., 2020, 27(2), 171–4.

Imai, Y.; Kuba, K.; Rao, S.; Huan, Y.; Guo, F.; Guan, B.; Yang, P.; Sarao, R.; Wada, T.; Leong-Poi, H.; Crackower, M.A.; Fukamizu, A.; Hui, C.C.; Hein, L.; Uhlig, S.; Slutsky, A.S.; Jiang, C.; Penninger, J.M. Angiotensin-converting Enzyme 2 Protects from Severe Acute Lung Failure. Nature, 2005, 436(7047), 112–6.

Kuba, K.; Imai, Y.; Rao, S.; Gao, H.; Guo, F.; Guan, B.; Huan, Y.; Yang, P.; Zhang, Y.; Deng, W.; Bao, L.; Zhang, B.; Liu, G.; Wang, Z.; Chappell, M.; Liu, Y.; Zheng, D.; Leibbrandt, A.; Wada, T.; Slutsky, A.S.; Liu, D.; Qin, C.; Jiang, C.; Penninger, J.M. A Crucial Role of Angiotensin Converting Enzyme 2 (ACE2) in SARS Coronavirus-induced Lung Injury. Nat. Med., 2005, 11(8), 875–9.

Crackower, M.A.; Sarao, R.; Oudit, G.Y.; Yagil, C.; Kozieradzki, I.; Scanga, S.E.; Oliveira-dos-Santos, A.J.; da Costa, J.; Zhang, L.; Pei, Y.; Scholey, J.; Ferrario, C.M.; Manoukian, A.S.; Chappell, M.C.; Backx, P.H.; Yagil, Y.; Penninger, J.M. Angiotensin-converting Enzyme 2 is an Essential Regulator of Heart Function. Nature, 2002, 417(6891), 822–8.

Xu, X.; Chen, P.; Wang, J.; Feng, J.; Zhou, H.; Li, X.; Zhong, W.; Hao, P. Evolution of the Novel Coronavirus from the Ongoing Wuhan Outbreak and Modeling of its Spike Protein for Risk of Human Transmission. Sci. Chin. Life Sci., 2020, 63(3), 457–60.

Wevers, B.A.; van der Hoek, L. Renin-angiotensin System in Human Coronavirus Pathogenesis. Future Virol., 2010, 5(2), 145–61.

Huentelman, M.J.; Zubcevic, J.; Hernandez Prada, J.A.; Xiao, X.; Dimitrov, D.S.; Raizada, M.K.; Ostrov, D.A. Structure-based Discovery of a Novel Angiotensin-converting Enzyme 2 Inhibitor. Hypertension (Dallas, Tex. : 1979), 2004, 44(6), 903–6.

Bonow, R.O.; Fonarow, G.C.; O’Gara, P.T.; Yancy, C.W. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol., 2020, 5(7), 751–3.

Kwong, J.C.; Schwartz, K.L.; Campitelli, M.A. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N. Engl. J. Med., 2018, 378(26), 2540–1.

Oudit, G.Y.; Kassiri, Z.; Jiang, C.; Liu, P.P.; Poutanen, S.M.; Penninger, J.M.; Butany, J. SARS-coronavirus Modulation of Myocardial ACE2 Expression and Inflammation in Patients with SARS. Eur. J. Clin. Investig., 2009, 39(7), 618–25.

Liu, P.P.; Blet, A.; Smyth, D.; Li, H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation, 2020, 142(1), 68–78.

Drucker, D.J. Coronavirus Infections and Type 2 Diabetes-shared Pathways with Therapeutic Implications. Endocr. Rev., 2020, 41(3), bnaa011.

Yang, J.K.; Lin, S.S.; Ji, X.J.; Guo, L.M. Binding of SARS Coronavirus to its Receptor Damages Islets and Causes Acute Diabetes. Acta Diabetol., 2010, 47(3), 193–9.

Booth, C.M.; Matukas, L.M.; Tomlinson, G.A.; Rachlis, A.R.; Rose, D.B.; Dwosh, H.A.; Walmsley, S.L.; Mazzulli, T.; Avendano, M.; Derkach, P.; Ephtimios, I.E.; Kitai, I.; Mederski, B.D.; Shadowitz, S.B.; Gold, W.L.; Hawryluck, L.A.; Rea, E.; Chenkin, J.S.; Cescon, D.W.; Poutanen, S.M.; Detsky, A.S. Clinical Features and Short-term Outcomes of 144 Patients with SARS in the Greater Toronto Area. JAMA, 2003, 289(21), 2801–9.

Alqahtani, F.Y.; Aleanizy, F.S.; Ali El Hadi Mohamed, R.; Alanazi, M.S.; Mohamed, N.; Alrasheed, M.M.; Abanmy, N.; Alhawassi, T. Prevalence of Comorbidities in Cases of Middle East Respiratory Syndrome Coronavirus: A Retrospective Study. Epidemiol. Infect., 2018, 47, 1–5.

Guo, W.; Li, M.; Dong, Y.; Zhou, H.; Zhang, Z.; Tian, C.; Qin, R.; Wang, H.; Shen, Y.; Du, K.; Zhao, L.; Fan, H.; Luo, S.; Hu, D. Diabetes is a Risk Factor for the Progression and Prognosis of COVID-19. Diabetes Metab. Res. Rev., 2020, 2020, e3319.

Chow, N.; Fleming-Dutra, K.; Gierke, R.; Hall, A.; Hughes, M.; Pilishvili, T.; Ritchey, M.; Roguski, K.; Skoff, T.; Ussery, E. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019 United States, February 12-March 28, 2020. MMWR Morb. Mortal. Wkly. Rep. 2020, 69(13), 382–6.

Seshasai, S.R.K.; Kaptoge, S.; Thompson, A.; Di Angelantonio, E.; Gao, P.; Sarwar, N.; Whincup, P.H.; Mukamal, K.J.; Gillum, R.F.; Holme, I.; Njolstad, I.; Fletcher, A.; Nilsson, P.; Lewington, S.; Collins, R.; Gudnason, V.; Thompson, S.G.; Sattar, N.; Selvin, E.; Hu, F.B.; Danesh, J. Diabetes Mellitus, Fasting Glucose, and Risk of Cause-specific Death. New Engl. J. Med., 2011, 364(9), 829–41.

Jin, X.; Lian, J.S.; Hu, J.H.; Gao, J.; Zheng, L.; Zhang, Y.M.; Hao, S.R.; Jia, H.Y.; Cai, H.; Zhang, X.L.; Yu, G.D.; Xu, K.J.; Wang, X.Y.; Gu, J.Q.; Zhang, S.Y.; Ye, C.Y.; Jin, C.L.; Lu, Y.F.; Yu, X.; Yu, X.P.; Huang, J.R.; Xu, K.L.; Ni, Q.; Yu, C.B.; Zhu, B.; Li, Y.T.; Liu, J.; Zhao, H.; Zhang, X.; Yu, L.; Guo, Y.Z.; Su, J.W.; Tao, J.J.; Lang, G.J.; Wu, X.X.; Wu, W.R.; Qv, T.T.; Xiang, D.R.; Yi, P.; Shi, D.; Chen, Y.; Ren, Y.; Qiu, Y.Q.; Li, L.J.; Sheng, J.; Yang, Y. Epidemiological, Clinical and Virological Characteristics of 74 Cases of Coronavirus-infected Disease 2019 (COVID-19) with Gastrointestinal Symptoms. Gut, 2020, 69(6), 1002–9.

Lighter, J.; Phillips, M.; Hochman, S.; Sterling, S.; Johnson, D.; Francois, F.; Stachel, A. Obesity in Patients Younger than 60 Years is a Risk Factor for Covid-19 Hospital Admission. Clin. Infect. Dis., 2020, 71(15), 896–7.

Porfidia, A.; Pola, R. Venous Thromboembolism in COVID-19 Patients. J. Thromb. Haemost., 2020, 18(6), 1516–7.

Tang, N.; Bai, H.; Chen, X.; Gong, J.; Li, D.; Sun, Z. Anticoagulant Treatment is Associated with Decreased Mortality in Severe Coronavirus Disease 2019 Patients with Coagulopathy. J. Thromb. Haemost., 2020, 18(5), 1094–9.

Li, X.; Dai, T.; Wang, H.; Shi, J.; Yuan, W.; Li, J.; Chen, L.; Zhang, T.; Zhang, S.; Kong, Y.; Yue, N.; Shi, H.; He, Y.; Hu, H.; Liu, F.; Yang, C. Clinical Analysis of Suspected Novel Coronavirus Pneumonia Patients with Anxiety and Depression. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2020, 49(1), 203–8.

Henry, B.M.; Lippi, G. Chronic Kidney Disease is Associated with Severe Coronavirus Disease 2019 (COVID-19) Infection. Int. Urol. Nephrol., 2020, 52(6), 1193–4.

Wong, S.H.; Lui, R.N.; Sung, J.J. Covid-19 and the Digestive System. J. Gastroenterol. Hepatol., 2020, 35(5), 744–8.

Cava, C.; Bertoli, G.; Castiglioni, I. In Silico Discovery of Candidate Drugs against Covid-19. Viruses, 2020, 12(4), 404.

Elfiky, A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp): A Molecular Docking Study. Life Sci., 2020, 253, 117592.

Hall, D.C. Jr.; Ji, H.F. A Search for Medications to Treat COVID-19 via In Silico Molecular Docking Models of the SARS-CoV-2 Spike Glycoprotein and 3CL Protease. Travel Med. Infect. Dis., 2020, 35, 101646.

Liu, S.; Zheng, Q.; Wang, Z. Potential Covalent Drugs Targeting the Main Protease of the SARS-CoV-2 Coronavirus. Bioinformatics, 2020, 36(11), 3295–8.

Savarino, A.; Boelaert, J.R.; Cassone, A.; Majori, G.; Cauda, R. Effects of Chloroquine on Viral Infections: An Old Drug Against Today’s Diseases. Lancet Infect. Dis., 2003, 3(11), 722–7.

Zhou, D.; Dai, S.M.; Tong, Q. COVID-19: A Recommendation to Examine the Effect of Hydroxychloroquine in Preventing Infection and Progression. J. Antimicrob. Chemother., 2020, 75(7), 1667–70.

Devaux, C.A.; Rolain, J.M.; Colson, P.; Raoult, D. New Insights on the Antiviral Effects of Chloroquine Against Coronavirus: What to Expect for COVID-19? Int. J. Antimicrob. Agents, 2020, 105938.

Yao, X.; Ye, F.; Zhang, M.; Cui, C.; Huang, B.; Niu, P.; Liu, X.; Zhao, L.; Dong, E.; Song, C.; Zhan, S.; Lu, R.; Li, H.; Tan, W.; Liu, D. 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, 71(15), 732–9.

Rossignol, J.F. Nitazoxanide, a New Drug Candidate for the Treatment of Middle East Respiratory Syndrome Coronavirus. J. Infect. Public Health, 2016, 9(3), 227–30.

Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and Chloroquine Effectively Inhibit the Recently Emerged Novel Coronavirus (2019-nCoV) In Vitro. Cell Res., 2020, 30(3), 269–71.

Lu, C.C.; Chen, M.Y.; Chang, Y.L. Potential Therapeutic Agents Against COVID-19: What we know so Far. J. Chin. Med. Assoc., 2020, 83(6), 534–6.

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, 56(1), 105949.

Gao, J.; Tian, Z.; Yang, X. Breakthrough: Chloroquine Phosphate has Shown Apparent Efficacy in Treatment of COVID-19 Associated Pneumonia in Clinical Studies. Biosci. Trends, 2020, 14(1), 72–3.

Millan-Onate, J.; Millan, W.; Mendoza, L.A.; Sanchez, C.G.; Fernandez-Suarez, H.; Bonilla-Aldana, D.K.; Rodriguez- Morales, A.J. Successful Recovery of COVID-19 Pneumonia in a Patient from Colombia after Receiving Chloroquine and Clarithromycin. Ann. Clin. Microbiol. Antimicrob., 2020, 19(1), 16.

Tang, W.; Cao, Z.; Han, M.; Wang, Z.; Chen, J.; Sun, W.; Wu, Y.; Xiao, W.; Liu, S.; Chen, E.; Chen, W.; Wang, X.; Yang, J.; Lin, J.; Zhao, Q.; Yan, Y.; Xie, Z.; Li, D.; Yang, Y.; Liu, L.; Qu, J.; Ning, G.; Shi, G.; Xie, Q. Hydroxychloroquine in Patients with Mainly Mild to Moderate Coronavirus Disease 2019: Open Label, Randomised Controlled Trial. BMJ, 2020, 369, m1849.

Borba, M.G.S.; Val, F.F.A.; Sampaio, V.S.; Alexandre, M.A.A.; Melo, G.C.; Brito, M.; Mourao, M.P.G.; Brito-Sousa, J.D.; Baia-da-Silva, D.; Guerra, M.V.F.; Hajjar, L.A.; Pinto, R.C.; Balieiro, A.A.S.; Pacheco, A.G.F.; Santos, J.D.O. Jr.; Naveca, F.G.; Xavier, M.S.; Siqueira, A.M.; Schwarzbold, A.; Croda, J.; Nogueira, M.L.; Romero, G.A.S.; Bassat, Q.; Fontes, C.J.; Albuquerque, B.C.; Daniel-Ribeiro, C.T.; Monteiro, W.M.; Lacerda, M.V.G.; CloroCovid, T. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA Netw Open, 2020, 3(4), e208857.

Jiang, S.; Li. L.; Ru, R.; Zhang, C.; Rao, Y.; Lin, B.; Wang, R.; Chen, N.; Wang, X.; Cai, H.; Sheng, J.; Zhou, J.; Lu, X.; Qiu, Y. Pharmaceutical Care for Severe and Critically Ill Patients with Corona Virus Disease 2019 (COVID-19). Zhejiang Da Xue Xue Bao Yi Xue Ban, 2020, 49(1), 158–69.

Singh, A.K.; Singh, A.; Shaikh, A.; Singh, R.; Misra, A. Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 with or Without Diabetes: A Systematic Search and a Narrative Review with a Special Reference to India and Other Developing Countries. Diabetes Metab. Syndr., 2020, 14(3), 241–6.

Sheahan, T.P.; Sims, A.C.; Graham, R.L.; Menachery, V.D.; Gralinski, L.E.; Case, J.B.; Leist, S.R.; Pyrc, K.; Feng, J.Y.; Trantcheva, I.; Bannister, R.; Park, Y.; Babusis, D.; Clarke, M.O.; Mackman, R.L.; Spahn, J.E.; Palmiotti, C.A.; Siegel, D.; Ray, A.S.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Broad-spectrum Antiviral GS-5734 Inhibits Both Epidemic and Zoonotic Coronaviruses. Sci. Transl. Med., 2017, 9(396), eaal3653.

Gordon, C.J.; Tchesnokov, E.P.; Feng, J.Y.; Porter, D.P.; Gotte, M. The Antiviral Compound Remdesivir Potently Inhibits RNA-dependent RNA Polymerase from Middle East Respiratory Syndrome Coronavirus. J. Biol. Chem., 2020, 295(15), 4773–9.

Warren, T.K.; Jordan, R.; Lo, M.K.; Ray, A.S.; Mackman, R.L.; Soloveva, V.; Siegel, D.; Perron, M.; Bannister, R.; Hui, H. C.; Larson, N.; Strickley, R.; Wells, J.; Stuthman, K.S.; Van Tongeren, S.A.; Garza, N.L.; Donnelly, G.; Shurtleff, A.C.; Retterer, C.J.; Gharaibeh, D.; Zamani, R.; Kenny, T.; Eaton, B.P.; Grimes, E.; Welch, L.S.; Gomba, L.; Wilhelmsen, C.L.; Nichols, D.K.; Nuss, J.E.; Nagle, E.R.; Kugelman, J.R.; Palacios, G.; Doerffler, E.; Neville, S.; Carra, E.; Clarke, M.O.; Zhang, L.; Lew, W.; Ross, B.; Wang, Q.; Chun, K.; Wolfe, L.; Babusis, D.; Park, Y.; Stray, K.M.; Trancheva, I.; Feng, J.Y.; Barauskas, O.; Xu, Y.; Wong, P.; Braun, M.R.; Flint, M.; McMullan, L.K.; Chen, S.S.; Fearns, R.; Swaminathan, S.; Mayers, D.L.; Spiropoulou, C.F.; Lee, W.A.; Nichol, S.T.; Cihlar, T.; Bavari, S. Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola virus in Rhesus Monkeys. Nature, 2016, 531(7594), 381–5.

Sheahan, T.P.; Sims, A.C.; Leist, S.R.; Schäfer, A.; Won, J.; Brown, A.J.; Montgomery, S.A.; Hogg, A.; Babusis, D.; Clarke, M.O.; Spahn, J.E.; Bauer, L.; Sellers, S.; Porter, D.; Feng, J.Y.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Comparative Therapeutic Efficacy of Remdesivir and Combination Lopinavir, Ritonavir, and Interferon Beta Against MERS-CoV. Nat. Commun., 2020, 11(1), 222.

Wang, Y.; Zhang, D.; Du, G.; Du, R.; Zhao, J.; Jin, Y.; Fu, S.; Gao, L.; Cheng, Z.; Lu, Q.; Hu, Y.; Luo, G.; Wang, K.; Lu, Y.; Li, H.; Wang, S.; Ruan, S.; Yang, C.; Mei, C.; Wang, Y.; Ding, D.; Wu, F.; Tang, X.; Ye, X.; Ye, Y.; Liu, B.; Yang, J.; Yin, W.; Wang, A.; Fan, G.; Zhou, F.; Liu, Z.; Gu, X.; Xu, J.; Shang, L.; Zhang, Y.; Cao, L.; Guo, T.; Wan, Y.; Qin, H.; Jiang, Y.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Cao, B.; Wang, C. Remdesivir in Adults with Severe COVID-19: A Randomised, Double-blind, Placebo-controlled, Multicentre Trial. Lancet, 2020, 395, 1569–78.

Antinori, S.; Cossu, M.V.; Ridolfo, A.L.; Rech, R.; Bonazzetti, C.; Pagani, G.; Gubertini, G.; Coen, M.; Magni, C.; Castelli, A.; Borghi, B.; Colombo, R.; Giorgi, R.; Angeli, E.; Mileto, D.; Milazzo, L.; Vimercati, S.; Pellicciotta, M.; Corbellino, M.; Torre, A.; Rusconi, S.; Oreni, L.; Gismondo, M.R.; Giacomelli, A.; Meroni, L.; Rizzardini, G.; Galli, M. Compassionate Remdesivir Treatment of Severe Covid-19 Pneumonia in Intensive Care Unit (ICU) and Non-ICU Patients: Clinical Outcome and Differences in Post-treatment Hospitalisation Status. Pharmacol. Res., 2020, 158, 104899.

Dong, L.; Hu, S.; Gao, J. Discovering Drugs to Treat Coronavirus Disease 2019 (COVID-19). Drug Discov. Ther., 2020, 14(1), 58–60.

Zhu, Z.; Lu, Z.; Xu, T.; Chen, C.; Yang, G.; Zha, T.; Lu, J.; Xue, Y. Arbidol Monotherapy is Superior to Lopinavir/Ritonavir in Treating COVID-19. J. Infect., 2020, 81(1), e21–3.

Deng, L.; Li, C.; Zeng, Q.; Liu, X.; Li, X.; Zhang, H.; Hong, Z.; Xia, J. Arbidol Combined with LPV/r Versus LPV/r Alone Against Corona Virus Disease 2019: A Retrospective Cohort Study. J. Infect., 2020, 81(1), e1–5.

Xu, K.; Cai, H.; Shen, Y.; Ni, Q.; Chen, Y.; Hu, S.; Li, J.; Wang, H.; Yu, L.; Huang, H.; Qiu, Y.; Wei, G.; Fang, Q.; Zhou, J.; Sheng, J.; Liang, T.; Li, L. Management of Corona Virus Disease-19 (COVID-19): The Zhejiang Experience. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2020, 49(1), 147–57.

Chu, C.M.; Cheng, V.C.; Hung, I.F.; Wong, M.M.; Chan, K.H.; Chan, K.S.; Kao, R.Y.; Poon, L.L.; Wong, C.L.; Guan, Y.; Peiris, J.S.; Yuen, K.Y. Role of Lopinavir/Ritonavir in the Treatment of SARS: Initial Virological and Clinical Findings. Thorax, 2004, 59(3), 252–6.

de Wilde, A.H.; Jochmans, D.; Posthuma, C.C.; Zevenhoven- Dobbe, J.C.; van Nieuwkoop, S.; Bestebroer, T.M.; van den Hoogen, B.G.; Neyts, J.; Snijder, E.J. Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture. Antimicrob. Agents Chemother., 2014, 58(8), 4875–84.

Yao, T.T.; Qian, J.D.; Zhu, W.Y.; Wang, Y.; Wang, G.Q. 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, 92(6), 556–63.

Choy, K.T.; Wong, A.Y.L.; Kaewpreedee, P.; Sia, S.F.; Chen, D.; Hui, K.P.Y.; Chu, D.K.W.; Chan, M.C.W.; Cheung, P.P.H.; Huang, X.; Peiris, M.; Yen, H.L. Remdesivir, Lopinavir, Emetine, and Homoharringtonine Inhibit SARS-CoV-2 Replication In Vitro. Antiviral Res., 2020, 178, 104786.

Jun, L.; Tao, Z.; Qibin, W.; Yongcheng, D.; Zizhong, Y. Safety Analysis of Lopinavir/Ritonavir Tablets in 40 Hospitalized Patients with Coronavirus Disease 2019. Chin. J. Hosp. Pharm., 2020, 40(10), 1086–8.

Nakamura, K.; Hikone, M.; Shimizu, H.; Kuwahara, Y.; Tanabe, M.; Kobayashi, M.; Ishida, T.; Sugiyama, K.; Washino, T.; Sakamoto, N.; Hamabe, Y. A Sporadic COVID-19 Pneumonia Treated with Extracorporeal Membrane Oxygenation in Tokyo, Japan: A Case Report. J. Infect. Chemother., 2020, 26(7), 756–61.

Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N. Engl. J. Med., 2020, 382(19), 1787–99.

Ford, N.; Vitoria, M.; Rangaraj, A.; Norris, S.L.; Calmy, A.; Doherty, M. Systematic Review of the Efficacy and Safety of Antiretroviral Drugs Against SARS, MERS or COVID-19: Initial Assessment. J. Int. AIDS Soc., 2020, 23(4), e25489.

Guo, W.; Ming, F.; Dong, Y.; Zhang, Q.; Zhang, X.; Mo, P.; Feng, Y.; Liang, K. A Survey for COVID-19 among HIV/AIDS Patients in Two Districts of Wuhan, China. SSRN, 2020, https://dx.doi. org/10.2139/ssrn.3550029.

Deeks, E.D. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs, 2018, 78(10), 1013–24.

Mingming S.; Hongming Z.; Jiu-yan C.; Y., Y., Rational use and Pharmaceutical Care of Lopinavir/Ritonavir in the Treatment of Patients with Corona Virus Disease 2019. Chin. J. Hosp. Pharm., 2020, 40(7), 753–6.

Stockman, L.J.; Bellamy, R.; Garner, P. SARS: Systematic Review of Treatment Effects. PLoS Med., 2006, 3(9), e343.

Schneider, W.M.; Chevillotte, M.D.; Rice, C.M. Interferon- Stimulated Genes: A Complex Web of Host Defenses. Annu. Rev. Immunol., 2014, 32, 513–45.

Sallard, E.; Lescure, F.X.; Yazdanpanah, Y.; Mentre, F.; Peiffer- Smadja, N. Type 1 Interferons as a Potential Treatment Against COVID-19. Antiviral Res., 2020, 178, 104791.

Tan, E.L.C.; Ooi, E.E.; Lin, C.Y.; Tan, H.C.; Ling, A.E.; Lim, B.; Stanton, L.W. Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs. Emerg. Infect. Dis. 2004, 10(4), 581–6.

Zhou, Q.; Chen, V.; Shannon, C.P.; Wei, X.S.; Xiang, X.; Wang, X.; Wang, Z.H.; Tebbutt, S.J.; Kollmann, T.R.; Fish, E.N. Interferon-alpha2b Treatment for COVID-19. Front. Immunol., 2020, 11, 1061.

Zhang, H.; Kang, Z.; Gong, H.; Xu, D.; Wang, J.; Li, Z.; Cui, X.; Xiao, J.; Meng, T.; Zhou, W.J.B. The Digestive System is a Potential Route of 2019-nCov Infection: A Bioinformatics Analysis Based on Single-cell Transcriptomes. bioRxiv, 2020, https://doi. org/10.1101/2020.01.30.927806.

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 (London, England), 2020, 395(10223), 497–506.

Costanzo, M.; De Giglio, M.A.R.; Roviello, G.N. SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/ Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus. Curr. Med. Chem., 2020, 27(27), 4536–41.

Zhou, Y.; Fu, B.; Zheng, X.; Wang, D.; Zhao, C.; qi, Y.; Sun, R.; Tian, Z.; Xu, X.; Wei, H. Aberrant Pathogenic GM-CSF+ T Cells and Inflammatory CD14+ CD16+ Monocytes in Severe Pulmonary Syndrome Patients of a New Coronavirus. bioRxiv 2020, 2020, 945576.

Aziz, M.; Fatima, R.; Assaly, R. Elevated Interleukin-6 and Severe COVID-19: A Meta-Analysis. J. Med. Virol., 2020, 92(11), 2283–5.

Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA, 2020, 323(18), 1824–36.

Luo, S.; Yang. L.; Wang, C.; Liu, C.; Li, D. Clinical Observation of 6 Severe COVID-19 Patients Treated with Plasma Exchange or Tocilizumab. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2020, 49(1), 227–31.

Radbel, J.; Narayanan, N.; Bhatt, P.J. Use of Tocilizumab for COVID-19 Infection-induced Cytokine Release Syndrome: A Cautionary Case Report. Chest, 2020, 158(1), e15–9.

Tian, X.; Li, C.; Huang, A.; Xia, S.; Lu, S.; Shi, Z.; Lu, L.; Jiang, S.; Yang, Z.; Wu, Y.; Ying, T. Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-specific Human Monoclonal Antibody. Emerg. Microb. Infect., 2020, 9(1), 382–5.

Zheng, M.; Song, L. Novel Antibody Epitopes Dominate the Antigenicity of Spike Glycoprotein in SARS-CoV-2 Compared to SARS-CoV. Cell. Mol. Immunol., 2020,

Russell, C.D.; Millar, J.E.; Baillie, J.K. Clinical Evidence Does not Support Corticosteroid Treatment for 2019-nCoV Lung Injury. Lancet (London, England), 2020, 395(10223), 473–5.

Zhou, W.; Liu, Y.; Tian, D.; Wang, C.; Wang, S.; Cheng, J.; Hu, M.; Fang, M.; Gao, Y. Potential Benefits of Precise Corticosteroids Therapy for Severe 2019-nCoV Pneumonia. Signal Transduct. Target. Ther., 2020, 5(1), 18.

Xia, S.; Zhu, Y.; Liu, M.; Lan, Q.; Xu, W.; Wu, Y.; Ying, T.; Liu, S.; Shi, Z.; Jiang, S.; Lu, L. Fusion Mechanism of 2019-nCoV and Fusion Inhibitors Targeting HR1 Domain in Spike Protein. Cell. Mol. Immunol., 2020, 17(7), 765–7.

Nguyen, T.M.; Zhang, Y.; Pandolfi, P.P. Virus Against Virus: A Potential Treatment for 2019-nCov (SARS-CoV-2) and Other RNA Viruses. Cell Res., 2020, 30(3), 189–90.

Monteil, V.; Kwon, H.; Prado, P.; Hagelkruys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Del Pozo, C.H.; Prosper, F.; Romero, J.P.; Wirnsberger, G.; Zhang, H.; Slutsky, A.S.; Conder, R.; Montserrat, N.; Mirazimi, A.; Penninger, J.M. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical- Grade Soluble Human ACE2. Cell, 2020, 181(4), 905–13.e7.

Lei, C.; Qian, K.; Li, T.; Zhang, S.; Fu, W.; Ding, M.; Hu, S. Neutralization of SARS-CoV-2 Spike Pseudotyped Virus by Recombinant ACE2-Ig. Nat. Commun., 2020, 11(1), 2070.

Carr, A.C.; Rosengrave, P.C.; Bayer, S.; Chambers, S.; Mehrtens, J.; Shaw, G.M. Hypovitaminosis C and Vitamin C Deficiency in Critically Ill Patients Despite Recommended Enteral and Parenteral Intakes. Crit. Care, 2017, 21(1), 300.

Boretti, A.; Banik, B.K. Intravenous Vitamin C for Reduction of Cytokines Storm in Acute Respiratory Distress Syndrome. PharmaNutrition, 2020, 12, 100190.

Hernandez, A.; Papadakos, P.J.; Torres, A.; Gonzalez, D.A.; Vives, M.; Ferrando, C.; Baeza, J. Two Known Therapies Could be Useful as Adjuvant Therapy in Critical Patients Infected by COVID-19. Rev. Esp. Anestesiol. Reanim., 2020, 67(5), 245–52.

Iii, A.A.F.; Kim, C.; Lepler, L.; Malhotra, R.; Debesa, O.; Natarajan, R.; Fisher, B. J.; Syed, A.; DeWilde, C.; Priday, A.; Kasirajan, V. Intravenous Vitamin C as Adjunctive Therapy for Enterovirus/Rhinovirus Induced Acute Respiratory Distress Syndrome. World J. Crit. Care Med, 2017, 6(1), 85–90.

Linjie, H.; Fuchao, C.; Xueqiang, J.; Zhihao, L.; Wan, W. Clinical characteristics and therapy of novel corona virus pneumonia: 71 cases retrospective analysis. Central South Pharmacy 2020, 18(5), 739–42.

Hantoushzadeh, S.; Norooznezhad, A.H. Inappropriate Antibiotic Consumption as a Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with Coronavirus Disease 2019 (COVID-19). Arch. Med. Res., 2020, 51(4), 347–348.

Caly, L.; Druce, J.D.; Catton, M.G.; Jans, D.A.; Wagstaff, K.M. The FDA-Approved Drug Ivermectin Inhibits the Replication of SARS-CoV-2 In Vitro. Antiviral Res., 2020, 178, 104787.

Gharebaghi, R.; Heidary, F.; Moradi, M.; Parvizi, M. Metronidazole; a Potential Novel Addition to the COVID-19 Treatment Regimen. Arch. Acad. Emerg. Med., 2020, 8(1), e40.

Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and is Blocked by a Clinically Proven Protease Inhibitor. Cell, 2020, 181(2), 271–80.e8.

Rosa, S.G.V.; Santos, W.C. Clinical Trials on Drug Repositioning for COVID-19 Treatment. Rev. Pan Salud Publica, 2020, 44, e40.

Maggio, R.; Corsini, G.U. Repurposing the Mucolytic Cough Suppressant and TMPRSS2 Protease Inhibitor Bromhexine for the Prevention and Management of SARS-CoV-2 Infection. Pharmacol. Res., 2020, 157, 104837.

Clark, W.F.; Huang, S.S. Introduction to Therapeutic Plasma Exchange. Transfus. Apher. Sci., 2019, 58(3), 228–9.

Harzallah, I.; Debliquis, A.; Drenou, B. Lupus Anticoagulant is Frequent in Patients with Covid-19. J. Thromb. Haemost., 2020, 18(8), 2064–5.

Ma, J.; Xia, P.; Zhou, Y.; Liu, Z.; Zhou, X.; Wang, J.; Li, T.; Yan, X.; Chen, L.; Zhang, S.; Qin, Y.; Li, X. Potential Effect of Blood Purification Therapy in Reducing Cytokine Storm as a Late Complication of Critically Ill COVID-19. Clin. Immunol., 2020, 214, 108408.

Shi, H.; Zhou, C.; He, P.; Huang, S.; Duan, Y.; Wang, X.; Lin, K.; Zhou, C.; Zhang, X.; Zha, Y. Successful Treatment of Plasma Exchange Followed by Intravenous Immunogloblin in a Critically Ill Patient with 2019 Novel Coronavirus Infection. Int. J. Antimicrob. Agents, 2020, 56(2), 105974.

Bloch, E.M.; Shoham, S.; Casadevall, A.; Sachais, B.S.; Shaz, B.; Winters, J.L.; van Buskirk, C.; Grossman, B.J.; Joyner, M.; Henderson, J.P.; Pekosz, A.; Lau, B.; Wesolowski, A.; Katz, L.; Shan, H.; Auwaerter, P.G.; Thomas, D.; Sullivan, D.J.; Paneth, N.; Gehrie, E.; Spitalnik, S.; Hod, E.; Pollack, L.; Nicholson, W.T.; Pirofski, L.A.; Bailey, J.A.; Tobian, A.A. Deployment of Convalescent Plasma for the Prevention and Treatment of COVID-19. J. Clin. Invest., 2020, 130(6), 2757–65.

Ahn, J.Y.; Sohn, Y.; Lee, S.H.; Cho, Y.; Hyun, J.H.; Baek, Y.J.; Jeong, S.J.; Kim, J.H.; Ku, N.S.; Yeom, J.S.; Roh, J.; Ahn, M.Y.; Chin, B.S.; Kim, Y.S.; Lee, H.; Yong, D.; Kim, H.O.; Kim, S.; Choi, J.Y. Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea. J. Korean Med. Sci., 2020, 35(14), e149.

Ye, M.; Fu, D.; Ren, Y.; Wang, F.; Wang, D.; Zhang, F.; Xia, X.; Lv, T. Treatment with Convalescent Plasma for COVID-19 Patients in Wuhan, China. J. Med. Virol., 2020, 92(10), 1890–901.

Zhang, B.; Liu, S.; Tan, T.; Huang, W.; Dong, Y.; Chen, L.; Chen, Q.; Zhang, L.; Zhong, Q.; Zhang, X.; Zou, Y.; Zhang, S. Treatment With Convalescent Plasma for Critically Ill Patients With SARS-CoV-2 Infection. Chest, 2020, 158(1), e9–13.

Zeng, Q.L.; Yu, Z.J.; Gou, J.J.; Li, G.M.; Ma, S.H.; Zhang, G.F.; Xu, J.H.; Lin, W.B.; Cui, G.L.; Zhang, M.M.; Li, C.; Wang, Z.S.; Zhang, Z.H.; Liu, Z.S. Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in COVID-19 Patients. J. Infect. Dis., 2020, 222(1), 38–43.

Calder, P.C.; Carr, A.C.; Gombart, A.F.; Eggersdorfer, M. Optimal Nutritional Status for a Well-Functioning Immune System is an Important Factor to Protect against Viral Infections. Nutrients, 2020, 12(4), 1181.

Zhang, J.; Zeng, H.; Gu, J.; Li, H.; Zheng, L.; Zou, Q. Progress and Prospects on Vaccine Development against SARS-CoV-2. Vaccines (Basel), 2020, 8(2), 153.

Ahn, D.G.; Shin, H.J.; Kim, M.H.; Lee, S.; Kim, H.S.; Myoung, J.; Kim, B.T.; Kim, S.J. Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19). J. Microbiol. Biotechnol., 2020, 30(3), 313–24.

Feng-Cai, Z.; Li, Y.H.; Guan, X.H.; Hou, L.H.; Wang, W.J.; Li, J.X.; Wu, S.P.; Wang, B.S.; Wang, Z.; Wang, L.; Jia, S.Y.; Jiang, H.D.; Wang, L.; Jiang, T.; Hu, Y.; Gou, J.B.; Xu, S.B.; Xu, J.J.; Wang, X.W.; Wang, W.; Chen, W. Safety, Tolerability, and Immunogenicity of a Recombinant Adenovirus Type-5 Vectored COVID-19 Vaccine: A Dose-escalation, Open-label, Non-randomised, First-in-human Trial. Lancet, 2020, 395(10240), 1845–54.

Folegatti, P.M.; Ewer, K.J.; Aley, P.K.; Angus, B.; Becker, S.; Belij- Rammerstorfer, S.; Bellamy, D.; Bibi, S.; Bittaye, M.; Clutterbuck, E.A.; Dold, C.; Faust, S.N.; Finn, A.; Flaxman, A.L.; Hallis, B.; Heath, P.; Jenkin, D.; Lazarus, R.; Makinson, R.; Minassian, A.M.; Pollock, K.M.; Ramasamy, M.; Robinson, H.; Snape, M.; Tarrant, R.; Voysey, M.; Green, C.; Douglas, A.D.; Hill, A.V.S.; Lambe, T.; Gilbert, S.C.; Pollard, A.J.; Aboagye, J.; Adams, K.; Ali, A.; Allen, E.; Allison, J.L.; Anslow, R.; Arbe-Barnes, E.H.; Babbage, G.; Baillie, K.; Baker, M.; Baker, N.; Baker, P.; Baleanu, I.; Ballaminut, J.; Barnes, E.; Barrett, J.; Bates, L.; Batten, A.; Beadon, K.; Beckley, R.; Berrie, E.; Berry, L.; Beveridge, A.; Bewley, K.R.; Bijker, E.M.; Bingham, T.; Blackwell, L.; Blundell, C.L.; Bolam, E.; Boland, E.; Borthwick, N.; Bower, T.; Boyd, A.; Brenner, T.; Bright, P.D.; Brown-O’Sullivan, C.; Brunt, E.; Burbage, J.; Burge, S.; Buttigieg, K.R.; Byard, N.; Puig, I.C.; Calvert, A.; Camara, S.; Cao, M.; Cappuccini, F.; Carr, M.; Carroll, M.W.; Carter, V.; Cathie, K.; Challis, R.J.; Charlton, S.; Chelysheva, I.; Cho, J.S.; Cicconi, P.; Cifuentes, L.; Clark, H.; Clark, E.; Cole, T.; Colin- Jones, R.; Conlon, C.P.; Cook, A.; Coombes, N.S.; Cooper, R.; Cosgrove, C.A.; Coy, K.; Crocker, W.E.M.; Cunningham, C.J.; Damratoski, B.E.; Dando, L.; Datoo, M.S.; Davies, H.; De Graaf, H.; Demissie, T.; Di Maso, C.; Dietrich, I.; Dong, T.; Donnellan, F.R.; Douglas, N.; Downing, C.; Drake, J.; Drake-Brockman, R.; Drury, R.E.; Dunachie, S.J.; Edwards, N.J.; Edwards, F.D.L.; Edwards, C.J.; Elias, S.C.; Elmore, M.J.; Emary, K.R.W.; English, M.R.; Fagerbrink, S.; Felle, S.; Feng, S.; Field, S.; Fixmer, C.; Fletcher, C.; Ford, K.J.; Fowler, J.; Fox, P.; Francis, E.; Frater, J.; Furze, J.; Fuskova, M.; Galiza, E.; Gbesemete, D.; Gilbride, C.; Godwin, K.; Gorini, G.; Goulston, L.; Grabau, C.; Gracie, L.; Gray, Z.; Guthrie, L.B.; Hackett, M.; Halwe, S.; Hamilton, E.; Hamlyn, J.; Hanumunthadu, B.; Harding, I.; Harris, S.A.; Harris, A.; Harrison, D.; Harrison, C.; Hart, T.C.; Haskell, L.; Hawkins, S.; Head, I.; Henry, J.A.; Hill, J.; Hodgson, S.H.C.; Hou, M.M.; Howe, E.; Howell, N.; Hutlin, C.; Ikram, S.; Isitt, C.; Iveson, P.; Jackson, S.; Jackson, F.; James, S.W.; Jenkins, M.; Jones, E.; Jones, K.; Jones, C.E.; Jones, B.; Kailath, R.; Karampatsas, K.; Keen, J.; Kelly, S.; Kelly, D.; Kerr, D.; Kerridge, S.; Khan, L.; Khan, U.; Killen, A.; Kinch, J.; King, T.B.; King, L.; King, J.; Kingham-Page, L.; Klenerman, P.; Knapper, F.; Knight, J.C.; Knott, D.; Koleva, S.; Kupke, A.; Larkworthy, C.W.; Larwood, J.P.J.; Laskey, A.; Lawrie, A.M.; Lee, A.; Ngan Lee, K.Y.; Lees, E.A.; Legge, H.; Lelliott, A.; Lemm, N.M.; Lias, A.M.; Linder, A.; Lipworth, S.; Liu, X.; Liu, S.; Lopez Ramon, R.; Lwin, M.; Mabesa, F.; Madhavan, M.; Mallett, G.; Mansatta, K.; Marcal, I.; Marinou, S.; Marlow, E.; Marshall, J.L.; Martin, J.; McEwan, J.; McInroy, L.; Meddaugh, G.; Mentzer, A.J.; Mirtorabi, N.; Moore, M.; Moran, E.; Morey, E.; Morgan, V.; Morris, S.J.; Morrison, H.; Morshead, G.; Morter, R.; Mujadidi, Y. F.; Muller, J.; Munera-Huertas, T.; Munro, C.; Munro, A.; Murphy, S.; Munster, V.J.; Mweu, P.; Noé, A.; Nugent, F.L.; Nuthall, E.; O’Brien, K.; O’Connor, D.; Oguti, B.; Oliver, J.L.; Oliveira, C.; O’Reilly, P.J.; Osborn, M.; Osborne, P.; Owen, C.; Owens, D.; Owino, N.; Pacurar, M.; Parker, K.; Parracho, H.; Patrick-Smith, M.; Payne, V.; Pearce, J.; Peng, Y.; Peralta Alvarez, M.P.; Perring, J.; Pfafferott, K.; Pipini, D.; Plested, E.; Pluess-Hall, H.; Pollock, K.; Poulton, I.; Presland, L.; Provstgaard-Morys, S.; Pulido, D.; Radia, K.; Lopez, F.R.; Rand, J.; Ratcliffe, H.; Rawlinson, T.; Rhead, S.; Riddell, A.; Ritchie, A.J.; Roberts, H.; Robson, J.; Roche, S.; Rohde, C.; Rollier, C.S.; Romani, R.; Rudiansyah, I.; Saich, S.; Sajjad, S.; Salvador, S.; Sanchez Riera, L.; Sanders, H.; Sanders, K.; Sapaun, S.; Sayce, C.; Schofield, E.; Screaton, G.; Selby, B.; Semple, C.; Sharpe, H.R.; Shaik, I.; Shea, A.; Shelton, H.; Silk, S.; Silva-Reyes, L.; Skelly, D.T.; Smee, H.; Smith, C.C.; Smith, D.J.; Song, R.; Spencer, A.J.; Stafford, E.; Steele, A.; Stefanova, E.; Stockdale, L.; Szigeti, A.; Tahiri-Alaoui, A.; Tait, M.; Talbot, H.; Tanner, R.; Taylor, I.J.; Taylor, V.; Te Water Naude, R.; Thakur, N.; Themistocleous, Y.; Themistocleous, A.; Thomas, M.; Thomas, T. M.; Thompson, A.; Thomson-Hill, S.; Tomlins, J.; Tonks, S.; Towner, J.; Tran, N.; Tree, J.A.; Truby, A.; Turkentine, K.; Turner, C.; Turner, N.; Turner, S.; Tuthill, T.; Ulaszewska, M.; Varughese, R.; Van Doremalen, N.; Veighey, K.; Verheul, M.K.; Vichos, I.; Vitale, E.; Walker, L.; Watson, M.E.E.; Welham, B.; Wheat, J.; White, C.; White, R.; Worth, A.T.; Wright, D.; Wright, S.; Yao, X.L.; Yau, Y. Safety and Immunogenicity of the ChAdOx1 nCoV-19 Vaccine Against SARS-CoV-2: A Preliminary Report of a Phase 1/2, Single-Blind, Randomised Controlled Trial. Lancet, 2020, 396(10249), 467–78.

Logunov, D.Y.; Dolzhikova, I.V.; Zubkova, O.V.; Tukhvatullin, A.I.; Shcheblyakov, D.V.; Dzharullaeva, A.S.; Grousova, D.M.; Erokhova, A.S.; Kovyrshina, A.V.; Botikov, A.G.; Izhaeva, F.M.; Popova, O.; Ozharovskaya, T.A.; Esmagambetov, I.B.; Favorskaya, I.A.; Zrelkin, D.I.; Voronina, D.V.; Shcherbinin, D.N.; Semikhin, A.S.; Simakova, Y.V.; Tokarskaya, E.A.; Lubenets, N.L.; Egorova, D.A.; Shmarov, M.M.; Nikitenko, N.A.; Morozova, L.F.; Smolyarchuk, E.A.; Kryukov, E.V.; Babira, V.F.; Borisevich, S.V.; Naroditsky, B.S.; Gintsburg, A.L. Safety and Immunogenicity of an rAd26 and rAd5 Vector-based Heterologous Prime-boost COVID-19 Vaccine in Two Formulations: Two Open, Non-randomised Phase 1/2 Studies from Russia. Lancet, 2020, 396(10255), 887–97.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.