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Klin Monbl Augenheilkd 2021; 238(05): 569-578
DOI: 10.1055/a-1423-8961
DOI: 10.1055/a-1423-8961
Übersicht
Recent Antiviral Treatment and Vaccination Strategies Against SARS-CoV-2
Article in several languages: English | deutsch
Abstract
Since the end of 2019, the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been spreading worldwide and has caused severe health and economic issues on a global scale. By the end of February 2021, more than 100 million SARS-CoV-2 cases had been reported worldwide. SARS-CoV-2 causes the coronavirus disease 2019 (COVID-19) that can be divided into three phases: An early phase with fever and cough (phase I), a pulmonary vascular disease (phase II) and a hyperinflammatory syndrome (phase III). Since viral replication plays a particularly important role in the early stage of the disease and the patientʼs immune system in the later course of infection, different therapeutic options arise depending on the stage of the disease. The antiviral nucleoside analogue remdesivir is the only antiviral compound with conditional approval in the European Union. Treatment with remdesivir should be initiated early (within the first seven days of symptom onset) in patients receiving supplemental oxygen without invasive ventilation. In turn, the anti-inflammatory corticosteroid dexamethasone should be administered later in the course of disease in patients receiving oxygen therapy. Since autopsies indicate an increased frequency of thromboembolic events due to COVID-19, additional treatment with anticoagulants is recommended. Since the development of novel antivirals may take years, the application of convalescent plasma from patients who recovered from a SARS-CoV-2 infection for the treatment of COVID-19 is reasonable. However, large-scale studies indicated low efficacy of convalescent plasma. Furthermore, vaccination of the population is essential to control the pandemic. Currently, the mRNA vaccine Tozinameran from BioNTech and Pfizer, the mRNA-1273 vaccine from Moderna as well as the vector vaccine AZD1222 from AstraZeneca are licensed in the European Union. All three vaccines have demonstrated high efficacy in large clinical trials. In addition to these licensed vaccines, many others are being tested in clinical trials. In the present article, an overview of therapeutic options for COVID-19 as well as vaccines for protection against SARS-CoV-2 is provided.
Publication History
Received: 26 February 2021
Accepted: 10 March 2021
Article published online:
21 May 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
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References/Literatur
- 1 Zhou P, Yang XL, Wang XG. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579: 270-273 DOI: 10.1038/s41586-020-2012-7.
- 2 Guan WJ, Ni ZY, Hu Y. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020; 382: 1708-1720 DOI: 10.1056/NEJMoa2002032.
- 3 Cai Y, Zhang J, Xiao T. et al. Distinct conformational states of SARS-CoV-2 spike protein. Science 2020; 369: 1586 DOI: 10.1126/science.abd4251.
- 4 Ziegler CGK, Allon SJ, Nyquist SK. et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 2020; 181: 1016-1035.e19 DOI: 10.1016/j.cell.2020.04.035.
- 5 Böhmer MM, Buchholz U, Corman VM. et al. Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series. Lancet Infect Dis 2020; 20: 920-928 DOI: 10.1016/S1473-3099(20)30314-5.
- 6 The Lancet Respiratory Medicine. COVID-19 transmission-up in the air. Lancet Respir Med 2020; 8: 1159 DOI: 10.1016/s2213-2600(20)30514-2.
- 7 Mondelli MU, Colaneri M, Seminari EM. et al. Low risk of SARS-CoV-2 transmission by fomites in real-life conditions. Lancet Infect Dis 2020; DOI: 10.1016/S1473-3099(20)30678-2.
- 8 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: P507-P513 DOI: 10.1016/S0140-6736(20)30211-7.
- 9 Tian S, Xiong Y, Liu H. et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020; 33: 1007-1014 DOI: 10.1038/s41379-020-0536-x.
- 10 Zhang Y, Geng X, Tan Y. et al. New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. Biomed Pharmacother 2020; 127: 110195 DOI: 10.1016/j.biopha.2020.110195.
- 11 Ackermann M, Verleden SE, Kuehnel M. et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med 2020; 383: 120-128 DOI: 10.1056/NEJMoa2015432.
- 12 Tan JY, Sim XYJ, Wee LE. et al. A comparative study on the clinical features of COVID-19 with non-SARS-CoV-2 respiratory viral infections. J Med Virol 2021; 93: 1548-1555 DOI: 10.1002/jmv.26486.
- 13 World Health Organization. Therapeutics and COVID-19: living guideline. Accessed January 10, 2021 at: https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline
- 14 Wolff D, Nee S, Hickey NS. et al. Risk factors for Covid-19 severity and fatality: a structured literature review. Infection 2021; 49: 15-28 DOI: 10.1007/s15010-020-01509-1.
- 15 Streeck H, Schulte B, Kümmerer BM. et al. Infection fatality rate of SARS-CoV2 in a super-spreading event in Germany. Nat Commun 2020; 11: 5829 DOI: 10.1038/s41467-020-19509-y.
- 16 Xie Y, Bowe B, Maddukuri G. et al. Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with covid-19 and seasonal influenza: cohort study. BMJ 2020; 371: m4677 DOI: 10.1136/bmj.m4677.
- 17 Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant 2020; 39: 405-407 DOI: 10.1016/j.healun.2020.03.012.
- 18 Liu J, Li S, Liu J. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763 DOI: 10.1016/j.ebiom.2020.102763.
- 19 Robert Koch-Institut. Hinweise zu Erkennung, Diagnostik und Therapie von Patienten mit COVID-19. Accessed February 11, 2021 at: https://www.rki.de/DE/Content/Kommissionen/Stakob/Stellungnahmen/Stellungnahme-Covid-19_Therapie_Diagnose.html
- 20 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: 269-271 DOI: 10.1038/s41422-020-0282-0.
- 21 Savarino A, Boelaert JR, Cassone A. et al. Effects of chloroquine on viral infections: an old drug against todayʼs diseases. Lancet Infect Dis 2003; 3: 722-727 DOI: 10.1016/S1473-3099(03)00806-5.
- 22 Gautret P, Lagier JC, Parola P. et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56: 105949 DOI: 10.1016/j.ijantimicag.2020.105949.
- 23 RECOVERY Collaborative Group. Horby P, Mafham M, Linsell L. et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med 2020; 383: 2030-2040 DOI: 10.1056/NEJMoa2022926.
- 24 Cavalcanti AB, Zampieri FG, Rosa RG. et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Engl J Med 2020; 383: 2041-2052 DOI: 10.1056/NEJMoa2019014.
- 25 Skipper CP, Pastick KA, Engen NW. et al. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial. Ann Intern Med 2020; 173: 623-631 DOI: 10.7326/m20-4207.
- 26 Tang W, Cao Z, Han M. et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 2020; 369: m1849 DOI: 10.1136/bmj.m1849.
- 27 Andreani J, Le Bideau M, Duflot I. et al. In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect. Microb Pathog 2020; 145: 104228 DOI: 10.1016/j.micpath.2020.104228.
- 28 RECOVERY Collaborative Group. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397: P605-P612 DOI: 10.1016/S0140-6736(21)00149-5.
- 29 Furtado RHM, Berwanger O, Fonseca HA. et al. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. Lancet 2020; 396: 959-967 DOI: 10.1016/S0140-6736(20)31862-6.
- 30 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: 271-280.e8 DOI: 10.1016/j.cell.2020.02.052.
- 31 Richardson P, Griffin I, Tucker C. et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet 2020; 395: e30-e31 DOI: 10.1016/S0140-6736(20)30304-4.
- 32 Kalil AC, Patterson TF, Mehta AK. et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med 2021; 384: 795-807 DOI: 10.1056/NEJMoa2031994.
- 33 Sheahan TP, Sims AC, Leist SR. et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 2020; 11: 222 DOI: 10.1038/s41467-019-13940-6.
- 34 National Institute of Allergy and Infectious Diseases. NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19. Accessed February 7, 2021 at: https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
- 35 Grein J, Ohmagari N, Shin D. et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med 2020; 382: 2327-2336 DOI: 10.1056/NEJMoa2007016.
- 36 Beigel JH, Tomashek KM, Dodd LE. et al. Remdesivir for the Treatment of Covid-19 – Final Report. N Engl J Med 2020; 383: 1813-1826 DOI: 10.1056/NEJMoa2007764.
- 37 Spinner CD, Gottlieb RL, Criner GJ. et al. Effect of Remdesivir vs. Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA 2020; 324: 1048-1057 DOI: 10.1001/jama.2020.16349.
- 38 WHO Solidarity Trial Consortium. Pan H, Peto R, Henao-Restrepo AM. et al. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med 2021; 384: 497-511 DOI: 10.1056/NEJMoa2023184.
- 39 Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci 2017; 93: 449-463 DOI: 10.2183/pjab.93.027.
- 40 Oestereich L, Lüdtke A, Wurr S. et al. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 2014; 105: 17-21 DOI: 10.1016/j.antiviral.2014.02.014.
- 41 Udwadia ZF, Singh P, Barkate H. et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis 2021; 103: 62-71 DOI: 10.1016/j.ijid.2020.11.142.
- 42 Doi Y, Hibino M, Hase R. et al. A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19. Antimicrob Agents Chemother 2020; 64: e01897-e01920 DOI: 10.1128/aac.01897-20.
- 43 FUJIFILM. Anti-influenza drug Avigan® Tablet Meets Primary Endpoint in Phase III Clinical Trial in Japan for COVID-19 patients. Accessed February 9, 2021 at: https://www.fujifilm.com/jp/en/news/hq/5451
- 44 RECOVERY Collaborative Group. Horby P, Lim WS, Emberson JR. et al. Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med 2021; 384: 693-704 DOI: 10.1056/NEJMoa2021436.
- 45 WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Sterne JAC, Murthy S, Diaz JV. et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA 2020; 324: 1330-1341 DOI: 10.1001/jama.2020.17023.
- 46 Rosas I, Bräu N, Waters M. et al. Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia. medRxiv 2020; DOI: 10.1101/2020.08.27.20183442.
- 47 Salama C, Han J, Yau L. et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med 2021; 384: 20-30 DOI: 10.1056/NEJMoa2030340.
- 48 Stone JH, Frigault MJ, Serling-Boyd NJ. et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med 2020; 383: 2333-2344 DOI: 10.1056/NEJMoa2028836.
- 49 Gordon AC, Mouncey PR, Al-Beidh F. et al. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 – Preliminary report. medRxiv 2021; DOI: 10.1101/2021.01.07.21249390.
- 50 Nadkarni GN, Lala A, Bagiella E. et al. Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19. J Am Coll Cardiol 2020; 76: 1815-1826 DOI: 10.1016/j.jacc.2020.08.041.
- 51 van Griensven J, Edwards T, de Lamballerie X. et al. Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. N Engl J Med 2016; 374: 33-42 DOI: 10.1056/NEJMoa1511812.
- 52 Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 2007; 357: 1450-1451 DOI: 10.1056/NEJMc070359.
- 53 Cheng Y, Wong R, Soo YO. et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005; 24: 44-46 DOI: 10.1007/s10096-004-1271-9.
- 54 Chen L, Xiong J, Bao L. et al. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020; 20: 398-400 DOI: 10.1016/S1473-3099(20)30141-9.
- 55 Barnes CO, Jette CA, Abernathy ME. et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 2020; 588: 682-687 DOI: 10.1038/s41586-020-2852-1.
- 56 Duan K, Liu B, Li C. et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020; 117: 9490 DOI: 10.1073/pnas.2004168117.
- 57 Shen C, Wang Z, Zhao F. et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA 2020; 323: 1582-1589 DOI: 10.1001/jama.2020.4783.
- 58 Salazar E, Christensen PA, Graviss EA. et al. Treatment of Coronavirus Disease 2019 Patients with Convalescent Plasma Reveals a Signal of Significantly Decreased Mortality. Am J Pathol 2020; 190: 2290-2303 DOI: 10.1016/j.ajpath.2020.08.001.
- 59 European Commission. An EU programme of COVID-19 convalescent plasma collection and transfusion. Accessed February 9, 2021 at: https://ec.europa.eu/health/sites/health/files/blood_tissues_organs/docs/guidance_plasma_covid19_en.pdf
- 60 Simonovich VA, Burgos Pratx LD, Scibona P. et al. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med 2020; 384: 619-629 DOI: 10.1056/NEJMoa2031304.
- 61 Agarwal A, Mukherjee A, Kumar G. et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ 2020; 371: m3939 DOI: 10.1136/bmj.m3939.
- 62 Lindemann M, Lenz V, Knop D. et al. Convalescent plasma treatment of critically ill intensive care COVID-19 patients. Transfusion 2021; DOI: 10.1111/trf.16392.
- 63 Jeyanathan M, Afkhami S, Smaill F. et al. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol 2020; 20: 615-632 DOI: 10.1038/s41577-020-00434-6.
- 64 Walsh EE, Frenck jr. RW, Falsey AR. et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med 2020; 383: 2439-2450 DOI: 10.1056/NEJMoa2027906.
- 65 Wang H, Zhang Y, Huang B. et al. Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell 2020; 182: 713-721.e9 DOI: 10.1016/j.cell.2020.06.008.
- 66 Mercado NB, Zahn R, Wegmann F. et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature 2020; 586: 583-588 DOI: 10.1038/s41586-020-2607-z.
- 67 Krammer F. SARS-CoV-2 vaccines in development. Nature 2020; 586: 516-527 DOI: 10.1038/s41586-020-2798-3.
- 68 Yang J, Zheng Y, Gou X. et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020; 94: 91-95 DOI: 10.1016/j.ijid.2020.03.017.
- 69 Polack FP, Thomas SJ, Kitchin N. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020; 383: 2603-2615 DOI: 10.1056/NEJMoa2034577.
- 70 Jackson LA, Anderson EJ, Rouphael NG. et al. An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. N Engl J Med 2020; 383: 1920-1931 DOI: 10.1056/NEJMoa2022483.
- 71 Baden LR, El Sahly HM, Essink B. et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2021; 384: 403-416 DOI: 10.1056/NEJMoa2035389.
- 72 Voysey M, Clemens SAC, Madhi SA. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021; 397: 99-111 DOI: 10.1016/S0140-6736(20)32661-1.
- 73 Hoffmann M, Arora P, Groß R. et al. SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination. bioRxiv 2021; DOI: 10.1101/2021.02.11.430787.
- 74 Sailer-Kronlachner M. COVID-19 mit Fokus auf den geriatrischen Patienten. Abschlussarbeit des ÖÄK Diplomlehrganges Geriatrie 2020. Accessed February 9, 2021 at: https://www.arztakademie.at/fileadmin/template/main/Geriatrie/Publikationen_2020/Sailer-Kronlachner_AA_COVID-19_mit_Fokus_auf_den_geriatrischen_Patienten…pdf
- 75 World Health Organization. Draft landscape and tracker of COVID-19 candidate vaccines. 16 March 2021. Accessed January 22, 2021 at: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines