COVID-19: general overview, pharmacological options and ventilatory support strategies
Keywords:
Coronavirus, COVID-19, pneumonia, severe acute respiratory syndrome, pharmacologic treatment, respiratory failure, non-invasive ventilationAbstract
The novel coronavirus called “Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2) caused an outbreak in December 2019, starting from the Chinese city of Wuhan, in the Hubei province, and rapidly spreading to the rest of the world. Consequently, the World Health Organization (WHO) declared that the coronavirus disease of 2019 (COVID-19) can be characterized as a pandemic. During COVID-19 several immunological alterations have been observed: in plasma of severe patients, inflammatory cytokines are at a much higher concentration (“cytokine storm”). These aspects are associated with pulmonary inflammation and parenchymal infiltrates with an extensive lung tissue damage in COVID-19 patients. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials (RCTs) for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments are currently being evaluated worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. As for ventilatory strategies, at the moment there are still no consistent data published about the different approaches and how they may influence disease progression. What will probably represent the real solution to this pandemic is the identification of a safe and effective vaccine, for which enormous efforts and investments are being put in place. This review will summarize the state-of-the-art of COVID-19 current treatment options and those potentially available in the future, as well as high flow oxygen therapy and non-invasive mechanical ventilation approaches.
References
Zhang Y-Z, Holmes EC. A Genomic perspective on the origin and emergence of SARS-CoV-2. Cell 2020;181:223–7.
Corman VM, Muth D, Niemeyer D, Drosten C. Hosts and sources of endemic human coronaviruses. Adv Virus Res. 2018;100:163-188.
van Regenmortel MHV, Mahy BWJ. Emerging issues in virus taxonomy. Emerg Infect Dis 2004;10:8–13.
Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J 2019;16:69.
WHO. Coronavirus Disease 2019. Accessed: June 12, 2020. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–4.
Chinese Clinical Trials. Accessed: July 14, 2020. Available from: http://www.chictr.org.cn/abouten.aspx
Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med 2020;26:450–2.
Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res 2020; 24:91–8.
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel Coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS Coronavirus. J Virol 2020;94:e00127-20.
Gralinski LE, Menachery VD. Return of the Coronavirus: 2019-nCoV. Viruses 2020;12:135.
Ding Y, He L, Zhang Q, Che X, Hou J, Wang H, Shen H, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 2004;203:622–30.
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395:565–74.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420–2.
Tian S, Hu W, Niu L, Liu H, Xu H, Xiao S-Y. Pulmonary pathology of early-phase 2019 novel Coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 2020;15:700–4.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endothelitis in COVID-19. Lancet 2020;395:1417–8.
Guan W, Ni Z, Hu Y, Liang WH, Ou CQ, He JX, Liu L, et al. Clinical characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020;382):1708–20.
van Erp EA, Luytjes W, Ferwerda G, van Kasteren PB. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol 2019;10:548.
Bernstein KE, Khan Z, Giani JF, Cao D-Y, Bernstein EA, Shen XZ. Angiotensin-converting enzyme in innate and adaptive immunity. Nat Rev Nephro. 2018;14:325–36.
Demers KR, Reuter MA, Betts MR. CD8 + T-cell effector function and transcriptional regulation during HIV pathogenesis. Immunol Rev 2013;254:190–206.
Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 2020;26:453–5.
Prompetchara E, Ketloy C PT. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pacific J Allergy Immunol 2020;38:1–9.
Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res 2014;59:118–28.
Tian S, Xiong Y, Liu H, Niu L, Guo J, Liao M, et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020;33:1007-14.
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020;71:762-8.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020;382:e38.
Chan JF-W, Yuan S, Kok K-H, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020;395:514–23.
Butowt R, von Bartheld CS. Anosmia in COVID-19: Underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist 2020. doi: 10.1177/1073858420956905
WHO. Clinical management of COVID-19 - Interim Guidance. Accessed October 15, 2020. Available from: www.who.int/publications/i/item/clinical-management-of-covid-19
Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China. JAMA 2020;323):1239.
National Health Commission of the People’s Republic of China. Guideline for the diagnosis and treatment of COVID-19 infections (version 1-8). 2020. Accessed October 15, 2020. Available from: http://regional.chinadaily.com.cn/
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62.
Iba T, Levy JH, Warkentin TE, Thachil J, Poll T, Levi M. Diagnosis and management of sepsis‐induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost 2019;17:1989–94.
Luo W, Yu H, Gou J, Li X, Sun Y, Li J, Liu L. Clinical pathology of critical patient with novel Coronavirus pneumonia (COVID-19). Preprints 2020;2020020407. Available from: https://www.preprints.org/manuscript/202002.0407/v1
Kanne JP, Little BP, Chung JH, Elicker BM, Ketai LH. Essentials for radiologists on COVID-19: An update - Radiology Scientific Expert Panel. Radiology 2020;296:E113-4.
Ye Z, Zhang Y, Wang Y, Huang Z, Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Eur Radiol 2020;1-9.
Koo HJ, Lim S, Choe J, Choi S-H, Sung H, Do K-H. Radiographic and CT features of viral pneumonia. RadioGraphics 2018;38:719–39.
Maffessanti M, Dalpiaz G. Diffuse lung diseases. Milan: Springer Verlag; 2006.
Waseda Y, Johkoh T, Egashira R, Sumikawa H, Saeki K, Watanabe S, et al. Antisynthetase syndrome: Pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases. Eur J Radiol 2016;85:1421–6.
Stower H. Lopinavir–ritonavir in severe COVID-19. Nat Med 2020;26:465.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269–71.
Du Y, Chen X. Favipiravir: Pharmacokinetics and concerns about clinical trials for 2019‐nCoV infection. Clin Pharmacol Ther 2020;108:242-7.
Lu C-C, Chen M-Y, Chang Y-L. Potential therapeutic agents against COVID-19. J Chinese Med Assoc 2020;83:534-6.
De Clercq E. New nucleoside analogues for the treatment of hemorrhagic fever virus infections. Chem Asian J 2019;14:3962–8.
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020;19:149–50.
de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci USA 2020;117:6771–6.
Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323:1582.
Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio 2018;9. doi: 10.1128/mBio.00221-18
Ferner RE, Aronson JK. Remdesivir in covid-19. BMJ 2020;369:m1610.
BBC News [Internet]. Remdesivir: Drug has “clear-cut” power to fight coronavirus. Available from: https://www.bbc.com/news/health-52478783
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, et al. Remdesivir for the treatment of Covid-19 - Final report. N Engl J Med 2020. doi: 10.1056/NEJMoa2007764
WHO Solidarity trial consortium, Pan H, Peto R, Abdool K, Quarraisha A, Alejandria M, et al. Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results. medRxiv 2020. doi: 10.1101/2020.10.15.20209817
Chu CM. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252–6.
Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen K-Y. Coronaviruses — drug discovery and therapeutic options. Nat Rev Drug Discov 2016;15:327–47.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med.2020;382:1787-99.
Chow EJ, Doyle JD, Uyeki TM. Influenza virus-related critical illness: prevention, diagnosis, treatment. Crit Care 2019;23:214.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 Novel Coronavirus–infected pneumonia in Wuhan, China. JAMA 2020;323:1061.
Frisk-Holmberg M, Bergqvist Y, Englund U. Chloroquine intoxication. Br J Clin Pharmacol1983;15:502–3.
Chauhan A, Tikoo A. The enigma of the clandestine association between chloroquine and HIV-1 infection. HIV Med 2015;16:585–90.
Helal GK, Gad MA, Abd-Ellah MF, Eid MS. Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients. J Med Virol 2016;88:2170–8.
Mehra MR, Desai SS, Ruschitzka F, Patel AN. RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet 2020. doi: 10.1016/S0140-6736(20)31180-6
Mehra MR, RuschitzkRa, Patel AN. Retraction - Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis. Lancet 2020. doi: 10.1016/S0140-6736(20)31324-6
Simmons G, Bertram S, Glowacka I, Glowacka I, Steffen I, Chaipan C, et al. Different host cell proteases activate the SARS-coronavirus spike-protein for cell–cell and virus–cell fusion. Virology 2011;413:265-74.
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;14:72-3.
Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M, 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;105949.
Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect 2020;50:384.
Mehra MR, Desai SS, Ruschitzka F, Patel AN. RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet 2020:S0140-6736(20)31180-6.
Recovery Trial [Internet]. Hydroxychloroquine results Accessed: August 9, 2020. Available from: https://www.recoverytrial.net/results/hydroxychloroquine-results
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, 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;e200994.
Chen R, Tang X, Tan S, Liang BL, Wan ZY, Fang JQ, et al. Treatment of severe acute respiratory syndrome with glucosteroids. Chest 2006;12):1441–52.
Zhao JP, Hu Y, Du RH, Chen ZS, Jin Y, Zhou M, et al. [Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia].[Article in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi 2020. doi: 10.3760/cma.j.issn.1001-0939.2020.0007
Ma Q, Qi D, Deng XY, Yuan GD, Tian WG, Cui Y, et al. Corticosteroid therapy for patients with severe novel Coronavirus disease 2019. Eur Rev Med Pharmacol Sci 2020;24:8194-201.
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020;395:473–5.
RECOVERY Collaborative Group, Horby P, Wei SL, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19 - Preliminary report. N Engl J Med 2020. doi: 10.1056/NEJMoa2021436
Kaneko Y, Kato M, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, et al. Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study). Ann Rheum Dis 2018;77:1268–75.
Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev 2020;19:102568.
Menzella F, Fontana M, Salvarani C, Massari M, Ruggiero P, Scelfo C, et al. Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation. Crit Care 2020;24:589.
Scott LJ. Sarilumab: First global approval. Drugs 2017;77:705–12.
Lamb YN, Deeks ED. Sarilumab: A review in moderate to severe rheumatoid arthritis. Drugs 2018;78:929–40.
Schett G, Manger B, Simon D, Caporali R. COVID-19 revisiting pathways inflammatory diseases of arthritis. Nat Rev Rheumatol 2020;16:465-70.
Marí Sáez A, Ronse M, Delamou A, Haba N, Bigey F, van Griensven J, et al. The plasma mobile, 'A gift from heaven': The impact of health technology transfer on trial perceptions and expectations during the Ebola-Tx Trial, Conakry. PLoS Negl Trop Dis 2020;14:e0008206.
Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA 2020;324:1-11.
Perotti C, Baldanti F, Bruno R, Del Fante C, Seminari E, Casari S, et al. Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial. Haematologica 2020. doi: 10.3324/haematol.2020.261784
Mucha SR, Quraishy N. Convalescent plasma for COVID-19. Cleve Clin J Med 2020. doi: 10.3949/ccjm.87a.ccc056
Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med 2020;46:1099-102.
Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. Covid-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med 2020;201:1299-300.
Tonelli R, Fantini R, Tabbì L, Castaniere I, Pisani L, Pellegrino MR, et al. Inspiratory effort assessment by esophageal manometry early predicts noninvasive ventilation outcome in de novo respiratory failure. A pilot study. Am J Respir Crit Care Med 2020;202:558-67.
Allen K, Hoffman L. Enteral nutrition in the mechanically ventilated patient. Nutr Clin Pract 2019;34:540–57.
Takasaki Y, Kido T, Semba K. Dexmedetomidine facilitates induction of noninvasive positive pressure ventilation for acute respiratory failure in patients with severe asthma. J Anesth 2009;23:147–50.
Devlin JW, Nava S, Fong JJ, Bahhady I, Hill NS. Survey of sedation practices during noninvasive positive-pressure ventilation to treat acute respiratory failure. Crit Care Med 2007;35:2298-E4.
Muriel A, Peñuelas O, Frutos-Vivar F, Arroliga AC, Abraira V, Thille AW, et al. Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis. Intensive Care Med 2015;41:1586–600.
Chad T, Sampson C. Prone positioning in conscious patients on medical wards: A review of the evidence and its relevance to patients with COVID-19 infection. Clin Med (Lond) 2020;20:e97-103.
Tang K-Q, Yang S-L, Zhang B, Liu HX, Ye DY, Zhang HZ, et al. Ultrasonic monitoring in the assessment of pulmonary recruitment and the best positive end-expiratory pressure. Medicine (Baltimore) 2017;96:e8168.
Poston JT, Patel BK, Davis AM. Management of critically ill adults with COVID-19. JAMA 2020;323:1839-41.
Ikuyama Y, Wada Y, Tateishi K, Kitaguchi Y, Yasuo M, Ushiki A, et al. Successful recovery from critical COVID-19 pneumonia with extracorporeal membrane oxygenation: A case report. Respir Med Case Rep 2020;30:101113.
Parke RL, McGuinness SP. Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle. Respir Care 2013;58:1621-4.
Franco C, Facciolongo N, Tonelli R, Dongilli R, Vianello A, Pisani L, et al. Feasibility and clinical impact of out-of-ICU non-invasive respiratory support in patients with COVID-19 related pneumonia. Eur Respir J 2020:2002130.
Rochwerg B, Granton D, Wang DX, Helviz Y, Einav S, Frat JP, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med 2019;45:563-72.
Geng S, Mei Q, Zhu C, Yang T, Yang Y, Fang X, Pan A. High flow nasal cannula is a good treatment option for COVID-19. Heart Lung 2020;49:444-5.
Karamouzos V, Fligou F, Gogos C, Velissaris D. High flow nasal cannula oxygen therapy in adults with COVID-19 respiratory failure. A case report. Monaldi Arch Chest Dis 2020;90:1323. doi: 10.4081/monaldi.2020.1323
Hammer Q, Ruckert T, Romagnani C. Natural killer cell specificity for viral infections. Nat Immunol 2018;19:800-8.
Seeking Alpha [Internet]. Sorrento and Celularity to initiate emergency allogeneic natural killer (NK) cell therapy development for coronavirus infection. Accessed: August 9, 2020. Available from: https://seekingalpha.com/pr/17762358-sorrento-and-celularity-to-initiate-emergency-allogeneic-natural-killer-nk-cell-therapy
Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA 2007;104:11002–7.
Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007;179:1855–63.
Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 2009;175:303-13.
Matthay MA, Goolaerts A, Howard JP, Lee JW. Mesenchymal stem cells for acute lung injury: preclinical evidence. Crit Care Med 2010;38:S569–73.
Kumamoto M, Nishiwaki T, Matsuo N, Kimura H, Matsushima K. Minimally cultured bone marrow mesenchymal stem cells ameliorate fibrotic lung in- jury. Eur Respir J 2009;34:740–8.
Quan L, Zhang Y, Crielaard BJ, Dusad A, Lele SM, Rijcken CJF, et al. Nanomedicines for inflammatory arthritis: head-to-head comparison of glucocorticoid-containing polymers, micelles, and liposomes. ACS Nano 2014;8:458-66.
Banciu M, Metselaar JM, Schiffelers RM, Storm G. Liposomal glucocorticoids as tumor-targeted anti-angiogenic nanomedicine in B16 melanoma-bearing mice. J Steroid Biochem Mol Biol 2008;111:101-10.
Crielaard BJ, Lammers T, Morgan ME, Chaabane L, Carboni S, Greco B, et al. Macrophages and liposomes in inflammatory disease: friends or foes? Int J Pharm 2011;416:499-506.
Bartneck M, Scheyda KM, Warzecha KT, Rizzo LY, Hittatiya K, Luedde T, et al. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials 2015;37:367-82.
Lammers T, Sofias AM, van der Meel R, Schiffelers R, Storm G, Tacke F, et al. Dexamethasone nanomedicines for COVID-19. Nat Nanotechnol.2020;15:622-4.
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med 2020. doi: 10.1056/NEJMoa2022483
National Institutes of Health [Internet]. NIH-Moderna investigational COVID-19 vaccine shows promise in mouse studies. Accessed August 9, 2020. https://www.nih.gov/news-events/news-releases/nih-moderna-investigational-covid-19-vaccine-shows-promise-mouse-studies
Published
Issue
Section
License
Mattioli 1885 has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
How to Cite
