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Aging and disease    2020, Vol. 11 Issue (6) : 1481-1495     DOI: 10.14336/AD.2020.0903
Review Article |
COVID-19 in Elderly Adults: Clinical Features, Molecular Mechanisms, and Proposed Strategies
Ya Yang, Yalei Zhao, Fen Zhang, Lingjian Zhang, Lanjuan Li*
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
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Coronavirus disease 2019 (COVID-19) is causing problems worldwide. Most people are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but elderly populations are more susceptible. Elevated susceptibility and death rates in elderly COVID-19 patients, especially those with age-related complications, are challenges for pandemic prevention and control. In this paper, we review the clinical features of elderly patients with COVID-19 and explore the related molecular mechanisms that are essential for the exploration of preventive and therapeutic strategies in the current pandemic. Furthermore, we analyze the feasibility of currently recommended potential novel methods against COVID-19 among elderly populations.

Keywords COVID-19      elderly      clinical feature      molecular mechanism      strategy     
Corresponding Authors: Li Lanjuan   
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These authors contrinuted equally to this work.

Just Accepted Date: 10 September 2020   Issue Date: 19 November 2020
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Yang Ya
Zhao Yalei
Zhang Fen
Zhang Lingjian
Li Lanjuan
Cite this article:   
Yang Ya,Zhao Yalei,Zhang Fen, et al. COVID-19 in Elderly Adults: Clinical Features, Molecular Mechanisms, and Proposed Strategies[J]. Aging and disease, 2020, 11(6): 1481-1495.
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Figure1.  Interaction of SARS-CoV-2 with ACE2 and CD26. To enter the host cells, SARS-CoV-2 binds to membrane-bound ACE2 with the assistance of Furin and TMPRSS2. SARS-CoV-2 infections could create positive feedback loops that increase ACE2 expression and promote viral dissemination. On the other hand, SARS-CoV-2 infections may induce ACE2 shedding. ACE2 downregulation could lead to accumulation of Ang II, therefore inducing cytokine storm and ARDS. Activation of CD26 on T lymphocytes may partially contribute to the high expression of IL-6 in COVID-19 patients.
TreatmentAgentRelated Target/PathwaysPotential efficacy in COVID-19
Antiviral drugsRemdesivir
LPV/RTV Favipiravir Arbidol
Reduces the production of viral RNA
Inhibits antiretroviral protease Targets RNA-dependent RNA polymerase Perturbs the virus membrane structure
Shortens the recovery time in COVID-19 patients
Shortens the viral shedding duration in patients Induces a shorter viral clearance time and greater improvement rate in chest imaging Shorter duration of positive RNA test compared to those treated with LPV/RTV
Antisenescence drugsAzithromycin
Chloroquine; hydroxychloroquine Rapamycin
Targets and removes senescent cells; inhibits IL-6 and IL-1β expression; extends the lifespan of myofibroblasts
Prevents the induction and accumulation of β-Gal; inhibits the replication of SARS-CoV in vitro Downregulates the IL-6 pathway; reduces the number of senescent T-cells through the mTOR-NLRP3-IL-1β axis
Reduces airway inflammation; antifibrosis
Reduces the viral load in COVID-19 patients Prevents and treats the severity of COVID-19 patients
ACE2-related therapyACE2 activator
ACE2 inhibitor Human recombinant soluble ACE2
Avoids binding of S protein of SARS-CoV-2 to ACE2
Inhibits ACE2 expression Directly binds to SARS-CoV-2 in the circulation
Requires scientific and clinical evidence
Still under debate Blocks SARS-CoV-2 infection; prevents lung injury
CD26 inhibitorLinagliptinAttenuates DM-induced activation of NLRP3 inflammatory bodiesDecreases the concentration of cytokines, especially TNF-α and IL-6
Immunosuppressive TherapyTocilizumab; sarilumab; siltuximab
cyclosporine-cyclophilin A complex Corticosteroids
Directly targets IL-6 receptors
Halts the expression of TNF-α and IL-2; blocks the replication of coronaviruses Inhibits innate and adaptive immune responses as well as immune cells
Improves clinical outcomes in severe cases
Anti-inflammatory and antiviral properties in COVID-19 Improves clinical outcomes in COVID-19 patients with ARDS
MSC transplantation/Advantages in anti-inflammation, antifibrosis and injury repairImproves pulmonary function and symptoms of patients
Artificial liver system/Attenuates the cytokine stormReduces the mortality of severe patients exhibiting rapid disease progression
Table 1  Potential strategies for the treatment of COVID-19.
[1] Gasmi A, Noor S, Tippairote T, Dadar M, Menzel A, Bjorklund G (2020). Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic. Clin Immunol, 215:108409.
[2] Wu J, Li W, Shi X, Chen Z, Jiang B, Liu J, et al. (2020). Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19). J Intern Med.
[3] Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. (2020). Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ, 368:m1091.
[4] Koff WC, Williams MA (2020). Covid-19 and Immunity in Aging Populations - A New Research Agenda. N Engl J Med, in press.
[5] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 395:1054-1062.
[6] Chan-Yeung M, Xu RH (2003). SARS: epidemiology. Respirology, 8 Suppl:S9-14.
[7] Kobayashi T, Jung SM, Linton NM, Kinoshita R, Hayashi K, Miyama T, et al. (2020). Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19). J Clin Med, 9.
[8] Malavolta M, Giacconi R, Brunetti D, Provinciali M, Maggi F (2020). Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats. Cells, 9.
[9] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. (2020). Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med, 382:1708-1720.
[10] Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ (2020). SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. Geroscience, 42:505-514.
[11] Wang B, Li R, Lu Z, Huang Y (2020). Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging (Albany NY), 12:6049-6057.
[12] Zhang J, Wang X, Jia X, Li J, Hu K, Chen G, et al. (2020). Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin Microbiol Infect, 26:767-772.
[13] Liu K, Chen Y, Lin R, Han K (2020). Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J Infect, 80:e14-e18.
[14] Lei S, Jiang F, Su W, Chen C, Chen J, Mei W, et al. (2020). Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection. EClinicalMedicine, 21:100331.
[15] Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. (2020). Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med, in press.
[16] To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, et al. (2020). Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis, 20:565-574.
[17] Chu CM, Poon LL, Cheng VC, Chan KS, Hung IF, Wong MM, et al. (2004). Initial viral load and the outcomes of SARS. CMAJ, 171:1349-1352.
[18] Yu X, Sun S, Shi Y, Wang H, Zhao R, Sheng J (2020). SARS-CoV-2 viral load in sputum correlates with risk of COVID-19 progression. Crit Care, 24:170.
[19] Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. (2020). Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ, 369:m1443.
[20] Yousefzadeh MJ, Zhao J, Bukata C, Wade EA, McGowan SJ, Angelini LA, et al. (2020). Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell, 19:e13094.
[21] Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579:270-273.
[22] Bassendine MF, Bridge SH, McCaughan GW, Gorrell MD (2020). COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity? J Diabetes.
[23] Sternberg A, Naujokat C (2020). Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination. Life Sci, 257:118056.
[24] Ragia G, Manolopoulos VG (2020). Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies. Eur J Clin Pharmacol, in press.
[25] Zhou L, Niu Z, Jiang X, Zhang Z, Zheng Y, Wang Z, et al. (2020). Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases. bioRxiv.
[26] Vankadari N, Wilce JA (2020). Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect, 9:601-604.
[27] Patel S, Rauf A, Khan H, Abu-Izneid T (2017). Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies. Biomed Pharmacother, 94:317-325.
[28] Khemais-Benkhiat S, Idris-Khodja N, Ribeiro TP, Silva GC, Abbas M, Kheloufi M, et al. (2016). The Redox-sensitive Induction of the Local Angiotensin System Promotes Both Premature and Replicative Endothelial Senescence: Preventive Effect of a Standardized Crataegus Extract. J Gerontol A Biol Sci Med Sci, 71:1581-1590.
[29] Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. (2020). Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA, in press.
[30] Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. (2020). 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, 181:1016-1035 e1019.
[31] Smith JC, Sausville EL, Girish V, Yuan ML, Vasudevan A, John KM, et al. (2020). Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract. Dev Cell, 53:514-529 e513.
[32] Xie X, Chen J, Wang X, Zhang F, Liu Y (2006). Age- and gender-related difference of ACE2 expression in rat lung. Life Sci, 78:2166-2171.
[33] Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. (2005). Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 436:112-116.
[34] Rodriguez-Puertas R (2020). ACE2 Activators for the Treatment of Covid 19 Patients. J Med Virol, in press.
[35] Datta PK, Liu F, Fischer T, Rappaport J, Qin X (2020). SARS-CoV-2 pandemic and research gaps: Understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy. Theranostics, 10:7448-7464.
[36] Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, et al. (2002). Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature, 417:822-828.
[37] Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, et al. (2005). Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J, 26:369-375; discussion 322-364.
[38] Chen L, Li X, Chen M, Feng Y, Xiong C (2020). The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res, 116:1097-1100.
[39] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395:497-506.
[40] Guo J, Huang F, Liu J, Chen Y, Wang W, Cao B, et al. (2015). The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes. Sci Rep, 5:10942.
[41] de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, et al. (2006). Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med, 12:1203-1207.
[42] Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA (2018). MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine, 104:8-13.
[43] Kuppalli K, Rasmussen AL (2020). A glimpse into the eye of the COVID-19 cytokine storm. EBioMedicine, 55:102789.
[44] Rothan HA, Byrareddy SN (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun, 109:102433.
[45] Aziz M, Fatima R, Assaly R (2020). Elevated Interleukin-6 and Severe COVID-19: A Meta-Analysis. J Med Virol, in press.
[46] Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y, et al. (2020). Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis, in press.
[47] Ershler WB (1993). Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc, 41:176-181.
[48] Hirano T, Murakami M (2020). COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome. Immunity, 52:731-733.
[49] de Wit E, van Doremalen N, Falzarano D, Munster VJ (2016). SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol, 14:523-534.
[50] Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. (2005). A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med, 11:875-879.
[51] Li C, Wang Y, Qiu Q, Shi T, Wu Y, Han J, et al. (2014). Qishenyiqi protects ligation-induced left ventricular remodeling by attenuating inflammation and fibrosis via STAT3 and NF-kappaB signaling pathway. PLoS One, 9:e104255.
[52] Strollo R, Pozzilli P (2020). DPP4 inhibition: preventing SARS-CoV-2 infection and/or progression of COVID-19? Diabetes Metab Res Rev, in press.
[53] Abbott CA, Baker E, Sutherland GR, McCaughan GW (1994). Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene. Immunogenetics, 40:331-338.
[54] Kim KM, Noh JH, Bodogai M, Martindale JL, Yang X, Indig FE, et al. (2017). Identification of senescent cell surface targetable protein DPP4. Genes Dev, 31:1529-1534.
[55] Wu Z, McGoogan JM (2020). Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA, in press.
[56] Mubarak A, Alturaiki W, Hemida MG (2019). Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development. J Immunol Res, 2019:6491738.
[57] Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, et al. (2013). Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 495:251-254.
[58] Nassar MS, Bakhrebah MA, Meo SA, Alsuabeyl MS, Zaher WA (2018). Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: epidemiology, pathogenesis and clinical characteristics. Eur Rev Med Pharmacol Sci, 22:4956-4961.
[59] Gralinski LE, Baric RS (2015). Molecular pathology of emerging coronavirus infections. J Pathol, 235:185-195.
[60] Ahmed AE (2017). The predictors of 3- and 30-day mortality in 660 MERS-CoV patients. BMC Infect Dis, 17:615.
[61] Klemann C, Wagner L, Stephan M, von Horsten S (2016). Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clin Exp Immunol, 185:1-21.
[62] Abbott CA, McCaughan GW, Levy MT, Church WB, Gorrell MD (1999). Binding to human dipeptidyl peptidase IV by adenosine deaminase and antibodies that inhibit ligand binding involves overlapping, discontinuous sites on a predicted beta propeller domain. Eur J Biochem, 266:798-810.
[63] Yu DM, Slaitini L, Gysbers V, Riekhoff AG, Kahne T, Knott HM, et al. (2011). Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding. Scand J Immunol, 73:102-111.
[64] Cordero OJ, Salgado FJ, Nogueira M (2009). On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol Immunother, 58:1723-1747.
[65] Ikeda T, Kumagai E, Iwata S, Yamakawa A (2013). Soluble CD26/Dipeptidyl Peptidase IV Enhances the Transcription of IL-6 and TNF-alpha in THP-1 Cells and Monocytes. PLoS One, 8:e66520.
[66] Wicinski M, Gorski K, Walczak M, Wodkiewicz E, Slupski M, Pawlak-Osinska K, et al. (2019). Neuroprotective Properties of Linagliptin: Focus on Biochemical Mechanisms in Cerebral Ischemia, Vascular Dysfunction and Certain Neurodegenerative Diseases. Int J Mol Sci, 20.
[67] Goh KJ, Choong MC, Cheong EH, Kalimuddin S, Duu Wen S, Phua GC, et al. (2020). Rapid Progression to Acute Respiratory Distress Syndrome: Review of Current Understanding of Critical Illness from COVID-19 Infection. Ann Acad Med Singapore, 49:108-118.
[68] Yi Y, Lagniton PNP, Ye S, Li E, Xu RH (2020). COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci, 16:1753-1766.
[69] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395:507-513.
[70] Yousefi B, Valizadeh S, Ghaffari H, Vahedi A, Karbalaei M, Eslami M (2020). A global treatments for coronaviruses including COVID-19. J Cell Physiol.
[71] Li G, De Clercq E (2020). Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov, 19:149-150.
[72] Brown AJ, Won JJ, Graham RL, Dinnon KH 3rd, Sims AC, Feng JY, et al. (2019). Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res, 169:104541.
[73] Sheahan TP, Sims AC, Leist SR, Schafer A, Won J, Brown AJ, et al. (2020). Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun, 11:222.
[74] Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. (2020). A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med, 382:1787-1799.
[75] Antinori S, Cossu MV, Ridolfo AL, Rech R, Bonazzetti C, Pagani G, et al. (2020). 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, 158:104899.
[76] Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. (2020). Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, 395:1569-1578.
[77] Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. (2020). Remdesivir for the Treatment of Covid-19 - Preliminary Report.N Engl J Med, in press.
[78] Beigel JH, Tomashek KM, Dodd LE (2020). Remdesivir for the Treatment of Covid-19 - Preliminary Report. Reply. N Engl J Med, 383.
[79] Venkatasubbaiah M, Dwarakanadha Reddy P, Satyanarayana SV (2020). Literature-based review of the drugs used for the treatment of COVID-19. Curr Med Res Pract, 10:100-109.
[80] Bhatnagar T, Murhekar MV, Soneja M, Gupta N, Giri S, Wig N, et al. (2020). Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: Protocol for restricted public health emergency use. Indian J Med Res, 151:184-189.
[81] Yan D, Liu XY, Zhu YN, Huang L, Dan BT, Zhang GJ, et al. (2020). Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection. Eur Respir J, in press.
[82] Cheng CY, Lee YL, Chen CP, Lin YC, Liu CE, Liao CH, et al. (2020). Lopinavir/ritonavir did not shorten the duration of SARS CoV-2 shedding in patients with mild pneumonia in Taiwan. J Microbiol Immunol Infect, in press.
[83] Costanzo M, De Giglio MAR, Roviello GN (2020). 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.
[84] Du YX, Chen XP (2020). Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection. Clin Pharmacol Ther, in press.
[85] Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. (2020). Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing), in press.
[86] Galiano V, Villalain J (2016). The Location of the Protonated and Unprotonated Forms of Arbidol in the Membrane: A Molecular Dynamics Study. J Membr Biol, 249:381-391.
[87] Zhu Z, Lu Z, Xu T, Chen C, Yang G, Zha T, et al. (2020). Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19. J Infect, 81:e21-e23.
[88] Deng L, Li C, Zeng Q, Liu X, Li X, Zhang H, et al. (2020). Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study. J Infect, 81:e1-e5.
[89] Khan S, Ali A, Shi H, Siddique R, Shabana, Nabi G, et al. (2020). COVID-19: Clinical aspects and therapeutics responses. Saudi Pharm J, 28:1004-1008.
[90] Yang C, Ke C, Yue D, Li W, Hu Z, Liu W, et al. (2020). Effectiveness of Arbidol for COVID-19 Prevention in Health Professionals. Front Public Health, 8:249.
[91] Jomah S, Asdaq SMB, Al-Yamani MJ (2020). Clinical efficacy of antivirals against novel coronavirus (COVID-19): A review. J Infect Public Health, in press.
[92] Ozsvari B, Nuttall JR, Sotgia F, Lisanti MP (2018). Azithromycin and Roxithromycin define a new family of "senolytic" drugs that target senescent human fibroblasts. Aging (Albany NY), 10:3294-3307.
[93] Mosquera RA, De Jesus-Rojas W, Stark JM, Yadav A, Jon CK, Atkins CL, et al. (2018). Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model. Pediatr Pulmonol, 53:567-574.
[94] Tang F, Li R, Xue J, Lan J, Xu H, Liu Y, et al. (2017). Azithromycin attenuates acute radiation-induced lung injury in mice. Oncol Lett, 14:5211-5220.
[95] Gbinigie K, Frie K (2020). Should azithromycin be used to treat COVID-19? A rapid review. BJGP Open.
[96] Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, Kumar J, Tesoriero J, et al. (2020). Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State. JAMA, in press.
[97] Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000). Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci, 113(Pt 20):3613-3622.
[98] Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, et al. (2020). Angiotensin-converting enzyme-2 (ACE2), SARS-CoV-2 and pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol, in press.
[99] Devaux CA, Rolain JM, Colson P, Raoult D (2020). New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents, 55:105938.
[100] Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res, 30:269-271.
[101] Huang M, Tang T, Pang P, Li M, Ma R, Lu J, et al. (2020). Treating COVID-19 with Chloroquine. J Mol Cell Biol, 12:322-325.
[102] Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. (2005). Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J, 2:69.
[103] Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, 105949.
[104] Mahevas M, Tran VT, Roumier M, Chabrol A, Paule R, Guillaud C, et al. (2020). Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ, 369:m1844.
[105] Abd El-Aziz TM, Stockand JD (2020). Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status. Infect Genet Evol, 83:104327.
[106] Demidenko ZN, Zubova SG, Bukreeva EI, Pospelov VA, Pospelova TV, Blagosklonny MV (2009). Rapamycin decelerates cellular senescence. Cell Cycle, 8:1888-1895.
[107] Bielas J, Herbst A, Widjaja K, Hui J, Aiken JM, McKenzie D, et al. (2018). Long term rapamycin treatment improves mitochondrial DNA quality in aging mice. Exp Gerontol, 106:125-131.
[108] Arriola Apelo SI, Lamming DW (2016). Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island. J Gerontol A Biol Sci Med Sci, 71:841-849.
[109] Sargiacomo C, Sotgia F, Lisanti MP (2020). COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Aging (Albany NY), 12:6511-6517.
[110] Singh M, Jensen MD, Lerman A, Kushwaha S, Rihal CS, Gersh BJ, et al. (2016). Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study. J Frailty Aging, 5:204-207.
[111] Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F (2020). Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2.Cell Discov, 6:14.
[112] Omarjee L, Janin A, Perrot F, Laviolle B, Meilhac O, Mahe G (2020). Targeting T-cell senescence and cytokine storm with rapamycin to prevent severe progression in COVID-19. Clin Immunol, 216:108464.
[113] Zheng Y, Li R, Liu S (2020). Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines. J Med Virol, in press.
[114] Dhawale VS, Amara VR, Karpe PA, Malek V, Patel D, Tikoo K (2016). Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model. Toxicol Appl Pharmacol, 306:17-26.
[115] Prata LO, Rodrigues CR, Martins JM, Vasconcelos PC, Oliveira FM, Ferreira AJ, et al. (2017). Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis. Exp Biol Med (Maywood), 242:8-21.
[116] Cheng H, Wang Y, Wang GQ (2020).Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol, in press.
[117] Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD (2020). Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med, 382:1653-1659.
[118] Chung MK, Karnik S, Saef J, Bergmann C, Barnard J, Lederman MM, et al. (2020). SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. EBioMedicine, 58:102907.
[119] Rico-Mesa JS, White A, Anderson AS (2020). Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB.Curr Cardiol Rep, 22:31.
[120] Sienko J, Kotowski M, Bogacz A, Lechowicz K, Drozdzal S, Rosik J, et al. (2020). COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients. Clin Interv Aging, 15:1231-1240.
[121] Khan A, Benthin C, Zeno B, Albertson TE, Boyd J, Christie JD, et al. (2017). A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care, 21:234.
[122] Alexandre J, Cracowski JL, Richard V, Bouhanick B, Drugs C-wgotFSoPT (2020).Renin-angiotensin-aldosterone system and COVID-19 infection. Ann Endocrinol (Paris).
[123] Monteil V, Kwon H, Prado P, Hagelkruys A, Wimmer RA, Stahl M, et al. (2020). Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell, 181:905-913 e907.
[124] Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, et al. (2020). COVID-19 infection: the perspectives on immune responses. Cell Death Differ, 27:1451-1454.
[125] Chen CF, Chien CH, Yang YP, Chou SJ, Wang ML, Huo TI, et al. (2020). Role of Dipeptidyl Peptidase 4 Inhibitors in Diabetic Patients with Coronavirus-19 Infection. J Chin Med Assoc.
[126] Kawasaki T, Chen W, Htwe YM, Tatsumi K, Dudek SM (2018). DPP4 inhibition by sitagliptin attenuates LPS-induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol, 315:L834-L845.
[127] Birnbaum Y, Bajaj M, Qian J, Ye Y (2016). Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome. BMJ Open Diabetes Res Care, 4:e000227.
[128] Berger JP, SinhaRoy R, Pocai A, Kelly TM, Scapin G, Gao YD, et al. (2018). A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice. Endocrinol Diabetes Metab, 1:e00002.
[129] Tang S, Ma W, Bai P (2017). A Novel Dynamic Model Describing the Spread of the MERS-CoV and the Expression of Dipeptidyl Peptidase 4. Comput Math Methods Med, 2017:5285810.
[130] Iacobellis G (2020). COVID-19 and diabetes: Can DPP4 inhibition play a role? Diabetes Res Clin Pract, 162:108125.
[131] Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. (2020). Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 117:10970-10975.
[132] Buonaguro FM, Puzanov I, Ascierto PA (2020).Anti-IL6R role in treatment of COVID-19-related ARDS. J Transl Med, 18:165.
[133] Morena V, Milazzo L, Oreni L, Bestetti G, Fossali T, Bassoli C, et al. (2020). Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy. Eur J Intern Med.
[134] Alijotas-Reig J, Esteve-Valverde E, Belizna C, Selva-O'Callaghan A, Pardos-Gea J, Quintana A, et al. (2020). Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review. Autoimmun Rev, 102569.
[135] Pfefferle S, Schopf J, Kogl M, Friedel CC, Muller MA, Carbajo-Lozoya J, et al. (2011). The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors. PLoS Pathog, 7:e1002331.
[136] Vandewalle J, Luypaert A, De Bosscher K, Libert C (2018). Therapeutic Mechanisms of Glucocorticoids.Trends Endocrinol Metab, 29:42-54.
[137] Luce JM, Montgomery AB, Marks JD, Turner J, Metz CA, Murray JF (1988). Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock.Am Rev Respir Dis, 138:62-68.
[138] Meduri GU, Schwingshackl A, Hermans G (2016). Prolonged Glucocorticoid Treatment in ARDS: Impact on Intensive Care Unit-Acquired Weakness. Front Pediatr, 4:69.
[139] Fadel R, Morrison AR, Vahia A, Smith ZR, Chaudhry Z, Bhargava P, et al. (2020). Early Short Course Corticosteroids in Hospitalized Patients with COVID-19. Clin Infect Dis.
[140] Stockman LJ, Bellamy R, Garner P (2006). SARS: systematic review of treatment effects. PLoS Med, 3:e343.
[141] Zha L, Li S, Pan L, Tefsen B, Li Y, French N, et al. (2020). Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19). Med J Aust, 212:416-420.
[142] Klingemann H, Matzilevich D, Marchand J (2008).Mesenchymal Stem Cells - Sources and Clinical Applications. Transfus Med Hemother, 35:272-277.
[143] Han KH, Ro H, Hong JH, Lee EM, Cho B, Yeom HJ, et al. (2011). Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response. Transpl Immunol, 25:7-15.
[144] Zanoni M, Cortesi M, Zamagni A, Tesei A (2019). The Role of Mesenchymal Stem Cells in Radiation-Induced Lung Fibrosis.Int J Mol Sci, 20.
[145] Takeda K, Ning F, Domenico J, Okamoto M, Ashino S, Kim SH, et al. (2018). Activation of p70S6 Kinase-1 in Mesenchymal Stem Cells Is Essential to Lung Tissue Repair. Stem Cells Transl Med, 7:551-558.
[146] Shao M, Xu Q, Wu Z, Chen Y, Shu Y, Cao X, et al. (2020). Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p. Stem Cell Res Ther, 11:37.
[147] Chen J, Hu C, Chen L, Tang L, Zhu Y, Xu X, et al. (2020). Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic Influenza A (H7N9) infection, a hint for COVID-19 treatment. Engineering (Beijing).
[148] Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. (2020). Transplantation of ACE2(-) Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis, 11:216-228.
[149] Rademacher S, Oppert M, Jorres A (2011).Artificial extracorporeal liver support therapy in patients with severe liver failure. Expert Rev Gastroenterol Hepatol, 5:591-599.
[150] Liu X, Zhang Y, Xu X, Du W, Su K, Zhu C, et al. (2015). Evaluation of plasma exchange and continuous veno-venous hemofiltration for the treatment of severe avian influenza A (H7N9): a cohort study. Ther Apher Dial, 19:178-184.
[151] Liu J, Dong YQ, Yin J, He G, Wu X, Li J, et al. (2020). Critically ill patients with COVID-19 with ECMO and artificial liver plasma exchange: A retrospective study. Medicine (Baltimore), 99:e21012.
[152] Zhang Y, Yu L, Tang L, Zhu M, Jin Y, Wang Z, et al. (2020). A Promising Anti-Cytokine-Storm Targeted Therapy for COVID-19: The Artificial-Liver Blood-Purification System. Engineering (Beijing), in press.
[153] Zabetakis I, Lordan R, Norton C, Tsoupras A (2020). COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation. Nutrients, 12.
[154] Laviano A, Koverech A, Zanetti M (2020).Nutrition support in the time of SARS-CoV-2 (COVID-19). Nutrition, 74:110834.
[155] Power SE, Jeffery IB, Ross RP, Stanton C, O'Toole PW, O'Connor EM, et al. (2014). Food and nutrient intake of Irish community-dwelling elderly subjects: who is at nutritional risk? J Nutr Health Aging, 18:561-572.
[156] Li T, Zhang Y, Gong C, Wang J, Liu B, Shi L, et al. (2020). Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China. Eur J Clin Nutr, in press.
[157] Haase H, Rink L (2009).The immune system and the impact of zinc during aging. Immun Ageing, 6:9.
[158] Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, et al. (2020). 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, in press.
[159] Monto AS, Rotthoff J, Teich E, Herlocher ML, Truscon R, Yen HL, et al. (2004). Detection and control of influenza outbreaks in well-vaccinated nursing home populations. Clin Infect Dis, 39:459-464.
[160] Ventura MT, Casciaro M, Gangemi S, Buquicchio R (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clin Mol Allergy, 15:21.
[161] Sheikh A, Sheikh A, Sheikh Z, Dhami S, Sridhar D (2020). What's the way out? Potential exit strategies from the COVID-19 lockdown. J Glob Health, 10:010370.
[162] To KK, Hung IF, Ip JD, Chu AW, Chan WM, Tam AR, et al. (2020). COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis, in press.
[163] Ibarrondo FJ, Fulcher JA, Goodman-Meza D, Elliott J, Hofmann C, Hausner MA, et al. (2020). Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19. N Engl J Med, in press.
[164] Lloyd-Sherlock P, Ebrahim S, Geffen L, McKee M (2020).Bearing the brunt of covid-19: older people in low and middle income countries. BMJ, 368:m1052.
[165] Lloyd-Sherlock PG, Kalache A, McKee M, Derbyshire J, Geffen L, Casas FG (2020). WHO must prioritise the needs of older people in its response to the covid-19 pandemic. BMJ, 368:m1164.
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