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.
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.
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.
Potential efficacy in COVID-19
Remdesivir 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
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 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
Attenuates DM-induced activation of NLRP3 inflammatory bodies
Decreases the concentration of cytokines, especially TNF-α and IL-6
Tocilizumab; 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
Advantages in anti-inflammation, antifibrosis and injury repair
Improves pulmonary function and symptoms of patients
Artificial liver system
Attenuates the cytokine storm
Reduces the mortality of severe patients exhibiting rapid disease progression
Table 1 Potential strategies for the treatment of COVID-19.
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