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Pharmacol Ther ; 221: 107745, 2021 05.
Article in English | MEDLINE | ID: covidwho-922109

ABSTRACT

While COVID-19, the disease driven by SARS-CoV-2 has ignited interest in the host immune response to this infection, it has also highlighted the lack of treatment options for the damaging inflammatory responses driven by pathogens that precipitate the acute respiratory distress syndrome (ARDS). With the global prevalence of SARS-CoV-2 and the likelihood of a second winter spike alongside seasonal flu, the need for effective and targeted anti-inflammatory agents is even more pressing. Here we discuss the aetiology of COVID-19 and the common signalling pathways driven by SARS-CoV-2, namely p38 MAP kinase. We highlight that p38 MAP kinase becomes elevated with increasing age, thereby driving many of the inflammatory pathways that precipitate death in old people with the added drawback of impairing vaccine efficacy in this susceptible age group. Finally, we review drugs available to inhibit p38 MAP kinase, their risks-versus-benefits as well as suggested dosing regimen to combat over-exuberant innate immune responses and potentially reverse vaccine inefficacy in older patients.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19 Drug Treatment , MAP Kinase Signaling System/drug effects , Pneumonia/drug therapy , Protein Kinase Inhibitors/therapeutic use , Respiratory Distress Syndrome/drug therapy , Anti-Inflammatory Agents/pharmacology , COVID-19/epidemiology , COVID-19/immunology , Clinical Trials as Topic/methods , Humans , Immunity, Innate/drug effects , Immunity, Innate/immunology , MAP Kinase Signaling System/physiology , Pneumonia/epidemiology , Pneumonia/immunology , Protein Kinase Inhibitors/pharmacology , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/immunology
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