Treating exuberant, non-resolving inflammation in the lung; Implications for acute respiratory distress syndrome and COVID-19

https://doi.org/10.1016/j.pharmthera.2020.107745Get rights and content

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.

Keywords

ARDS
COVID-19
Inflammation
p38 MAP kinase
SARS-CoV-2

Abbreviations

ARDS
Acute respiratory distress syndrome
Ang
Angiotensin
ACE
Angiotensin converting enzyme
COPD
Chronic obstructive pulmonary disorder
COVID-19
Coronavirus disease 2019
IFN
Interferon
IL
Interleukin
LPS
Lipopolysaccharide
MAP kinase
Mitogen-activated protein kinase
NETs
Neutrophil extracellular traps
PHE
Public Health England
SASP
Senescence-associated secretory phenotype
SARS-CoV
Severe acute respiratory syndrome coronavirus
TNF
Tumour necrosis factor

Cited by (0)

View Abstract