How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

Abstract

Inflammatory and immune processes are defensive mechanisms that aim to remove harmful agents. As a response to infections, inflammation and immune response contribute to the pathophysiological mechanisms of diseases. Coronavirus disease 2019 (COVID-19), whose underlying mechanisms remain not fully elucidated, has posed new challenges for the knowledge of pathophysiology. Chiefly, the inflammatory process and immune response appear to be unique features of COVID-19 that result in developing a hyper-inflammatory syndrome, and air pollution, the world’s largest health risk factor, may partly explain the behaviour and fate of COVID-19. Understanding the mechanisms involved in the progression of COVID-19 is of fundamental importance in order to avoid the late stage of the disease, associated with a poor prognosis. Here, the role of the inflammatory and immune mediators in COVID-19 pathophysiology is discussed.

Correlation of myeloid‐derived suppressor cells with C‐reactive protein, ferritin and lactate dehydrogenase levels in patients with severe COVID‐19

“…MDSCs themselves contribute to inflammation and coagulation by producing IL‐1β, TNF‐α, IL‐6 and IL‐8. 39 Takano et al reported that PMN‐MDSCs are positively correlated with IL‐8 levels in patients with COVID‐19 and that IL‐8 plays a role in the recruitment of PMN‐MDSCs to peripheral blood following the onset of severe COVID‐19. 31 Increased IL‐1β, TNF‐α, IL‐6 and IL‐8 levels are associated with increased CRP, D‐dimer and ferritin, causing severe inflammation and coagulation in COVID‐19.…”

“…In viral infections including SARS‐CoV‐2, TNF‐α causes elevated serum ferritin and LDH levels, as well as thrombocytopenia, lymphopenia and haemolysis. MDSCs themselves contribute to inflammation and coagulation by producing IL‐1β, TNF‐α, IL‐6 and IL‐8 39 . Takano et al reported that PMN‐MDSCs are positively correlated with IL‐8 levels in patients with COVID‐19 and that IL‐8 plays a role in the recruitment of PMN‐MDSCs to peripheral blood following the onset of severe COVID‐19 31 .…”

Epigenetics at the Intersection of COVID-19 Risk and Environmental Chemical Exposures

“…Exposure to air pollutants is associated with the generation of reactive oxygen species (ROS) and pulmonary inflammation, resulting in adverse health effects such as asthma and decreased lung function [ 45 , 46 ]. Chronic exposure to air pollutants results in degradation of multiple body systems, including the respiratory and immune systems that are largely involved in COVID-19 response [ 47 , 48 ]. This inflammatory response is partially mediated by TLRs, a key portion of the physiological response to SARS-CoV-2 [ 12 ••, 13 ••, 49 ].…”

The Role of Alveolar Edema in COVID-19

“…Besides ventilation-perfusion mismatch, intravascular coagulation and alveolar edema, COVID-19 ARDS is a very complex disease, with intrapulmonary shunting, impaired lung diffusion, inflammation, etc. [103][104][105][106][107][108][109]. We cannot expect that early oxygen therapy and pulmonary edema treatments can prevent every COVID-19 patient from the development of ARDS.…”