Implications of Low-grade Inflammation in SARS-CoV-2 Immunopathology.

Introduction: Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19's immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment.

Objective: Describe the main immunopathogenic alterations of COVID-19 in patients of advanced age or with chronic non-communicable diseases.

Data acquisition: We carried out a bibliographic search of primary references in PubMed, Elsevier, Science Direct and SciELO. A total of 270 articles met our initial search criteria. Duplicate articles or those unrelated to at least one chronic comorbidity, senescence or inflammation and those that studied only patient clinical characteristics, laboratory tests or treatments were excluded. Finally, our selection included 124 articles for analysis: 10 meta-analyses, 24 original research articles, 67 review articles, 9 editorials, 9 comments, 3 books and 2 websites.

Development: Hypertension and diabetes mellitus are the most common comorbidities in COVID-19 patients. Risk of developing severe manifestations of the disease, including death, is increased in senescent and obese patients and those with cardiovascular disease, cancer or chronic obstructive pulmonary disease. Low-grade chronic inflammation is characteristic of all these conditions, reflected in a pro-inflammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, inflammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute inflammation overlap with the patient's pro-inflammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifies already-existing alterations, causing failures in the immune system's control mechanisms. The resulting cytokine storm causes an uncontrolled systemic inflammatory response marked by high serum levels of inflammatory biomarkers and a pro-inflammatory cytokine profile with decompensation of underlying diseases. In asthma, chronic eosinophilic inflammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors.

Conclusions: Low-grade chronic inflammation present in advanced age and chronic diseases-but not in bronchial asthma-produces a pro-inflammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.