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

Abstract

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 ACQUISITIONWe 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 infl ammation 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 infl ammation is characteristic of all these conditions, refl ected in a proinfl ammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, infl ammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute infl ammation overlap with the patient's pro-infl ammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifi es already-existing alterations, causing failures in the immune system's control mechanisms. The resulting cytokine storm causes an uncontrolled systemic infl ammatory response marked by high serum levels of infl ammatory biomarkers and a pro-infl ammatory cytokine profi le with decompensation of underlying diseases. In asthma, chronic eosinophilic infl ammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors.CONCLUSIONS Low-grade chronic infl ammation present in advanced age and chronic diseases-but not in bronchial asthma-produces a pro-infl ammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.

Immunosenescence and COVID-19

“…Generally, low grade inflammation, whether due to the causes described above, or to the chronic inflammatory diseases at paucisymptomatic state is conductive for immune dysregulation and increased severity of COVID-19 ( Bonafe et al, 2020 , Suarez-Reyes and Villegas-Valverde, 2021 ).…”

The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers

“…Overall, these findings suggest that “long COVID” might be a systemic, long-lasting condition occurring in some patients with a previous history of SARS-CoV-2 infection, independently of the severity of the initial disease 27 , 28 , 29 . This can partly be due to the presence of microvascular involvement even in “silent” forms of COVID-19 30 , 31 , 32 , 33 , or to the presence of chronic low-grade inflammation which can trigger symptoms of long COVID 34 , 35 even in asymptomatic patients. The presence of these combined factors can potentially increase the likelihood of developing erectile dysfunction (ED) in COVID-19 long haulers ( figure 1 ).…”

Nutritional risk, not obesity, is associated with mortality in critically ill COVID-19 patients

“…A similar situation has been documented in patients with diabetes [50] , which may promote greater virus absorption and infection. Aso, the prolonged low-grade inflammation promotes a pro-inflammatory state with changes in the immune system and endothelial dysfunction, thus contributing to greater severity of COVID-19 [51] , [52] , [53] .…”