Fig. 1

COVID-19 and Inflammaging. Inflammaging (highlighted in yellow). Systemic, sustained chronic inflammation due to persistent tissue damage, environmental stressors, unhealthy lifestyle, and social and psychological stress is associated with the risk of developing many chronic diseases. Older, obese, and/or smokers with precipitating conditions, are at higher risk. Exogenous compounds such as bacteria or viral fragments including elements of microbiota (pathogen-associated molecular patterns, or PAMPs) or endogenously produced chemical compounds that structurally mimic exogenous compounds (damage-associated molecular patterns or DAMPs) interact with sensors, expressed on the cell surface and in the cytoplasm, to trigger inflammatory responses and pro-inflammatory cytokine secretion (eg. tumor necrosis factor [TNF], interleukin-1 [IL-1], IL-6, and IL-8, and type 1 interferon) that contribute to the state of chronic subclinical systemic inflammation seen in aging (termed inflammaging). Immunobiography, the individual’s history of exposure to certain microorganisms (eg. HIV and CMV) or antigens, may condition the degree and characteristic of the inflammatory response to various stimuli. Inflammaging, which results in an increased incidence and worsening of age-related conditions, is characterized clinically by higher levels of several inflammatory blood biomarkers, including C-reactive protein (CRP), IL-6, IL-18, and TNF. COVID-19 (highlighted in blue). SARS-CoV-2 infection, like SARS-CoV-1 and MERS CoV, can unleash a powerful, and apparently uncontrolled acute inflammatory response in individuals who may be more susceptible because of biological differences in their response to PAMPS, DAMPS, and factors related to immunobiography. Interestingly, prognostic factors for mortality from COVID-19 are similar to those that have been found associated with a high likelihood and prospective risk of chronic inflammation, namely older age, male sex, obesity, smoking, cardiovascular diseases, asthma or other respiratory disease, cancer, autoimmune diseases, multimorbidity, and frailty. This similarity may suggest that the same mechanisms underlying inflammaging are also those that modulate the clinical course of COVID-19 across a wide range of severity, from a mild flu-like syndrome to a severe respiratory failure with high mortality risk. In those with more severe disease, high concentrations of pro-inflammatory mediators, which has been named ‘the cytokine storm,’ affects levels of pro-inflammatory cytokines/chemokines typical of T helper 1 cell response such as IL-6, IFNγ, IP-10, and MCP1. COVID-19 disease severity in hospitalized patients is characterized by severe pneumonia associated with an overt inflammatory reaction typified by high plasma CRP and IL-6, low albumin, high sedimentation rate, low eosinophils, and lymphopenia, often leading to intensive care treatment