The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”

Abstract

Purpose Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by "inflamm-aging". It is highly likely that "inflamm-aging" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. Methods A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. Results The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of "inflamm-aging", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.

IL-4/IL-13 remodeling pathway of COVID-19 lung injury

“…Regarding the population analyzed, our findings support the literature that shows age as a risk factor and describes comorbidities associated with the severe form of COVID-19 and fatal outcomes 14 – 16 . Although we have not found a statistical difference in gender distribution, male patients were prevalent (66.6%) in the COVID-19 group (as well as in the H1N1 group = 80%).…”

“…Contrary to H1N1pdm09, COVID19 lethality is concentrated in older than 65 years of patients-following long periods of mechanical ventilation. Therefore, it is difficult to discard the influence of age, strength and duration of mechanical ventilation in the parameters examined in this report 14 – 16 . So, it is essential to interpret our findings with caution and validate them in other samples.…”

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

“…ACE2 acts as mediator of coronavirus entry into the cells, but also contributes to diffuse alveolar damage through imbalances in the renin-angiotensin system. These immunologic reactions in severe COVID-19 may characterize the cytokine storm phenomenon: a massive release of macrophage migration inhibitory factor (MIF), tumour necrosis factor (TNF)-α, and interleukin (IL)-1, IL-2R, IL-6, IL-8, and IL-10 from host cells and immune cells [5,6]. These in ammatory cells and factors will lead to the typical ARDS (Acute respiratory distress syndrome) pathology with acute diffuse alveolar damage, pulmonary oedema, and formation of hyaline membranes [7].…”

COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms

“…Importantly, age is one of the key aspects contributing to the severity of the disease. The elderly are at high risk of developing severe or critical disease [227,247]. Age-related elevated levels of pro-inflammatory cytokines (inflammation) [247][248][249][250], immunosenescence and cellular stress of ageing cells [125,227,247,251,252] may contribute to the risk.…”