Age Related Differences in Monocyte Subsets and Cytokine Pattern during Acute COVID-19—A Prospective Observational Longitudinal Study

Abstract

The COVID-19 pandemic drastically highlighted the vulnerability of the elderly population towards viral and other infectious threats, illustrating that aging is accompanied by dysregulated immune responses currently summarized in terms like inflammaging and immunoparalysis. To gain a better understanding on the underlying mechanisms of the age-associated risk of adverse outcome in individuals experiencing a SARS-CoV-2 infection, we analyzed the impact of age on circulating monocyte phenotypes, activation markers and inflammatory cytokines including interleukin 6 (IL-6), IL-8 and tumor necrosis factor (TNF) in the context of COVID-19 disease progression and outcome in 110 patients. Our data indicate no age-associated differences in peripheral monocyte counts or subset composition. However, age and outcome are associated with differences in monocyte activation status. Moreover, a distinct cytokine pattern of IL-6, IL-8 and TNF in elderly survivors versus non-survivors, which consolidates over the time of hospitalization, suggests that older patients with adverse outcomes experience an inappropriate immune response, reminiscent of an inflammaging driven immunoparalysis. Our study underscores the value, necessity and importance of longitudinal monitoring in elderly COVID-19 patients, as dynamic changes after symptom onset can be observed, which allow for a differentiated insight into confounding factors that impact the complex pathogenesis following an infection with SARS-CoV-2.

Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study

“…Our group previously documented similar trends of serum IL-6 among critically ill patients receiving immunomodulatory therapies [18,32]. Other studies have demonstrated that persistently elevated serum IL-6 levels during COVID-19 are independently associated with in-hospital mortality, and rises of serum IL-6, IL-8 and TNF-α are probably age-dependent, translating to poorer outcomes among the elderly [22,24,33]. Pro-inflammatory cytokine responses in blood were detectable for ≥3 weeks after SARS-CoV-2 infection [34].…”

Immunosenescence and COVID-19

“…Although highly speculative at this time, the notion of early SARS-CoV-2 infection bearing on immunobiography and increasing inflammaging may have some merit. It was found that severe COVID-19 is associated with higher levels of proinflammatory cytokines leading from inflammaging to immunoparalysis ( Muller and Di Benedetto, 2021 , Pirabe et al, 2021 ).…”

Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID‐19 and after yellow fever vaccination

“…Multiple studies have described the association of higher age with more severe COVID‐19 disease outcomes [27]. Age‐associated changes in the immune response such as altered cytokine responses in elderly patients have been shown to contribute to more severe COVID‐19 [28]. Interestingly, in aged mice, upregulation of CD86 is reduced after TLR2 and influenza‐induced stimulation [29].…”