Do inflammaging and coagul-aging play a role as conditions contributing to the co-occurrence of the severe hyper-inflammatory state and deadly coagulopathy during COVID-19 in older people?

Abstract

The 2019 Coronavirus pneumonia (COVID-19) is a new infectious respiratory disease, which has caused a pandemic that has become the world's leading public health emergency, threatening people of all ages worldwide, especially the elderly. Complications of COVID-19 are closely related to an upregulation of the inflammatory response revealed by the pro-inflammatory profile of plasma cytokines (to the point of causing a cytokine storm), which is also a contributing cause of the associated coagulation disorders with venous and arterial thromboembolisms, causing multiple organ dysfunction and failure. In severe fulminant cases of COVID-19, there is an activation of coagulation and consumption of clotting factors leading to a deadly disseminated intravascular coagulation (DIC). It is well established that human immune response changes with age, and also that the pro-inflammatory profile of plasma cytokines is upregulated in both healthy and diseased elderly people. In fact, normal aging is known to be associated with a subclinical, sterile, low-grade, systemic pro-inflammatory state linked to the chronic activation of the innate immune system, a phenomenon known as “inflammaging”. Inflammaging may play a role as a condition contributing to the co-occurrence of the severe hyper-inflammatory state (cytokine storm) during COVID-19, and also in other severe infections (sepsis) in older people. Moreover, we must consider the impact of inflammation on coagulation due to the crosstalk between inflammation and coagulation. The systemic inflammatory state and coagulation disorders are closely related, a phenomenon that here we call “coagul-aging” (Giunta S.). In this review, we discuss the various degrees of inflammation in older adults after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the adverse effects of aging on the inflammatory response and coagulation system. It is important to note that although there is no gender difference in susceptibility to COVID-19 infection, however, due to differences in angiotensin-converting enzyme 2 (ACE2) expression, innate immunity, and comorbidities, older men exhibit more severe disease and higher mortality than older women. There are currently no FDA-approved specific antiviral drugs that can be used against the virus. Therapies used in patients with COVID-19 consist of remdesivir, dexamethasone, low-molecular-weight heparin, in addition to monoclonal antibodies against the spike protein of SARS-CoV-2 in the early phase of the disease. Future pharmacological research should also consider targeting the possible role of the underlying scenario of inflammaging in healthy older people to prevent or mitigate disease complications. It is worth mentioning that some specific cytokine antagonists and traditional Chinese medicine preparations can reduce the elderly's inflammatory state.

Impact of Age and Sex on COVID-19 Severity Assessed From Radiologic and Clinical Findings

“…In our study, the individual variance in the level of interleukin-6 (IL-6) was considerable among patients. A recent study found evidence to suggest that elderly patients were prone to a cytokine storm (Xu et al, 2021). Because of the high variance, there are conflicting findings on whether the age difference in IL-6 is notable (Zhao et al, 2020) or not (Peng et al, 2021).…”

Role of Inflammaging on the Reproductive Function and Pregnancy

“… Zambon et al 2018 [ 28 ] Research article Maternal obesity, periodontal disease and systemic and local inflammatory status during pregnancy. Pregnant Obesity, GDM and periodontal disease may synergistically amplify the inflammatory and oxidative status in pregnancy Xu et al 2021 [ 26 ] Review Inflammaging and severe hyper-inflammatory state during COVID-19 and other severe infections (sepsis). General Inflammaging and coagulating determine adverse course of viral and bacterial severe infections.…”

“…Several chronic comorbidities, including cardiovascular, metabolic, neoplastic, and autoimmune diseases, are strongly associated with inflammaging in a self-feeding vicious cycle where inflammaging may increase the risk of developing diseases and the disease itself exasperates the underlying age-related inflammation and immunosenescence. Inflammaging may also play a role in contributing to severe hyperinflammatory state and cytokine storm in case of superimposed infections, as in case of sepsis in elderly or SARS-CoV-2 infection [ 26 ].…”

Disseminated Intravascular Coagulation in Varying Age Groups Based on Clinical Conditions

“…Common causes of DIC in the elderly population include sepsis and cancer, especially acute myeloid leukemia (AML) [ 28 ]. However, research on the outcomes of DIC for the geriatric age group with these conditions are currently limited.…”