Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

Abstract

The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.

COVID-19 and the elderly

“…Inflammaging should play a key role in the pathogenic process leading to "cytokine storm" that cause serious organ damage. Though the antibody production after vaccination is also weakened, vaccination is strongly recommended for older people [10].…”

“…They are also playing a pivotal role in limiting viral infection [11]. Aging associated changes in NK cell count, phenotype, and functions may have a direct impact on COVID-19 disease progression [10]. NK cell number is reduced in COVID-19 patients.…”

Centenarians born before 1919 are resistant to COVID-19

“…So, men have higher pro-inflammatory activity and lower acquired activity than observed in women [ 9 , 12 ]. These differences, that contribute to health- and life-span disparities between genders, fit very well with pathophysiological mechanisms of COVID-19 [ 8 ].…”

“…As previously stated, older patients are at higher risk of getting severe COVID-19, including death. Accordingly, as of March 31, 2021, at the beginning of mass vaccination of the older people, almost 86% of SARS-CoV-2 positive Italian patients that died were patients over 70 years old, with a median of 82 years (range 0–109), more than 30 years higher than that registered in infected people (median age 47) [ 8 ]. Disease severity in older patients is thought to be mainly due to the presence of comorbidities in older people.…”

“…However, the ageing of the immune system, i.e ., immunosenescence, closely associated with a low-grade inflammatory status called "inflamm-ageing," also plays a key role. The age-related remodelling of both innate and adaptive immune response makes older people particularly vulnerable to new infectious agents never encountered before as SARS-CoV-2, while inflamm-ageing enhances the pro-inflammatory effects of the infection [ 8 , 9 ].…”