Influence of aging on deterioration of patients with COVID-19

Abstract

Aging is an important factor affecting the deterioration of patients with coronavirus disease 2019 (COVID-19). The aging and degeneration of various tissues and organs in the elderly lead to impaired organ function. Underlying conditions such as chronic lung disease, cardiovascular disease, and diabetes in aged patients are associated with higher mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily interacts with the cell surface receptor angiotensin-converting enzyme (ACE) 2 and other accessory proteins such as 78 kDa glucose-regulated protein 78 (GRP78) and CD147. Thus, altered receptor signals in aging and chronic disease play a role in SARS-CoV-2 infection, and are associated with a higher risk of deterioration in different organs. In this review, after a brief introduction to the link between aging and receptors for SARS-CoV-2, we focus on the risk of deterioration in different organs of COVID-19 patients considering aging as the main factor. We further discuss the structural and/or physiological changes in the immune system and organs (lung, heart, kidney, vessels, nerve system), as well as those associated with diabetes, in aging patients, and speculate on the most likely mechanisms underlying the deterioration of COVID-19 patients.

Keywords: ACE2; CD147; COVID-19; GRP78; aging.

Figure 1

The effects of aging on the organism and its relationship with COVID-19-associated deterioration. Aging patients are more susceptible to SARS-CoV-2, which leads to the exacerbation of COVID-19. Aging has a negative impact on the human organ system, causing its functional decline. The aging process is accompanied by a state of low-grade inflammation, and the elderly are more susceptible to SARS-CoV-2 infection. Under the influence of the virus, the damage to infected aging patients is further worsened, resulting in serious secondary diseases. In the figure, "↑" means the number increases, the function or effect is enhanced; "↓" means the number decreases, the function or effect is weakened. ERS: endoplasmic reticulum stress; ACE2: angiotensin-converting enzyme 2; TMPRSS2: transmembrane protease serine 2; ADAM17: a disintegrin and metalloprotease 17; ARDS: acute respiratory distress syndrome; AKI: acute kidney injury; PKC: protein kinase C; ROS: reactive oxygen species; CKD: chronic kidney disease; DIC: disseminated intravascular coagulation.

Figure 2

Deaths per 1,000 COVID−19 cases by age group in major epidemic areas. Data from references [, –104] have been amalgamated with the above data to fit the new data. After standardizing the data for each group, the probability of death at each age was fitted and multiplied by 1,000. The ggplot2 package in R version 4.0.0 was used to draw a line graph. Marine green represents New York, red represents China, blue represents South Korea, yellow represents Italy, grass green represents ISS, and purple represents the fitting data. In the line graph, the number of deaths per 1,000 COVID-19 patients increases with age.