Aging & COVID-19 susceptibility, disease severity, and clinical outcomes: The role of entangled risk factors

Abstract

The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) in late 2019 has been associated with a high rate of mortality and morbidity. It has been determined that the old population are not only at an increased risk for affliction with COVID-19 infection, but also atypical presentations, severe forms of the disease, and mortality are more common in this population. A plethora of mechanisms and risk factors contribute to the higher risk of infection in the old population. For instance, aging is associated with an increment in the expression of Angiotensin-Converting Enzyme-2 (ACE-2), the receptor for SARS-CoV-2 spike protein, which precipitates replication of the virus in the old population. On the other hand, immune dysregulation and changes in gut microbiota as a result of aging can contribute to the cytokine storm, one of the main indicators of disease severity. Decrement in sex steroids, especially in women, as well as growth hormone, both of which have crucial roles in immune regulation, is a key contributor to disease severity in old age. Senescence-associated oxidative stress and mitochondrial dysfunction in both pneumocytes and immune cells contribute to the severity of infection in an exacerbative manner. In addition, lifestyle-associated factors such as nutrition and physical activity, which are compromised in old age, are known as important factors in COVID-19 infection. Aging-associated comorbidities, especially cardiovascular diseases and Diabetes Mellitus, also put older adults at an increased risk of complications, and disease severity.

COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials

“…No prespecified limitations applied for dose or type of vitamin D and follow-up durations. The exclusion criteria were: (1) studies with no control/comparator group; (2) study types other than RCTs such as observational studies and trial-protocols. In case of duplicate articles, only a recent report with all relevant information was included.…”

“…As of 5 th August 2021 and WHO, there have been 200,174,883 confirmed COVID-19 cases, including 4,255,892 deaths [1]. Multiple risk factors in the form of age, comorbidities, exaggerated immune response in the form of cytokine storm, oxidative stress, activation of pro-coagulation factors and severe inflammation contribute to the disease progression [2].…”

Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies

“…Replicative and/or stress-induced cellular senescence of immune cells results in compromised and inappropriate cellular function and cell responses of e.g., innate and humoral immunity [ 31 ]. This is largely responsible for the increased susceptibility of elderly subjects to infection with influenza virus or with SARS-CoV-2 [ 32 , 33 , 34 ]. Replicative senescence of resident cells induces the senescence-associated secretory phenotype (SASP), which is characterized by resident senescent cells secreting pro-inflammatory factors that can alter the cellular microenvironment and shift neighbouring healthy proliferating cells into a more senescent- and pro-inflammatory state.…”

Immune Responses against SARS-CoV-2—Questions and Experiences

“…It remains unknown which main determinants are responsible for a shift to a bad course. Advanced age [15], cardiovascular disease (CVD), and obesity [16] can also include the genetic factors that could be involved in causing severe COVID-19 [15]. Nevertheless, a minor subset of young and middle-aged individuals also develop massive inflammatory responses and need intensive care treatment with mechanical ventilation [14].…”