Perception into the position of getting old in response to SARS-CoV-2 an infection
Older adults and people with underlying diseases are at higher risk of developing severe coronavirus disease (COVID-19), which is caused by the infectious agent coronavirus 2 (SARS-CoV-2).
Previous studies have shown that older people are at greater risk for COVID-19 due to physiological changes associated with aging and potential comorbidities such as diabetes, high blood pressure, and heart problems.
Researchers at the University of California at Irvine set out to determine the differences between young people and older adults in their host responses to SARS-CoV-2. The team showed that COVID-19 was linked to a significant shift in plasma inflammatory factors regardless of the severity of the disease. The research is published on the pre-print server medRxiv *.
Aging and Immune Response
The effects of aging on the immune system show up at several levels, including decreased production of T lymphocytes (T cells) and B lymphocytes (B cells) in the bone marrow and thymus, and decreased function of mature lymphocytes or white blood cells.
Many viral respiratory diseases predispose older adults to serious illness, including the current COVID-19 pandemic that has infected over 104 million people. More than 2.26 million died of the virus disease.
When a person becomes infected with SARS-CoV-2, the virus targets the pulmonary airways and alveolar epithelial cells, macrophages in the lungs, and vascular endothelial cells. The infection triggers a robust innate and adaptive immune response to eradicate the virus. In worse cases, the immune system gets out of hand and triggers a cytokine storm. Most people with severe COVID-19 develop acute respiratory distress syndrome (ARDS) and multiple organ failure.
In the United States, the estimated death rate from COVID-19 is 1 to 2 percent, while 40 to 80 percent of patients develop mild or no symptoms. Age is a major risk factor for developing severe COVID-19. However, more data is needed to explain why this group is hardest hit by the pandemic.
The elderly are most likely to develop serious complications associated with COVID-19, including respiratory failure, shortness of breath, pneumonia, and ARDS. In addition, aging is linked to immunodeficiency, leading to a significant increase in susceptibility to viral infections of the respiratory tract, increased underlying inflammation, also known as "inflammation", and a weakened vaccination response. Aging is also linked to decreased T and B cells, increased circulatory inflammation mediators such as interleukin-6 (IL-6) and C21 reactive protein, and increased effector memory cells.
Influence of Aging on Host Response to COVID-19
The study offers new insights into the effects of aging on the host's response to SARS-CoV-2 infection. The researchers conducted the study to determine the differences between young and older people when it comes to how their immune systems fight the threat of SARS-CoV-2.
It is estimated that an estimated 80 percent of COVID-19 deaths occur in people over the age of 65. People with comorbidities are also at greater risk for serious illnesses, and most older people have these underlying health conditions.
The researchers carried out a phenotypic transcription and functional study of the peripheral mononuclear cells in order to arrive at the study results. They collected blood samples from patients enrolled at the University of California's Irvine Medical Center (UCIMC) and participating in the National Institutes of Health (NIH) ACT-1 study. The team stratified blood samples based on the severity of the disease, including healthy donors, mild or moderate COVID-19, and severe COVID-19.
Age has also been viewed as a factor in which those who are less than 60 years old are young and those who are more than 60 years old. Patients with asymptomatic and mild illness were identified as patients with a positive SARS-CoV-2 result for reasons unrelated to COVID-19 symptoms, including elective surgery, heart attacks, and exacerbation of autoimmune diseases.
Meanwhile, seriously ill patients have been profiled, including those in need of hospitalization or admission to the intensive care unit (ICU). Her blood samples were drawn lengthways over several days after symptoms appeared.
The researchers collected the whole blood samples in EDTA vacutainer tubes, while peripheral blood mononuclear cells (PBMC) and blood plasma samples were also isolated. The team used the Human XL Cytokine Discovery Premixed Kit to measure immune mediators, which can be used to test cytokines, chemokines, growth factors, and effector molecules.
Other tests included an antibody-enzyme-linked immunosorbent assay (ELISA), single cell RNA sequencing, and PBMC and monocyte immunophenotyping.
The researchers performed a combination of immunological, transcellomic and functional single cell tests using blood samples from 49 healthy donors, 20 mild or asymptomatic COVID-19 patients, and 47 seriously ill COVID-19 patients, with longitudinal sampling on days 10 after the onset of symptoms (DPS).
The study results showed that elderly patients had profound lymphopenia, where white blood cells, including B cells, T cells, and natural killer cells (NK cells), were reduced. The lymphopenia worsened over time and is associated with lower plasma cytokine levels, which are viral for T cell survival in elderly patients with severe disease.
In addition, single cell RNA sequencing showed increased activation, cytotoxicity, exhaustion, and type 1 interferon signaling in memory T cells and NK cells. Although cytokine storms can be seen in healthy and aged groups, older adults showed elevated levels of chemokines, which mobilize inflammatory myeloid cells. Eventually, the team observed the redistribution of dendritic cells (DC) and monocytes with severe disease associated with rewiring towards a more regulatory phenotype.
The team concluded that many of these critical changes in the body and immune system were reversed in younger people, but not in older people.
The researchers recommend future studies to stratify young and old patients according to clinical outcomes. In this way, the determinants of disease resolution and survival in severe COVID-19 patients can be identified.
"More importantly, considering the influence of age on qualitative differences in humoral responses and the long-term persistence of T-cell responses to SARS-CoV-2 is crucial for the development of vaccine and therapy strategies in the elderly population "the researchers conclude.
* Important NOTE
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.