In a recent study published in the journal Science Translational Medicineresearchers investigated the impact of aging on the immune response, viral dynamics and nasal microbiome in 1031 hospitalized patients with coronavirus disease 2019 (COVID-19), using advanced profiling techniques to understand age-related differences in disease severity disease and immune function.
Study: Polyomic host-microbe profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology. Image credit: Corona Borealis Studio / Shutterstock
Record
Age is an important risk factor for severe COVID-19 outcomes, with the elderly facing dramatically higher risks of complications and mortality than younger individuals. Despite high vaccination rates, the elderly are still profoundly vulnerable. Aging is associated with increased levels of inflammatory cytokines, such as interleukin-6 (IL-6), which are critical markers of the severity of COVID-19, suggesting a link between aging and disease pathophysiology. Studies show that aging reduces both innate and adaptive immune responses, including reduced production of type I interferon (IFN). In addition, older adults exhibit enhanced inflammatory responses and impaired immune signaling when infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Further research is needed to fully understand the complex interactions between aging, variations in the immune response, and severity of COVID-19 to improve treatment strategies and outcomes for older populations.
About the study
The present study used data from 1,031 participants enrolled in the ImmunoPhenotyping Assessment in a COVID-19 Observational Cohort (IMPACC) involving 20 hospitals at 15 medical centers in the United States from May 5, 2020, to March 19, 2021. They involved hospitalized individuals reverse transcription polymerase chain reaction (rt-PCR) confirmed SARS-CoV-2 infections, showing typical symptoms of COVID-19. Blood and respiratory tract samples were collected within 72 hours of hospitalization according to a standardized protocol between participating institutions. Ethical approval was granted under the public health surveillance exemption, with participants consenting to further participation and data use.
Statistical analysis was performed using R software. Baseline assessments were made within 72 hours of hospital admission, followed by longitudinal assessments at subsequent visits. Data analysis applied various statistical methods depending on the type of data and required adjustments for factors such as age, sex, and baseline disease severity. For longitudinal studies, age groups were divided into quintiles and analyzed for changes in viral abundance and immune response, using linear and generalized additive models to account for observed nonlinear patterns. All p values were adjusted using the Benjamini-Hochberg method, considering results statistically significant at p <0.05.
Study results
The study involved analysis of blood and nasal swab samples from 1,031 unvaccinated adults hospitalized with COVID-19. These participants were part of the IMPACC cohort, drawn from 20 hospitals in the United States. They were categorized into five age quintiles, ranging from 18 to 96 years old, with each group comprising between 187 and 223 people. Specimens were collected at the time of hospital admission and during up to five follow-up visits. The age distribution showed that older people were often more severely affected by the disease, evident in both initial symptom severity and outcome, including mortality.
At the initial hospital visit, usually within 72 hours of admission, a series of diagnostic tests were performed. These included transcriptional profiling of peripheral blood mononuclear cells (PBMCs) and nasal swabs, serum inflammatory protein profiling, whole blood mass cytometry (CyTOF), nasal transcription and SARS-CoV-2 antibody (Ab) assays. An important finding from these initial trials was that older adults had higher viral loads and experienced delayed viral clearance compared to younger patients. In addition, age-related differences in immune cell populations were observed, with older adults showing higher proportions of various monocyte subtypes and activated T cells but lower levels of primary T and B cells.
Longitudinal analysis of the study revealed that these differences persisted over time, affecting viral load dynamics, antibody titers and immune response. Notably, older participants not only maintained high levels of the virus for longer but also showed more significant fluctuations in antibody levels over time. In addition, analysis of immune cells by CyTOF highlighted that with advancing age, certain types of immune cells, including different classes of monocytes and differentiated natural killer cells, increased, suggesting changes in the composition and function of the immune system with age.
Changes in cytokine and chemokine levels measured in the participants’ serum further underscored the impact of aging on the immune response. Older subjects showed increased levels of inflammatory markers at hospital admission, which were associated with more severe disease outcomes.
In addition, the analysis was extended to the nasal microbiome and upper respiratory tract gene expression, revealing age-related changes in microbial composition and host gene activity. Changes in Toll-like receptor signaling and other immune pathways were evident, suggesting that the elderly experience different immunomodulations, possibly influencing their susceptibility to severe outcomes.
