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Influence of age on innate and adaptive immunity in COVID-19 patients

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The current 2019 coronavirus disease (COVID-19) pandemic has posed a major public health crisis and has affected every country in the world. The disease is caused by the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is associated with rapid human transmission.

To study: Effect of age on innate and adaptive immunity in hospitalized COVID-19 patients. Image Credit: Soonthorn Wongsaita / Shutterstock.com

Background

COVID-19 can manifest with symptoms ranging from a mild cough and cold to severe pneumonia, while some people can also be asymptomatic carriers. Patients usually have common flu-like symptoms 3 to 7 days after exposure to the virus.

Recent evidence supports the strong association of innate immunity in determining the severity of COVID-19. Notably, aging is a predisposing factor for serious disease and a poor prognosis, as it is associated with a physiological decline in immune competence and a deregulated inflammatory response.

A new study published in the Journal of Clinical Medicine studies how age influences SARS-CoV-2 replication, innate and adaptive immune responses, and clinical outcomes in recently hospitalized COVID-19 patients.

About the study

This study was conducted under the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Aarhus University Hospital.

Overall, 205 hospitalized COVID-19 patients confirmed by polymerase chain reaction (PCR) were included in the present study. Peripheral blood mononuclear cells (PBMCs), plasma, nasopharyngeal swabs, and clinical data, such as days of symptom onset, were collected from all patients. Participants were divided into two groups, including those under 65 (116 patients) and those over 65 (89 patients).

Study results

It was noted that patients younger than 65 had a longer median time to onset of symptoms after hospital admission than the older age group. However, younger patients experienced more symptoms like cough, dyspnea, fatigue, and headache. Comparatively, patients in the older age group had more co-morbidities and a greater chance of requiring nasal oxygen therapy on admission.

Quantification from oropharyngeal swabs revealed that COVID-19 patients over 65 had a significantly higher viral load during the first eight days after symptom onset. Sequencing of the viral genome revealed that the predominant SARS-CoV-2 strain of B.1.177 was present in 50% and 27.4% of the under 65 and over 65 age groups, respectively. Additionally, patients in the older age group had increased C-reactive protein (CRP), increased ferritin, and increased levels of interleukin 6 (IL-6), as well as a delay. longer recovery and higher disease progression until ICU admission or death.

Comparatively, patients under 65 years of age exhibited significantly higher expression of classical monocytes, including CD169 and CD47, during the first eight days of symptom onset, as well as increased expression of intermediate monocytes. Consistent with these results, higher levels of natural killer (NK) cell activation, cytokine production capacity and secreted IL-2 were recorded in those under 65 years of age.

Overall, aging was found to be a major risk factor for hyper-inflammation, poor virologic control, and progression of COVID-19 disease among the older patient group.

Dendritic cells (DCs), which harbor immune regulatory functions crucial for COVID-19 outcomes, exhibit lower activation and decreased antigen cross-presentation ability in geriatric patients. The results also showed a reduction in NK cell maturation, as well as differentiation and functional markers, in patients over 65 years of age.

In addition, reduced activation of effector and memory CD8 T cells, as well as reduced plasma interferon γ (IFN-γ) levels, have been reported in those over 65 years of age. The increased depletion of CD8 T lymphocytes (PD-1 expression) in the over 65 age group correlated with the immune invasion strategy of SARS-CoV-2, thus indicating the disruption of the early lymphocyte response. T in this population.

Conclusion

The results presented here suggest strong associations between aging, SARS-CoV-2 viral load, inflammation, and disease prognosis. Geriatric patients have reduced monocyte activation, reduced monocyte antigen presentation capacity, and increased levels of IFN-induced protein 10 (IP-10) cytokines in the early phase of COVID-19 symptomatic, which can contribute to serious illness.

These results confirm that aging interferes with the balance between innate cellular and pro-inflammatory immune responses during SARS-CoV-2 infection. Collectively, the results describe impaired innate and adaptive immunity in the elderly during the early phase of infection, which likely results in a lack of virologic control and a higher risk of disease progression in COVID- 19.


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