Effect of Age on Innate and Adaptive Immunity in Hospitalized COVID-19 Patients

Lamin B Cham,Martin Tolstrup,Rikke Olesen,Jesper Damsgaard Gunst,Kristoffer Grønhøj,Hien Ngo,Ida Monrad,Marie Høst Pahus,Mads Kjolby,Ole S Søgaard

doi:10.3390/jcm10204798

Lamin B Cham, Martin Tolstrup + Show 8 more

Open Access

https://doi.org/10.3390/jcm10204798

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Abstract

An effective but balanced cellular and inflammatory immune response may limit the severity of coronavirus disease (COVID-19), whereas uncontrolled inflammation leads to disease progression. Older age is associated with higher risk of COVID-19 and a worse outcome, but the underlying immunological mechanisms for this age-related difference are not clear. We investigated the impact of age on viral replication, inflammation, and innate and adaptive cellular immune responses in 205 hospitalized COVID-19 patients. During the early symptomatic phase of COVID-19, we found that patients above 65 years had significantly higher viral load, higher levels of proinflammatory markers, and inadequate mobilization and activation of monocytes, dendritic cells, natural killer cells, and CD8 T cells compared to those below 65 years. Our study points toward age-related deficiencies in the innate immune cellular response to SARS-CoV-2 as a potential cause of poorly controlled viral replication and inflammation during the early symptom phase and subsequent disease progression.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
We found higher proportions of exhausted PD-1 (Figure 5e) positive effector memory and central memory CD8 T cells in older compared to younger COVID-19 patients in the early phase of symptom onset
Our results showed that aging perturbs the balance in the cellular innate immune and proinflammatory response during SARS-CoV-2 infection and that older age was strongly associated with impairment of both innate and adaptive immunity in COVID-19

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The outbreak and spread of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has posed one of the most serious global health and socioeconomic crises of our time [1,2]. The pandemic has affected every nation across the globe [3], infecting over 235 million people and claiming over 4.8 million lives estimated by the World Health. Unlike the previous coronavirus outbreaks, recent globalization coupled with the rapid SARS-CoV-2 person to person transmission are key factors for the highly efficient spread across nations [4,5,6,7,8]

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