New study helps explain how elderly individuals react differently to COVID-19 than young people
Findings underscore that age is an important risk factor for the severity of COVID-19
(Boston)—The COVID-19 pandemic resulted in over 700 million infections and 7 million deaths worldwide. While age is recognized as a risk factor for severe COVID-19, the reasons for this are not yet fully understood.
A new study by researchers at Boston University Chobanian & Avedisian School of Medicine suggests that the immune response of lung endothelial cells, which line the blood vessels, is too low during the early stage of COVID-19 infection as demonstrated in a preclinical model. Additionally, the researchers analyzed all genes expressed in purified endothelial cells, which had never been done before.
“The susceptibility to SARS-CoV-2 infection increases proportionally with age, placing older individuals at a significantly higher risk of developing severe COVID-19. Therefore, gaining insight into age-dependent pathological changes during SARS-CoV-2 infection is imperative for effectively safeguarding vulnerable populations,” said corresponding author Markus Bosmann, MD, associate professor of medicine, pathology & laboratory medicine at the school.
The researchers used four groups of endothelial cell conditions with susceptibility to SARS-CoV-2. The first two groups, consisting of young and old models, remained uninfected as controls. The other two groups, also young and old, were infected with SARS-CoV-2. Endothelial cells from all sets of conditions were isolated after two days, and their transcriptomes (their expressed genes) were analyzed and classified as biological programs of the host response. The clinical severity of infection was monitored and found to be more severe with advanced age.
According to Bosmann, a suppressed immune landscape is a key driver of age-associated endothelial dysfunction during COVID-19. “While these findings currently do not have immediate implications for treating COVID-19, targeting these immune pathways in endothelial cells may have prognostic and therapeutic benefits although further studies, including dissecting these functional changes at a single-cell level, are needed,” he adds.
These findings appear online in the journal Frontiers in Immunology.
Funding for this study was provided by the National Institutes of Health 1UL1TR001430 (to MB and SS), the National Institutes of Health 1R01HL141513 (to MB), the National Institutes of Health 1R21ES032882, 1K22AI144050 (to FD), Aniara Diagnostica (Coagulation Research Grant 2020–2021 to SS), a Boston University Start-up fund (to FD), a Peter Paul Career Development Professorship (to FD), and utilized a Ventana Discovery Ultra autostainer and Vectra Polaris whole slide scanner that were purchased with funding from National Institutes of Health grants S10OD026983 & S10OD030269 (to NC). FD and DK were also supported by a National Institute of Health Transition Award (K22 AI144050) and a T32 training grant in immunology (T32AI007309), respectively. CR acknowledges funding from the Forschungsinitiative Rheinland-Pfalz and ReALity (project MORE), the BMBF Cluster4Future CurATime (project MicrobAIome; 03ZU1202CA). CR was awarded a Fellowship from the Gutenberg Research College at Johannes Gutenberg-University Mainz. CR is a member of the Center for Translational Vascular Biology (CTVB), the Research Center for Immunotherapy (FZI), and the Potentialbereich EXPOHEALTH at the Johannes Gutenberg-University Mainz.
Note to Editor:
Authors MB and FD were funded by ARCA Biopharma for another project on COVID-19. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
JOURNAL
Frontiers in Immunology
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Animal tissue samples
ARTICLE TITLE
Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infection
ARTICLE PUBLICATION DATE
7-Jun-2024
COI STATEMENT
Authors MB and FD were funded by ARCA Biopharma for another project on COVID-19. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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