Poster Presentation Lorne Infection and Immunity 2023

Novel strategy to identify monocytes subsets contributing to increased COVID-19 disease severity in older individuals (#126)

Salimeh Ebrahimnezhaddarzi 1 , Jingling Zhou 2 , Alistair Deller-blue 1 , Hans Kek 1 , Irene Boo 1 , James McMahon 3 4 , Bradley J Gardiner 4 , Anna Coldham 4 , Gilda Tachedjian 1 3 5 , Heidi Drummer 1 3 5 , Anthony Jaworowski 1 4 , Anna C Hearps 1 4
  1. Disease Elimination Program , Burnet Institute, Melbourne, VIC, Australia
  2. Emerging Infections Program, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia
  3. Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  4. Department of Infectious Diseases, The Alfred and Monash University, Melbourne, Victoria, Australia
  5. Department of Microbiology, Monash University, Melbourne, VIC, Australia

Introduction: Coronavirus disease-19 (COVID-19) can cause substantial morbidity and mortality, particularly in older individuals. In this study, we investigated whether an altered inflammatory status of monocyte subpopulations in older people may contribute to severe COVID-19.

 

Methods: PBMC samples were obtained from the Alfred Hospital COVID-19 Biobank in two groups of younger (n=21, median age 30 years [range 21-40]) and older (n=14, median age 69 years [61-96]) individuals within 8 days of diagnosis. Control individuals were SARS-CoV-2 negative of comparable age and sex. Monocytes were assessed for immunophenotype and intracellular levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β measured in unstimulated cells and following LPS treatment. A novel panel of cell surface markers which are stably expressed on stimulated monocytes (CD86, CD33, HLA-DR, CCR2 and CD64) was applied to identify monocyte subsets.

 

Results: In addition to the traditional classical, intermediate and non-classical subsets, the novel phenotyping panel identified a new subpopulation of monocytes which expressed lower levels of HLA-DR, CD33 and CD64 and produced less pro-inflammatory cytokines than classical and intermediate monocytes. The proportion of this novel subpopulation was higher in COVID-19+ individuals than in age-matched controls in both stimulated and unstimulated conditions (p<0.0001 and p<0.02 respectively). Monocytes from older COVID-19+ individuals had lower levels of TNF compared to older controls at baseline (p=0.005 in intermediate monocytes). Monocytes from both younger and older COVID19+ individuals produced less of the pro-inflammatory cytokines IL-6, TNF and IL-1β when stimulated ex vivo as compared to controls.

 

Discussion & Conclusion: We identified a unique subpopulation of monocytes which are expanded in COVID19. Further, monocytes from COVID19+ individuals showed impaired inflammatory responses to stimulation, indicating a form of tolerance which was more pronounced in older individuals. Understanding altered inflammatory responses in COVID19 may illuminate the mechanisms contributing to severe hyper-inflammatory disease.