RT Journal Article SR Electronic T1 Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202101314 DO 10.26508/lsa.202101314 VO 5 IS 4 A1 Emily Speranza A1 Jyothi N Purushotham A1 Julia R Port A1 Benjamin Schwarz A1 Meaghan Flagg A1 Brandi N Williamson A1 Friederike Feldmann A1 Manmeet Singh A1 Lizzette Pérez-Pérez A1 Gail L Sturdevant A1 Lydia M Roberts A1 Aaron Carmody A1 Jonathan E Schulz A1 Neeltje van Doremalen A1 Atsushi Okumura A1 Jamie Lovaglio A1 Patrick W Hanley A1 Carl Shaia A1 Ronald N Germain A1 Sonja M Best A1 Vincent J Munster A1 Catharine M Bosio A1 Emmie de Wit YR 2022 UL https://www.life-science-alliance.org/content/5/4/e202101314.abstract AB Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model of SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at predefined time points in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication were limited. Transcriptional signatures of inflammation-associated genes in bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both cohorts. However, age-specific divergence of immune responses emerged during the post-acute phase. Older animals exhibited sustained local inflammatory innate responses, whereas local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, and persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling suggests that age may delay or impair antiviral cellular immune responses and delay efficient return to immune homeostasis.