Background
COVID-19 continues to be a health challenge with critical knowledge gaps existing in the understanding of mechanisms driving severity in comorbid conditions. Clinical observations points to a higher susceptibility to COVID-19 in people living with HIV (PLHIV) but the precise mechanisms are still unknown.
Methods
Our group was amongst few that established the rhesus macaque model of COVID-19 infection early on during the pandemic. We are now leveraging this established NHP model of COVID-19 with the long-standing, highly validated, pathogenic AIDS NHP model to study a central hypothesis that underlying SIV infection and the resulting immune activation promotes severity of COVID-19 presentation by profiling the dynamics of viral titers (measured via molecular virology), induced tissue pathology (measured via live PET/CT imaging and conventional histopathology), and underlying immunological perturbations (measured via flow cytometry and single cell transcriptomics).
Results
Macaques infected with SIV develop acute immunodeficiency within 2-4 weeks and progress to chronic AIDS over 5-6 months. When infected with SARS-CoV-2 these macaques develop mild-to-moderate COVID-19 with an extended acute hyperinflammatory state. Co-infected macaques demonstrate higher etiology of either diseases, enhanced lung and brain involvement as measured by PET/CT. Post SARS-CoV-2 infection in SIV coinfected macaque, the F-18 FDG uptake increased in lymph nodes, brain and gut during the acute phase followed by a decline in the post-acute phase. Investigations of the underlying specific immune mechanisms revealed perturbations in the airway myeloid cell composition, T cell phenotypes, activation status and antigenic responsiveness.
Conclusions
Our study elucidates the dynamic immunological landscape and mechanistic interplays in the host coinfected with SIV and SARS-CoV-2. COVID-19 in SIV co-infected macaques is characterized by extended acute hyperinflammatory phase and delayed resolution of disease. Mechanistic insights developed by this study may inform future development of immunotherapeutic interventions for combating COVID-19 as well as PASC in PLHIV.