Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

Abstract

We investigated the immune events following SARS-COV-2 infection, from the acute inflammatory state up to four weeks post infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. The acute phase was characterized by a rapid migration of CD16+ monocytes from the blood and concomitant increase in CD16+ macrophages in the lungs. We identified two subsets of interstitial macrophages (HLA- DR+ CD206–), a transitional CD11c+ CD16+ population that was directly associated with IL-6 levels in plasma, and one long lasting CD11b+ CD16+ population. Strikingly, monocytes were a correlate of viral replication in bronchial brushes and levels of TARC (CCL17), and worse disease outcomes were associated with high levels of cell infiltration in lungs and CD11b+ CD16+ macrophages accumulation. Importantly, this accumulation was long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with less signs of disease had a high IL-10:IL-6 ratio. Our results unravel cellular mechanisms of COVID-19 and validate NHP as models to test immune therapies.

A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

“…Additionally, the lung tissue abnormalities revealed by chest radiography were similar in the kinetics of progression and depth to previous reports [6,15,16,20,[45][46][47][48]. Together, these observations suggest that SARS CoV-2 infection in the Rhesus model is clinically mild, a conclusion confirming some [6,8,11], but not all [64] previous reports. SARS-CoV-2 infection in microsphere/adjuvant vaccinated macaques progressed in a pattern different from the unvaccinated controls.…”

“…This was primarily due to macaque availability at the time the study was conducted. However, this appears to have been both a strength [64] and weakness of the experimental design, as we found similar lung pathology in the cynomolgus macaque as well as similar patterns of BAL gene expression as the controls Rhesus subjects [72],…”

“…This was primarily due to macaque availability at the time the study was conducted. However, this appears to have been both a strength [64] and weakness of the experimental design, as we found similar lung pathology in the cynomolgus macaque as well as similar patterns of BAL gene expression as the controls Rhesus subjects [72], of 43 and 5) we did not study the effects of adjuvant alone on SARS-Cov-2 infection in the Rhesus macaques. Previous experience with this microsphere CTL vaccine platform in a murine Ebola virus model has shown that adjuvant alone was not sufficient to confer protection against lethal virus challenge.…”

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

“…This is consistent with data showing acute systemic inflammatory activity during SARS-CoV-2 infection. 23,26,67,68 The ratio of tryptophan to kynurenine is predominantly mediated by indoleamine 2,3-dioxygenase activity and is generally associated with inflammation as well as immunomodulation in both infectious diseases and chronic inflammatory conditions, including neurological diseases such as Parkinson's disease, 69 diabetes, 70 and several autoimmune conditions such as rheumatoid arthritis, 71 systemic lupus erythematosus, 72 and primary sclerosing cholangitis. 73 Plasma taurine concentrations were also increased in the acute phase of COVID-19 23 but also appear substantially elevated in the 3 month follow-up patients with respect to controls (Figure 2C).…”

Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike Protein Subunit 1

“…We have previously suggested a key role for these cells in mediating severity of COVID-19 (7)(8)(9). Monocyte and monocyte-derived macrophage infiltration into the lungs has been linked to severe COVID-19 in single cell RNA sequencing studies (10)(11)(12)(13) and postmortem analyses (14)(15)(16)(17) in human patients, as well as during experimental infections in animal models including mice (18,19), hamsters (20), and various non-human primates (21)(22)(23)(24)(25). Monocytes in individuals infected with SARS-CoV-2 display phenotypic changes associated with hyperinflammation, including reduced HLA-DR expression (26)(27)(28), increased CD16 expression (27,(29)(30)(31), and increased cytokine production (32)(33)(34)(35).…”