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| Status |
Public on Oct 20, 2020 |
| Title |
Vascular Disease and Thrombosis in SARS-CoV-2 Infected Humans and Rhesus Macaques |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details that underlie these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular and cellular pathways associated with SARS-CoV-2 pathogenesis, we performed transcriptomic analyses of bronchoalveolar lavage (BAL) samples and peripheral blood, and proteomics analyses of serum from infected rhesus macaques. We observed upregulation of macrophage signatures, complement cascade pathways, platelet activation, and markers of thrombosis in BAL and peripheral blood as well as extensive macrophage infiltrates in lung. These observations coincided with robust induction of interferon and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFa and NF-κB as well as downstream signaling pathways. These findings suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2 induced vascular disease. Our findings also suggest potential novel therapeutic targets for COVID-19 disease.
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| Overall design |
Nine adult rhesus macaques (6 to 12 years of age) with a total of 1.1 × 10^6 plaque-forming units (PFU) (Group Gr_I; N = 3), 1.1×10^5 PFU (Group Gr_II;N=3), or 1.1×10^4 PFU (Group Gr_III; N = 3) of SARS-CoV-2. PBMC were collected pre-infection, and 1, 2, 4, 7, 10 and 14 days post-infection. Bronchoalveolar lavage (BAL) was collected 1, 2, 4, 7, 10 and 14 days post-infection, and from 6 additional rhesus macques who were not infected.
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| Contributor(s) |
Aid M, Martinot AJ, Estes JD, Barouch DH, Tharp GK |
| Citation(s) |
33065030 |
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| Submission date |
Aug 23, 2020 |
| Last update date |
Oct 20, 2020 |
| Contact name |
Gregory K Tharp |
| E-mail(s) |
gktharp@emory.edu
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| Phone |
404-727-7797
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| Organization name |
Yerkes National Primate Research Center
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| Department |
Developmental and Cognitive Neuroscience
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| Lab |
Genomics Core
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| Street address |
954 Gatewood Dr
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30329-4208 |
| Country |
USA |
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| Platforms (1) |
| GPL27943 |
Illumina NovaSeq 6000 (Macaca mulatta) |
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| Samples (123)
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| Relations |
| BioProject |
PRJNA658795 |
| SRA |
SRP278518 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156701_p20040_MacaM_DESeq2_NormCount.txt.gz |
6.7 Mb |
(ftp)(http) |
TXT |
| GSE156701_p20040_MacaM_RawCount.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE156701_p20050_MacaM_DESeq2_NormCount.txt.gz |
7.2 Mb |
(ftp)(http) |
TXT |
| GSE156701_p20050_MacaM_RawCount.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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