PT  - JOURNAL ARTICLE
AU  - Dhiraj K. Singh
AU  - Ekaterina Aladyeva
AU  - Shibali Das
AU  - Bindu Singh
AU  - Ekaterina Esaulova
AU  - Amanda Swain
AU  - Mushtaq Ahmed
AU  - Journey Cole
AU  - Chivonne Moodley
AU  - Smriti Mehra
AU  - Larry S. Schlesinger
AU  - Maxim N. Artyomov
AU  - Shabaana A. Khader
AU  - Deepak Kaushal
TI  - Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
AID  - 10.1101/2021.06.28.450153
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.28.450153
4099  - http://biorxiv.org/content/early/2021/06/28/2021.06.28.450153.short
4100  - http://biorxiv.org/content/early/2021/06/28/2021.06.28.450153.full
AB  - The emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. While studies have reported immune profiling using single cell RNA sequencing in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. We performed longitudinal single-cell RNA sequencing of bronchoalveolar lavage (BAL) cell suspensions from adult rhesus macaques infected with SARS-CoV-2 (n=6) to delineate the early dynamics of immune cells changes. The bronchoalveolar compartment exhibited dynamic changes in transcriptional landscape 3 days post-SARS-CoV-2-infection (3dpi) (peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline). We observed the accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I IFN response was highly induced in the plasmacytoid dendritic cells. The presence of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin converting enzyme 2 (ACE2) expression was also observed. These macrophages were significantly recruited to the lungs of macaques at 3dpi and harbored SARS-CoV-2, while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery. The recruitment of a myeloid cell-mediated Type I IFN response is associated with the rapid clearance of SARS-CoV-2 infection in macaques.Competing Interest StatementThe authors have declared no competing interest.