Myeloid cell interferon responses correlate with clearance of SARS-CoV-2

Singh, D. K.; Aladyeva, E.; Das, S.; Singh, B.; Esaulova, E.; Swain, A.; Ahmed, M.; Cole, J.; Moodley, C.; Mehra, S.; Schlesinger, L.; Artyomov, M.; Khader, S. A.; Kaushal, D.

doi:10.1101/2021.06.28.450153

bioRxiv · 10.1101/2021.06.28.450153

Myeloid cell interferon responses correlate with clearance of SARS-CoV-2

Singh, D. K.·Aladyeva, E.·Das, S.·Singh, B.·Esaulova, E.·Swain, A.·Ahmed, M.·Cole, J.·Moodley, C.·Mehra, S.·Schlesinger, L.·Artyomov, M.·Khader, S. A.·Kaushal, D.

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Abstract

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.

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Singh, D. K., Aladyeva, E., Das, S., Singh, B., Esaulova, E., Swain, A., Ahmed, M., Cole, J., Moodley, C., Mehra, S., Schlesinger, L., Artyomov, M., Khader, S. A., Kaushal, D.. 2021-06-28. Myeloid cell interferon responses correlate with clearance of SARS-CoV-2. https://doi.org/10.1101/2021.06.28.450153

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