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

Dhiraj K. Singh, Ekaterina Aladyeva, Shibali Das, Bindu Singh, Ekaterina Esaulova, Amanda Swain, Mushtaq Ahmed, Journey Cole, Chivonne Moodley, Smriti Mehra, Larry S. Schlesinger, Maxim N. Artyomov (), Shabaana A. Khader () and Deepak Kaushal ()
Additional contact information
Dhiraj K. Singh: Texas Biomedical Research Institute
Ekaterina Aladyeva: Washington University in St. Louis
Shibali Das: Washington University in St. Louis
Bindu Singh: Texas Biomedical Research Institute
Ekaterina Esaulova: Washington University in St. Louis
Amanda Swain: Washington University in St. Louis
Mushtaq Ahmed: Washington University in St. Louis
Journey Cole: Texas Biomedical Research Institute
Chivonne Moodley: Texas Biomedical Research Institute
Smriti Mehra: Texas Biomedical Research Institute
Larry S. Schlesinger: Texas Biomedical Research Institute
Maxim N. Artyomov: Washington University in St. Louis
Shabaana A. Khader: Washington University in St. Louis
Deepak Kaushal: Texas Biomedical Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq 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. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates 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) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor 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.

Date: 2022
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DOI: 10.1038/s41467-022-28315-7

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