Single Cell Transcriptome Identifies FCGR3B Upregulated Subtype of Alveolar Macrophages in Patients with Critical COVID-19

Nassir, Nasna; Tambi, Richa; Bankapur, Asma; Al Heialy, Saba; Karuvantevida, Noushad; Khansaheb, Hamdah Hassan; Zehra, Binte; Begum, Ghausia; Hameid, Reem Abdel; Ahmed, Awab; Deesi, Zulfa; Alkhajeh, Abdulmajeed; Uddin, K M Furkan; Akter, Hosneara; Safizadeh Shabestari, Seyed Ali; Almidani, Omar; Islam, Amirul; Gaudet, Mellissa; Kandasamy, Richard Kumaran; Loney, Tom; Tayoun, Ahmad Abou; Nowotny, Norbert; Woodbury-Smith, Marc; Rahman, Proton; Kuebler, Wolfgang M.; Al Mashshadani, Mahmood; Casanova, Jean-Laurent; Berdiev, Bakhrom K.; Alsheikh-Ali, Alawi; Uddin, Mohammed

Understanding host cell heterogeneity is critical for unravelling disease mechanism. Utilizing large scale single-cell transcriptomics, we analysed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAM) where genes associated with severe COVID-19 comorbidities are significantly upregulated in broncho-alveolar lavage fluid (BALF) of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis as well as a potential therapeutic target.