The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres
Authors: Stephenson Emily , Reynolds Gary , Botting Rachel A , Calero-Nieto Fernando J , Morgan Michael , Tuong Zewen Kelvin , Bach Karsten , Sungnak Waradon , Worlock Kaylee B , Yoshida Masahiro , Kumasaka Natsuhiko , Kania Katarzyna , Engelbert Justin , Olabi Bayanne , Spegarova Jarmila Stremenova , Wilson Nicola K , Mende Nicole , Jardine Laura , Gardner Louis CS , Goh Issac , Horsfall Dave , McGrath Jim , Webb Simone , Mather Michael W. , Lindeboom Rik GH , Dann Emma , Huang Ni , Polanski Krzysztof , Prigmore Elena , Gothe Florian , Scott Jonathan , Payne Rebecca P , Baker Kenneth F , Hanrath Aidan T , van der Loeff Ina CD Schim , Barr Andrew S , Sanchez-Gonzalez Amada , Bergamaschi Laura , Mescia Federica , Barnes Josephine L , Kilich Eliz , de Wilton Angus , Saigal Anita , Saleh Aarash , Janes Sam M , Smith Claire M , Gopee Nusayhah , Wilson Caroline , Coupland Paul , Coxhead Jonathan M , Kiselev Vladimir Y , van Dongen Stijn , Bacardit Jaume , King Hamish W ,   Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Rostron Anthony J , Simpson A John , Hambleton Sophie , Laurenti Elisa , Lyons Paul A , Meyer Kerstin B , Nikolic Marko Z , Duncan Christopher JA , Smith Ken , Teichmann Sarah A , Clatworthy Menna R , Marioni John C , Gottgens Berthold , Haniffa Muzlifah 
Published: January 2021

The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+effector:effector memory T cells, and proliferating CD4+and CD8+T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.