Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

Carissimo, Guillaume; Xu, Weili; Kwok, Immanuel; Abdad, Mohammad Yazid; Chan, Yi-Hao; Fong, Siew-Wai; Puan, Kia Joo; Lee, Cheryl Yi-Pin; Yeo, Nicholas Kim-Wah; Amrun, Siti Naqiah; Chee, Rhonda Sin-Ling; How, Wilson; Chan, Stephrene; Fan, Bingwen Eugene; Andiappan, Anand Kumar; Lee, Bernett; Rötzschke, Olaf; Young, Barnaby Edward; Leo, Yee-Sin; Lye, David Chien; Renia, Laurent; Ng, Lai Guan; Larbi, Anis; Ng, Lisa FP

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.