No evidence that plasmablasts transdifferentiate into developing neutrophils in severe COVID‐19 disease

Objectives A recent single‐cell RNA sequencing study by Wilk et al. suggested that plasmablasts can transdifferentiate into ‘developing neutrophils’ in patients with severe COVID‐19 disease. We explore the evidence for this. Methods We downloaded the original data and code used by the authors in their study to replicate their findings and explore the possibility that regressing out variables may have led the authors to overfit their data. Results The lineage relationship between plasmablasts and developing neutrophils breaks down when key features are not regressed out, and the data are not overfitted during the analysis. Conclusion Plasmablasts do not transdifferentiate into developing neutrophils. The single‐cell RNA sequencing is a powerful technique for biological discovery and hypothesis generation. However, caution should be exercised in the bioinformatic analysis and interpretation of the data and findings cross‐validated by orthogonal techniques.
Single cell RNA sequencing can generate unexpected hypotheses. However, these should be rigorously tested and cross‐validated by orthogonal techniques. In this case, there is no evidence that plasmablasts differentiate into neutrophils in severe COVID‐19 disease.