Table 1.

Summary of single-cell technologies that have been applied to the study of COVID-19

Technology	Measurement	Methodology	Capacity	Pros and cons	Number of published or preprint COVID-19 articles*
Flow cytometry¶	Protein expression	Fluorophore-conjugated antibodies; cells are sorted into liquid droplets individually and flowed through a laser beam; the light emitted by each cell informs about marker expression	High throughput (millions of cells); up to ~30 markers	Pros: determination of immune cell subsets by well-defined surface markers and antibody panels; cells can be sorted for further analysis Cons: broad emission spectra of fluorophores	47
Mass cytometry (CyTOF)	Protein expression	Antibodies conjugated to heavy-metal isotopes; cells are nebulized and the metal-conjugated antibodies are ionized; signals are detected by a time-of-flight mass spectrometer	High throughput (up to millions of cells); many-dimensional (>40 cellular parameters/cell)	Pros: avoids spectral overlap between fluorophores Cons: slower flow rate than flow cytometry; expensive; destructive (not possible to sort cells for further analysis)	7
scRNA-seq	Gene expression	Single cells are isolated (e.g. through microfluidics, droplet-based methods, or flow cytometry-based sorting), lysed, and their transcripts captured. The subsequent workflow is similar to that of bulk RNA-seq	High dimensional (>10,000 features measured per cell)	Pros: comprehensive and unbiased sequencing	22
CITE-seq*	Simultaneous surface protein expression and gene expression	Barcoded, oligonucleotide-conjugated antibodies label single-cells that are analyzed by scRNA-seq	High dimensional (>100 proteins can be measured per cell in addition to (>10,000 genes)	Pros: gene expression integrated with multiomic profiling	4
scBCR/TCR-seq#	Immune antigen receptor repertoire	Single-cell V(D)J enriched libraries are generated utilizing microfluidics, 5′ molecular barcoding, and constant region–specific primers	Paired, full-length receptor sequences from T cells and/or B cells including isotypes.	Pros: comprehensive and unbiased sequencing; combination with multiomic profiling possible (gene and protein expression)	13

Abbreviations: CyTOF, cytometry by time of flight; CITE-seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing; scBCR/TCR seq, single-cell B-cell receptor/T-cell receptor sequencing; scRNA-seq, single-cell RNA sequencing.

^*CITE-seq includes scRNA-seq as part of the workflow; to omit redundancy we did not count the CITE-seq studies in the scRNA-seq row.

^¶Includes spectral flow cytometry (1 study), which is based on conventional flow cytometry but uses different optics and detectors.

^#scBCR/TCR-seq can also be multiomic; here we include 12 multiomic studies that incorporated scBCR/TCR-seq and one scBCR-seq study.