Single-cell RNA-seq (10x Genomics Chromium 5' v2), with CITE-seq surface protein, TCR, and BCR sequencing, of peripheral blood mononuclear cells from 351 patients who presented to the Massachusetts General Hospital emergency department with acute febrile respiratory illness during the first wave of the pandemic in 2020: 302 with a positive SARS-CoV-2 PCR test and 49 who tested negative. Blood was collected on days 0, 3, 7, and 28 while patients remained in hospital, and severity was scored on a 5-point scale (1 death, 2 intubation or ventilation, 3 supplemental oxygen, 4 hospitalization, 5 discharge). The study profiled 751 samples, of which 705 passed sample-level quality control and were used in the paper's analyses. Cells were split into four lineages that were each clustered separately: B cells (174,423 cells; 12 clusters), CD4 T cells (298,734; 14), CD8 T and NK cells (644,498; 13), and mononuclear phagocytes (857,663; 15). Cells that were not assigned to any of the four lineages are labelled 'Discarded'.