Acknowledgments
The authors thank patients and blood donors, their families and surrogates, and medical personnel. We thank L. Bershaw for recruitment of HD and RD. We thank S. Ngiow for essential infrastructure support and C. Ash for donation of computational equipment and design of schematic figures. We thank the Wherry lab for discussions and critically reading the manuscript. Funding: This work was supported by the University of Pennsylvania Institute for Immunology Glick COVID-19 research award (MRB), NIH AI105343, AI082630, and the Allen Institute for Immunology (EJW) and NIH grants HL137006 and H137915 (NJM). ACH was funded by grant CA230157 from the NIH. DM and JG were funded by T32 CA009140. ZC was funded by NIH grant CA234842. DAO was funded by NHLBI StARR: 1R38HL143613. NJM reports funding to her institution from Athersys, Inc., Biomarck, Inc., and the Marcus Foundation for Research. JRG is a Cancer Research Institute-Mark Foundation Fellow. JRG, JEW, CA, AH, and EJW are supported by the Parker Institute for Cancer Immunotherapy which supports the Cancer Immunology program at the University of Pennsylvania. The authors declare no conflicts of interest. Author contributions: DM, NJM, MJB, and EJW conceived the project; DM, JRG, AEB, and EJW designed experiments. NM conceived the clinical cohort, obtained clinical samples and metadata from COVID-19 patients and provided clinical input; OK and JD provided clinical samples from HD and RD. AEB and KD coordinated clinical sample procurement and processing. DM, ARG, LKC, MBP, NH, JK, AP, FC, and SFL processed patient samples. DM, ZC, and YJH stained and JEW acquired flow cytometry samples; JRG, AEB, and KN performed downstream flow cytometry analysis. HR and SCC performed qRT-PCR of PBMC. DM, SFL, and FC performed Luminex experiments. ECG, EMA, MEW, SG, CPA, MJB, and SEH analyzed COVID-19 patient plasma and provided antibody data. ACH and LAV provided additional clinical data; CA compiled and JRG, DO, and CA analyzed clinical metadata with input from ACH and LAV. JRG, DAO, SM, and EJW designed data analysis and JRG, ARG, CA, DAO, and SM performed computational and statistical analyses. DM, JRG, ARG, CA, and DAO compiled figures. LKC, MBP, SA, ACH, LAV, NJM and MB provided intellectual input. DM, AEB, ARG, JEW, and EJW wrote the manuscript; all authors reviewed the manuscript. Competing interests: E.J.W. has consulting agreements with and/or is on the scientific advisory board for Merck, Roche, Pieris, Elstar, and Surface Oncology. E.J.W. is a founder of Surface Oncology and Arsenal Biosciences. E.J.W. has a patent licensing agreement on the PD-1 pathway with Roche/Genentech. E.J.W. is an inventor on a patent (US Patent number 10,370,446) submitted by Emory University that covers the use of PD-1 blockade to treat infections and cancer. Data and materials availability: Flow Cytometry data collected in this study was deposited to the Human Pancreas Analysis Program (HPAP-RRID:SCR_016202) Database and Cytobank (61) (https://hpap.pmacs.upenn.edu). B cell data (https://premium.cytobank.org/cytobank/experiments/308353). Non Naive CD4 T cells (https://premium.cytobank.org/cytobank/experiments/308354). Non Naive CD8 T cells (https://premium.cytobank.org/cytobank/experiments/308357). This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.

The UPenn COVID Processing Unit
Zahidul Alam, Mary M. Addison, Katelyn T. Byrne, Aditi Chandra, Hélène C. Descamps, Yaroslav Kaminskiy, Jacob T. Hamilton, Julia Han Noll, Dalia K. Omran, Eric Perkey, Elizabeth M. Prager, Dana Pueschl, Jennifer B. Shah, Jake S. Shilan, Ashley N. Vanderbeck
All affiliated with the University of Pennsylvania Perelman School of Medicine Philadelphia, PA, USA.

Supplementary Materials
science.sciencemag.org/cgi/content/full/science.abc8511/DC1
Figs. S1 to S11
Table S1 to S8