We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support. Funding: We acknowledge support from the Ragon Institute of MGH, MIT and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, CIVIC75N93019C00052), the Gates Foundation Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), and the Musk Foundation. MBG, MRF, and NH received support from the American Lung Association and the MGH Executive Committee on Research. This work was also supported by the Translational Research Institute for Space Health through NASA Cooperative Agreement NNX16AO69A Author Contributions: P.K., C.W., D.A.L., and G.A. analyzed and interpreted the data. P.K., S.F., Y.C.B., M.J.G., K.B., and J.K. performed experiments. C.W. and D.A.L performed the analysis. M.G., M.F., N.H., D.D., B.C.R., M.R.L., K.M., J.T., and M.F.T managed samples and data collection for acutely ill COVID-19 patients. B.M.L., C.L.L., B.N.M., H.K.K., and J.D,M, collected samples for acutely ill COVID-19 patient. A.L.K.G., I.G., T.J.L., M.S.F., and N.S. processed samples for acutely ill COVID-19 patient. P.M., A.S.M., E.J.N. and E.R.M. managed samples and data collection for the Community-acquired COVID-19 cohort. R.M., C.H., J.F., A.S., and J.S.M., E.S.F. produced SARS-CoV-2 and OC43 antigens. G.A. and D.A.L. supervised the project. P.K., G.A., and C.W. drafted the manuscript. All authors critically reviewed the manuscript. Competing of interests: G.A. is a founder and equity holder for Seromyx Systems Inc., an employee and equity holder for Leyden Labs, has received financial support from Abbvie, BioNtech, GSK, Gilead, Merck, Moderna, Novartis, Pfizer, and Sanofi, and has a patent pending with systems serology. D.D., P.M., A.S.M, and E.R.M. are employees of Space Exploration Technologies Corp. E.S.F. is a founder, scientific advisor and equity holder for: Jengu Therapeutics (board member), Neomorph Inc and Civetta Therapeutics; an equity holder in C4 Therapeutics (CCCC); and a consultant to Novartis, Sanofi, AbbVie, Pfizer, Astellas, EcoR1 capital and Deerfield. The Fischer lab receives or has received research funding from Novartis, Ajax, and Astellas not related to this work. All other authors have declared that no conflict of interest exists. Data and materials availability: Codes code and scripts used for this study have been deposited in a public database and can be found here: https://sandbox.zenodo.org/record/905676#.YSkWQI5KhPZ. All data needed to evaluate the conclusions in the paper are also available in the dataset folder https://sandbox.zenodo.org/record/905676#.YSkWQI5KhPZ. All data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials. 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.