Summary: Continuous measurements of health status can be used to guide the care of patients and to manage the spread of infectious diseases. Conventional monitoring systems cannot be deployed outside of hospital settings, and existing wearables cannot capture key respiratory biomarkers. This paper describes an automated wireless device and a data analysis approach that overcome these limitations, tailored for COVID-19 patients, frontline health care workers, and others at high risk. Vital signs and respiratory activity such as cough can reveal early signs of infection and quantitate responses to therapeutics. Long-term trials on COVID-19 patients in clinical and home settings demonstrate the translational value of this technology. All relevant data are included in the article and [ SI Appendix ][1]. Additional supporting data are available from the corresponding authors on request. All request for raw and analyzed data and materials will be reviewed by the corresponding authors to verify whether the request is subject to any intellectual property or confidentiality obligations. Patient related data not included in the paper were generated as part of clinical trials and may be subject to patient confidentiality. [1]: https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2026610118/-/DCSupplemental