Engaging in decisions at end of life might be confounded by concurrent alteration in mood.We will discuss the mechanisms by which mood states may influence decision-making capacity as well as describe a psychiatric approach to determining decision-making capacity in patients with psychiatric comorbidities, especially in the setting of concomitant serious illness.Ultimately, thoughtful discussions and interdisciplinary consultation can support patient autonomy in the final chapter of their lives.

Background The COVID-19 pandemic has shined a harsh light on a critical deficiency in our health care system: our inability to access important information about patients’ values, goals, and preferences in the electronic health record (EHR). At Memorial Sloan Kettering Cancer Center (MSK), we have integrated and systematized health-related values discussions led by oncology nurses for newly diagnosed cancer patients as part of routine comprehensive cancer care. Such conversations include not only the patient’s wishes for care at the end of life but also more holistic personal values, including sources of strength, concerns, hopes, and their definition of an acceptable quality of life. In addition, health care providers use a structured template to document their discussions of patient goals of care. Objective To provide ready access to key information about the patient as a person with individual values, goals, and preferences, we undertook the creation of the Patient Values Tab in our center’s EHR to display this information in a single, central location. Here, we describe the interprofessional, interdisciplinary, iterative process and user-centered design methodology that we applied to build this novel functionality as well as our initial implementation experience and plans for evaluation. Methods We first convened a working group of experts from multiple departments, including medical oncology, health informatics, information systems, nursing informatics, nursing education, and supportive care, and a user experience designer. We conducted in-depth, semistructured, audiorecorded interviews of over 100 key stakeholders. The working group sought consensus on the tab’s main content, homing in on high-priority areas identified by the stakeholders. The core content was mapped to various EHR data sources. We established a set of high-level design principles to guide our process. Our user experience designer then created wireframes of the tab design. The designer conducted usability testing with physicians, nurses, and other health professionals. Data validation testing was conducted. Results We have already deployed the Patient Values Tab to a pilot sample of users in the MSK Gastrointestinal Medical Oncology Service, including physicians, advanced practice providers, nurses, and administrative staff. We have early evidence of the positive impact of this EHR innovation. Audit logs show increasing use. Many of the initial user comments have been enthusiastically positive, while others have provided constructive suggestions for additional tab refinements with respect to format and content. Conclusions It is our challenge and obligation to enrich the EHR with information about the patient as a person. Realization of this capability is a pressing public health need requiring the collaboration of technological experts with a broad range of clinical leaders, users, patients, and families to achieve solutions that are both principled and practical. Our new Patient Values Tab represents a step forward in this important direction.

As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest. When evaluating immune response in the context of SARS-CoV-2, we identify dominant epitope regions and motifs which demonstrate potential to classify mild from severe disease and relate to neutralization activity. We highlight SARS-CoV-2 epitopes that are cross-reactive with other coronaviruses and demonstrate decreased epitope signal for mutant SARS-CoV-2 strains. Collectively, the evolution of SARS-CoV-2 mutants towards reduced antibody response highlight the importance of data-driven development of the vaccines and therapies to treat COVID-19.

Winston A. Haynes, Kathy Kamath, Joel Bozekowski, Elisabeth Baum-Jones, Melissa 3 Campbell, Arnau Casanovas-Massana, Patrick S. Daugherty, Charles S. Dela Cruz, 4 Abhilash Dhal, Shelli F. Farhadian, Lynn Fitzgibbons, John Fournier, Michael Jhatro, 5 Gregory Jordan, Debra Kessler, Jon Klein, Carolina Lucas, Larry L. Luchsinger, Brian 6 Martinez, Mary C. Muenker, Lauren Pischel, Jack Reifert, Jaymie R. Sawyer, Rebecca 7 Waitz, Elsio A. Wunder Jr., Minlu Zhang, Yale IMPACT Team, Akiko Iwasaki, Albert I. Ko, 8 John C. Shon 9 10 1 Serimmune, Inc., Goleta, CA, USA 11 2 Department of Pediatrics, Section of Pediatric Infectious Diseases, Yale School of Medicine, 12 New Haven, CT, USA 13 3 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, 14 CT, USA 15 4 Department of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale School 16 of Medicine, New Haven, CT, USA 17 5 Department of Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, 18 CT, USA 19 6 Santa Barbara Cottage Hospital, Santa Barbara, CA, USA 20 7 New York Blood Center, New York, NY, USA 21 8 Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA 22 9 Howard Hughes Medical Institute, Chevy Chase, MD, USA 23 † These authors contributed equally 24 * Correspondence to: john.shon@serimmune.com 25 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted November 26, 2020. ; https://doi.org/10.1101/2020.11.23.20235002 doi: medRxiv preprint

Fine scale delineation of epitopes recognized by the antibody response to SARS-CoV-2 infection will be critical to understanding disease heterogeneity and informing development of safe and effective vaccines and therapeutics. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify epitope binding specificities with single amino acid resolution. We applied SERA broadly, across human, viral and viral strain proteomes in multiple cohorts with a wide range of outcomes from SARS-CoV-2 infection. We identify dominant epitope motifs and profiles which effectively classify COVID-19, distinguish mild from severe disease, and relate to neutralization activity. We identify a repertoire of epitopes shared by SARS-CoV-2 and endemic human coronaviruses and determine that a region of amino acid sequence identity shared by the SARS-CoV-2 furin cleavage site and the host protein ENaC-alpha is a potential cross-reactive epitope. Finally, we observe decreased epitope signal for mutant strains which points to reduced antibody response to mutant SARS-CoV-2. Together, these findings indicate that SERA enables high resolution of antibody epitopes that can inform data-driven design and target selection for COVID-19 diagnostics, therapeutics and vaccines.

ABSTRACT Despite the high level of morbidity and mortality worldwide, there is increasing evidence for asymptomatic carriers of the novel coronavirus SARS-CoV-2. We analyzed blood specimens from 1,559 healthy blood donors, collected in the greater New York metropolitan area between the months of March and July 2020 for antibodies to SARS-CoV-2 virus. Using our proprietary technology, SERA (Serum Epitope Repertoire Analysis), we observed a significant increase in SARS-CoV-2 seropositivity rates over the four-month period, from 0% [95% CI: 0 - 1.5%] (March) to 11.6% [6.0 - 21.2%] (July). Follow-up ELISA tests using S1 and nucleocapsid viral proteins confirmed most of these results. Our findings are consistent with seroprevalence studies within the region and with reports that SARS-COV-2 infections can be asymptomatic or cause only mild symptoms. IMPORTANCE The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has caused vast morbidity and mortality worldwide, yet several studies indicate that there may be a significant number of infected people who are asymptomatic or exhibit mild symptoms. In this study, samples were collected from healthy blood donors in a region of rapidly increasing disease burden (New York metropolitan area) and we hypothesized that a subset would be seropositive to SARS-CoV-2. People who experienced mild or no symptoms during SARS-CoV-2 infection may represent a source for convalescent plasma donors.