Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN-specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non-COVID-19 controls revealed a lack of type I IFN-stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN-specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN-specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.

These experiments were based on human clinical autologous transplantation of the lower third molar into the space of an extracted first molar and homologous transplantation of human teeth. These operations have been repeated by many clinicians 1-5 and radiographic and clinical evidence have been submitted as criteria for success. This type of clinical research left many questions unanswered. Further work was started, 6-8 using the rhesus monkey as the experimental animal.The rhesus monkey was selected because its physiology and anatomy are similar to those of the human being and because it is not a laboratory inbred strain. The clinical procedure was duplicated in every respect, except that the rhesus monkey was substituted for the human subject.Because of the anatomical characteristics of the rhesus monkey, the lower third molar has not proved to be a good tooth for transplanting. It is too large to readily fit into the region of the jaw to which it would be transferred. Reports on this work are inconclusive because of the variable factors encountered.9 The experiment was repeated, except that transfers between right and left mandibular incisors were made, other conditions being the same. Materials and MethodsForty autologous operations were performed, involving lower permanent central incisors. The right incisor was removed and the socket was prepared for the left lower incisor. The left lower incisor was then removed and its socket prepared for the lower right incisor. After the immediate transfer of the teeth was made, the gingival tissues were sutured from labial to lingual aspects across the contacts. No other method was used to stabilize the transplants.Twenty monkeys of either sex were used, the development of the teeth to be transplanted being the guiding factor for the selection of the monkeys. Radiographs were used to determine root growth. In previous autologous operations, general experience has indicated that the stage of development of the donor tooth should include approximately a third of the root formation. Consequently, the donor tooth is not a tooth germ and is not a tooth bud; rather, it is a fully developed and calcified crown with a partially developed root.During the operation, a tooth was extracted from its own socket and, for the short time it took to prepare the recipient socket, it was kept in a gauze sponge moistened with physiologic saline solution. Antibiotics were not used after the operation. Periodic radiographs were made for longterm studies and, in most instances, were made 6 months after transplantations.At postoperative intervals of 4, 8, 21, and 31 days and 3, 7, 9, and 11 months, the monkeys were sacrificed and tissue preparations were made for observation. Monkeys were anesthetized with pentobarbital sodium* injected into the saphenous vein and sacrificed by perfusion, under positive pressure in the ascending aorta, with an isotonic saline solution until clear fluid was observed flowing from an outlet opening that was made into the heart and then with a 10 percent neutral ...

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Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus, students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at our final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There were also nominally significant increases in the students’ knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater diversity in AI. This work can guide AI training programs aspiring to engage and educate students entirely online, and motivate people in AI to strive towards increasing diversity and inclusion in this field.