A general strategy is described for the de novo design of proteins. In this strategy the sequence locations of hydrophobic and hydrophilic residues were specified explicitly, but the precise identities of the side chains were not constrained and varied extensively. This strategy was tested by constructing a large collection of synthetic genes whose protein products were designed to fold into four-helix bundle proteins. Each gene encoded a different amino acid sequence, but all sequences shared the same pattern of polar and nonpolar residues. Characterization of the expressed proteins indicated that most of the designed sequences folded into compact alpha-helical structures. Thus, a simple binary code of polar and nonpolar residues arranged in the appropriate order can drive polypeptide chains to collapse into globular alpha-helical folds.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features and outcomes of COVID-19 among immunosuppressed patients, who are at presumed risk for more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. We review the existing literature on COVID-19 among immunocompromised populations ranging from cancer patients and solid organ transplant recipients to patients with HIV and those receiving immunomodulatory therapy for autoimmune disease. Patients with malignancy and solid organ transplant recipients may be at increased risk of severe COVID-19 disease and death whereas for those with other types of immunocompromise, current evidence is less clear. Overall, further prospective, controlled studies are needed to determine the attributable risk of immunocompromising conditions and therapies on COVID-19 disease prognosis.

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.

The coronavirus disease 2019 (COVID‐19) pandemic caused by SARS coronavirus 2 (SARS‐CoV‐2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features, disease course, and serologic response of COVID‐19 among immunosuppressed patients such as solid organ transplant (SOT) recipients, who are at presumed risk for more severe disease, are not well characterized. We describe our institutional experience with COVID‐19 among 10 SOT patients, including the clinical presentation, treatment modalities, and outcomes of 7 renal transplant recipients, 1 liver transplant recipient, 1 heart transplant recipient, and 1 lung transplant recipient. In addition, we report the serologic response in SOT recipients, documenting a positive IgG response in all 7 hospitalized patients. We also review the existing literature on COVID‐19 in SOT recipients to consolidate the current knowledge on COVID‐19 in the SOT population for the transplant community.

The COVID-19 pandemic has had a profound impact on the nation's health care system, including on graduate medical education (GME) training programs. Traditionally, residency and fellowship training program applications involve in-person interviews conducted on-site, with only a minority of programs offering interviews remotely via a virtual platform. However, in light of the COVID-19 pandemic, it is anticipated that most interviews will be conducted virtually for the 2021 application cycle and possibly beyond. Therefore, GME Please see the end of this article for information about the authors.