Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 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 of 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 patients with cancer 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.
Based on existing data on COVID-19 among immunosuppressed patients, it appears that organ transplant and cancer patients may be at increased risk of severe disease and mortality, whereas the risk among patients with other types of immunocompromise is less clear.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 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 of 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 patients with cancer 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.
Based on existing data on COVID-19 among immunosuppressed patients, it appears that organ transplant and cancer patients may be at increased risk of severe disease and mortality, whereas the risk among patients with other types of immunocompromise is less clear.
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.
Subspecialty fellowship is a common career path for internal medicine (IM) residents, but little is published on residency program curricula for guiding residents through the process of applying to ...subspecialty fellowships. We describe a toolkit to guide IM residents through this process.
We developed and implemented the Fellowship Application Toolkit for IM residents at the University of California, San Francisco, from 2018 to 2020. Educational strategies included live workshops, written resources, and one-to-one coaching, consisting of five components: fellowship application guidebook, Fellowship Application Information Night, alumni contact list, personal statement resources and coaches, and virtual interview workshop and mock interviews. Residents were surveyed both pre- and postintervention to evaluate these resources' use and efficacy.
Survey response rates were 21 of 41 (51%) in 2018, 25 of 41 (61%) in 2019, and 24 of 43 (56%) in 2020. Most respondents indicated the resources were extremely or very effective, including 30 of 36 (83%) who used the guidebook, 31 of 37 (84%) who attended the Fellowship Application Information Night, 10 of 15 (67%) who used the alumni contact list, nine of 10 (90%) who used the personal statement resources, and 12 of 14 (86%) who attended the virtual interview workshop. Respondents strongly or somewhat agreed that the overall efficacy of the residency's fellowship advising improved from pre- to postintervention (four of 17 24% in 2018 vs. 17 of 21 81% in 2020,
< .001).
Our Fellowship Application Toolkit was effective at supporting IM residents applying to fellowships.
The traditional model for subspecialty education in internal medicine (IM) residencies is a short inpatient consult rotation, which often lacks outpatient exposure and continuity with faculty. Our IM ...residency program developed a longitudinal subspecialty clinic (LSC) experience, which pairs categorical IM residents with a faculty preceptor in their subspecialty of interest. Residents work in their preceptor's clinic for one half-day per week during ambulatory blocks throughout the PGY2 year.
To evaluate the LSC program's educational impact and determine best practices for successful implementation.
From May to July 2019, we surveyed residents and preceptors who participated in an LSC between 2014 and 2019, gathering quantitative and qualitative data on their experiences
Survey response rates were 66.4% (N=93/140) for residents, 57.7% (N=15/26) for preceptors. Most residents and preceptors were very or extremely satisfied with their LSC experience (83.3% and 71.4%, respectively). Most residents and preceptors reported that the LSC experience was very or extremely effective in enabling residents to explore their subspecialty of interest (76.0%, 86.7%), form a mentoring relationship with their preceptor (71.3%, 80.0%), obtain a letter of recommendation (76.1%, 64.3%), prepare for fellowship (76.3%, 66.7%), gain exposure to outpatient subspecialty practice (90.0%, 73.3%), and gain medical knowledge (84.6%, 80.0%).
Our data showed that LSCs are effective in facilitating longitudinal subspecialty career exploration, mentorship, and education for residents. Opportunities for improvement include developing a more structured curriculum, addressing scheduling issues, and adding the option to extend the experience to the PGY3 year.
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Background. Although the rate of mother-to-child transmission of hepatitis C virus (HCV) is low, the effect of HCV exposure in utero on the fetal immune system is unknown. Methods. Umbilical cord ...blood was obtained from 7 neonates born to HCV-seropositive, HCV RNA-positive women and 8 neonates born to HCV-seronegative women. Cord blood mononuclear cells were analyzed by immunophenotyping and by intracellular cytokine staining after HCV-specific and polyclonal stimulation. Plasma was analyzed for anti-HCV immunoglobulin M (IgM), cytokine/granzyme concentrations, and indoleamine 2,3-dioxygenase (IDO) activity. Results. HCV-exposed neonates had significantly lower levels of regulatory T cells expressing HLA-DR, lower CD4⁺ and CD8⁺ T cell activation, and lower plasma levels of pro-inflammatory markers than did controls. However, CD4⁺ and CD8⁺ T cells from HCV-exposed neonates had higher IFN-γ production in response to polyclonal stimulation than did T cells from controls. IDO activity was similar between groups. No HCV-specific T cell responses or anti-HCV IgM were detected in any neonates. Conclusions. HCV-exposed neonates showed a relative suppression of immune activation and pro-inflammatory markers, which was counterbalanced by an increased production capacity for IFN-γ. These results suggest that HCV encounters the fetal immune system in utero, and alters the balance between suppressive and pro-inflammatory responses.
Abstract
We assessed the real-world utility of universal broad-range polymerase chain reaction sequencing for pathogen detection. Among 1062 clinical samples, 107/1062 (10.1%) had a clinically ...significant, positive result, with substantial variation by specimen type. Clinical management was changed in 44/1062 (4.1%). These data can help maximize utility of this emerging diagnostic.
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 α-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 α-helical folds.
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