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Dr. Jeremy R. Chapman, Editor-in-Chief, Transplantation

Emerging Microbiology Diagnostics for Transplant Infections: On the Cusp of a Paradigm Shift

Azar MM, Gaston DC, Kotton CN, et al.
Transplantation: : July 2020 - Volume 104 - Issue 7 - p 1358-1384

Infection is seemingly permanently interconnected with transplantation, obvious through the impact of immunosuppression on host response to infection, but also through the underlying susceptibility of the chronic disease cohort we care for and potentially in the future to ensure tolerance to an organ does not translate into tolerance of a virus. Keeping up to date with the technologies used in the microbiology laboratory is thus crucial for all transplant clinicians. In this paper we get a transplant eye view of what is already here and what is coming soon to provide speed and accuracy unachievable by simply trying to grow organisms in the lab. multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics, and gas chromatography mass spectrometry are changing the face of infectious disease diagnostics. This is a great article to allow you keep up to speed in this area.

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Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report
The RECOVERY Collaborative Group*

NEJM July 17,2020; DOI: 10.1056/NEJMoa2021436

This is a controlled, open-label trial comparing COVID patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization(age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation(23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio,1.19; 95% CI, 0.91 to 1.55).

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

NEJM July 14, 2020, DOI: 10.1056/NEJMoa2022483

This is a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.

Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro & David D. Ho

Nature, July 22, 2020; https://doi.org/10.1038/s41586-020-2571-7

This article reports the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease.Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. Several of those monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

 J. Hadjadj et al., Science 10.1126/science.abc6027 (2020).

This article performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

July 23 - A ‘bio-artificial’ pancreas grown in a lab with the aid of placental stem cells, and a DIY insulin-monitoring and release system are being developed to give people with insulin-dependent diabetes an alternative to waiting for a pancreas transplant.

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July 13 - Injured and unusable lungs were restored with respirators and pig blood. The procedure one day may increase the supply of organs for transplant.

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July 22 - To better understand the association between CKD, osteoporosis, and HT, Dr. Löfdahl and colleagues conducted a study that was published in Transplantation Direct.The study team investigated bone mineral density (BMD) progression and incidence of osteoporosis in conjunction with CKD in patients who underwent HT, following patients for up to 10 years (median, 6.1 years).

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July 23 - The new findings build on research from 2019, when scientists from the University of Cape Town and NIH reported that people living with HIV who received kidney transplants from deceased donors with HIV had high overall survival and kidney graft survival after five years.

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July 23 - The latest annual transplantation report produced by NHS Blood and Transplant (NHSBT) has confirmed the number of organ transplants taking place suddenly dropped when COVID-19 hit the UK in March 2020.

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In accordance with the TTS By-Laws, a Business Meeting will be held shortly after the close of the TTS 2020 Virtual Congress. The meeting will be help on Sunday, September 20, at 8 AM Montreal time and will last approximately one hour. The agenda will include an update on the TTS finances, the announcement of the TTS 2024 Congress location, a presentation for the TTS 2022 Congress in Buenos Aires, the announcement of the 2020-2022 Councilors and Officers and the official change of TTS Presidency. All members are invited to participate.

As this meeting will be virtually, we will send all members a link to join this meeting shortly before the meeting takes place.

Sincerely,

John Fung
Secretary, The Transplantation Society

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