ABSTRACT
Background: SARS-CoV-2, associated with COVID-19, can include dysfunction in many organs including the kidney. Early in the pandemic, a high incidence of acute kidney injury (AKI), with an associated increase in mortality, was observed, particularly in those with severe respiratory failure. Given the effect on the kidney and limited availability of biopsied tissue, we designed a non-invasive protocol to isolate and sequence renal cells from the urine of patients with COVID-19 to identify the cellular and molecular mechanisms of COVID-19-related AKI, and the impact of immunomodulatory treatment. Method(s): Three groups of hospitalized patients, AKI with and without COVID-19 and COVID-19 without AKI, were recruited at Michigan Medicine (N=48). We documented >90 clinical parameters, including serum creatinine trends, treatment exposure to IL-6 inhibitors, and patient outcomes. Urine samples near peak AKI were collected and immediately processed for single cell RNA sequencing (scRNAseq);profiles were generated on the 10x Genomics platform and clustered using Seurat. Differentially expressed gene profiles were generated in a cell type selective manner. Result(s): Urine scRNAseq profiles from 44,440 cells clustered into 5 major celltypes, based on cell marker assignment. Renal cells comprised 12% of the recovered cells. Comparing renal cells from COVID-19-related AKI group to either of the two other groups identified 129 up-regulated and 89 down-regulated genes in common (q<0.05). The COVID-19-related AKI renal cell profile was consistent with activation of one or more inflammatory cytokines including IFN-gamma, IL-6, and IL-1beta. Conversely, patients exposed to IL-6 inhibitors had a reduced expression of inflammatory marker genes. Conclusion(s): This study demonstrates the successful isolation and generation of cell type transcriptional profiles of renal cells in the urine of patients with COVID-19, with or without AKI, and non-COVID-19 AKI. Expression profiles in renal cells were consistent with intra-renal inflammatory activation in COVID-19-related AKI. Association of profiles with renal function and patient outcomes may identify predictive markers of COVID-19-related AKI and potential targets for therapeutic modulation.
ABSTRACT
This report describes SARS-CoV-2 genomic surveillance conducted by the Department of Defense (DoD) Global Emerging Infections Surveillance Branch and the Next-Generation Sequencing and Bioinformatics Consortium (NGSBC) in response to the COVID-19 pandemic. Samples and sequence data were from SARS-CoV-2 infections occurring among Military Health System (MHS) beneficiaries from 1 March to 31 December 2020. There were 1,366 MHS samples sequenced from 10 countries, 36 U.S states or territories, and 5 Geographic Combatant Commands, representing approxi-mately 2% of DoD cases in 2020. Genomes from these samples were compared with other public sequences;observed trends were similar to those of Centers for Disease Control and Prevention national surveillance in the U.S. with B.1, B.1.2, and other sub-lineages comprising the dominant variants of SARS-CoV-2. Sequence data were used to monitor transmission dynamics on U.S. Navy ships and at military training centers and installations. As new variants emerge, DoD medical and public health practitioners should maxi-mize the use of genomic surveillance resources within DoD to inform force health protection measures. © 2022, Armed Forces Health Surveillance Center. All rights reserved.
ABSTRACT
A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-kappa B pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of activin. To evaluate this, the role for activin A was examined in a hamster model of SARS-CoV-2 infection, via blockade of activin A signaling. The hamster model demonstrated that use of an anti-activin A antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.
ABSTRACT
Aim: Surgical training has been significantly impacted by COVID-19. Social distancing requirements mandated a change in face-to-face teaching with many deaneries adopting 'virtual' sessions. Surgical training does not immediately lend itself to e-learning owing to its hands-on nature. We describe our experiences in developing a virtual teaching program for Core Surgical Trainees within the Wessex Deanery. We provide tips, tricks, and pitfalls for educators to establish or improve similar programs. Method: From June 2020 monthly, in-person teaching was replaced with virtual sessions. Quantitative and qualitative feedback directed improvements in the program. In addition to knowledge-based lectures we integrated on-line learning tools (LapPass) and utilised surgical videos to ensure continued development of surgical skills. Mock MRCS and ST3 interviews were conducted remotely using 'break-out rooms. Where face-to-face teaching was essential (Boot Camp, Field Camp) safety was ensured with reduced numbers (split sessions), social distancing and appropriate PPE. Results: All trainees strongly agreed (67%) or agreed (33%) that virtual teaching works well. There were no significant differences in feedback scores compared with face-to-face teaching. Attendance increased by 42%. Interactivity was maintained with 'cameras on, mics off', polling apps and chat box function. Advantages include uploading webinars for future review, ability for educators to present from multiple locations, increased availability and breadth of speakers and reduced burden on clinical commitments. Conclusions: The COVID-19 pandemic has dictated an evolution of surgical teaching. Virtual teaching has many advantages over face-to-face and should continue to play a part in postgraduate medical education, even after social distancing restrictions are lifted.