Challenges in Harnessing Shared Within-Host Severe Acute Respiratory Syndrome Coronavirus 2 Variation for Transmission Inference.

Background: The limited variation observed among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consensus sequences makes it difficult to reconstruct transmission linkages in outbreak settings. Previous studies have recovered variation within individual SARS-CoV-2 infections but have not yet measured the informativeness of within-host variation for transmission inference. Methods: We performed tiled amplicon sequencing on 307 SARS-CoV-2 samples, including 130 samples from 32 individuals in 14 households and 47 longitudinally sampled individuals, from 4 prospective studies with household membership data, a proxy for transmission linkage. Results: Consensus sequences from households had limited diversity (mean pairwise distance, 3.06 single-nucleotide polymorphisms [SNPs]; range, 0-40). Most (83.1%, 255 of 307) samples harbored at least 1 intrahost single-nucleotide variant ([iSNV] median, 117; interquartile range [IQR], 17-208), above a minor allele frequency threshold of 0.2%. Pairs in the same household shared significantly more iSNVs (mean, 1.20 iSNVs; 95% confidence interval [CI], 1.02-1.39) than did pairs in different households infected with the same viral clade (mean, 0.31 iSNVs; 95% CI, .28-.34), a signal that decreases with increasingly stringent minor allele frequency thresholds. The number of shared iSNVs was significantly associated with an increased odds of household membership (adjusted odds ratio, 1.35; 95% CI, 1.23-1.49). However, the poor concordance of iSNVs detected across sequencing replicates (24.8% and 35.0% above a 0.2% and 1% threshold) confirms technical concerns that current sequencing and bioinformatic workflows do not consistently recover low-frequency within-host variants. Conclusions: Shared within-host variation may augment the information in consensus sequences for predicting transmission linkages. Improving sensitivity and specificity of within-host variant identification will improve the informativeness of within-host variation.

Establishment of the large-scale longitudinal multi-omics dataset in COVID-19 patients: data profile and biospecimen.

Understanding and monitoring virus-mediated infections has gained importance since the global outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Studies of high-throughput omics-based immune profiling of COVID-19 patients can help manage the current pandemic and future virus-mediated pandemics. Although COVID-19 is being studied since past 2 years, detailed mechanisms of the initial induction of dynamic immune responses or the molecular mechanisms that characterize disease progression remains unclear. This study involved comprehensively collected biospecimens and longitudinal multi-omics data of 300 COVID-19 patients and 120 healthy controls, including whole genome sequencing (WGS), single-cell RNA sequencing combined with T cell receptor (TCR) and B cell receptor (BCR) sequencing (scRNA(+scTCR/BCR)-seq), bulk BCR and TCR sequencing (bulk TCR/BCR-seq), and cytokine profiling. Clinical data were also collected from hospitalized COVID-19 patients, and HLA typing, laboratory characteristics, and COVID-19 viral genome sequencing were performed during the initial diagnosis. The entire set of biospecimens and multi-omics data generated in this project can be accessed by researchers from the National Biobank of Korea with prior approval. This distribution of largescale multi-omics data of COVID-19 patients can facilitate the understanding of biological crosstalk involved in COVID-19 infection and contribute to the development of potential methodologies for its diagnosis and treatment. [BMB Reports 2022; 55(9): 465-471].

COVID-19 Positivity Following an In-Person Surgical Society Meeting: A Cross-Sectional Survey Study.

INTRODUCTION: Many surgical societies have recently resumed in-person meetings after canceling or adopting virtual formats during the COVID-19 pandemic. These meetings implemented safety measures to limit viral exposure and ensure participant safety. While there have been anecdotal reports of COVID-19 cases after attendance, no large-scale assessments have been undertaken. The objective of this study was to evaluate COVID-19 positivity following an in-person surgical society meeting. METHODS: An online survey was administered to participants of the Society for Asian Academic Surgeons annual meeting, which was held in Chicago, Illinois in September 2021. This survey assessed vaccination status, in-person versus virtual conference attendance, and COVID-19 testing and symptoms in the 7 d immediately following the meeting. RESULTS: Among the 220 meeting participants, 173 attended in person (79%). There were 91 survey respondents (41% response rate): 67% attending physicians, 27% trainees, and 6% medical students. Nearly, all (99%) reported being fully vaccinated against COVID-19. COVID-19 testing was sought within 7 d of the meeting by 15% of in-person respondents, and all reported negative results. Among individuals who were not tested, no one reported development of symptoms (cough, shortness of breath, fever, new loss of taste/smell, etc.). CONCLUSIONS: Among in-person attendees of a recent surgical society meeting, no one reported positive COVID-19 testing after the meeting, and individuals who were not tested denied developing symptoms. While these results are encouraging, societies hosting meetings should continue to proactively assess the safety of in-person meetings to promptly identify outbreaks and opportunities for improvement.

Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases.

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.

Variation in Severe Acute Respiratory Syndrome Coronavirus 2 Bioaerosol Production in Exhaled Breath.

We developed a simple, noninvasive mask sampling method to quantify and sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from exhaled breath. We found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.

Variation in Severe Acute Respiratory Syndrome Coronavirus 2 Bioaerosol Production in Exhaled Breath

We developed a simple, noninvasive mask sampling method to quantify and sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from exhaled breath. We found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.

THE ROLE OF WHOLE BLOOD DEFA1 MRNA AS A BIOMARKER FOR COVID SEVERITY

Using both microarrays and RNA sequencing, Defensin alpha 1 (DEFA1) was identified as a sensitive biomarker of neutrophil activation. DEFA1 levels measured by ddPCR may provide a quick novel test to discriminate outcomes, severity and need for ICU admission in COVID19+ patients. B Methods: b Whole blood was collected in RNA stabilizing "Tempus" tubes from COVID19+ ICU patients, floor patients incidentally COVID19+, and a healthy COVID19 negative control group from 30 Oct 2020 - 14 Apr 2021. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

How to Optimize Your Research During a Pandemic - A Summary of Discussions From the Association for Academic Surgery Town Hall and Lessons Learned From 2020.

The year 2020 was an unprecedented year for all of us, including for the academic surgery research community. Both stay-at-home and social distancing restrictions posed challenges to our personal and professional lives. The Association for Academic Surgery held its inaugural webinar-based panel discussion titled Association for Academic Surgery Town Hall with its topic on how to optimize research during a pandemic. This article summarizes the highlights from that discussion and lessons learned from the academic surgery research community in 2020.

SARS-CoV-2 Subgenomic RNA Kinetics in Longitudinal Clinical Samples.

BACKGROUND: Given the persistence of viral RNA in clinically recovered coronavirus disease 2019 (COVID-19) patients, subgenomic RNAs (sgRNAs) have been reported as potential molecular viability markers for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few data are available on their longitudinal kinetics, compared with genomic RNA (gRNA), in clinical samples. METHODS: We analyzed 536 samples from 205 patients with COVID-19 from placebo-controlled, outpatient trials of peginterferon Lambda-1a (Lambda; n = 177) and favipiravir (n = 359). Nasal swabs were collected at 3 time points in the Lambda (days 1, 4, and 6) and favipiravir (days 1, 5, and 10) trials. N-gene gRNA and sgRNA were quantified by quantitative reverse transcription polymerase chain reaction. To investigate the decay kinetics in vitro, we measured gRNA and sgRNA in A549ACE2+ cells infected with SARS-CoV-2, following treatment with remdesivir or dimethylsulfoxide control. RESULTS: At 6 days in the Lambda trial and 10 days in the favipiravir trial, sgRNA remained detectable in 51.6% (32/62) and 49.5% (51/106) of the samples, respectively. Cycle threshold (Ct) values for gRNA and sgRNA were highly linearly correlated (marginal R 2 = 0.83), and the rate of increase did not differ significantly in the Lambda trial (1.36 cycles/d vs 1.36 cycles/d; P = .97) or the favipiravir trial (1.03 cycles/d vs 0.94 cycles/d; P = .26). From samples collected 15-21 days after symptom onset, sgRNA was detectable in 48.1% (40/83) of participants. In SARS-CoV-2-infected A549ACE2+ cells treated with remdesivir, the rate of Ct increase did not differ between gRNA and sgRNA. CONCLUSIONS: In clinical samples and in vitro, sgRNA was highly correlated with gRNA and did not demonstrate different decay patterns to support its application as a viability marker.

Impact of the coronavirus disease 2019 pandemic on surgical research and lessons for the future.

BACKGROUND: The current coronavirus disease 2019 pandemic has had an unprecedented impact on all physicians and has resulted in dramatic changes to clinical and research operations. No study has yet looked at the impact of coronavirus disease 2019 on the surgical research community. In this study, we sought to understand the impact of the pandemic and its associated restrictions on academic surgeons. METHODS: We surveyed members of the Association for Academic Surgery and the Society of University Surgeons. Survey questions included demographics, current challenges to basic and clinical research activities, attitudes toward remote work and productivity maintenance, and the solutions implemented to maintain productivity. RESULTS: Of 301 respondents, 70% cited a negative impact on research productivity due to mandatory building shutdowns, minimized personnel as a result of social distancing, and suspensions of animal work and clinical trials, with senior faculty and division chiefs and chairs more likely to report a negative impact (P = .001). Only 11% of respondents are documenting their financial losses, and only 19% indicated they received appropriate guidance regarding why and how to monitor the financial impact of the pandemic. Researchers have attempted to maintain research productivity through a focus on remote work, including manuscript writing, grant writing, and data analysis. Some participants have found silver linings, including more time to dedicate to research and family as a result of fewer clinical duties. CONCLUSION: Productivity strategies developed during the pandemic, including writing, remote work and meetings, and structured scheduling, are lessons that will allow the surgical research community to be resilient in the face of future disruptions.