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Coronavirus disease 2019 (COVID-19), which is caused by infection with SARSCoV-2, presents with a broad constellation of both respiratory and nonrespiratory symptoms, although it is primarily considered a respiratory disease. Gastrointestinal symptoms--including nausea, abdominal pain, vomiting, and diarrhea--rank chief among these. When coupled with the presence of viral RNA in fecal samples, the presence of gastrointestinal symptoms raises relevant questions regarding whether SARS-CoV-2 can productively infect the upper or lower gastrointestinal tract. Despite the well-documented prevalence of gastrointestinal symptoms and the high rate of SARS-CoV-2 fecal RNA shedding, the biological, clinical, and epidemiological relevance of these findings is unclear. Furthermore, the isolation of replication-competent virus from fecal samples has not been reproducibly and rigorously demonstrated. Although SARS-CoV-2 shedding likely occurs in a high proportion of patients, gastrointestinal symptoms affect only a subset of individuals. Herein, we summarize what is known about gastrointestinal symptoms and fecal viral shedding in COVID-19, explore the role of the gut microbiome in other respiratory diseases, speculate on the role of the gut microbiota in COVID-19, and discuss potential future directions. Taking these concepts together, we propose that studying gut microbiota perturbations in COVID-19 will enhance our understanding of the symptomology and pathophysiology of this novel devastating disease. [ABSTRACT FROM AUTHOR]

Encouragement of students across all communities through scientific outreach programs is critical to engaging the next generation, exciting young minds to pursue careers in science and medicine. Herein, we present a uniquely structured and widely influential science outreach program. Founded in 2005, the Duke Chemistry Outreach (DCO) employs a pedagogical approach to outreach that aims to teach its audience a new scientific concept, while instilling a pure enjoyment of science. DCO has performed 583 events reaching over 70,000 participants throughout 2,270 hours, with the majority of events in Durham, the surrounding North Carolinian communities, and across 8 other states. The flexibility and diversity of this outreach program creates a framework amendable for others to adopt in both secondary and higher education settings. Across 14 years, 581 events, and reaching 70,000 audience members, the Duke Chemistry Outreach program has engaged the surrounding community through fun scientific demonstrations. This Community Page article provides examples and guidelines to encourage others to establish similar programs. [ABSTRACT FROM AUTHOR]

Microbial source tracking (MST) identifies sources of fecal contamination in the environment using host-associated fecal markers. While there are numerous bacterial MST markers that can be used herein, there are few such viral markers. Here, we designed and tested novel viral MST markers based on tomato brown rugose fruit virus (ToBRFV) genomes. We assembled eight nearly complete genomes of ToBRFV from wastewater and stool samples from the San Francisco Bay Area in the United States. Next, we developed two novel probe-based reverse transcription-PCR (RT-PCR) assays based on conserved regions of the ToBRFV genome and tested the markers' sensitivities and specificities using human and non-human animal stool as well as wastewater. The ToBRFV markers are sensitive and specific; in human stool and wastewater, they are more prevalent and abundant than a commonly used viral marker, the pepper mild mottle virus (PMMoV) coat protein (CP) gene. We used the assays to detect fecal contamination in urban stormwater samples and found that the ToBRFV markers matched cross-assembly phage (crAssphage), an established viral MST marker, in prevalence across samples. Taken together, these results indicate that ToBRFV is a promising viral human-associated MST marker. [ABSTRACT FROM AUTHOR]

Importance: There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC)., Objective: To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms., Design, Setting, and Participants: This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration., Interventions: Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days., Main Outcomes and Measures: Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline., Results: Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade., Conclusions and Relevance: The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC., Trial Registration: ClinicalTrials.gov Identifier: NCT05576662.

Drug-resistant bacteria are outpacing traditional antibiotic discovery efforts. Here, we computationally screened 444,054 previously reported putative small protein families from 1,773 human metagenomes for antimicrobial properties, identifying 323 candidates encoded in small open reading frames (smORFs). To test our computational predictions, 78 peptides were synthesized and screened for antimicrobial activity in vitro, with 70.5% displaying antimicrobial activity. As these compounds were different compared with previously reported antimicrobial peptides, we termed them smORF-encoded peptides (SEPs). SEPs killed bacteria by targeting their membrane, synergizing with each other, and modulating gut commensals, indicating a potential role in reconfiguring microbiome communities in addition to counteracting pathogens. The lead candidates were anti-infective in both murine skin abscess and deep thigh infection models. Notably, prevotellin-2 from Prevotella copri presented activity comparable to the commonly used antibiotic polymyxin B. Our report supports the existence of hundreds of antimicrobials in the human microbiome amenable to clinical translation., Competing Interests: Declaration of interests C.d.l.F.-N. provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L., Peptidus, and Phare Bio. De la Fuente is also on the Advisory Board of the Peptide Drug Hunting Consortium (PDHC). The de la Fuente lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work. A.S.B. is on the scientific advisory board of Caribou Biosciences and Cantata Biosciences and is a scientific founder on the scientific advisory board and the Board of Directors for Stylus Medicine. An invention disclosure associated with the work has been submitted., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)