The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks multiple human proteins during infection and viral replication. To examine whether any viral proteins employ human E3 ubiquitin ligases, we evaluated the stability of SARS-CoV-2 proteins with inhibition of the ubiquitin proteasome pathway. Using genetic screens to dissect the molecular machinery involved in the degradation of candidate viral proteins, we identified human E3 ligase RNF185 as a regulator of protein stability for the SARS-CoV-2 envelope protein. We found that RNF185 and the SARS-CoV-2 envelope co-localize to the endoplasmic reticulum (ER). Finally, we demonstrate that the depletion of RNF185 significantly increases SARS-CoV-2 viral titer in a cellular model. Modulation of this interaction could provide opportunities for novel antiviral therapies.

Pediatric Surgical Waitlist in Low Middle Income Countries during the COVID-19 Pandemic

Purpose COVID-19 led to significant reduction in surgery worldwide. Studies, however, of the effect on surgical volume for pediatric patients in low- and middle-income countries (LMICs) are limited. Methods A survey was developed to estimate waitlists in LMICs for priority surgical conditions in children. The survey was piloted and revised before it was deployed over email to 19 surgeons. Pediatric surgeons at 15 different sites in 8 countries in Sub-Saharan Africa and Ecuador completed the survey from February 2021 to June 2021. The survey included the total number of children awaiting surgery and estimates for specific conditions. Respondents were also able to add additional procedures. Results Public hospitals had longer wait times than private facilities. The median waitlist was 90 patients and the median wait time was 2 months for elective surgeries. Conclusion Lengthy surgical wait times affect surgical access in LMICs. COVID-19 had been associated with surgical delays around the world, exacerbating existing surgical backlogs. Our results revealed significant delays for elective, urgent and emergent cases across Sub-Saharan Africa. Stakeholders should consider approaches to scale the limited surgical and perioperative resources in LMICs, create mitigation strategies for future pandemics, and establish ways to monitor waitlists on an ongoing basis.

Pediatric Surgical Waitlist in Low Middle Income Countries During the COVID-19 Pandemic.

INTRODUCTION: Coronavirus disease-19 led to a significant reduction in surgery worldwide. Studies, however, of the effect on surgical volume for pediatric patients in low-income and middle-income countries (LMICs) are limited. METHODS: A survey was developed to estimate waitlists in LMICs for priority surgical conditions in children. The survey was piloted and revised before it was deployed over email to 19 surgeons. Pediatric surgeons at 15 different sites in eight countries in sub-Saharan Africa and Ecuador completed the survey from February 2021 to June 2021. The survey included the total number of children awaiting surgery and estimates for specific conditions. Respondents were also able to add additional procedures. RESULTS: Public hospitals had longer wait times than private facilities. The median waitlist was 90 patients, and the median wait time was 2 mo for elective surgeries. CONCLUSIONS: Lengthy surgical wait times affect surgical access in LMICs. Coronavirus disease-19 had been associated with surgical delays around the world, exacerbating existing surgical backlogs. Our results revealed significant delays for elective, urgent, and emergent cases across sub-Saharan Africa. Stakeholders should consider approaches to scale the limited surgical and perioperative resources in LMICs, create mitigation strategies for future pandemics, and establish ways to monitor waitlists on an ongoing basis.

COVID-19, Racial Injustice, and Medical Student Engagement With Global Health: A Single-Institution Survey.

INTRODUCTION: United States medical schools continue to respond to student interest in global health (GH) and the evolution of the field through strengthening related curricula. The COVID-19 pandemic and superimposed racial justice movements exposed chasms in the US healthcare system. We sought to explore the possible relationship between the pandemic, US racial justice movements, and medical student interest in GH to inform future academic offerings that best meet student needs. METHODS: A novel, mixed-methods 30-question Qualtrics survey was disseminated twice (May-August 2021) through email and social media to all current students. Data underwent descriptive and thematic analysis. RESULTS: Twenty students who self-identified as interested in GH responded to the survey. Most (N = 13, 65%) were in preclinical training, and half were women (N = 10, 50%). Five (25%) selected GH definitions with paternalistic undertones, 11 (55%) defined GH as noncontingent on geography, and 12 (60%) said the pandemic and US racial justice movement altered their definitions to include themes of equity and racial justice. Eighteen (90%) became interested in GH before medical school through primarily volunteering (N = 8, 40%). Twelve (60%) students plan to incorporate GH into their careers. CONCLUSIONS: Our survey showed most respondents entered medical school with GH interest. Nearly all endorsed a changed perspective since enrollment, with a paradigm shift toward equity and racial justice. Shifts were potentially accelerated by the global pandemic, which uncovered disparities at home and abroad. These results highlight the importance of faculty and curricula that address global needs and how this might critically impact medical students.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study

OBJECTIVES: Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either “early” (within 14 d of intubation) or “late” (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, –16 to –8;p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, –23 to –9 d;p < 0.001) and 22 days (95% CI, –31 to –12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0;95% CI, 1.8–5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Impact of the COVID-19 Pandemic on Pediatric Surgical Volume in Four Low- and Middle-Income Country Hospitals: Insights from an Interrupted Time Series Analysis.

BACKGROUND: The impact of the COVID-19 pandemic on surgical care delivery in low- and middle-income countries (LMIC) has been challenging to assess due to a lack of data. This study examines the impact of COVID-19 on pediatric surgical volumes at four LMIC hospitals. METHODS: Retrospective and prospective pediatric surgical data collected at hospitals in Burkina Faso, Ecuador, Nigeria, and Zambia were reviewed from January 2019 to April 2021. Changes in surgical volume were assessed using interrupted time series analysis. RESULTS: 6078 total operations were assessed. Before the pandemic, overall surgical volume increased by 21 cases/month (95% CI 14 to 28, p < 0.001). From March to April 2020, the total surgical volume dropped by 32%, or 110 cases (95% CI - 196 to - 24, p = 0.014). Patients during the pandemic were younger (2.7 vs. 3.3 years, p < 0.001) and healthier (ASA I 69% vs. 66%, p = 0.003). Additionally, they experienced lower rates of post-operative sepsis (0.3% vs 1.5%, p < 0.001), surgical site infections (1.3% vs 5.8%, p < 0.001), and mortality (1.6% vs 3.1%, p < 0.001). CONCLUSIONS: During the COVID-19 pandemic, children's surgery in LMIC saw a sharp decline in total surgical volume by a third in the month following March 2020, followed by a slow recovery afterward. Patients were healthier with better post-operative outcomes during the pandemic, implying a widening disparity gap in surgical access and exacerbating challenges in addressing the large unmet burden of pediatric surgical disease in LMICs with a need for immediate mitigation strategies.

ZINC USE IS ASSOCIATED WITH IMPROVED OUTCOMES IN COVID-19: RESULTS FROM THE CRUSH-COVID REGISTRY

B Introduction: b Previous work has shown correlations of zinc deficiency and poor outcomes in COVID-19 patients.i Little is known, however, about the use of zinc supplementation and its potential benefits in hospitalized COVID-19 positive individuals. B Conclusions: b Zinc use may be associated with improved clinical outcomes in hospitalized COVID-19 patients. [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.)

A PANDEMIC WITHIN AN EPIDEMIC: EVALUATION OF COVID-19 IN THE OBESE POPULATION

B Conclusion: b This supports the growing body of evidence that obesity has the potential to serve as an independent predictor for outcomes of COVID-19 patients. Evidence has shown increased morbidity and mortality among obese COVID-19 patients. Patients were stratified into healthy weight (BMI < 25), overweight (BMI 25 - 29.9), obese (BMI 30 -39.9), and morbidly obese (BMI > 40) categories. [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.)

Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19.

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. METHODS: A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. RESULTS: Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. CONCLUSIONS: Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

Postoperative COVID-19 Pneumonia following Resection of a Large Thoracic Chondrosarcoma.

CASE: A 57-year-old man presenting with two months of insidious shoulder pain was found to have a large thoracic chondrosarcoma invading the spinal canal. The patient's orthopedic oncologist organized an interdisciplinary team including interventional radiology, thoracic surgery, neurosurgery, and plastic surgery. This allowed safe, en bloc tumor resection. The patient's postoperative course was complicated by COVID-19 pneumonia, which was rapidly identified and medically managed with full recovery. CONCLUSION: Postoperative COVID-19 pneumonia can present insidiously and mimic other postoperative complications. Early identification and testing can promote rapid isolation, proper personal protective equipment use, and guide outcome-improving treatments.