Recent Submissions

  • Pregnancy and the Risk of In-Hospital Coronavirus Disease 2019 (COVID-19) Mortality.

    Pineles, Beth L; Goodman, Katherine E; Pineles, Lisa; O'Hara, Lyndsay M; Nadimpalli, Gita; Magder, Laurence S; Baghdadi, Jonathan D; Parchem, Jacqueline G; Harris, Anthony D (Wolters Kluwer Health, 2022-04-05)
    Objective: To evaluate whether pregnancy is an independent risk factor for in-hospital mortality among patients of reproductive age hospitalized with coronavirus disease 2019 (COVID-19) viral pneumonia. Methods: We conducted a retrospective cohort study (April 2020-May 2021) of 23,574 female inpatients aged 15-45 years with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code for COVID-19 discharged from 749 U.S. hospitals in the Premier Healthcare Database. We used a viral pneumonia diagnosis to select for patients with symptomatic COVID-19. The associations between pregnancy and in-hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation were analyzed using propensity score-matched conditional logistic regression. Models were matched for age, marital status, race and ethnicity, Elixhauser comorbidity score, payer, hospital number of beds, season of discharge, hospital region, obesity, hypertension, diabetes mellitus, chronic pulmonary disease, deficiency anemias, depression, hypothyroidism, and liver disease. Results: In-hospital mortality occurred in 1.1% of pregnant patients and 3.5% of nonpregnant patients hospitalized with COVID-19 and viral pneumonia (propensity score-matched odds ratio [OR] 0.39, 95% CI 0.25-0.63). The frequency of ICU admission for pregnant and nonpregnant patients was 22.0% and 17.7%, respectively (OR 1.34, 95% CI 1.15-1.55). Mechanical ventilation was used in 8.7% of both pregnant and nonpregnant patients (OR 1.05, 95% CI 0.86-1.29). Among patients who were admitted to an ICU, mortality was lower for pregnant compared with nonpregnant patients (OR 0.33, 95% CI 0.20-0.57), though mechanical ventilation rates were similar (35.7% vs 38.3%, OR 0.90, 95% CI 0.70-1.16). Among patients with mechanical ventilation, pregnant patients had a reduced risk of in-hospital mortality compared with nonpregnant patients (0.26, 95% CI 0.15-0.46). Conclusion: Despite a higher frequency of ICU admission, in-hospital mortality was lower among pregnant patients compared with nonpregnant patients with COVID-19 viral pneumonia, and these findings persisted after propensity score matching.
  • Exacerbation of COVID-19 mortality by the fragmented United States healthcare system: A retrospective observational study.

    Campbell, Travis; Galvani, Alison P; Friedman, Gerald; Fitzpatrick, Meagan C (Elsevier, 2022-05-12)
    Background Before widespread vaccination, the United States was disproportionately affected by COVID-19 with a mortality rate several times that of other affluent societies. Comparing regions with different rates of health insurance, we assess how much of this excess mortality may be due to the relatively large population without health insurance. Methods We use daily surveillance data from the US Centers for Disease Control and Prevention (CDC) stratified by region, age group, gender, and race in regression analysis of daily COVID-19 cases, hospitalization, and mortality. COVID-19 data have been matched with structural characteristics of the region including average proportion with health insurance. As checks, we have estimated regressions for different time periods, different groups of states, and by comparing adjacent counties between states with and without Medicaid expansion. Findings Groups with lower health insurance coverage had significantly higher mortality as well as greater case counts and hospitalization. Early in the pandemic, they were also less likely to be tested for COVID-19. Applying our regression estimates, we estimate that had there been full health insurance coverage of the population, there would have been 60,000 fewer deaths, 26% of the total death toll in the period of this analysis. Interpretation Our study demonstrates that a significant share of COVID-19 mortality in the United States, and much of the excess mortality in the United States compared with other countries, is due to our reliance on a system of market-driven healthcare. Providing universal insurance coverage should be part of our campaign to reduce COVID-19 mortality. It also suggests that these concerns should not be restricted to COVID-19 but apply across all diseases, contributing to many unnecessary deaths in the United States each year even apart from the COVID-19 pandemic.
  • Estimated Transmission Outcomes and Costs of SARS-CoV-2 Diagnostic Testing, Screening, and Surveillance Strategies among a Simulated Population of Primary School Students

    Bilinski, Alyssa; Ciaranello, Andrea; Fitzpatrick, Meagan C.; Giardina, John; Shah, Maunank; Salomon, Joshua A.; Kendall, Emily A. (American Medical Association, 2022-01-01)
    Importance: In addition to illness, the COVID-19 pandemic has led to historic educational disruptions. In March 2021, the federal government allocated $10 billion for COVID-19 testing in US schools. Objective: Costs and benefits of COVID-19 testing strategies were evaluated in the context of full-time, in-person kindergarten through eighth grade (K-8) education at different community incidence levels. Design, Setting, and Participants: An updated version of a previously published agent-based network model was used to simulate transmission in elementary and middle school communities in the United States. Assuming dominance of the delta SARS-CoV-2 variant, the model simulated an elementary school (638 students in grades K-5, 60 staff) and middle school (460 students grades 6-8, 51 staff). Exposures: Multiple strategies for testing students and faculty/staff, including expanded diagnostic testing (test to stay) designed to avoid symptom-based isolation and contact quarantine, screening (routinely testing asymptomatic individuals to identify infections and contain transmission), and surveillance (testing a random sample of students to identify undetected transmission and trigger additional investigation or interventions). Main Outcomes and Measures: Projections included 30-day cumulative incidence of SARS-CoV-2 infection, proportion of cases detected, proportion of planned and unplanned days out of school, cost of testing programs, and childcare costs associated with different strategies. For screening policies, the cost per SARS-CoV-2 infection averted in students and staff was estimated, and for surveillance, the probability of correctly or falsely triggering an outbreak response was estimated at different incidence and attack rates. Results: Compared with quarantine policies, test-to-stay policies are associated with similar model-projected transmission, with a mean of less than 0.25 student days per month of quarantine or isolation. Weekly universal screening is associated with approximately 50% less in-school transmission at one-seventh to one-half the societal cost of hybrid or remote schooling. The cost per infection averted in students and staff by weekly screening is lowest for schools with less vaccination, fewer other mitigation measures, and higher levels of community transmission. In settings where local student incidence is unknown or rapidly changing, surveillance testing may detect moderate to large in-school outbreaks with fewer resources compared with schoolwide screening. Conclusions and Relevance: In this modeling study of a simulated population of primary school students and simulated transmission of COVID-19, test-to-stay policies and/or screening tests facilitated consistent in-person school attendance with low transmission risk across a range of community incidence. Surveillance was a useful reduced-cost option for detecting outbreaks and identifying school environments that would benefit from increased mitigation. © 2022 American Medical Association. All rights reserved.
  • The cost-effectiveness of standalone HEPA filtration units for the prevention of airborne SARS CoV-2 transmission.

    Zafari, Zafar; de Oliveira, Pedro M; Gkantonas, Savvas; Ezeh, Chinenye; Muennig, Peter Alexander (Springer Nature, 2022-05-12)
    Objective: Airborne infection from aerosolized SARS-CoV-2 poses an economic challenge for businesses without existing heating, ventilation, and air conditioning (HVAC) systems. The Environmental Protection Agency notes that standalone units may be used in areas without existing HVAC systems, but the cost and effectiveness of standalone units has not been evaluated. Study design: Cost-effectiveness analysis with Monte Carlo simulation and aerosol transmission modeling. Methods: We built a probabilistic decision-analytic model in a Monte Carlo simulation that examines aerosol transmission of SARS-CoV-2 in an indoor space. As a base case study, we built a model that simulated a poorly ventilated indoor 1000 square foot restaurant and the range of Covid-19 prevalence of actively infectious cases (best-case: 0.1%, base-case: 2%, and worst-case: 3%) and vaccination rates (best-case: 90%, base-case: 70%, and worst-case: 0%) in New York City. We evaluated the cost-effectiveness of improving ventilation rate to 12 air changes per hour (ACH), the equivalent of hospital-grade filtration systems used in emergency departments. We also provide a customizable online tool that allows the user to change model parameters. Results: All 3 scenarios resulted in a net cost-savings and infections averted. For the base-case scenario, improving ventilation to 12 ACH was associated with 54 [95% Credible Interval (CrI): 29-86] aerosol infections averted over 1 year, producing an estimated cost savings of $152,701 (95% CrI: $80,663, $249,501) and 1.35 (95% CrI: 0.72, 2.24) quality-adjusted life years (QALYs) gained. Conclusions: It is cost-effective to improve indoor ventilation in small businesses in older buildings that lack HVAC systems during the pandemic.
  • Multi-site observational maternal and infant COVID-19 vaccine study (MOMI-vax): a study protocol.

    Munoz, Flor M; Beigi, Richard H; Posavad, Christine M; Richardson, Barbra A; Chu, Helen Y; Bok, Karin; Campbell, James; Cardemil, Cristina; DeFranco, Emily; Frenck, Robert W; et al. (Springer Nature, 2022-05-12)
    Background: Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. Methods: The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. Discussion: Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. Trial registration: NCT05031468 .
  • Telemedicine Improves Access to Care for Spine Patients With Low Socioeconomic Status

    Ye, Ivan B.; Thomson, Alexandra E.; Chowdhury, Navid; Oster, Brittany; Miseo, Vincent S.; Jauregui, Julio J.; Cavanaugh, Daniel; Koh, Eugene; Gelb, Daniel; Ludwig, Steven (SAGE Publications Inc., 2022-01-01)
    Study Design: Retrospective cohort study. Objectives: The objective of this study is to compare the likelihood of missing a scheduled telemedicine and in-person appointments for spine patients. The secondary objective is to assess the impact of socioeconomic status on missed telemedicine and in-person appointments. Methods: Patients with scheduled outpatient appointments with orthopedic spine faculty between 2019 and 2021 were divided by appointment type: telemedicine (N = 4,387) and in-person (N = 3810). Socioeconomic status was assessed using Area Deprivation Index (ADI) stratified based on percentile: low (<25), medium (25–75), and high (>75) levels of socioeconomic disadvantage. The primary outcome measure was missed clinic appointments, which was defined as having at least one appointment that was cancelled or labeled “no show.” Results: Patients with in-person appointments missed appointments more often than patients with telemedicine visits (51.3% vs 24.7%, P <.001). Patients with high ADI missed their in-person appointments more often than patients with medium and low ADI (59.5% vs 52.2% and 47.5%, P <.001). There was no difference in missed telemedicine visits between patients with high, medium, and low ADI (27.6% vs 24.8% vs 23.8%, P =.294). Patients that missed an appointment were 41.9% more likely to be high ADI (OR 1.42, 95% CI 1.20–1.68, P <.001) and 13.4% more likely to be medium ADI (OR 1.13, 95% CI 1.03–1.26, P =.015) compared with low ADI patients. Conclusions: Telemedicine may serve a role in reducing disparity in appointment attendance. While further studies are needed to validate these findings, spine surgeons should consider offering telemedicine as an option to patients. © The Author(s) 2022.
  • Clinical Practice Issues for Liver Transplantation in COVID-19 Recovered Recipients.

    Shetty, Kirti; Lominadze, Zurabi; Saharia, Kapil; Challa, Suryanarayana Reddy; Montenegro, Maria; Meier, Raphael P H; Malik, Saad; Alvarez-Casas, Josue; Sakiani, Sasan; Jakhete, Neha; et al. (SAGE Publications Inc., 2022-04-12)
    The ongoing burden of COVID-19 in persons with end stage liver failure necessitates the development of sound and rational policies for organ transplantation in this population. Following our initial experience with two COVID-19 recovered recipients who died shortly after transplant, we adjusted our center policies, re-evaluated outcomes, and retrospectively analyzed the clinical course of the subsequent seven COVID-19 recovered recipients. There were two early deaths and 5 successful outcomes. Both deceased patients shared common characteristics in that they had positive SARS-CoV2 PCR tests proximal to transplant (7-17 days), had acute on chronic liver failure, and suffered thromboembolic phenomena. After a careful review of clinical and virological outcome predictors, we instituted policy changes to avoid transplantation in these circumstances. We believe that our series offers useful insights into the unique challenges that confront transplant centers in the COVID-19 era and could guide future discussions regarding this important area. © 2022, NATCO. All rights reserved.
  • Influence of Covid-19 Restrictions on Urban Violence.

    Lalchandani, Priti; Strong, Bethany L; Harfouche, Melike N; Diaz, Jose J; Scalea, Thomas M (SAGE Publications Inc., 2022-04-06)
    We investigated whether the COVID-19 pandemic affected rates of interpersonal violence (IV). A retrospective study was performed using city-wide crime data and the trauma registry at one high-volume trauma center pre-pandemic [PP] (March-October 2019) and during the pandemic [PA] (March-October 2020). The proportion of trauma admissions attributable to IV remained unchanged from PP to PA, but IV increased as a proportion of overall crime (34% to 41%, p<0.001). Assaults decreased, but there was a proportionate increase in penetrating trauma which was mostly attributable to firearms. Despite a reduction in admissions due to IV in the first 4 months of the pandemic, the rates of violence subsequently exceeded that of the same months in 2019. The cause of the observed increase of IV is multi-factorial. Future studies aimed at identifying the root causes are essential to mitigate violence during this ongoing health crisis. © The Author(s) 2022.
  • Diverging levels of COVID-19 governmental response satisfaction across middle eastern Arab countries: a multinational study.

    Itani, Rania; Karout, Samar; Khojah, Hani M J; Rabah, Makram; Kassab, Mohamad B; Welty, Francine K; AlBaghdadi, Mazen; Khraishah, Haitham; El-Dahiyat, Faris; Alzayani, Salman; et al. (Springer Nature, 2022-05-05)
    Background: Public acceptance of governmental measures are key to controlling the spread of infectious diseases. The COVID-19 pandemic has placed a significant burden on healthcare systems for high-income countries as well as low- and middle-income countries (LMICs). The ability of LMICs to respond to the challenge of the COVID-19 pandemic has been limited and may have affected the impact of governmental strategies to control the spread of COVID-19. This study aimed to evaluate and compare public opinion on the governmental COVID-19 response of high and LMICs in the Middle East and benchmark it to international countries. Methods: An online, self-administered questionnaire was distributed among different Middle Eastern Arab countries. Participants' demographics and level of satisfaction with governmental responses to COVID-19 were analyzed and reported. Scores were benchmarked against 19 international values. Results: A total of 7395 responses were included. Bahrain scored highest for satisfaction with the governmental response with 38.29 ± 2.93 on a scale of 40, followed by the Kingdom of Saudi Arabia (37.13 ± 3.27), United Arab Emirates (36.56 ± 3.44), Kuwait (35.74 ± 4.85), Jordan (23.08 ± 6.41), and Lebanon (15.39 ± 5.28). Participants' country of residence was a significant predictor of the satisfaction score (P < 0.001), and participants who suffered income reduction due to the pandemic, had a history of SARS-CoV-2 infection, and held higher educational degrees had significantly lower satisfaction scores (P < 0.001). When benchmarked with other international publics, countries from the Gulf Cooperation Council had the highest satisfaction level, Jordan had an average score, and Lebanon had one of the lowest satisfaction scores. Conclusion: The political crisis in Lebanon merged with the existing corruption were associated with the lowest public satisfaction score whereas the economical instability of Jordan placed the country just before the lowest position. On the other hand, the solid economy plus good planning and public trust in the government placed the other countries of the Gulf Cooperation Council on top of the scale. Further investigation is necessary to find out how the governments of other low-income countries may have handled the situation wisely and gained the trust of their publics. This may help convey a clearer picture to Arab governments that have suffered during the pandemic.
  • Update on guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: Emphasis on transition to chronic endemic state. An information statement from ASNC, IAEA, and SNMMI.

    Thompson, Randall C; Phillips, Lawrence M; Dilsizian, Vasken; Gutierrez, Diana Paez; Einstein, Andrew J; Crews, Suzanne F; Skali, Hicham; Jih, Felix Keng Yung; Dondi, Maurizio; Gimelli, Alessia; et al. (Springer Nature, 2022-05-02)
  • Humoral immunity against SARS-CoV-2 variants including omicron in solid organ transplant recipients after three doses of a COVID-19 mRNA vaccine.

    Saharia, Kapil K; Husson, Jennifer S; Niederhaus, Silke V; Iraguha, Thierry; Avila, Stephanie V; Yoo, Youngchae J; Hardy, Nancy M; Fan, Xiaoxuan; Omili, Destiny; Crane, Alice; et al. (Wiley-Blackwell, 2022-04-29)
    Following the initial vaccination series, 60.3% of SOTR showed no measurable neutralisation and only 18.9% demonstrated neutralising activity of > 90%. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titres against microbial recall antigens were higher. By contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titres against SARS-CoV-2 and its delta variants and fewer linear B-cell epitopes, indicating reduced B-cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titres and neutralising activity across alpha, beta and delta variants and to the induction of anti-SARS-CoV-2 CD4+ T cells in a subgroup of patients analysed. By contrast, we observed significantly lower antibody titres after the third dose with the omicron variant compared to the ancestral SARS-CoV-2 and the improvement in neutralising activity was much less pronounced than for all the other variants.
  • Rehabilitation at the Time of Pandemic: Patient Journey Recommendations.

    Negm, Ahmed M; Salopek, Adrian; Zaide, Mashal; Meng, Victoria J; Prada, Carlos; Chang, Yaping; Zanwar, Preeti; Santos, Flavia H; Philippou, Elena; Rosario, Emily R; et al. (Frontiers Media S.A., 2022-04-12)
    PURPOSE: The World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic in March 2020, causing almost 3.5 million coronavirus disease (COVID-19) related deaths worldwide. The COVID-19 pandemic has imposed a significant burden on healthcare systems, economies, and social systems in many countries around the world. The access and delivery of rehabilitation care were severely disrupted, and patients have faced several challenges during the COVID-19 outbreak. These challenges include addressing new functional impairments faced by survivors of COVID-19 and infection prevention to avoid the virus spread to healthcare workers and other patients not infected with COVID-19. In this scoping review, we aim to develop rehabilitation recommendations during the COVID-19 pandemic across the continuum of rehabilitation care. MATERIALS AND METHODS: Established frameworks were used to guide the scoping review methodology. Medline, Embase, Pubmed, CINAHL databases from inception to August 1, 2020, and prominent rehabilitation organizations' websites were searched. STUDY SELECTION: We included articles and reports if they were focused on rehabilitation recommendations for COVID-19 survivors or the general population at the time of the COVID-19 pandemic. DATA EXTRACTION: Two of our team members used the pre-tested data extraction form to extract data from included full-text articles. The strength and the quality of the extracted recommendations were evaluated by two reviewers using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: We retrieved 6,468 citations, of which 2,086 were eligible after removing duplicates. We excluded 1,980 citations based on the title and the abstract. Of the screened full-text articles, we included 106 studies. We present recommendations based on the patient journey at the time of the pandemic. We assessed the evidence to be of overall fair quality and strong for the recommendations. CONCLUSION: We have combined the latest research results and accumulated expert opinions on rehabilitation to develop acute and post-acute rehabilitation recommendations in response to the global COVID-19 pandemic. Further updates are warranted in order to incorporate the emerging evidence into rehabilitation guidelines.
  • Partial COVID-19 vaccination associated with reduction in postoperative mortality and SARS-CoV-2 infection.

    Prasad, Nikhil K; Englum, Brian R; Mayorga-Carlin, Minerva; Turner, Douglas J; Sahoo, Shalini; Sorkin, John D; Lal, Brajesh K (Elsevier, 2022-04-08)
    BACKGROUND: There are currently no data to guide decisions about delaying surgery to achieve full vaccination. METHODS: We analyzed data from patients undergoing surgery at any of the 1,283 VA medical facilities nationwide and compared postoperative complication rates by vaccination status. RESULTS: Of 87,073 surgical patients, 20% were fully vaccinated, 15% partially vaccinated, and 65% unvaccinated. Mortality was reduced in full vaccination vs. unvaccinated (Incidence Rate Ratio 0.77, 95% CI [0.62, 0.94]) and partially vaccinated vs. unvaccinated (0.75 [0.60, 0.94]). Postoperative COVID-19 infection was reduced in fully (0.18 [0.12, 0.26]) and partially vaccinated patients (0.34 [0.24, 0.48]). Fully vaccinated compared to partially vaccinated patients, had similar postoperative mortality (1.02, [0.78, 1.33]), but had decreased COVID-19 infection (0.53 [0.32, 0.87]), pneumonia (0.75 [0.62, 0.93]), and pulmonary failure (0.79 [0.68, 0.93]). CONCLUSIONS: Full and partial vaccination reduces postoperative complications indicating the importance of any degree of vaccination prior to surgery.
  • Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19.

    Ho, Cheng-Ying; Salimian, Mohammad; Hegert, Julia; O'Brien, Jennifer; Choi, Sun Gyeong; Ames, Heather; Morris, Meaghan; Papadimitriou, John C; Mininni, Joseph; Niehaus, Peter; et al. (2022-04-11)
    Importance: Loss of smell is an early and common presentation of COVID-19 infection. Although it has been speculated that viral infection of olfactory neurons may be the culprit, it is unclear whether viral infection causes injuries in the olfactory bulb region. Objective: To characterize the olfactory pathology associated with COVID-19 infection in a postmortem study. Design, Setting, and Participants: This multicenter postmortem cohort study was conducted from April 7, 2020, to September 11, 2021. Deceased patients with COVID-19 and control individuals were included in the cohort. One infant with congenital anomalies was excluded. Olfactory bulb and tract tissue was collected from deceased patients with COVID-19 and appropriate controls. Histopathology, electron microscopy, droplet digital polymerase chain reaction, and immunofluorescence/immunohistochemistry studies were performed. Data analysis was conducted from February 7 to October 19, 2021. Main Outcomes and Measures: (1) Severity of degeneration, (2) losses of olfactory axons, and (3) severity of microvasculopathy in olfactory tissue. Results: Olfactory tissue from 23 deceased patients with COVID-19 (median [IQR] age, 62 [49-69] years; 14 men [60.9%]) and 14 control individuals (median [IQR] age, 53.5 [33.25-65] years; 7 men [50%]) was included in the analysis. The mean (SD) axon pathology score (range, 1-3) was 1.921 (0.569) in patients with COVID-19 and 1.198 (0.208) in controls (P <.001), whereas axon density was 2.973 (0.963) × 104/mm2in patients with COVID-19 and 3.867 (0.670) × 104/mm2in controls (P =.002). Concomitant endothelial injury of the microvasculature was also noted in olfactory tissue. The mean (SD) microvasculopathy score (range, 1-3) was 1.907 (0.490) in patients with COVID-19 and 1.405 (0.233) in control individuals (P <.001). Both the axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell (mean [SD] axon pathology score, 2.260 [0.457] vs 1.63 [0.426]; P =.002; mean [SD] microvasculopathy score, 2.154 [0.528] vs 1.694 [0.329]; P =.02) but was not associated with clinical severity, timing of infection, or presence of virus. Conclusions and Relevance: This study found that COVID-19 infection is associated with axon injuries and microvasculopathy in olfactory tissue. The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 infection may be severe and permanent..
  • Coronavirus Disease 2019-Associated Mucormycosis: Risk Factors and Mechanisms of Disease.

    Narayanan, Shivakumar; Chua, Joel V; Baddley, John W (Oxford University Press, 2022-04-09)
    The severe surge of coronavirus disease 2019 (COVID-19) cases on the Indian subcontinent in early 2021 was marked by an unusually high number of COVID-19-associated mucormycosis (CAM) cases reported during this same period. This is significantly higher than predicted based on available data about prevalence and risk factors for this condition. This may be due to an unusual alignment of multiple risk factors for this condition. There is high background prevalence of mucormycosis in India likely from a high prevalence of risk factors, including undiagnosed or poorly controlled diabetes. COVID-19-induced immune dysregulation and immune suppression from steroid therapy increase the risk. The role of environmental exposure is unclear. System factors such as lack of access to healthcare during a pandemic may result in delayed diagnosis or suboptimal management with potentially poor outcomes. Here, we review currently identified risk factors and pathogenesis of CAM in a pandemic surge. © The Author(s) 2021.
  • Remdesivir for the Prevention of Invasive Mechanical Ventilation or Death in Coronavirus Disease 2019 (COVID-19): A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data.

    Paules, Catharine I; Gallagher, Shannon K; Rapaka, Rekha R; Davey, Richard T; Doernberg, Sarah B; Grossberg, Robert; Hynes, Noreen A; Ponce, Philip O; Short, William R; Voell, Jocelyn; et al. (Oxford University Press, 2022-04-09)
    This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.
  • Toward demystifying HIV as a risk factor for coronavirus disease 2019 complications.

    Gener, Alejandro R; Kottilil, Shyam (Wolters Kluwer Health, 2022-04)
  • Facemasks: Perceptions and use in an ED population during COVID-19.

    Eswaran, Vidya; Chang, Anna Marie; Wilkerson, R Gentry; O'Laughlin, Kelli N; Chinnock, Brian; Eucker, Stephanie A; Baumann, Brigitte M; Anaya, Nancy; Miller, Daniel G; Haggins, Adrianne N; et al. (Public Library of Science, 2022-04-13)
    STUDY OBJECTIVE: Facemask use is associated with reduced transmission of SARS-CoV-2. Most surveys assessing perceptions and practices of mask use miss the most vulnerable racial, ethnic, and socio-economic populations. These same populations have suffered disproportionate impacts from the pandemic. The purpose of this study was to assess beliefs, access, and practices of mask wearing across 15 urban emergency department (ED) populations. METHODS: This was a secondary analysis of a cross-sectional study of ED patients from December 2020 to March 2021 at 15 geographically diverse, safety net EDs across the US. The primary outcome was frequency of mask use outside the home and around others. Other outcome measures included having enough masks and difficulty obtaining them. RESULTS: Of 2,575 patients approached, 2,301 (89%) agreed to participate; nine had missing data pertaining to the primary outcome, leaving 2,292 included in the final analysis. A total of 79% of respondents reported wearing masks "all of the time" and 96% reported wearing masks over half the time. Subjects with PCPs were more likely to report wearing masks over half the time compared to those without PCPs (97% vs 92%). Individuals experiencing homelessness were less likely to wear a mask over half the time compared to those who were housed (81% vs 96%). CONCLUSIONS: Study participants reported high rates of facemask use. Respondents who did not have PCPs and those who were homeless were less likely to report wearing a mask over half the time and more likely to report barriers in obtaining masks. The ED may serve a critical role in education regarding, and provision of, masks for vulnerable populations.
  • Inhibition of the IFN-α JAK/STAT Pathway by MERS-CoV and SARS-CoV-1 Proteins in Human Epithelial Cells

    Zhang, Yamei; Gargan, Siobhan; Roche, Fiona M.; Frieman, Matthew; Stevenson, Nigel J. (MDPI AG, 2022-04-01)
    Coronaviruses (CoVs) have caused several global outbreaks with relatively high mortality rates, including Middle East Respiratory Syndrome coronavirus (MERS)-CoV, which emerged in 2012, and Severe Acute Respiratory Syndrome (SARS)-CoV-1, which appeared in 2002. The recent emergence of SARS-CoV-2 highlights the need for immediate and greater understanding of the immune evasion mechanisms used by CoVs. Interferon (IFN)-α is the body’s natural antiviral agent, but its Janus kinase/signal transducer and activators of transcription (JAK/STAT) signalling pathway is often antagonized by viruses, thereby preventing the upregulation of essential IFN stimulated genes (ISGs). Therapeutic IFN-α has disappointingly weak clinical responses in MERS-CoV and SARS-CoV-1 infected patients, indicating that these CoVs inhibit the IFN-α JAK/STAT pathway. Here we show that in lung alveolar A549 epithelial cells expression of MERS-CoV-nsp2 and SARS-CoV-1-nsp14, but not MERS-CoV-nsp5, increased basal levels of total and phosphorylated STAT1 & STAT2 protein, but reduced IFN-α-mediated phosphorylation of STAT1-3 and induction of MxA. While MERS-CoV-nsp2 and SARS-CoV-1-nsp14 similarly increased basal levels of STAT1 and STAT2 in bronchial BEAS-2B epithelial cells, unlike in A549 cells, they did not enhance basal pSTAT1 nor pSTAT2. However, both viral proteins reduced IFN-α-mediated induction of pSTAT1-3 and ISGs (MxA, ISG15 and PKR) in BEAS-2B cells. Furthermore, even though IFN-α-mediated induction of pSTAT1-3 was not affected by MERS-CoV-nsp5 expression in BEAS-2B cells, downstream ISG induction was reduced, revealing that MERS-CoV-nsp5 may use an alternative mechanism to reduce antiviral ISG induction in this cell line. Indeed, we subsequently discovered that all three viral proteins inhibited STAT1 nuclear translocation in BEAS-2B cells, unveiling another layer of inhibition by which these viral proteins suppress responses to Type 1 IFNs. While these observations highlight cell line-specific differences in the immune evasion effects of MERS-CoV and SARS-CoV-1 proteins, they also demonstrate the broad spectrum of immune evasion strategies these deadly coronaviruses use to stunt antiviral responses to Type IFN. © 2022 by the authors.
  • Understanding COVID-19 through human challenge models.

    Edwards, Kathryn M; Neuzil, Kathleen M (Springer Nature, 2022-03-31)

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