Recent Submissions

  • Gut Microbiota and COVID-19: Potential Implications for Disease Severity.

    Rocchi, Giulia; Giovanetti, Marta; Benedetti, Francesca; Borsetti, Alessandra; Ceccarelli, Giancarlo; Zella, Davide; Altomare, Annamaria; Ciccozzi, Massimo; Guarino, Michele Pier Luca (2022-09-15)
    The SARS-CoV-2 pandemic resulted in an unprecedented global crisis. SARS-CoV-2 primarily causes lung infection trough the binding of the virus with the ACE-2 cell receptor located on the surface of the alveolar epithelial cells. Notably, ACE-2 cell receptors are also expressed in the epithelial cells of the intestinal tract (GI). Recent data showed that the microbial communities of the GI might act as local and systematic inflammatory modulators. Gastrointestinal symptoms, including diarrhea, are frequently observed in infected individuals, and recent released data indicate that SARS-CoV-2 may also spread by fecal-oral transmission. Moreover, the gut microbiota's ecosystem can regulate and be regulated by invading pathogens, including viruses, facilitating an effective immune response, which in turn results in less severe diseases. In this regard, increased SARS-CoV-2 mortality and morbidities appear to be frequently observed in elderly immunocompromised patients and in people with essential health problems, such as diabetes, who, indeed, tend to have a less diverse gut microbiota (dysbiosis). Therefore, it is important to understand how the interaction between the gut microbiota and SARS-CoV-2 might shape the intensity of the infection and different clinical outcomes. Here, we provide insights into the current knowledge of dysbiosis during SARS-CoV-2 infection and methods that may be used to re-establish a more correct microbiota composition.
  • Decreased PRESET-Score corresponds with improved survival in COVID-19 veno-venous extracorporeal membrane oxygenation.

    Powell, Elizabeth K; Lankford, Allison S; Ghneim, Mira; Rabin, Joseph; Haase, Daniel J; Dahi, Siamak; Deatrick, Kristopher B; Krause, Eric; Bittle, Gregory; Galvagno, Samuel M; et al. (2022-09-16)
    Introduction: The PREdiction of Survival on ECMO Therapy Score (PRESET-Score) predicts mortality while on veno-venous extracorporeal membrane oxygenation (VV ECMO) for acute respiratory distress syndrome. The aim of our study was to assess the association between PRESET-Score and survival in a large COVID-19 VV ECMO cohort. Methods: This was a single-center retrospective study of COVID-19 VV ECMO patients from 15 March 2020, to 30 November 2021. Univariable and Multivariable analyses were performed to assess patient survival and score differences. Results: A total of 105 patients were included in our analysis with a mean PRESET-Score of 6.74. Overall survival was 65.71%. The mean PRESET-Score was significantly lower in the survivor group (6.03 vs 8.11, p < 0.001). Patients with a PRESET-Score less than or equal to six had improved survival compared to those with a PRESET-Score greater than or equal to 8 (97.7% vs. 32.5%, p < 0.001). In a multivariable logistic regression, a lower PRESET-Score was also predictive of survival (OR 2.84, 95% CI 1.75, 4.63, p < 0.001). Conclusion: We demonstrate that lower PRESET scores are associated with improved survival. The utilization of this validated, quantifiable, and objective scoring system to help identify COVID-19 patients with the greatest potential to benefit from VV-ECMO appears feasible. The incorporation of the PRESET-Score into institutional ECMO candidacy guidelines can help insure and improve access of this limited healthcare resource to all critically ill patients.
  • Vaccine-induced seroconversion in participants in the North Carolina COVID-19 community Research Partnership.

    Friedman-Klabanoff, DeAnna J; Tjaden, Ashley H; Santacatterina, Michele; Munawar, Iqra; Sanders, John W; Herrington, David M; Wierzba, Thomas F; Berry, Andrea A (2022-09-12)
    Well-regulated clinical trials have shown FDA-approved COVID-19 vaccines to be immunogenic and highly efficacious. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an mRNA COVID-19 vaccine in a cohort study of nearly 8000 adults residing in North Carolina to validate immunogenicity using a novel approach: at-home, participant administered point-of-care testing. Overall, 91.4% had documented seroconversion within 75 days of first vaccination (median: 31 days). Participants who were older and male participants were less likely to seroconvert (adults aged 41-65: adjusted hazard ratio [aHR] 0.69 [95% confidence interval (CI): 0.64, 0.73], adults aged 66-95: aHR 0.55 [95% CI: 0.50, 0.60], compared to those 18-40; males: aHR 0.92 [95% CI: 0.87, 0.98], compared to females). Participants with evidence of prior infection were more likely to seroconvert than those without (aHR 1.50 [95% CI: 1.19, 1.88]) and those receiving BNT162b2 were less likely to seroconvert compared to those receiving mRNA-1273 (aHR 0.84 [95% CI: 0.79, 0.90]). Reporting at least one new symptom after first vaccination did not affect time to seroconversion, but participants reporting at least one new symptom after second vaccination were more likely to seroconvert (aHR 1.11 [95% CI: 1.05, 1.17]). This data demonstrates the high community-level immunogenicity of COVID-19 vaccines, albeit with notable differences in older adults, and feasibility of using at-home, participant administered point-of-care testing for community cohort monitoring.
  • Estimating deaths averted and cost per life saved by scaling up mRNA COVID-19 vaccination in low-income and lower-middle-income countries in the COVID-19 Omicron variant era: a modelling study.

    Savinkina, Alexandra; Bilinski, Alyssa; Fitzpatrick, Meagan; Paltiel, A David; Rizvi, Zain; Salomon, Joshua; Thornhill, Thomas; Gonsalves, Gregg (2022-09-13)
    Objectives: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations. Design: We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. Setting: Low-income and lower-middle-income nations. Main outcome measures: Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. Findings: Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400-US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. Conclusions: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.
  • Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months.

    Sobieszczyk, Magdalena E; Maaske, Jill; Falsey, Ann R; Sproule, Stephanie; Robb, Merlin L; Frenck, Robert W; Tieu, Hong-Van; Mayer, Kenneth H; Corey, Lawrence; Neuzil, Kathleen M; et al. (2022-09-15)
    Background. We report updated safety, efficacy, and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) from an ongoing phase 3 trial. Methods. Adults at increased risk of SARS-CoV-2 infection were randomized (2:1), stratified by age, to receive 2 doses of AZD1222 or placebo. The primary efficacy end point was confirmed SARS-CoV-2 reverse-transcriptase PCR–positive (RT-PCR–positive) symptomatic COVID-19 at 15 or more days after a second dose in baseline SARS-CoV-2–seronegative participants. The 21,634 and 10,816 participants were randomized to AZD1222 and placebo, respectively. Findings. Data cutoff for this analysis was July 30, 2021; median follow-up from second dose was 78 and 71 days for the double-blind period (censoring at unblinding or nonstudy COVID-19 vaccination) and 201 and 82 days for the period to nonstudy COVID-19 vaccination (regardless of unblinding) in the AZD1222 and placebo groups, respectively. For the primary efficacy end point in the double-blind period (141 and 184 events; incidence rates: 39.2 and 118.8 per 1,000 person years), vaccine efficacy was 67.0% (P < 0.001). In the period to nonstudy COVID-19 vaccination, incidence of events remained consistently low and stable through 6 months in the AZD1222 group; for the primary efficacy end point (328 and 219 events; incidence rates: 36.4, 108.4) and severe/critical disease (5 and 13 events; incidence rates: 0.6, 6.4), respective vaccine efficacy estimates were 65.1% and 92.1%. AZD1222 elicited humoral immune responses over time, with waning at day 180. No emergent safety issues were seen. Conclusion. AZD1222 is safe and well tolerated, demonstrating durable protection and immunogenicity with median follow-up (AZD1222 group) of 6 months.
  • Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection

    Adenaiye, Oluwasanmi O.; Lai, Jianyu; Bueno de Mesquita, P. Jacob; Hong, Filbert; Youssefi, Somayeh; German, Jennifer; Tai, S. H.Sheldon; Albert, Barbara; Schanz, Maria; Weston, Stuart; et al. (Infectious Diseases Society of America, 2022-08-24)
    BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. METHODS: We recruited coronavirus disease 2019 (COVID-19) cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to 2 visits 2 days apart. We quantified and sequenced viral RNA, cultured virus, and assayed serum samples for anti-spike and anti-receptor binding domain antibodies. RESULTS: We enrolled 49 seronegative cases (mean days post onset 3.8 ± 2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 36% of fine (≤5 µm), 26% of coarse (>5 µm) aerosols, and 52% of fomite samples overall and in all samples from 4 alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6- to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4- to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. CONCLUSIONS: SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.
  • Prevention and Control of Coronavirus Disease 2019: Where Do We Go From Here?

    Neuzil, Kathleen M. (Infectious Diseases Society of America, 2022-08-24)
    Respiratory viruses have plagued humanity for millennia. The latest respiratory virus to emerge—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—has caused the pandemic of our lifetimes. The social, economic, and health consequences have been staggering, and the end is not yet in sight. Historic vaccine development efforts with rapid rollout of highly effective vaccines in the United States and elsewhere have prevented millions of cases and saved hundreds of thousands of lives. Yet, more than a year after emergency use authorization of coronavirus disease 2019 (COVID-19) vaccines, almost half of the global population remains unvaccinated, and <10% of people in low-income countries have received a single dose of vaccine. These large unvaccinated populations, and vaccinated populations with poor vaccine responses, remain at high risk for serious outcomes and death due to COVID-19
  • In-Person Medical Conferences During the COVID-19 Pandemic.

    Kern, Winfried V; Morgan, Daniel J (JAMA, 2022-09-01)
    In 2020, many business meetings and academic conferences were canceled or became virtual because of uncertainties regarding SARS-CoV-2 transmission and strict public health measures. In fact, rates of SARS-CoV-2 transmission at large indoor gatherings have remained largely unknown, although some appeared to have been superspreader events for the virus (eg, the 2020 Biogen conference in Boston, Massachusetts). Earlier studies of SARS-CoV-2 outbreaks on cruise ships have indicated protective effects of reducing the number of individuals on board and testing passengers and crew.1,2 The rate of SARS-CoV-2 seroconversion after a medical conference in Switzerland in September 2020 with stringent masking, physical distancing, supervised hand hygiene, and canceling of social events was 0 of 168 (<1%) at a time of community incidence of 65/100 000 population per week (<0.1%).3 With the advent of SARS-CoV-2 vaccines, more recent studies on larger sporting and cultural events that were generally outdoors have shown that vaccination, previous COVID-19 infection, a negative lateral flow test within 48 hours of the event, and adequate mask wearing, often together with spaced seating, were associated with a low risk of infection after the event.4,5 However, cases of infection resulting from transmission during such events (possibly including recent medical conferences6 ) could not be totally prevented, particularly when community transmission of SARS-CoV-2 was high.
  • Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults.

    Fraiman, Joseph; Erviti, Juan; Jones, Mark; Greenland, Sander; Whelan, Patrick; Kaplan, Robert M; Doshi, Peter (Elsevier, 2022-08-30)
    Introduction: In 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials. Methods: Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults (NCT04368728 and NCT04470427), focusing analysis on Brighton Collaboration adverse events of special interest. Results: Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI -0.4 to 20.6 and -3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI -23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI -3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39). Discussion: The excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes. These analyses will require public release of participant level datasets.
  • Research interrupted: applying the CONSERVE 2021 Statement to a randomized trial of rehabilitation during critical illness affected by the COVID-19 pandemic.

    Reid, Julie C; Molloy, Alex; Strong, Geoff; Kelly, Laurel; O'Grady, Heather; Cook, Deborah; Archambault, Patrick M; Ball, Ian; Berney, Sue; Burns, Karen E A; et al. (BMC, 2022-09-02)
    Rationale: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches. Methods: On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures. Results: Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol. Conclusions: We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management.
  • Leveraging lessons learned from the COVID-19 pandemic for HIV.

    Calder, Thomas; Tong, Tina; Hu, Dale J; Kim, Jerome H; Kotloff, Karen L; Koup, Richard A; Marovich, Mary A; McElrath, M Juliana; Read, Sarah W; Robb, Merlin L; et al. (Nature, 2022-08-29)
    The rapid development of COVID-19 vaccines and their deployment in less than a year is an unprecedented scientific, medical, and public health achievement. This rapid development leveraged knowledge from decades of HIV/AIDS research and advances. However, the search for an HIV vaccine that would contribute to a durable end to the HIV pandemic remains elusive. Here, we draw from the US government experience and highlight lessons learned from COVID-19 vaccine development, which include the importance of public-private partnerships, equitable inclusion of populations impacted by the infectious pathogen, and continued investment in basic research. We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.
  • SARS-CoV-2 variant spike and accessory gene mutations alter pathogenesis.

    McGrath, Marisa E; Xue, Yong; Dillen, Carly; Oldfield, Lauren; Assad-Garcia, N; Zaveri, Jayshree; Singh, Natasha; Baracco, Lauren; Taylor, Louis J; Vashee, Sanjay; et al. (National Academy of Sciences, 2022-08-30)
    The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the spike protein. Although these differences in spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome that may also affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through interference with innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other nonspike mutations on SARS-CoV-2 pathogenesis, we synthesized both viruses possessing deletions in the accessory genes as well as viruses where the WA-1 spike is replaced by each variant spike gene in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to both WA-1 and the full variant viruses. Our work has revealed that the accessory proteins contribute to SARS-CoV-2 pathogenesis and the nonspike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host. This work suggests that while spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may alter clinical disease presentation.
  • A Rapid and Sensitive Microfluidics-Based Tool for Seroprevalence Immunity Assessment of COVID-19 and Vaccination-Induced Humoral Antibody Response at the Point of Care.

    Rajsri, Kritika Srinivasan; McRae, Michael P; Simmons, Glennon W; Christodoulides, Nicolaos J; Matz, Hanover; Dooley, Helen; Koide, Akiko; Koide, Shohei; McDevitt, John T (MDPI, 2022-08-10)
    As of 8 August 2022, SARS-CoV-2, the causative agent of COVID-19, has infected over 585 million people and resulted in more than 6.42 million deaths worldwide. While approved SARS-CoV-2 spike (S) protein-based vaccines induce robust seroconversion in most individuals, dramatically reducing disease severity and the risk of hospitalization, poorer responses are observed in aged, immunocompromised individuals and patients with certain pre-existing health conditions. Further, it is difficult to predict the protection conferred through vaccination or previous infection against new viral variants of concern (VoC) as they emerge. In this context, a rapid quantitative point-of-care (POC) serological assay able to quantify circulating anti-SARS-CoV-2 antibodies would allow clinicians to make informed decisions on the timing of booster shots, permit researchers to measure the level of cross-reactive antibody against new VoC in a previously immunized and/or infected individual, and help assess appropriate convalescent plasma donors, among other applications. Utilizing a lab-on-a-chip ecosystem, we present proof of concept, optimization, and validation of a POC strategy to quantitate COVID-19 humoral protection. This platform covers the entire diagnostic timeline of the disease, seroconversion, and vaccination response spanning multiple doses of immunization in a single POC test. Our results demonstrate that this platform is rapid (~15 min) and quantitative for SARS-CoV-2-specific IgG detection.
  • A Machine Learning Framework for Detecting COVID-19 Infection Using Surface-Enhanced Raman Scattering.

    Ikponmwoba, Eloghosa; Ukorigho, Okezzi; Moitra, Parikshit; Pan, Dipanjan; Gartia, Manas Ranjan; Owoyele, Opeoluwa (MDPI, 2022-08-02)
    In this study, we explored machine learning approaches for predictive diagnosis using surface-enhanced Raman scattering (SERS), applied to the detection of COVID-19 infection in biological samples. To do this, we utilized SERS data collected from 20 patients at the University of Maryland Baltimore School of Medicine. As a preprocessing step, the positive-negative labels are obtained using Polymerase Chain Reaction (PCR) testing. First, we compared the performance of linear and nonlinear dimensionality techniques for projecting the high-dimensional Raman spectra to a low-dimensional space where a smaller number of variables defines each sample. The appropriate number of reduced features used was obtained by comparing the mean accuracy from a 10-fold cross-validation. Finally, we employed Gaussian process (GP) classification, a probabilistic machine learning approach, to correctly predict the occurrence of a negative or positive sample as a function of the low-dimensional space variables. As opposed to providing rigid class labels, the GP classifier provides a probability (ranging from zero to one) that a given sample is positive or negative. In practice, the proposed framework can be used to provide high-throughput rapid testing, and a follow-up PCR can be used for confirmation in cases where the model’s uncertainty is unacceptably high.
  • Immunomodulatory therapies for COVID-19.

    Mathur, Poonam; Kottilil, Shyamasundaran (Frontiers, 2022-08-03)
    Purpose: As COVID-19 disease progresses, the host inflammatory response contributes to hypoxemia and severe and critical illness. In these latter stages of disease, patients may benefit from immunomodulatory therapies to control the aberrant host inflammatory response. In this review, we provide an overview of these therapies and provide summaries of the studies that led to issuance of FDA Emergency Use Authorization or recommendation by the Infectious Diseases Society of America (IDSA). Materials and methods: We reviewed English-language studies, Emergency Use Authorizations (EUAs), and guidelines from March 2020 to present. Conclusion and relevance: There are several therapies with proposed benefit in severe and critical COVID-19 disease. Few have been issued FDA EUA or recommendation by the Infectious Diseases Society of America (IDSA). Physicians should be familiar with the evidence supporting use of these therapies and the patient populations most likely to benefit from each.
  • Geospatial Reach of the Maryland COVID-19 School Meals Response: Spring 2020.

    McGuirt, Jared T; Lane, Hannah; Cooper, M Chela; Sessoms-Parks, Leslie; Pulling Kuhn, Ann; Hager, Erin R (Elsevier, 2022-08-18)
    Objective. Examine characteristics of pandemic meal site (n = 602) location and meals served per site in Maryland, Spring 2020, following federal/state waivers for local meal site placement decision-making. Methods. Using geographic information systems, we connected meal sites to census tract-level data and generated service areas from sites and distances from population-weighted census tract centroids to the closest pandemic meal site. Regression analysis determined associations of census tract pandemic meal site count and meals served per site with socioeconomic and demographic variables. Results. Census tracts with more meal sites were urban (P < 0.001), food deserts (P < 0.001), and had higher percentages of children in poverty (P < 0.001). Sites serving fewer meals were in food deserts (P < 0.001) and areas with more children in poverty (P < 0.001). Conclusions and Implications. Waivers allowing local meal site placement decision-making supported meal sites in high-need areas. Geospatial approaches could optimize site locations to ensure maximum reach to populations in need. Additional supports may be needed to ensure children in poverty areas receive meals distributed at these sites.
  • The impact of COVID-19 restrictions on participant enrollment in the PREPARE trial.

    Pogorzelski, David; McKay, Paula; Weaver, Michael J; Jaeblon, Todd; Hymes, Robert A; Gaski, Greg E; Fraifogl, Joanne; Ahn, James S; Bzovsky, Sofia; Slobogean, Gerard; et al. (Elsevier, 2022-08-17)
    Background. At the initiation of the COVID-19 pandemic, restrictions forced researchers to decide whether to continue their ongoing clinical trials. The PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities) trial is a pragmatic cluster-randomized crossover trial in patients with open and closed fractures. PREPARE was enrolling over 200 participants per month at the initiation of the pandemic. We aim to describe how the COVID-19 research restrictions affected participant enrollment. Methods. The PREPARE protocol permitted telephone consent, however, sites were obtaining consent in-person. To continue enrollment after the initiation of the restrictions participating sites obtained ethics approval for telephone consent scripts and the waiver of a signature on the consent form. We recorded the number of sites that switched to telephone consent, paused enrollment, and the length of the pause. We used t-tests to compare the differences in monthly enrollment between July 2019 and November 2020. Results. All 19 sites quickly implement telephone consent. Fourteen out of nineteen (73.6%) sites paused enrollment due to COVID-19 restrictions. The median length of enrollment pause was 46.5 days (range, 7–121 days; interquartile range, 61 days). The months immediately following the implementation of restrictions had significantly lower enrollment. Conclusion. A pragmatic design allowed sites to quickly adapt their procedures for obtaining informed consent via telephone and allowed for minimal interruptions to enrollment during the pandemic.
  • Associations Between Gastrointestinal Symptoms and COVID-19 Severity Outcomes, Based on a Propensity Score-Weighted Analysis of a Nationwide Cohort.

    Shah, Shailja C; Canakis, Andrew; Halvorson, Alese E; Dorn, Chad; Wilson, Otis; Denton, Jason; Hauger, Richard; Hunt, Christine; Suzuki, Ayako; Matheny, Michael E; et al. (Elsevier, 2022-08-07)
    Background and Aims. Gastrointestinal (GI) symptoms are well-recognized manifestations of coronavirus disease 2019 (COVID-19). Our primary objective was to evaluate the association between GI symptoms and COVID-19 severity. Methods. In this nationwide cohort of US veterans, we evaluated GI symptoms (nausea/vomiting/diarrhea) reported 30 days prior to and including the date of positive SARS-CoV-2 testing (March 1, 2020-February 20, 2021). All patients had >1 year of prior baseline data and >60 days follow-up relative to the test date. We used propensity score (PS)-weighting to balance covariates in patients with vs. without GI symptoms. The primary composite outcome was severe COVID-19, defined as hospital admission, intensive care unit (ICU) admission, mechanical ventilation, or death within 60-days of positive testing. Results. Of 218,045 SARS-CoV-2 positive patients, 29,257 (13.4%) had GI symptoms. After PS-weighting, all covariates were balanced. In the PS-weighted cohort, patients with vs. without GI symptoms had severe COVID-19 more often (29.0% vs. 17.1%, P<0.001). When restricted to hospitalized patients (14.9%; n=32,430), patients with GI symptoms had similar frequencies of ICU admission and mechanical ventilation compared to patients without symptoms. There was a significant age interaction; among hospitalized patients >70 years old, lower COVID-19 associated mortality was observed in patients with vs. without GI symptoms, even after accounting for COVID-19-specific medical treatments. Conclusion. In the largest integrated US healthcare system, SARS-CoV-2 positive patients with GI symptoms experienced severe COVID-19 outcomes more often than those without symptoms. Additional research on COVID-19 associated GI symptoms may inform preventive efforts and interventions to reduce severe COVID-19.
  • PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19.

    Logue, James; Chakraborty, Arup R; Johnson, Robert; Goyal, Girija; Rodas, Melissa; Taylor, Louis J; Baracco, Lauren; McGrath, Marisa E; Haupt, Robert; Furlong, Brooke A; et al. (Nature, 2022-08-12)
    The ongoing COVID-19 pandemic has claimed more than 6 million lives and continues to test the world economy and healthcare systems. To combat this pandemic, the biological research community has shifted efforts to the development of medical countermeasures, including vaccines and therapeutics. However, to date, the only small molecules approved for the treatment of COVID-19 in the United States are the nucleoside analogue Remdesivir and the protease inhibitor Paxlovid, though multiple compounds have received Emergency Use Authorization and many more are currently being tested in human efficacy trials. One such compound, Apilimod, is being considered as a COVID-19 therapeutic in a Phase II efficacy trial. However, at the time of writing, there are no published efficacy data in human trials or animal COVID-19 models. Here we show that, while Apilimod and other PIKfyve inhibitors have potent antiviral activity in various cell lines against multiple human coronaviruses, these compounds worsen disease in a COVID-19 murine model when given prophylactically or therapeutically.
  • Not Feeling Swell: Superior Vena Cava (SVC) Syndrome Falsely Attributed to COVID-19 Vaccine Reaction

    McNeilly, Bryan P.; Wilkerson, R. Gentry (Elsevier, 2022-01-01)
    Background: The mass immunization campaign against Coronavirus disease 2019 (COVID-19) has resulted in more patients presenting to the emergency department (ED) with concern for a vaccine reaction. Case Report: A 68-year-old man presented to the ED reporting an allergic reaction to the COVID-19 vaccine. He initially noted swelling of his face, neck, and right arm after receiving the first dose of the vaccine. After his second dose of the vaccine, the swelling became more pronounced and prompted him to seek care. On examination, he had fullness of the neck and engorgement of the left external jugular vein, which were exacerbated when the patient raised his arms above his head, consistent with Pemberton's sign. Apart from the swelling of the head and neck, there were no other findings consistent with an allergic reaction. The presence of Pemberton's sign prompted a computed tomography scan of the chest with contrast, which revealed a paratracheal mass measuring 4.5 × 2.0 cm with marked narrowing of the superior vena cava (SVC). The patient was admitted to the hospital for SVC syndrome, and further workup revealed a non-small cell lung cancer. Why Should an Emergency Physician Be Aware of This?: Patients may misattribute their symptoms to a COVID vaccine reaction when they are, in fact, experiencing a more serious underlying disease. This case highlights the importance of a thorough physical examination and maintaining a broad differential diagnosis. In this case, the presence of Pemberton's sign raised suspicion for SVC syndrome, and prompted further workup. © 2022

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