Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT).

BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. OBJECTIVE: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. RESULTS: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. CONCLUSIONS: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48183.

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

Severe Acute Hemolytic Anemia Post Covid Vaccination

Case Report: A 26-year-old woman with a history of warm autoimmune hemolytic anemia, immune thrombocytopenia, triple positive antiphospholipid syndrome, and chronic migraine presented to the emergency department with worsening generalized fatigue for one week associated with headache, dyspnea on exertion, nausea, vomiting and lightheadedness. Of note, she had received her second dose of mRNA COVID-19 vaccine 4 days prior to presentation. On admission, patient was found to be severely anemic with a hemoglobin of 4.3g/dL which is decreased from her baseline hemoglobin of 9-10.5g/dL;however, W-AIHA precluded the administration of blood product until adequate blood with the appropriate antibodies could be acquired. During the hospitalization, hemoglobin decreased to 3.3g/dL. Patient was then administered the most compatible blood product which she tolerated well. Hematology was consulted who started the patient on hydroxychloroquine, high dose methylprednisolone, and Intravenous Immunoglobulin (IVIG). Throughout the admission, the patient remained asymptomatic. After 2 days of IVIG, three days of high dose glucocorticoids, and one unit of packed red blood cells, the patient's hemoglobin increased to 7.2g/dL. Patient was discharged home on prednisone taper and hydroxychloroquine. Conclusion(s): Episodes of hemolytic anemia after either the first or second dose of mRNA COVID vaccines are rare and have occurred in patients with known hematological pathology as well as patients without any history of hematologic or immunologic disorders. When taking the history of patients presenting with hemolytic anemia, it is important to query recent vaccinations as, while rare, mRNA COVID vaccine may well be the etiology. While this ultimately will likely not change patient management, this information would be beneficial for further study.

Guillian-Barre Syndrome Post Covid-19 Vaccination

Case Report: This is a 50-year-old man that presented to the ED complaining of generalized weakness and acute loss of ability to ambulate which has been progressing for a month. Patient began having left arm and leg weakness, which started in his fingertips of his left upper extremity and soon moved proximally to upper left arm. Symptoms then progressed to right upper and lower arms. Symptoms further continued to progress making the patient bedridden. On presentation, CT head showed a C1/C2 subluxation possibly chronic without significant focal soft tissue swelling. CT cervical spine showed C1-C2 subluxation, possibly chronic. MRI of brain was unremarkable pre and postcontrast without focal findings or abnormal enhancement and showed redemonstration of the C1-C2 subluxation as described on CT scan. MRI of cervical spine showed at the level of C1 there is spinal canal stenosis. However, there is no direct pressure upon the cord/medulla. Upon evaluation, patient had significant motor weakness and required maximal assistance for movement. Patient was moreover noted to have flaccidity of muscles associated with weakness with no bulbar weakness. Patient had no difficulty in breathing or with speech. A lumbar tap was performed which showed elevated protein, WBC, and glucose. Upon further investigation, patient stated that he received his (3rd dose) of the Moderna Vaccine for Covid-19 about a month before the onset of symptoms and felt fine. Two weeks later, he began experiencing subjective fevers, diarrhea, abdominal pain, and fatigue that lasted for a week and then self-resolved. Approximately another two weeks later is when patient began noticing his neurological symptoms. Possible Guillain-Barre Syndrome post Campylobacter Jejuni (C. Jejuni) infection vs. post Covid-19 vaccine induced GBS was suspected at this point and patient was started on Intravenous Immunoglobulin (IVIG). Stool cultures were collected for C.Jejuni which came back negative. Gastrointestinal Pathogen Panel PCR Feces also came back negative. Patient was discharged to a rehab center and planned to receive another round of IVIG for 5 days. Conclusion(s): Guillain Barre Syndrome (GBS) is a rare immune-mediated neurological disorder affecting peripheral nerves and nerve roots, that presents as acute sensorimotor neuropathy starting with distal paresthesia that progresses to weakness of legs and arms, noteably, flaccid paralysis. GBS has several triggers namely infections such as C. jejuni, cytomegalovirus, M. pneumoniae, Epstien-Barr virus and Zika virus. There has also been several case reports and studies that have shown increased incidence of GBS vaccines such as influenza vaccine. Furthermore, there has been several studies that have linked GBS to COVID-19 vaccine. With COVID-19 cases continuing to persist, and increasing advocacy for vaccination against the disease, GBS should be considered as very rare but possible side effect of the vaccine.

Financial Constraints and Their Impact on University Students of Different Nationalities in the United Arab Emirates

Financial constraints caused by the economic slowdown in 2020 and COVID-19 that followed, affecting the student motivation for academic achievements, are of strategic importance to the global higher education (HE) sectors. This study aims to examine the effects of financial constraints on the motivation and academic performance of students of different nationalities in the United Arab Emirates (UAE) during the pandemic. This study will help us recognize the challenges among students from different backgrounds and nationalities and develop remedial strategies with a global perspective. We used a Likert scale-based questionnaire to collect data on motivation level, and associated variables from a sample of 371 students enrolled in different colleges in the UAE. Statistical techniques such as t-test, F-test, and chi-square test were used to explore the relationship between the variables in the data. The findings of the study revealed that financial constraints during the pandemic did not significantly affect academic motivation, regardless of gender, nationality, and age. The participants expressed that they were prepared and aware of the sunk costs involved in education. However, as the financial impact of the pandemic extended beyond 2020, unemployment increased, and parents were less prepared to bear their children's education costs. This inevitably increased the responsibilities of the universities to provide financial support to deserving students. © 2023, Association for Social Studies Educa. All rights reserved.

Human-Induced Pluripotent Stem Cell-Based Model of the Blood-Brain at 10 Years: A Retrospective on Past and Current Disease Models.

The initial discovery and derivation of induced pluripotent stem cells (iPSCs) by Yamanaka and colleagues in 2006 revolutionized the field of personalized medicine, as it opened the possibility to model diseases using patient-derived stem cells. A decade of adoption of iPSCs within the community of the blood-brain barrier (BBB) significantly opened the door for modeling diseases at the BBB, a task until then considered challenging, if not impossible.In this book chapter, we provided an extensive review of the literature on the use of iPSC-based models of the human BBB to model neurological diseases including infectious diseases (COVID-19, Streptococcus, Neisseria) neurodevelopmental diseases (adrenoleukodystrophy, Allan-Herndon-Dudley Syndrome, Batten's disease, GLUT1 deficiency syndrome), and neurodegenerative diseases (Alzheimer's disease, the current findings and observations, but also the challenges and limitations inherent to the use of iPSC-based models in reproducing the human BBB during health and diseases in a Petri dish.

Mathematical Modeling of SARS-CoV-2 Omicron Wave under Vaccination Effects

Over the course of the COVID-19 pandemic millions of deaths and hospitalizations have been reported. Different SARS-CoV-2 variants of concern have been recognized during this pandemic and some of these variants of concern have caused uncertainty and changes in the dynamics. The Omicron variant has caused a large amount of infected cases in the US and worldwide. The average number of deaths during the Omicron wave toll increased in comparison with previous SARS-CoV-2 waves. We studied the Omicron wave by using a highly nonlinear mathematical model for the COVID-19 pandemic. The novel model includes individuals who are vaccinated and asymptomatic, which influences the dynamics of SARS-CoV-2. Moreover, the model considers the waning of the immunity and efficacy of the vaccine against the Omicron strain. This study uses the facts that the Omicron strain has a higher transmissibility than the previous circulating SARS-CoV-2 strain but is less deadly. Preliminary studies have found that Omicron has a lower case fatality rate compared to previous circulating SARS-CoV-2 strains. The simulation results show that even if the Omicron strain is less deadly it might cause more deaths, hospitalizations and infections. We provide a variety of scenarios that help to obtain insight about the Omicron wave and its consequences. The proposed mathematical model, in conjunction with the simulations, provides an explanation for a large Omicron wave under various conditions related to vaccines and transmissibility. These results provide an awareness that new SARS-CoV-2 variants can cause more deaths even if their fatality rate is lower.

Absence of pathogenic viruses in COVID-19 convalescent plasma.

BACKGROUND: It is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID-19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers. METHODS: The DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay. RESULTS: TTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS-CoV-2. DISCUSSION: There was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non-pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP.

An Exceptional Cause of Increased 18F-Fluorodeoxyglucose Uptake on PET/CT in a Thyroid Nodule.

A 41-year-old female underwent a cervical spine CT for the workup of posterior neck pain irradiating to the shoulders for several months. An incidental thyroid nodule was found and classified as Bethesda III on the Fine-needle aspiration cytology (FNAC) results. Three months later, the patient developed mild shortness of breath, dry cough, and fever. Chest X-ray revealed a mild enlargement in the bilateral hilar regions. CT showed mediastinal and bilateral hilar enlarged lymph nodes and pulmonary micronodules. The workup was further completed with a 18F-FDG PET/CT, showing intense FDG uptake in the mediastinal and bilateral hilar lymph nodes and increased uptake in the thyroid nodule. Endobronchial Ultrasound-guided Transbronchial needle aspiration (EBUS-TBNA) of a left hilar lymph node showed epithelioid non-necrotizing granulomas. Because of the FNAC results, size of the nodule and tracheal shift, thyroid lobectomy was performed one month later. Histopathological results also revealed multiple non-necrotizing epithelioid granulomas, suggesting systemic sarcoidosis with involvement of the thyroid. To our knowledge, this is the first report of thyroid sarcoidosis detected on 18F-FDG PET/CT. Although an increased FDG uptake in a thyroid nodule is usually suggestive of thyroid malignancy, toxic nodule, or follicular hyperplasia, our case report shows that it could also suggest thyroid sarcoidosis.

Mathematical Modeling of COVID-19 Dynamics under Two Vaccination Doses and Delay Effects

The aim of this paper is to investigate the qualitative behavior of the COVID-19 pandemic under an initial vaccination program. We constructed a mathematical model based on a nonlinear system of delayed differential equations. The time delay represents the time that the vaccine takes to provide immune protection against SARS-CoV-2. We investigate the impact of transmission rates, vaccination, and time delay on the dynamics of the constructed system. The model was developed for the beginning of the implementation of vaccination programs to control the COVID-19 pandemic. We perform a stability analysis at the equilibrium points and show, using methods of stability analysis for delayed systems, that the system undergoes a Hopf bifurcation. The theoretical results reveal that under some conditions related to the values of the parameters and the basic reproduction number, the system approaches the disease-free equilibrium point, but if the basic reproduction number is larger than one, the system approaches endemic equilibrium and SARS-CoV-2 cannot be eradicated. Numerical examples corroborate the theoretical results and the methodology. Finally, conclusions and discussions about the results are presented.

Anti-Glomerular Basement Membrane Disease Sans Kidney Involvement

Introduction: Anti-Glomerular Basement Membrane (anti-GBM) is an autoimmune disease involving glomerular and pulmonary capillaries diagnosed in 1 patient per million per year. Predominant lung involvement can be seen in 6% of patients most of which still demonstrate microscopic hematuria and biopsy with typical linear IgG immunofluorescence (99%). Case Description: We report a case of a 57-year-old man who presented with several weeks of dyspnea and myalgia, and was found to have acute kidney injury and multifocal tree-in-bud groundglass opacities throughout both lungs (Figure 1). His serum creatinine was elevated to 4.5 mg/dL from baseline of 0.8 mg/dL three months earlier but no proteinuria or hematuria. COVID19 was negative. Bronchoscopy showed blood throughout the tracheobronchial tree. Anti-GBM was elevated at 80 AU/mL. CRP was elevated at 17 mg/dL. Further work-up for other infectious or autoimmune causes was unremarkable. Kidney biopsy showed acute tubular necrosis (ATN), mixed interstitial inflammatory infiltrate, and one isolated fibrous cellular crescent. Immunofluorescence was negative. Due to the concern for progression of untreated anti-GBM disease, the patient was given high dose steroids, plasma exchange, and oral cyclophosphamide. His anti-GBM titer decreased to an undetectable level. Creatinine improved to 2.33 mg/dL. Discussion(s): This case brings to light a rare variant of anti-GBM with no detectable kidney involvement and presents a therapeutic dilemma. Two independent pathologists reviewed kidney biopsy and felt that crescent was a non-specific result of prior glomerular injury or pauci-immune focal glomerulonephritis. ANCA serologies were negative, and there were no other systemic manifestations. ATN was attributed to poor intake and Naproxen use. The patient received a typical anti-GBM treatment but more data are needed to support this approach in mild cases. (Figure Presented).

RNA Transfection with Hypoxia Inducible Factor-1alpha

Introduction: Ischemic necrosis of dermal flaps is a devastating complication of reconstructive surgery. The increasing prevalence of diabetes, obesity, and an aging population adds to this concern. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of the adaptive response to hypoxia, controls the expression of angiogenic growth factors. The development of biologically active, gene-specific mRNAs, especially in COVID-19 vaccines, has shown the ability for intracellular protein expression. We sought to express HIF-1alpha through mRNA transfection and determined its biological activity by measuring the upregulation of selected downstream targets. Method(s): 5'-methyl-capped poly-A tailed mRNA was generated using T7 RNA polymerase and verified by gel electrophoresis. Predominant and variant HIF-1alpha mRNA were transfected into primary human dermal fibroblasts via Lipofectamine in triplicate, and RNA levels were assessed using RT-qPCR. All gene expression levels were normalized to beta-actin expression levels Results: At one day after transfection, the levels of HIF-1alpha transcript were significantly higher in the cells transfected with predominant (p = 0.0104) and variant (p = 0.0007) HIF-1alpha transcripts relative to the control. Additionally, the expression of HIF-1alpha transcription product genes VEGF (p = 0.0274) and ANG-1 (p = 0.05) were significantly higher in the cells transfected with the HIF-1alpha transcripts than the control. Conclusion(s): Our approach led to the successful transfection of HIF-1alpha mRNA into human fibroblasts, resulting in upregulation of HIF-1alpha downstream angiogenic targets. Thus, the use of biologically active HIF-1alpha mRNA transfection offers a promising approach to inhibit ischemic necrosis.

Detection of COVID-19 pulmonary manifestations with radiotherapy simulation CT imaging.

COVID-19 is associated with characteristic lung CT findings. Radiotherapy simulation CT scans may reveal characteristic COVID-19 findings and identify patients with active or prior infection. We reviewed patients undergoing CT simulation at a major cancer center in an early epicenter of the COVID-19 pandemic in the United States. Scans were reviewed by radiation oncologists using established radiographic criteria for COVID-19 pneumonia. Radiographic classifications were compared with available COVID-19 PCR test results. A one-tailed t-test was used to compare the rate of positive COVID-19 tests in radiographically suspicious vs. non-suspicious groups. Scans deemed suspicious were re-reviewed by expert diagnostic radiologists. 414 CT simulation scans were performed on 400 patients. 119 patients had COVID-19 PCR test results available. Radiation oncologists considered 71 scans (17.1%) suspicious for COVID-19. Of these, 23 had corresponding COVID-19 PCR tests, and 3/23 (15.7%) were positive for COVID. 107 non-suspicious scans had corresponding COVID-19 test results, and 9 were positive (8.4%). The difference in positive test results between suspicious and non-suspicious groups was not significant (p = 0.23). Upon re-review by a diagnostic radiologist, 25 (35%) scans deemed suspicious by radiation oncologists were confirmed to meet criteria, while the rest were re-classified as "atypical" for COVID-19. We conclude that radiotherapy simulation CT scans can be reviewed for signs of COVID-19 pneumonia by radiation oncologists. However, suspicious CT simulation was not associated with a higher incidence of COVID infection compared with non-suspicious CT simulation, and there was low concordance between radiation oncologist and diagnostic radiologist classification of scans.

Conservation ethics in the time of the pandemic: Does increasing remote access advance social justice?

The COVID-19 pandemic is stimulating improvements in remote access and use of technology in conservation-related programs and research. In many cases, organizations have intended for remote engagement to benefit groups that have been marginalized in the sciences. But are they? It is important to consider how remote access affects social justice in conservation biology-i.e., the principle that all people should be equally respected and valued in conservation organizations, programs, projects, and practices. To support such consideration, we describe a typology of justice-oriented principles that can be used to examine social justice in a range of conservation activities. We apply this typology to three conservation areas: (1) remote access to US national park educational programs and data; (2) digitization of natural history specimens and their use in conservation research; and (3) remote engagement in conservation-oriented citizen science. We then address the questions: Which justice-oriented principles are salient in which conservation contexts or activities? How can those principles be best realized in those contexts or activities? In each of the three areas we examined, remote access increased participation, but access and benefits were not equally distributed and unanticipated consequences have not been adequately addressed. We identify steps that can and are being taken to advance social justice in conservation, such as assessing programs to determine if they are achieving their stated social justice-oriented aims and revising initiatives as needed. The framework that we present could be used to assess the social justice dimensions of many conservation programs, institutions, practices, and policies.

ATYPICAL PRESENTATION OF MUCORMYCOSIS IN A NONSEVERE COVID-19 PATIENT

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Coronavirus Disease 2019 (COVID-19) infection ranges from asymptomatic to severe disease as defined by WHO. Emerging fungal infections such as mucormycosis and aspergillosis have been described in critically ill patients, most notably in India, when treated with steroids due to severe COVID-19 [1]. We present a unique case of an atypical presentation of mucormycosis in a non-severe COVID-19 patient not treated with corticosteroids. CASE PRESENTATION: A 19-year-old male with type 1 diabetes mellitus presented to the emergency room for evaluation of shortness of breath, nausea and fatigue. History was significant for insulin noncompliance with home blood glucose in the 300s and a positive COVID-19 test one day prior to arrival. Initial vitals positive for tachycardia, tachypnea and hypertension while on room air. Labs showed leukocytosis 14,000 cells/uL, bicarbonate 7.2 mmol/L, anion gap 24.8, glucose 428 mg/dL, beta-hydroxybutyrate 58 mg/dL and nucleic acid amplification COVID-19 positive. Physical exam showed left eyelid and facial swelling, nasal congestion without sinus tenderness or other deformity, and kussmaul breathing pattern. CT face confirmed left periorbital cellulitis. Transfer to tertiary center for Ophthalmology evaluation was attempted but refused due to capacity. He was started on diabetic ketoacidosis treatment as well as broad spectrum antibiotics with the assistance of Infectious Disease, however COVID-19 treatments were held due to mild illness. Despite these interventions, he became stuporous and amphotericin was started. MR Brain showed findings suggestive of cavernous sinus thrombosis, acute ischemia and local mass effect. ENT then performed an endoscopic antrostomy with ethmoidectomy and biopsies were taken. Pathology resulted as invasive fungal sinusitis with 90° branching hyphae confirming mucormycosis and a lumbar drain was placed with intrathecal amphotericin started for concern of mucormycosis meningitis. The patient was ultimately transferred to a tertiary care center where he expired. DISCUSSION: Mucormycosis, an angioinvasive fungal infection affecting the immunocompromised and diabetics, is rare but deadly. The estimated prevalence in the United States is 0.16 per 10,000 hospital discharges [2] and bears a mortality rate of 46%. Recent systematic reviews report 275 cases of COVID associated mucormycosis with 233 in India [1] with 76.3% receiving corticosteroids prior to diagnosis [3], likely contributing to an immunocompromised state. Our case demonstrates that despite not receiving corticosteroids, even those with mild COVID-19 are at risk for this disease. CONCLUSIONS: Patients with diabetes, immunocompromised states, and now COVID-19, presenting with orbital symptoms warrant consideration of mucormycosis. Prompt management of the underlying condition, IV amphotericin, and possible debridement may increase survival. Reference #1: John TM, Jacob CN, Kontoyiannis DP. When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis. J Fungi (Basel). 2021 Apr 15;7(4):298. doi: 10.3390/jof7040298. PMID: 33920755;PMCID: PMC8071133. Reference #2: Kontoyiannis DP, Yang H, Song J, et al. Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study. BMC Infect Dis. 2016;16(1):730. Published 2016 Dec 1. doi:10.1186/s12879-016-2023-z Reference #3: Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 2021 Jul-Aug;15(4):102146. doi: 10.1016/j.dsx.2021.05.019. Epub 2021 May 21. PMID: 34192610;PMCID: PMC8137376 DISCLOSURES: No relevant relationships by james abraham No relevant relationships by christian ALMANZAR ZORRILLA No relevant relationships by Grace Johnson No relevant relationships by Thanuja Neerukonda No relevant relationships by Blake Spain No relevant re ationships by Michael Su No relevant relationships by Steven Tran No relevant relationships by Margarita Vanegas No relevant relationships by Alexandra Witt

Mathematical modeling to study the impact of immigration on the dynamics of the COVID-19 pandemic: A case study for Venezuela.

We propose two different mathematical models to study the effect of immigration on the COVID-19 pandemic. The first model does not consider immigration, whereas the second one does. Both mathematical models consider five different subpopulations: susceptible, exposed, infected, asymptomatic carriers, and recovered. We find the basic reproduction number R0 using the next-generation matrix method for the mathematical model without immigration. This threshold parameter is paramount because it allows us to characterize the evolution of the disease and identify what parameters substantially affect the COVID-19 pandemic outcome. We focus on the Venezuelan scenario, where immigration and emigration have been important over recent years, particularly during the pandemic. We show that the estimation of the transmission rates of the SARS-CoV-2 are affected when the immigration of infected people is considered. This has an important consequence from a public health perspective because if the basic reproduction number is less than unity, we can expect that the SARS-CoV-2 would disappear. Thus, if the basic reproduction number is slightly above one, we can predict that some mild non-pharmaceutical interventions would be enough to decrease the number of infected people. The results show that the dynamics of the spread of SARS-CoV-2 through the population must consider immigration to obtain better insight into the outcomes and create awareness in the population regarding the population flow.

Assessing the effects of COVID‐19‐induced hypoxia and ACE2 signaling on the human blood‐brain barrier in‐vitro

Introduction Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2). The portal of entry for the virus is peptidase ACE2, a major key player of the renin‐angiotensin‐aldosterone system (RAAS), resulting in severe lung injury. Although COVID‐19 mainly manifests as an acute respiratory distress syndrome (ARDS), there is increasing evidence of neurological symptoms in patients infected by COVID‐19. Yet, there is limited understanding of how COVID‐19 impacts the central nervous system (CNS). We speculate that such neurological symptoms maybe a consequence of a dysfunction of the blood‐brain barrier (BBB) with our central hypothesis that the neurological effects of SARS CoV‐2 are driven by chronic hypoxic stress‐impaired ACE2 at the BBB. Methods An in‐vitro human induced pluripotent stem cells (hiPSCs) BBB model was used in the study. Such model was exposed to various levels of hypoxia (1,5 and 10%) for up to 24 hours. In addition, normoxic cells were treated with Angiotensin II (AngII) or Angiotensin 1‐7 (degradation by product of AngII by ACE2). Changes in the barrier function was assessed using TEER, permeability to fluorescein and tight junction staining. Changes in ACE2 and MasR expression was assessed by immunofluorescence, whereas ACE2 shedding and HIF‐1 alpha expression was assessed by ELISA. Results Mild (10%) hypoxia was sufficient to induce the loss of barrier function. Secretion of ACE2 under hypoxia followed a biphasic pattern, with highest levels at 5% and 10%. Ang II and Ang1‐7 had little effect on the barrier function under normoxic condition. The hypoxic exposure induced shedding of the membrane bound ACE2 and molecular mechanism of hypoxic exposure in regulation of ACE2 occurs in a HIF1α‐ dependent manner. Discussion Our preliminary data suggest that our human model of the BBB responds to hypoxia and express critical components of RAAS. Both ACE2 and MasR negatively respond to mild hypoxia followed by a decreased barrier function with no changes in tight junction complex. Such loss was correlated with increased ACE2 shedding in HIF1α‐ dependent manner. We are currently investigating role of Ang 1‐7 in rescuing barrier function under hypoxic stress.

Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study.

BACKGROUND: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). METHODS: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. RESULTS: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. CONCLUSION: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.

Plasmonic Fluor-Enhanced Antigen Arrays for High-Throughput, Serological Studies of SARS-CoV-2.

Serological testing for acute infection or prior exposure is critical for patient management and coordination of public health decisions during outbreaks. Current methods have several limitations, including variable performance, relatively low analytical and clinical sensitivity, and poor detection due to antigenic drift. Serological methods for SARS-CoV-2 detection for the ongoing COVID-19 pandemic suffer from several of these limitations and serves as a reminder of the critical need for new technologies. Here, we describe the use of ultrabright fluorescent reagents, Plasmonic Fluors, coupled with antigen arrays that address a subset of these limitations. We demonstrate its application using patient samples in SARS-CoV-2 serological assays. In our multiplexed assay, SARS-CoV-2 antigens were spotted into 48-plex arrays within a single well of a 96-well plate and used to evaluate remnant laboratory samples of SARS-CoV-2 positive patients. Signal-readout was performed with Auragent Bioscience's Empower microplate reader, and microarray analysis software. Sample volumes of 1 µL were used. High sensitivity of the Plasmonic Fluors combined with the array format enabled us to profile patient serological response to eight distinct SARS-CoV-2 antigens and evaluate responses to IgG, IgM, and IgA. Sensitivities for SARS-CoV-2 antigens during the symptomatic state ranged between 72.5 and 95.0%, specificity between 62.5 and 100%, and the resulting area under the curve values between 0.76 and 0.97. Together, these results highlight the increased sensitivity for low sample volumes and multiplex capability. These characteristics make Plasmonic Fluor-enhanced antigen arrays an attractive technology for serological studies for the COVID-19 pandemic and beyond.

Coping with Coronavirus disease 2019: current state review and SWOT analysis to improve the urological services in Southeast Asia.

INTRODUCTION: We investigated the impact of Coronavirus Disease 2019 (COVID-19) pandemic on urological services by analyzing current attitudes and practices of urologists in the Southeast Asian (SEA) countries and create ways for improvement. MATERIALS AND METHODS: Quantitative data were used as critical indicators of workload of urological services from each country in SEA. Qualitative data analysis was done to describe the current state of attitudes of urologists against COVID-19 in the region. A strengths, weaknesses, opportunities, and threats (SWOT) analysis was performed to formulate strategic action plans. RESULTS: A total of seven urologists from six SEA countries completed the survey. Approximately 21-40% reduction in elective surgeries and outpatient visits, as stated by 42.9% and 57.1% of respondents, respectively was noted. Collectively, most respondents (71.4%) experienced <20% reduction in emergency visits. Various strategies were utilized as reaction to the pandemic. These include utilization of virtual communication platforms, pre-surgical COVID-19 screening, and limited number of accepted outpatient appointments and surgeries. Face to face patient consultations were still considered needed by many urologists although most countries had prohibited direct patient contact. The national response of countries such as Malaysia, Singapore, Thailand, and Vietnam were successful in controlling the pandemic. However, Indonesia and Philippines struggled because of the limited testing and tracing capabilities. Through the SWOT analysis, strategies were identified which can help overcome COVID-19 and any other future pandemics: (1) restarting the urological services in a safe and sustainable manner; (2) optimizing financial and infrastructural capacities; and (3) regional collaboration to strengthen the health systems. CONCLUSION: COVID-19 negatively impacted many health aspects, especially the delivery of urological services in SEA. Therefore, to ensure sustainability of urological services during the pandemic crisis, health care system should focus on safe, resilient, and adaptive approach with regional collaboration.