Generation and characterization of a multi-functional panel of monoclonal antibodies for SARS-CoV-2 research and treatment (preprint)

The Coronavirus disease 2019 (COVID19) pandemic caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is an ongoing threat to global public health. To this end, intense efforts are underway to develop reagents to aid in diagnostics, enhance preventative measures, and provide therapeutics for managing COVID-19. The recent emergence of SARS-CoV-2 Omicron variants with enhanced transmissibility, altered antigenicity, and significant escape of existing monoclonal antibodies and vaccines underlines the importance of the continued development of such agents. The SARS-CoV-2 spike protein and its receptor binding domain (RBD) are critical to viral attachment and host cell entry and are primary targets for antibodies elicited from both vaccination and natural infection. In this study, mice were immunized with two synthetic peptides (Pep 1 and Pep 2) within the RBD of the original Wuhan SARS-CoV-2, as well as the whole RBD as a recombinant protein (rRBD). Hybridomas were generated and a panel of three monoclonal antibodies, mAb CU-P1-1 against Pep 1, mAb CU-P2-20 against Pep 2, and mAb CU-28-24 against rRBD, were generated and further characterized. These mAbs were shown by ELISA to be specific for each immunogen/antigen. Monoclonal antibody CU-P1-1 has limited applicability other than in ELISA approaches and basic immunoblotting. Monoclonal antibody CU-P2-20 is shown to be favorable for ELISA, immunoblotting, and immunohistochemistry (IHC), however, not live virus neutralization. In contrast, mAb CU-28-24 is most effective at live virus neutralization as well as ELISA and IHC. Moreover, mAb CU-28-24 was active against rRBD proteins from Omicron variants B.2 and B.4/B5 as determined by ELISA, suggesting this mAb may neutralize live virus of these variants. Each of the immunoglobulin genes has been sequenced using Next Generation Sequencing, which allows the expression of respective recombinant proteins, thereby eliminating the need for long-term hybridoma maintenance. The synthetic peptides and hybridomas/mAbs are under the intellectual property management of the Clemson University Research Foundation, and the three CDRs have been submitted as an invention disclosure for further patenting and commercialization.

Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients. METHODS: We searched ClinicalTrials.gov in January 2021 for U.S./Canada-based trials where an angiotensin-converting enzyme inhibitors/ARB was a treatment arm, targeted outcomes could be extrapolated, and data sharing was allowed. Our primary outcome was a 7-point COVID-19 ordinal score measured 13 to 16 days post-enrollment. We analyzed data by fitting multilevel Bayesian ordinal regression models and standardizing the resulting predictions. RESULTS: 325 participants (156 losartan vs 169 control) from 4 studies contributed IPD. Three were randomized trials; one used non-randomized concurrent and historical controls. Baseline covariates were reasonably balanced for the randomized trials. All studies evaluated losartan. We found equivocal evidence of a difference in ordinal scores 13-16 days post-enrollment (model-standardized odds ratio [OR] 1.10, 95% credible interval [CrI] 0.76-1.71; adjusted OR 1.15, 95% CrI 0.15-3.59) and no compelling evidence of treatment effect heterogeneity among prespecified subgroups. Losartan had worse effects for those taking corticosteroids at baseline after adjusting for covariates (ratio of adjusted ORs 0.29, 95% CrI 0.08-0.99). Hypotension serious adverse event rates were numerically higher with losartan. CONCLUSIONS: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.

The Virtual Neurologic Exam: Instructional Videos and Guidance for the COVID-19 Era

Objective:To outline features of the neurologic examination that can be performed virtually through telemedicine platforms (the virtual neurological examination [VNE]), and provide guidance for rapidly pivoting in-person clinical assessments to virtual visits during the COVID-19 pandemic and beyond.Methods:The full neurologic examination is described with attention to components that can be performed virtually.Results:A screening VNE is outlined that can be performed on a wide variety of patients, along with detailed descriptions of virtual examination maneuvers for specific scenarios (cognitive testing, neuromuscular and movement disorder examinations).Conclusions:During the COVID-19 pandemic, rapid adoption of virtual medicine will be critical to provide ongoing and timely neurological care. Familiarity and mastery of a VNE will be critical for neurologists, and this article outlines a practical approach to implementation.

Changes in Pediatric Movement Behaviors During the COVID-19 Pandemic by Stages of Lockdown in Ontario, Canada: A Longitudinal Cohort Study.

BACKGROUND: Children's movement behaviors have been affected by the COVID-19 pandemic; however, little is known regarding movement behavior patterns over time by government-issued lockdowns. Our primary objective was to evaluate how children's movement behaviors changed by stages of lockdown/reopening in Ontario, Canada, from 2020 to 2021. METHODS: A longitudinal cohort study with repeated measures of exposure and outcomes was conducted. The exposure variables were dates from before and during COVID-19 when child movement behavior questionnaires were completed. Lockdown/reopening dates were included as knot locations in the spline model. The outcomes were daily screen, physical activity, outdoor, and sleep time. RESULTS: A total of 589 children with 4805 observations were included (53.1% boys, 5.9 [2.6] y). On average, screen time increased during the first and second lockdowns and decreased during the second reopening. Physical activity and outdoor time increased during the first lockdown, decreased during the first reopening, and increased during the second reopening. Younger children (<5 y) had greater increases in screen time and lower increases in physical activity and outdoor time than older children (≥5 y). CONCLUSIONS: Policy makers should consider the impact of lockdowns on child movement behaviors, especially in younger children.

How effective is rescue therapeutic plasma exchange in treatment of SARS-Coronavirus-2?

INTRODUCTION: After the FDA gave emergency approval for the use of therapeutic plasma exchange in treatment for SARS-Coronoavirus-2, we analyzed its efficacy in patients who had failed all other known therapies. METHODS: This was a prospective observational study of 42 patients with SARS-Coronoavirus-2 who had failed conventional therapy and were treated with therapeutic plasma exchange. Pre- and postexchange clinical and laboratory parameters were monitored. The patients were then also compared with a group of 147 patients with SARS-Coronoavirus-2 who were referred for stage 3 acute renal failure and dialysis from SARS-Coronoavirus-2. RESULTS: After therapeutic plasma exchange, there were significant improvements in some clinical parameters but mortality remained high; although better than the renal failure group (43.9% vs. 50.7%, p = 0.004). CONCLUSION: SARS-CoV-2 patients who failed all other therapies had significant mortality with therapeutic plasma exchange; however, their survival was better than SARS-CoV-2 patients with stage 3 acute renal failure.

Managing Medications and Medication Adherence Among US Adults During the Early Phase of the COVID-19 Pandemic.

Purpose: Before the COVID-19 pandemic and the disruptions it brought, medication adherence was already a challenging and complex health behavior. The purpose of this study was to describe patients' interactions in clinic, pharmacy, and home contexts and associated medication management and adherence during the early phase of the COVID-19 pandemic. Patients and Methods: A survey questionnaire was developed using the Medication Adherence Context and Outcomes framework and distributed via social media between May and July 2020 targeting adults taking a daily prescribed medication. Survey questions assessed sociodemographics, interactions with healthcare providers, clinics, pharmacies, medication management experiences, habit strength, and life chaos perceptions during the pandemic. Medication adherence was assessed by the self-report BAASIS© scale to measure implementation, discontinuation, and overall nonadherence. Results: A total of 134 adults from the United States, mean age 50.0 (SD 16.1) years were included in this analysis. Respondents took a median of 3.50 (interquartile range 4) daily medications. Delays in seeing a provider were reported by 47 (35.1%). Pharmacy encounters were impacted; 25 (18.7%) indicated their method for obtaining medication changed. Medication nonadherence was reported among 62 (46.3%) and was significantly greater among those who delayed prescription refills (p=0.032), pillbox users (p=0.047), and those who experienced greater life chaos (p=0.040) and lower habit strength (p<0.001) in the early phase of the pandemic. Conclusion: Although the early phase of the pandemic affected access to care for nearly one-third of the sample, distance-accessible care options and strategies to obtain needed services without being in-person supported respondents medication management. Helpful strategies included provider accessibility, telehealth, home delivery/mail-order, drive-thru's, 90-day supplies, and online/automatic refills. Methods to develop and reestablish habits are critical. Care providers in clinic and pharmacy settings can educate and remind patients about services like distance-accessible technologies and online ordering of medications and establishing routines to support medication adherence.

The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans. Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities. Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2. In addition, 2 biorepository sites, a data processing center, and a coordinating center have been established under the direction of the Veterans Affairs Office of Research and Development. Phase 1 of VA SHIELD comprises 34 157 samples. Of these, 83.8% had positive tests for SARS-CoV-2, with the remainder serving as contemporaneous controls. The samples include nasopharyngeal swabs (57.9%), plasma (27.9%), and sera (12.5%). The associated clinical and demographic information available permits the evaluation of biological data in the context of patient demographics, clinical experience and management, vaccinations, and comorbidities. Conclusions: VA SHIELD is representative of US national diversity with a significant potential to impact national healthcare. VA SHIELD will support future projects designed to better understand SARS-CoV-2 and other emergent healthcare crises. To the extent possible, VA SHIELD will facilitate the discovery of diagnostics and therapeutics intended to diminish COVID-19 morbidity and mortality and to reduce the impact of new emerging threats to the health of US Veterans and populations worldwide.

Jobs, Housing, and Mask Wearing: Cross-Sectional Study of Risk Factors for COVID-19.

BACKGROUND: Many studies have focused on the characteristics of symptomatic patients with COVID-19 and clinical risk factors. This study reports the prevalence of COVID-19 in an asymptomatic population of a hospital service area (HSA) and identifies factors that affect exposure to the virus. OBJECTIVE: The aim of this study is to measure the prevalence of COVID-19 in an HSA, identify factors that may increase or decrease the risk of infection, and analyze factors that increase the number of daily contacts. METHODS: This study surveyed 1694 patients between April 30 and May 13, 2020, about their work and living situations, income, behavior, sociodemographic characteristics, and prepandemic health characteristics. This data was linked to testing data for 454 of these patients, including polymerase chain reaction test results and two different serologic assays. Positivity rate was used to calculate approximate prevalence, hospitalization rate, and infection fatality rate (IFR). Survey data was used to analyze risk factors, including the number of contacts reported by study participants. The data was also used to identify factors increasing the number of daily contacts, such as mask wearing and living environment. RESULTS: We found a positivity rate of 2.2%, a hospitalization rate of 1.2%, and an adjusted IFR of 0.55%. A higher number of daily contacts with adults and older adults increases the probability of becoming infected. Occupation, living in an apartment versus a house, and wearing a face mask outside work increased the number of daily contacts. CONCLUSIONS: Studying prevalence in an asymptomatic population revealed estimates of unreported COVID-19 cases. Occupational, living situation, and behavioral data about COVID-19-protective behaviors such as wearing a mask may aid in the identification of nonclinical factors affecting the number of daily contacts, which may increase SARS-CoV-2 exposure.

The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice.

Introduction: Acute kidney injury (AKI) is a common multifactorial adverse effect of surgery, circulatory obstruction, sepsis or drug/toxin exposure that often results in morbidity and mortality. Sphingolipid metabolism is a critical regulator of cell survival and pathologic inflammation processes involved in AKI. Opaganib (also known as ABC294640) is a first-in-class experimental drug targeting sphingolipid metabolism that reduces the production and activity of inflammatory cytokines and, therefore, may be effective to prevent and treat AKI. Methods: Murine models of AKI were used to assess the in vivo efficacy of opaganib including ischemia-reperfusion (IR) injury induced by either transient bilateral occlusion of renal blood flow (a moderate model) or nephrectomy followed immediately by occlusion of the contralateral kidney (a severe model) and lipopolysaccharide (LPS)-induced sepsis. Biochemical and histologic assays were used to quantify the effects of oral opaganib treatment on renal damage in these models. Results: Opaganib suppressed the elevations of creatinine and blood urea nitrogen (BUN), as well as granulocyte infiltration into the kidneys, of mice that experienced moderate IR from transient bilateral ligation. Opaganib also markedly decreased these parameters and completely prevented mortality in the severe renal IR model. Additionally, opaganib blunted the elevations of BUN, creatinine and inflammatory cytokines following exposure to LPS. Conclusion: The data support the hypotheses that sphingolipid metabolism is a key mediator of renal inflammatory damage following IR injury and sepsis, and that this can be suppressed by opaganib. Because opaganib has already undergone clinical testing in other diseases (cancer and Covid-19), the present studies support conducting clinical trials with this drug with surgical or septic patients at risk for AKI.

Self-reported impact of COVID-19 on Quality of Life for Cervical Cancer Patients at Georgetown Public Hospital

Objective: To assess the self-reported impact of COVID- 19 on the quality of life for cervical cancer patients at the Georgetown Public Hospital. Design and Methods: A qualitative study was conducted with face-to-face interviews of 25 respondents using a modified European Organization for Research and Treatment of Cancer Quality of Life Score (EORTCQLQ-30) from Oncology Clinic and Ward E at Georgetown Public Hospital. Result(s): 48% respondents were 48-55 years age group. 40% were Afro-Guyanese. 28% had diarrhoel symptoms before COVID-19. 40% of the respondents worried about painful sex. 32% of the respondents had vaginal dryness during intercourse. 40% had pain or a burning feelings while urinating. 36% had problems doing work. 32% of respondents had psychological problems such as worry, depression, and difficulty in remembering things. 28% had expressed that medical treatment interfered with their family life, social activity (44%), financial difficulties (48%) and limited in pursuing hobbies or other leisure time activities (48%). Conclusion(s): Cervical cancer patients after diagnosis, experience challenges related to treatment, diet, emotional function, social support, spritual wellbeing, and pain which eventually lead to a deterioration of their quality of life.

Real-world effectiveness of steroids in severe COVID-19: a retrospective cohort study.

INTRODUCTION: Randomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19. METHODS: Clinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality. RESULTS: 1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31-0.72)). CONCLUSION: The protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.

Atrial fibrillation is a risk factor for major adverse cardiovascular events in COVID-19.

Background: New-onset atrial fibrillation (AF) during COVID-19 infection is associated with worse cardiovascular outcomes and mortality, with new-onset AF being associated with worse clinical outcomes than recurrent AF. However, it is not known whether a prior history of AF is an independent cardiovascular risk factor predicting worse outcomes in COVID-19 patients. The present investigation sought to determine whether AF should be considered a risk factor for worse outcomes in COVID-19 illness. Methods: From March 2020-September 2021 patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n = 3623) were propensity matched to non-AF SARS-CoV-2 positive patients (n = 3610). Multivariable Cox hazard regression was used to determine subsequent MACE (all-cause death, myocardial infarction, HF and stroke) risk among patients with and without AF. Results: COVID-19 patients with a prior history of AF were more likely to be hospitalized, require ICU care, supplemental oxygen, and ventilator support compared COVID-19 patients without a history of AF. There was a 1.40 times higher rate of MACE in the COVID-19 patients with prior AF compared to patients without prior AF (p < 0.0001). The increased rate of MACE in patients with a prior AF was primarily secondary to increases in heart failure hospitalization and death. This finding was confirmed even after controlling for acute AF during COVID-19 illness (HR 1.22, p = 0.0009). Conclusion: AF history was shown to be an independent risk factor for MACE during a COVID-19 illness. Both recurrent and principally new-onset AF were associated with an increased risk of poor clinical outcomes during COVID-19 illness.

Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial.

BACKGROUND: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. METHODS: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed. FINDINGS: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. INTERPRETATION: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. FUNDING: Humanigen.

Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense.

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of Bloc1s1 mRNA encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Inactivation of the Bloc1s1 gene impaired the ability to assemble BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Bloc1s1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus murine hepatitis virus also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.

Recent Progress in the Development of Opaganib for the Treatment of Covid-19.

The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Recent work demonstrates that opaganib also has antiviral activity against several viruses including SARS-CoV-2. A recently completed multinational Phase 2/3 clinical trial of opaganib in patients hospitalized with Covid-19 demonstrated that opaganib can be safely administered to these patients, and more importantly, resulted in a 62% decrease in mortality in a large subpopulation of patients with moderately severe Covid-19. Furthermore, acceleration of the clearance of the virus was observed in opaganib-treated patients. Understanding the biochemical mechanism for the anti-SARS-CoV-2 activity of opaganib is essential for optimizing Covid-19 treatment protocols. Opaganib inhibits three key enzymes in sphingolipid metabolism: sphingosine kinase-2 (SK2); dihydroceramide desaturase (DES1); and glucosylceramide synthase (GCS). Herein, we describe a tripartite model by which opaganib suppresses infection and replication of SARS-CoV-2 by inhibiting SK2, DES1 and GCS. The potential impact of modulation of sphingolipid signaling on multi-organ dysfunction in Covid-19 patients is also discussed.

Preliminary investigation and intervention of the suspected plague outbreak in Madunga, Babati District-Tanzania.

BACKGROUND: Rodents are known to be reservoirs of plague bacteria, Yesinia pestis in the sylvatic cycle. A preliminary investigation of the suspected plague outbreak was conducted in Madunga Ward, Babati District Council in Manyara Region December-2019-January 2020 Following reported two cases which were clinically suspected as showing plague disease symptoms. METHOD: The commensal and field rodents were live trapped using Sherman traps in Madunga Ward, where plague suspect cases were reported and, in the Nou-forest reserve areas at Madunga Ward, Babati District Council, to assess plague risk in the area. Fleas were collected inside the houses using light traps and on the rodents 'body after anaesthetizing the captured rodent to determine flea indices which are used to estimate the risk of plague transmission. Lung impression smears were made from sacrificed rodents to examine for possible bipolar stained Yersinia spp bacilli. RESULTS: A total of 86 rodents consisting of ten rodent species were captured and identified from the study sites. Nine forest rodent species were collected. Field/fallow rodent species were dominated by Mastomys natalensis. whereas domestic rodent species captured was Rattus rattus. Overall lung impression smear showed bipolar stain were 14 (16.28%) while House Flea Index (HFI) was 3.1 and Rodent Flea Index (RFI) was 1.8. CONCLUSION: The findings of this study have shown that, the presence of bipolar stained bacilli in lung impression smears of captured species of rodents indicates (not confirmed) possible circulation of Yesrsinia pests in rodents and the high flea indices in the area which included the most common flea species known to be plague vectors in Tanzania could have played transmission role in this suspected outbreak. The study recommends surveillance follow-up in the area and subject collected samples to the standard plague confirmatory diagnosis.

Feasibility of and Experience with Telehealth Based Patient Self-referral for COVID-19 Monoclonal Antibody Therapy (preprint)

BackgroundMonoclonal antibody (mAb) treatment for COVID-19 has been underutilized due to logistical challenges, lack of access and variable treatment awareness among patients and providers. The use of telehealth during the pandemic provides an opportunity to increase access to COVID care. MethodsThis is a single-center descriptive study of telehealth-based patient self-referral for mAb therapy between March 1, 2021 to October 31, 2021 at Baltimore Convention Center Field Hospital (BCCFH). ResultsAmong the 1001 self-referral patients, the mean age was 47, and most were female (57%) white (66%), and had a primary care provider (62%). During the study period, self-referrals increased from 14 per month in March to 427 in October resulting in a 30-fold increase. About 57% of self-referred patients received a telehealth visit, and of those 82% of patients received mAb infusion therapy, either onsite or at other infusion sites. The median time from self-referral to onsite infusion was 2 days (1-3 IQR). DiscussionOur study shows the integration of telehealth with a self-referral process improved access to mAb infusion. A high proportion of self-referrals were appropriate and led to timely treatment. Incorporation of self-referral and telehealth for monoclonal antibody therapy led to successful timely infusions. This approach helped those without traditional avenues for care and avoided potential delay for patients seeking referral from their medical providers.

Racial Disparities in Hesitancy and Utilization of Monoclonal Antibody Infusion Treatment of COVID-19 (preprint)

Background and MethodsWe conducted a single center cross-sectional study to investigate racial disparities in the hesitancy and utilization of monoclonal antibody (mAb) treatment of COVID-19 among treatment eligible patients who were referred to the infusion center between January 4, 2021 and May 14, 2021. ResultsAmong the 2,406 eligible participants, African Americans were significantly more likely to underutilize mAb treatment (OR 1.8; 95% CI 1.5-2.1) and miss treatment opportunities due to monoclonal hesitancy (OR 1.7, 95% CI 1.3-2.1). ConclusionAddressing racial disparities in mAb delivery is an opportunity to bridge the racial inequities in COVID-19 care.