Hiv Viral Load Suppression and Racial Disparities during the Covid-19 Pandemic in Nyc

Background: Antiretroviral therapy is highly effective in achieving HIV viral load suppression (VLS) but requires sustained engagement in care. The COVID-19 pandemic disrupted medical care, and its impact on engagement in HIV care and VLS remains unclear. Health information exchanges (HIEs) enable examination of patient care across multiple health systems. We sought to leverage HIE data to examine the effect of pandemic-related disruptions in HIV care on VLS and to explore racial/ethnic disparities in VLS. Method(s): We performed a retrospective observational study of people living with HIV (PLWH) using de-identified data from Healthix, an HIE encompassing >20 million patients and 8,000 healthcare facilities in the greater New York City (NYC) region, between 1/1/2018 and 7/14/2022. We identified PLWH based on HIV viral load (VL) tests and HIV diagnosis codes (ICD and SNOMED). We established two cohorts: PLWH engaged in care in 2020 with >=1 VL test in 2019, 2020, and 2021(Group A) and PLWH not engaged in care in 2020 with >=1 VL test in 2019 and 2021 but 0 VL tests in 2020 (Group B). HIV VLS outcomes were categorized as suppressed (< 200 copies/mL) or not suppressed ( >200 copies/mL) using the last VL in 2019, first VL in 2021, and last recorded VL. We compared proportions using X2-tests and fit a group-stratified logistic regression to examine the effect of race/ethnicity on VLS. Result(s): We identified 711,358 VL tests representing 81,122 patients at 249 facilities. Of these patients, 36,199 met our definition of PLWH. Of those, 12,448 met the inclusion criteria for Group A, and 3,377 met the inclusion criteria for Group B. In 2019, Group B had a lower VLS proportion than Group A (85.9% vs 88.1%, X2 = 12.3, p< 0.0001). In 2021, this gap increased;the proportion of VLS was 80.7% in Group B and 88.0% in Group A (X2 = 121.8, p< 0.00001). Most recently, VLS in Group B had increased to 85.6%, but the inter-group gap in VLS had grown from 2.2% to 4.4%. Within both groups, Black and Hispanic patients had lower odds of VLS than white patients. This disparity was greatest in Group B when they reengaged in care in 2021, with 72.0% of Black patients (OR 0.30, 95% CI 0.22-0.42), and 79.1% of Hispanic patients (OR 0.45, 95% CI 0.31-0.63), compared to 89.5% of white patients achieving VLS. Conclusion(s): VLS remained high among PLWH who stayed engaged in care in 2020, dropped among PLWH who disengaged in care, and was lower in minoritized groups even after controlling for engagement in care.

Inhibition of Protein N-Glycosylation Blocks SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) extensively N-glycosylates its spike proteins, which are necessary for host cell invasion and the target of both vaccines and immunotherapies. These N-glycans are predicted to modulate spike binding to the host receptor by stabilizing its open conformation and host immunity evasion. Here, we investigated the essentiality of both the host N-glycosylation pathway and SARS-CoV-2 N-glycans for infection. Ablation of host N-glycosylation using RNA interference or inhibitors, including FDA-approved drugs, reduced the spread of the infection, including that of variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta). Under these conditions, cells produced fewer virions and some completely lost their infectivity. Furthermore, partial enzymatic deglycosylation of intact virions showed that surface-exposed N-glycans are critical for cell invasion. Altogether, we propose protein N-glycosylation as a targetable pathway with clinical potential for treatment of COVID-19. IMPORTANCE The coronavirus SARS-CoV-2 uses its spike surface proteins to infect human cells. Spike proteins are heavily modified with several N-glycans, which are predicted to modulate their function. In this work, we show that interfering with either the synthesis or attachment of spike N-glycans significantly reduces the spread of SARS-CoV-2 infection in vitro, including that of several variants. As new SARS-CoV-2 variants, with various degrees of resistance against current vaccines, are likely to continue appearing, halting virus glycosylation using repurposed human drugs could result in a complementary strategy to reducing the spread of COVID-19 worldwide.

Rare Diagnosis of Para-infectious SARS-COV2 Associated Acute Transverse Myelitis Based off Clinical Presentation and CSF Studies with Negative Imaging: A Case Report

Case Diagnosis: Rare Diagnosis of Para-Infectious SARS-COV2 Associated Acute Transverse Myelitis Based Off Clinical Presentation and CSF Studies with Negative Imaging Case Description or Program Description: Patient was admitted for two weeks of ascending paresthesias and weakness of his lower extremities around ten days after recovering from a mild SARS-COV2 associated illness. While in the hospital, his weakness progressed to flaccid paralysis of his lower extremities with a sensory level at T10. Initial workup including magnetic resonance imaging (MRI) of his brain, cervical, thoracic and lumbar spine were negative. Initial electrodiagnostic (EMG) testing was unrevealing. He received a course of intravenous immunoglobulins followed by a five day course of intravenous solumedrol, both of which did not result in any improvement. Multiple weeks into admission, the patient began to exhibit hand intrinsic weakness and paresthesias, so plasmapheresis was attempted without any change in his symptoms. Setting(s): Major Academic and Referral Center with Level 1 Adult Trauma Assessment/Results: After admission to our inpatient rehabilitation unit, repeat MRIs of his cervical and thoracic spine were again unrevealing. Initial cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein and positive oligoclonal bands (2). Repeat EMG obtained after his upper extremity symptoms began did not reveal a cause for his weakness. Inflammatory and neoplastic workups were negative. He also developed upper motor neuron signs on neurological examination late in his admission. Discussion (relevance): There are documented cases of neurologic complications, specifically transverse myelitis, associated with the multi-systemic inflammatory/ immunological response in the post-infectious period of SARS-COV2. What is exceedingly rare, but documented, is a diagnosis based on clinical presentation, elevated CSF protein and lymphocytes alone with the exclusion of other diagnoses. Conclusion(s): The neurologic complications of SARSCOV2 in the post-infectious period include transverse myelitis and in rare cases like this, can present without the typical findings seen on imaging of the spinal cord.

Post COVID-19 Infection Multisystem Inflammatory Syndrome in Adults Presenting with Pain, Ascending Weakness, and Paresthesias: A Case Report

Case Diagnosis: Post COVID-19 infection multisystem inflammatory syndrome in adults presenting in a 28-year-old African American female with pain, ascending weakness, paresthesias, and chest pain. Case Description or Program Description: Patient with documented COVID-19 infection 5 weeks prior to arrival and presented with pain, paresthesias, and weakness in the bilateral lower extremities. Symptoms began shortly after patient recovered from COVID-19 infection, however, patient developed ascending weakness extending into the hands with left sided chest pain, prompting patient to present for evaluation. Setting(s): Major academic and referral center with level 1 adult trauma. Assessment/Results: Lumbar puncture and cerebrospinal fluid studies were not suggestive of Guillain- Barre syndrome. Imaging of the entire neuraxis was unremarkable. Echocardiogram revealed new onset heart failure with reduced ejection fraction of 35% consistent with non-ischemic cardiomyopathy and cardiac imaging was not suggestive of amyloidosis. EMG was consistent with primarily axonal greater than motor peripheral polyneuropathy. Further inflammatory workup revealed elevated erythrocyte sedimentation rate and C reactive protein. Paraneoplastic workup was unremarkable. Patient was started on intravenous immunoglobulin (IVIG) for suspected Multisystem Inflammatory Syndrome in Adults (MIS-A), however, patient developed infusion reaction shortly after infusion began and IVIG was discontinued pending hemodynamic stability. Discussion (relevance): Post COVID-19 multisystem inflammatory syndrome is seen more commonly in children than in adults per literature review. Clinicians must be mindful of potential MIS-A in adult patients with symptoms mimicking Guillain-Barre syndrome with negative workup and imaging, especially with concomitant cardiovascular compromise and elevated inflammatory markers. This case demonstrates one of the various presentations documented of MIS-A and is important for accurate diagnosis of this syndrome in the future. Conclusion(s): Post COVID-19 patients presenting with symptoms similar to Guillain-Barre syndrome with negative workup should be evaluated for MIS-A as this syndrome can affect multiple organ systems simultaneously, such as the nervous system and cardiovascular system as seen in this patient.

Patient-reported health outcomes of SARS-CoV-2-tested patients presenting to emergency departments: a propensity score-matched prospective cohort study.

OBJECTIVE: This study aimed to compare the long-term physical and mental health outcomes of matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive and SARS-CoV-2-negative patients controlling for seasonal effects. STUDY DESIGN: This was a retrospective cohort study. METHODS: This study enrolled patients presenting to emergency departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network. We enrolled consecutive eligible consenting patients who presented between March 1, 2020, and July 14, 2021, and were tested for SARS-CoV-2. Research assistants randomly selected four site and date-matched SARS-CoV-2-negative controls for every SARS-CoV-2-positive patient and interviewed them at least 30 days after discharge. We used propensity scores to match patients by baseline characteristics and used linear regression to compare Veterans RAND 12-item physical health component score (PCS) and mental health component scores (MCS), with higher scores indicating better self-reported health. RESULTS: We included 1170 SARS-CoV-2-positive patients and 3716 test-negative controls. The adjusted mean difference for PCS was 0.50 (95% confidence interval [CI]: -0.36, 1.36) and -1.01 (95% CI: -1.91, -0.11) for MCS. Severe disease was strongly associated with worse PCS (ß = -7.4; 95% CI: -9.8, -5.1), whereas prior mental health illness was strongly associated with worse MCS (ß = -5.4; 95% CI: -6.3, -4.5). CONCLUSION: Physical health, assessed by PCS, was similar between matched SARS-CoV-2-positive and SARS-CoV-2-negative patients, whereas mental health, assessed by MCS, was worse during a time when the public experienced barriers to care. These results may inform the development and prioritization of support programs for patients.

An Analysis of Serological Response and Infection Outcomes Following Oxford Astra-Zeneca (azd1222) and Pfizer-Biontech (mRNA BNT162b2) SARS-CoV-2 Vaccines in Kidney and Pancreas Transplant Patients

Purpose: SARS-CoV-2 is associated with high mortality among transplant recipients. This study aims to compare the humoral responses between the Oxford-Astra- Zeneca(AZ) and BNT162b2(Pfizer-BioNTech) vaccines in transplant recipients Methods: We recruited 920 kidney and SPK transplant patients receiving at least one dose of SARS-CoV-2 vaccine excluding patients with virus pre-exposure. Serological status was determined using the COVID-SeroKlir ELISA (Kantaro-EKF). Patients with corrected antibody level less than 0.7AU/mL were considered seronegative. Result(s): 495 AZ and 141 Pfizer patients had a sample post-first and 593 post-second dose (346 AZ vs 247 Pfizer) analysed. Following the 1st dose 25.7% of patients seroconverted (26.6% AZ and 22.8% Pfizer). Post-second dose 42.8% of AZ patients seroconverted (148/346) compared to 52.6% of Pfizer (130/247, p=0.02, HR 1.48, CI 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have a significantly higher response than AZ patients (median 2.6 vs 1.78AU/ mL, Mann-Whitney p=0.005), still lower than the one observed in general population. Patients on mycophenolate had a reduced seroconversion rate (42.2% vs 61.4%, p=0.001, HR 2.17) and reduced antibody levels (0.47 vs. 1.22 AU/mL, p=0.001) and this effect was dose dependent (p=0.05). Prednisolone reduced the seroconversion rate from 58.2% to 43.6% (p=0.03,HR 1.8) among Pfizer but not AZ recipients. This result was internally validated in two time points. Regression analysis has shown that antibody levels were reduced by older age (p=0.002), mycophenolate (p=0.001), AZ vaccine (vs Pfizer) (p=0.001) and male gender (p=0.02). There was no difference on infection rate post 2nd dose among the two vaccines but 14/15 serious post-vaccine infections leading to admission occurred to patients who did not seroconvert. Conclusion(s): Both seroconversion and antibody levels are lower following AZ compared to Pfizer vaccinated transplant patients following two vaccine doses. Mycophenolate, older age, male gender are also factors affecting the antibody response. Serious post vaccine infections are limited to patients without antibody response. Transplant patients remain at serious risk of SARS-CoV-2 infection.

Examining diversity and community engagement dermatology residency positions in the United States

Introduction: Diversity and Community Engagement (DCE) residency positions have recently emerged to promote diversity and encourage academic investigation in caring for underserved populations. DCE residents pursue traditional medical and surgical residency training plus scholarly work and leadership in diversity, equity, inclusion, and community engagement. We describe DCE dermatology residency positions to provide a roadmap for educators who are interested in creating similar positions. Methods: Websites of 138 ACGME-accredited dermatology residency programs were reviewed, which revealed DCE residency positions affiliated with Duke School of Medicine and University of Pennsylvania. Semistructured interviews were held with key faculty members at these institutions to discuss program vision and to identify associated benefits and challenges. Results: The vision of these programs was to prioritize increasing DCE initiatives by recruiting residents who had sustained interest in research, educational programs, and/or community service specific to diversity and inclusion. DCE residents were encouraged to pursue their interests through clinical electives and scholarly work;many completed research projects on diseases that disproportionately affect people of color. Key benefits of these positions include expanded curriculum on diversity and inclusion and increased community outreach efforts by all faculty and residents. Other benefits include demonstrated department commitment to diversity and community engagement, which contributed to increased underrepresented in medicine residency applicants. Challenges include initial conceptualization of program funding and maintaining community outreach initiatives during the COVID-19 pandemic. Discussion: DCE residency positions provide personalized graduate medical education and may foster the next generation of leaders who are dedicated to caring for underserved populations.

Syrian refugee labour and food insecurity in middle eastern agriculture during the early COVID-19 pandemic. (Special Issue: COVID-19 and the world of work (part II).)

Drawing on ethnographic data from the 2019 SyrianFoodFutures and the 2020 From the FIELD projects, this article provides insights into the early effects of the COVID-19 pandemic on refugee labour in agriculture in Iraq, Jordan, Lebanon, Syria and Turkey. In spring 2020, movement restrictions and supply chain disruptions caused displaced Syrian farmworkers to lose their jobs and face increased food insecurity. The authors situate their findings in the context of host countries' use of legal ambiguity in governing refugees, Middle Eastern agriculture's reliance on migrant labour, and the region's long-standing food insecurity. They conclude that formalizing refugee labour cannot alone address exploitation.

SARS-CoV-2 enzyme-linked immunosorbent assays as proxies for plaque reduction neutralisation tests.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb, but are not amenable to mass testing as they take several days and require use of SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 receptor binding domain (S1-RBD), and spike subunit 2 (S2) and nucleocapsid protein (NP), at predicting the presence and magnitude of NAb determined by PRNT. IgG S2 + NP ELISA was 96.8% [95% CI 83.8-99.9] sensitive and 88.9% [95% CI 51.8-99.7] specific at predicting the presence of NAbs (PRNT80 > 1:40). IgG and IgM S1-RBD ELISAs correlated with PRNT titre, with higher ELISA results increasing the likelihood of a robust neutralising response. The IgM S1-RBD assay can be used as a rapid, high throughput test to approximate the magnitude of NAb titre.

Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS.

Methods of SARS-CoV-2 Inactivation.

Inactivation methods allow for hazard group 3 (HG3) pathogens to be disposed of and used safely in downstream experiments and assays to be carried out at lower containment levels. Commonly used viral inactivation methods include heat inactivation, fixation methods, ultraviolet (UV) light and detergent inactivation. Here we describe known methods used to inactivate SARS-CoV-2 for safe downstream biological assays.

Analysis of SARS-CoV-2 in Nasopharyngeal Samples from Patients with COVID-19 Illustrates Population Variation and Diverse Phenotypes, Placing the Growth Properties of Variants of Concern in Context with Other Lineages.

New variants of SARS-CoV-2 are continuing to emerge and dominate the global sequence landscapes. Several variants have been labeled variants of concern (VOCs) because they may have a transmission advantage, increased risk of morbidity and/or mortality, or immune evasion upon a background of prior infection or vaccination. Placing the VOCs in context with the underlying variability of SARS-CoV-2 is essential in understanding virus evolution and selection pressures. Dominant genome sequences and the population genetics of SARS-CoV-2 in nasopharyngeal swabs from hospitalized patients were characterized. Nonsynonymous changes at a minor variant level were identified. These populations were generally preserved when isolates were amplified in cell culture. To place the Alpha, Beta, Delta, and Omicron VOCs in context, their growth was compared to clinical isolates of different lineages from earlier in the pandemic. The data indicated that the growth in cell culture of the Beta variant was more than that of the other variants in Vero E6 cells but not in hACE2-A549 cells. Looking at each time point, Beta grew more than the other VOCs in hACE2-A549 cells at 24 to 48 h postinfection. At 72 h postinfection there was no difference in the growth of any of the variants in either cell line. Overall, this work suggested that exploring the biology of SARS-CoV-2 is complicated by population dynamics and that these need to be considered with new variants. In the context of variation seen in other coronaviruses, the variants currently observed for SARS-CoV-2 are very similar in terms of their clinical spectrum of disease. IMPORTANCE SARS-CoV-2 is the causative agent of COVID-19. The virus has spread across the planet, causing a global pandemic. In common with other coronaviruses, SARS-CoV-2 genomes can become quite diverse as a consequence of replicating inside cells. This has given rise to multiple variants from the original virus that infected humans. These variants may have different properties and in the context of a widespread vaccination program may render vaccines less effective. Our research confirms the degree of genetic diversity of SARS-CoV-2 in patients. By comparing the growth of previous variants to the pattern seen with four variants of concern (VOCs) (Alpha, Beta, Delta, and Omicron), we show that, at least in cells, Beta variant growth exceeds that of Alpha, Delta, and Omicron VOCs at 24 to 48 h in both Vero E6 and hACE2-A549 cells, but by 72 h postinfection, the amount of virus is not different from that of the other VOCs.

Novel quantification of regional fossil fuel CO2 reductions during COVID-19 lockdowns using atmospheric oxygen measurements.

It is not currently possible to quantify regional-scale fossil fuel carbon dioxide (ffCO2) emissions with high accuracy in near real time. Existing atmospheric methods for separating ffCO2 from large natural carbon dioxide variations are constrained by sampling limitations, so that estimates of regional changes in ffCO2 emissions, such as those occurring in response to coronavirus disease 2019 (COVID-19) lockdowns, rely on indirect activity data. We present a method for quantifying regional signals of ffCO2 based on continuous atmospheric measurements of oxygen and carbon dioxide combined into the tracer "atmospheric potential oxygen" (APO). We detect and quantify ffCO2 reductions during 2020-2021 caused by the two U.K. COVID-19 lockdowns individually using APO data from Weybourne Atmospheric Observatory in the United Kingdom and a machine learning algorithm. Our APO-based assessment has near-real-time potential and provides high-frequency information that is in good agreement with the spread of ffCO2 emissions reductions from three independent lower-frequency U.K. estimates.

European Association of Urology COVID intermediate prioritisation group is poorly predictive of pathological high-risk among patients with renal tumours

Introduction & Objectives: The purpose of prioritisation is to minimise harm while safeguarding access to health care in times of reduced clinical resources. The EAU Guideline Office Rapid Reaction Group (GORRG) issued priority recommendations for use during the COVID-19 pandemic. We evaluated if the clinical prioritisation for suspected renal cell carcinoma (RCC) planned for surgery matched final pathological risk. Materials & Methods: From 23 March 2020 at the beginning of the first lock-down in the UK, patients with suspected RCC were prioritised according to GORRG recommendations until 10 October 2020. To increase statistical power, GORRG prioritisation was also retrospectively assigned to pre-lockdown RCC surgical cases, dating back to April 5 2019. Patient and tumour characteristics were assessed, as was priority group according to GORRG, TNM, and postoperative risk according to 2003 Leibovich scores. We assessed concordance between pre-operative GORGG prioritisation group and post-operative risk, and if stratification could be further improved by subgrouping of size. Results: 351 patients with suspected RCC were prioritised and underwent surgery, of which 16 were benign and 335 were RCC after specimen analysis. The intermediate priority group did not match the pathological risk group in 47.7%, with 25.7% and 16.4% of the group being pathological low and high risk, respectively. The low GORRG priority group harboured 14.9% intermediate and 1.06% high risk RCC, and the high GORRG priority group 27.9% intermediate and no low risk RCC respectively. Within the GORRG intermediate group, 34.2% of cT1b tumours were low risk, and 32.3% of cT2a tumours high risk. Analysing at 1 cm increments, 45.1% of 4-5cm tumours were low risk. The area under the receiver operating characteristics curve for priority groups in predicting matched postoperative risk group was 0.60 (95% CI 0.55-0.65). The sankey diagram shows patients categorised according to EAU GORGG guidelines (left) and pathological risk (right).(Figure Presented)Conclusions: The recommended prioritisation system can be error prone and should be prudently applied based on the centre’s needs. Particularly amongst the intermediate group, centres with clinical capacity should not defer intervention of cT2a tumours for longer than absolutely necessary and in severely limited resources may consider intermediate priority tumours <5cm as low priority.

CPC-containing oral rinses inactivate SARS-CoV-2 variants and are active in the presence of human saliva.

Introduction. The importance of human saliva in aerosol-based transmission of SARS-CoV-2 is now widely recognized. However, little is known about the efficacy of virucidal mouthwash formulations against emergent SARS-CoV-2 variants of concern and in the presence of saliva.Hypothesis. Mouthwashes containing virucidal actives will have similar inactivation effects against multiple SARS-CoV-2 variants of concern and will retain efficacy in the presence of human saliva.Aim. To examine in vitro efficacy of mouthwash formulations to inactivate SARS-CoV-2 variants.Methodology. Inactivation of SARS-CoV-2 variants by mouthwash formulations in the presence or absence of human saliva was assayed using ASTM International Standard E1052-20 methodology.Results. Appropriately formulated mouthwashes containing 0.07 % cetylpyridinium chloride but not 0.2 % chlorhexidine completely inactivated SARS-CoV-2 (USA-WA1/2020, Alpha, Beta, Gamma, Delta) up to the limit of detection in suspension assays. Tests using USA-WA1/2020 indicates that efficacy is maintained in the presence of human saliva.Conclusions. Together these data suggest cetylpyridinium chloride-based mouthwashes are effective at inactivating SARS-CoV-2 variants. This indicates potential to reduce viral load in the oral cavity and mitigate transmission via salivary aerosols.

Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2.

A key element for the prevention and management of coronavirus disease 2019 is the development of effective therapeutics. Drug combination strategies offer several advantages over monotherapies. They have the potential to achieve greater efficacy, to increase the therapeutic index of drugs and to reduce the emergence of drug resistance. We assessed the in vitro synergistic interaction between remdesivir and ivermectin, both approved by the US Food and Drug Administration, and demonstrated enhanced antiviral activity against severe acute respiratory syndrome coronavirus-2. Whilst the in vitro synergistic activity reported here does not support the clinical application of this combination treatment strategy due to insufficient exposure of ivermectin in vivo, the data do warrant further investigation. Efforts to define the mechanisms underpinning the observed synergistic action could lead to the development of novel treatment strategies.

Transitioning From In-Person to Remote Clinical Research on Depression and Traumatic Brain Injury During the COVID-19 Pandemic: Study Modifications and Preliminary Feasibility From a Randomized Controlled Pilot Study.

BACKGROUND: Telehealth has provided many researchers, especially those conducting psychosocial research, with the tools necessary to transition from in-person to remote clinical trials during the COVID-19 pandemic. A growing body of research supports the effectiveness of telemental health for a variety of psychiatric conditions, but few studies have examined telemental health for individuals with comorbid medical diagnoses. Furthermore, little is known about the remote implementation of clinical trials examining telemental health interventions. OBJECTIVE: This paper outlines the procedural modifications used to facilitate conversion of an in-person randomized controlled trial of cognitive behavioral therapy (CBT) for depression in individuals with traumatic brain injury (TBI; CBT-TBI) to a telemental health study administered remotely. METHODS: Given the nature of remote implementation and specific challenges experienced by individuals with TBI, considerations related to treatment delivery, remote consent, data management, neuropsychological assessment, safety monitoring, and delivery of supportive material have been discussed. Feasibility, acceptability, and safety were evaluated by examining attendance and participant responses on self-report measures of treatment satisfaction and suicidal behavior. RESULTS: High rates of treatment attendance, assessment completion, study retention, and satisfaction with the intervention and modality were reported by participants who completed at least one telemental health CBT-TBI session. CONCLUSIONS: Study modifications are necessary when conducting a study remotely, and special attention should be paid to comorbidities and population-specific challenges (eg, cognitive impairment). Preliminary data support the feasibility, acceptability, and safety of remotely conducting a randomized controlled trial of CBT-TBI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03307070; https://clinicaltrials.gov/ct2/show/NCT03307070.

Development of a partnership to improve palliative care services for children in the Gambia

Background Paediatric palliative care services in LMIC countries compete for resources with many other priorities. Their provision is desirable and includes advocacy, training health and community care workers, policy development and mentorship. Objectives The THET J&J start-up grants provided an ideal opportunity to establish a partnership with the Ministry of Health (MoH). The long term aim being to develop children's palliative care services in The Gambia. A needs assessment was carried out in early 2020. We hope reporting the results raises awareness of the gaps and possible solutions in LMIC. Methods The study took the form of a cross-sectional design with a focus on estimating the need for CPC and gaps at the country level. A mixed methods approach utilising both quantitative and qualitative data was used. Both primary and secondary data sources were used. The estimation of the need for CPC was based on estimation techniques using the prevalence and mortality of the specific diseases known to require palliative care. The response to the need and existing gaps were analysed using interviews and focus groups with key persons as well as survey data from service providers. Ethical approval for this study was given by the University of the Gambia, School of Medicine. Reference number R020 004 Results Five organisations completed a Capacity Self-Assessment Tool, 17 staff from 5 facilities were interviewed and 2 Focus Group Discussions were conducted (8 staff). The leading cause of death in children was heart disease, then lower respiratory infections and neonatal disorders, with HIV/AIDS being 5th, Tuberculosis 7th and cancer 9th. Under 5 mortality is 47.8 per 1,000 live births. It was not possible to estimate prevalence. Facility capacity assessment to provide CPC ranged from 23%-74%. Themes identified were a need to improve diagnostic ability;a desire for training;improve access and utilisation of medicines;and provide support for families. Training in Palliative care is on the nursing and medical students syllabus. Senior staff were keen for more training. Topics that staff felt anxious about were breaking bad news, anticipating palliative needs and use of medication. Conclusions The establishment of a training and mentoring service for staff in palliative care is required and desired. Paediatric diagnostic facilities need improved including equipment and access to specialist opinions eg an echocardiogram. in the main hospital in Banjul. The use of online Palliative training through lectures and modules, supported by scheduled in person visits is thought to be a good solution particularly in the current Covid-19 situation. 1 online lecture session has already taken place for 30 participants, supported by the MoH. This had good media coverage and promoted CPC awareness within the country. M.Sowe is currently undertaking a Palliative Care Diploma in Uganda partly funded by this grant. The World Bank has recently provided funding for specialist paediatrician secondment to The Gambia to improve paediatric services and a memorandum of understanding for patient pathways has been signed with the much larger neighbouring country of Senegal.