Impact of COVID-19 on rural and nonrural recovery housing in the United States

This study aimed to assess the impact of COVID-19 on recovery housing (RH), an important resource for individuals in recovery from substance use disorder (SUD). A cross-sectional survey was disseminated electronically between June and July of 2020 to RH owners and operators affiliated with Oxford House or the National Alliance of Recovery Residences nationwide. The survey intended to develop an understanding of the impact of COVID-19 on RH in terms of (a) resident housing access, (b) mitigation strategies to reduce COVID-19 spread, (c) RH financials, and (d) health and well-being of residents and staff. Impacts were assessed among all houses in the sample and then by rurality of RH location (rural vs. nonrural). Among 1,419 respondents, only 4.6% reported positive COVID-19 cases, and 85% reported having implemented centers for disease control-recommended policies. More than half (59%) reported financial impacts, and close to half (49%) reported COVID-19 had "a lot of impact" on residents attending meetings. Rural RH represented only 9% of respondents and a greater fraction of rural RH respondents reported spending more on all COVID-19 expense categories compared to nonrural RH respondents. Compared to nonrural RH, rural RH were significantly more likely to report having a process for evaluating COVID-19 (p = .007), wearing masks (p = .047), taking temperatures (p = .042), and spending more on food due to COVID-19 (p = .015). With SUD rates and the associated morbidity and mortality from SUD continuing to rise, addressing the financial viability of RH, an important resource supporting individuals in recovery is crucial. (PsycInfo Database Record (c) 2023 APA, all rights reserved) Impact Statement This study suggests that recovery housing, an important resource for individuals seeking or in recovery from a substance use disorder (SUD), is proactive in ensuring resident safety during national emergencies such as COVID-19. The most prominent impacts found in this study were financial (for the recovery home) and residents' ability to attend mutual aid recovery support meetings. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19.

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes.

Recovery housing predictors of closure risk during covid-19

Background COVID-19 has had widespread health and economic costs in the United States and around the world, especially for individuals with substance use disorders (SUDs). An important resource to assist those in recovery from SUDs is recovery housing, a housing model that utilizes peer support to help individuals on their path to recovery. Recovery housing has faced additional challenges due to COVID-19. Method We used cross-sectional survey data and a probit regression model to determine important predictors of recovery housing closure risk during COVID-19. Results We found that populations served, COVID-19 policies enacted, and house location are significant predictors of closure risk. We showed that, even when important differences between rural and non-rural houses are controlled for, rural houses are less likely to report being at risk of closing due to COVID-19. Conclusion Rurality remained an important predictor of closure risk, regardless of house characteristics. This may suggest inherent differences across rurality not included in our model. Recovery houses, in both rural and non-rural areas, continue to need support to offer important recovery services as the pandemic continues. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Implementation of genomic surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings

The COVID-19 pandemic highlighted the importance of global genomic surveillance to monitor the emergence and spread of SARS-CoV-2 variants and inform public health decision-making. Until December 2020 there was minimal capacity for viral genomic surveillance in most Caribbean countries. To overcome this constraint, the COVID-19: Infectious disease Molecular epidemiology for PAthogen Control & Tracking (COVID-19 IMPACT) project was implemented to establish rapid SARS-CoV-2 whole genome nanopore sequencing at The University of the West Indies (UWI) in Trinidad and Tobago (T&T) and provide needed SARS-CoV-2 sequencing services for T&T and other Caribbean Public Health Agency Member States (CMS). Using the Oxford Nanopore Technologies MinION sequencing platform and ARTIC network sequencing protocols and bioinformatics pipeline, a total of 3610 SARS-CoV-2 positive RNA samples, received from 17 CMS, were sequenced in-situ during the period December 5th 2020 to December 31st 2021. Ninety-one Pango lineages, including those of five variants of concern (VOC), were identified. Genetic analysis revealed at least 260 introductions to the CMS from other global regions. For each of the 17 CMS, the percentage of reported COVID-19 cases sequenced by the COVID-19 IMPACT laboratory ranged from 0·02% to 3·80% (median = 1·12%). Sequences submitted to GISAID by our study represented 73·3% of all SARS-CoV-2 sequences from the 17 CMS available on the database up to December 31st 2021. Increased staffing, process and infrastructural improvement over the course of the project helped reduce turnaround times for reporting to originating institutions and sequence uploads to GISAID. Insights from our genomic surveillance network in the Caribbean region directly influenced non-pharmaceutical countermeasures in the CMS countries. However, limited availability of associated surveillance and clinical data made it challenging to contextualise the observed SARS-CoV-2 diversity and evolution, highlighting the need for development of infrastructure for collecting and integrating genomic sequencing data and sample-associated metadata.

Clinical features, management and outcomes of peritoneal dialysis patients during Delta and Omicron waves of COVID-19 infections.

INTRODUCTION: There were discrete outbreaks of SARS-CoV-2 infection in 2021 (Delta wave) and 2022 (Omicron wave) in Singapore, which affected patients receiving peritoneal dialysis (PD). METHODS: This study included all PD patients with COVID-19 infection from a single center between October 2021 and March 2022. The clinical presentation, management and outcomes of patients during the Delta and Omicron outbreaks were compared. RESULTS: A total of 44 PD patients developed SARS-CoV-2 infection (23 during the Delta wave and 21 during the Omicron wave): median age 66 (60.5-68.5) years, male (63.6%), Chinese ethnic (77.3%), diabetes mellitus (56.8%), and cardiovascular disease (45.5%). Approximately, 93.2% received two doses of the mRNA COVID-19 vaccine. Cough (81.8%) and fever (54.5%) were common presenting symptoms. Chest radiography showed ground glass opacity in 23.5% of patients, consolidation in 55.6%, and bilateral lung involvement in 33.3%. Eleven patients (25.6%) received antiviral therapy (Remdesivir), 7 (16.3%) received steroid, and 4 (9.3%) received monoclonal antibodies. Patients infected during the Delta wave were more likely to be hospitalized (73.9 vs 14.3%; p < 0.001) and receive antiviral therapy (39.1 vs 10.0%; p = 0.03) than those during the Omicron wave. The overall mortality rate was 11.4%, with significantly higher mortality during the Delta wave than during the Omicron wave (21.7 vs 0%; p = 0.03). CONCLUSIONS: The mortality rate was high among infected PD patients during Delta wave of COVID-19 infection. However, during the Omicron wave, most infected patients were treated in the community with favorable outcomes.

Availability and prioritisation of COVID-19 vaccines among patients with advanced chronic kidney disease and kidney failure during the height of the pandemic: a global survey by the International Society of Nephrology.

OBJECTIVE: Patients with advanced chronic kidney disease (CKD) or kidney failure receiving replacement therapy (KFRT) are highly vulnerable to COVID-19 infection, morbidity and mortality. Vaccination is effective, but access differs around the world. We aimed to ascertain the availability, readiness and prioritisation of COVID-19 vaccines for this group of patients globally. SETTING AND PARTICIPANTS: Collaborators from the International Society of Nephrology (ISN), Dialysis Outcomes and Practice Patterns Study and ISN-Global Kidney Health Atlas developed an online survey that was administered electronically to key nephrology leaders in 174 countries between 2 July and 4 August 2021. RESULTS: Survey responses were received from 99 of 174 countries from all 10 ISN regions, among which 88/174 (50%) were complete. At least one vaccine was available in 96/99 (97%) countries. In 71% of the countries surveyed, patients on dialysis were prioritised for vaccination, followed by patients living with a kidney transplant (KT) (62%) and stage 4/5 CKD (51%). Healthcare workers were the most common high priority group for vaccination. At least 50% of patients receiving in-centre haemodialysis, peritoneal dialysis or KT were estimated to have completed vaccination at the time of the survey in 55%, 64% and 51% of countries, respectively. At least 50% of patients in all three patient groups had been vaccinated in >70% of high-income countries and in 100% of respondent countries in Western Europe.The most common barriers to vaccination of patients were vaccine hesitancy (74%), vaccine shortages (61%) and mass vaccine distribution challenges (48%). These were reported more in low-income and lower middle-income countries compared with high-income countries. CONCLUSION: Patients with advanced CKD or KFRT were prioritised in COVID-19 vaccination in most countries. Multiple barriers led to substantial variability in the successful achievement of COVID-19 vaccination across the world, with high-income countries achieving the most access and success.

NAVKIDS2 trial: a multi-centre, waitlisted randomised controlled trial of a patient navigator intervention in children with chronic kidney disease - statistical analysis plan and update to the protocol.

BACKGROUND: This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published. METHODS/DESIGN: The original protocol was published in BMC Nephrology ( https://doi.org/10.1186/s12882-019-1325-y ) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1-2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0-16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213 . Prospectively registered on 12 July 2018.

Epidemiology of peritoneal dialysis outcomes.

Peritoneal dialysis (PD) is an important home-based treatment for kidney failure and accounts for 11% of all dialysis and 9% of all kidney replacement therapy globally. Although PD is available in 81% of countries, this provision ranges from 96% in high-income countries to 32% in low-income countries. Compared with haemodialysis, PD has numerous potential advantages, including a simpler technique, greater feasibility of use in remote communities, generally lower cost, lesser need for trained staff, fewer management challenges during natural disasters, possibly better survival in the first few years, greater ability to travel, fewer dietary restrictions, better preservation of residual kidney function, greater treatment satisfaction, better quality of life, better outcomes following subsequent kidney transplantation, delayed need for vascular access (especially in small children), reduced need for erythropoiesis-stimulating agents, and lower risk of blood-borne virus infections and of SARS-CoV-2 infection. PD outcomes have been improving over time but with great variability, driven by individual and system-level inequities and by centre effects; this variation is exacerbated by a lack of standardized outcome definitions. Potential strategies for outcome improvement include enhanced standardization, monitoring and reporting of PD outcomes, and the implementation of continuous quality improvement programmes and of PD-specific interventions, such as incremental PD, the use of biocompatible PD solutions and remote PD monitoring.

The impact of the COVID-19 pandemic on the mental health of dentists in Wales.

Introduction The COVID-19 pandemic has had a large impact on dentistry across Wales. Dentists were facing significant levels of psychological distress prior to the pandemic, so it was important to monitor dentists' mental health during this unprecedented challenge.Aims To gain both an understanding of the impact that the COVID-19 pandemic has been having on the mental health of dentists working in Wales, as well as understanding the levels of stress the pandemic has caused. We also aimed to understand the specific causes of stress.Results High levels of stress were found, with 82% of respondents saying stress levels in the dental team have increased noticeably. Three-quarters of respondents have gone to work despite not feeling mentally well enough. Working conditions and financial pressures caused by the pandemic have directly impacted the mental health of many dentists. As a result, they have been using both adaptive and maladaptive coping methods to cope with the stress of the pandemic, with over one-third of respondents drinking alcohol more frequently than before the pandemic.Conclusions The pandemic has had a profound impact on the professional lives of dentists working in Wales. Their interactions with patients and colleagues have been greatly affected, as well as their work and working conditions. These have all substantially contributed to increased stress levels. Without significant improvements to the working conditions of dentists, as well as continued psychological support, large-scale burnout in the future is not only possible, but likely.

GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2.

Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.

Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain.

A series of amino acid based 7H-pyrrolo[2,3-d]pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis. Structure activity studies identified compound 15c as a low-micromolar inhibitor of Mac1 in two ADP-ribose binding assays. This compound also demonstrated inhibition in an enzymatic assay of Mac1 and displayed a thermal shift comparable to ADPr in the melting temperature of Mac1 supporting binding to the target protein. A structural model reproducibly predicted a binding mode where the pyrrolo pyrimidine forms a hydrogen bonding network with Asp22 and the amide backbone NH of Ile23 in the adenosine binding pocket and the carboxylate forms hydrogen bonds to the amide backbone of Phe157 and Asp156, part of the oxyanion subsite of Mac1. Compound 15c also demonstrated notable selectivity for coronavirus macrodomains when tested against a panel of ADP-ribose binding proteins. Together, this study identified several low MW, low µM Mac1 inhibitors to use as small molecule chemical probes for this potential anti-viral target and offers starting points for further optimization.

Potent Protease Inhibitors of Highly Pathogenic Lagoviruses: Rabbit Hemorrhagic Disease Virus and European Brown Hare Syndrome Virus.

Rabbit hemorrhagic disease (RHD) and European brown hare syndrome (EBHS) are highly contagious diseases caused by lagoviruses in the Caliciviridae family. These infectious diseases are associated with high mortality and a serious threat to domesticated and wild rabbits and hares, including endangered species such as riparian brush rabbits (Sylvilagus bachmani riparius). In the United States (U.S.), only isolated cases of RHD had been reported until Spring 2020. However, RHD caused by GI.2/rabbit hemorrhagic disease virus (RHDV)2/b was unexpectedly reported in April 2020 in New Mexico and has subsequently spread to several U.S. states, infecting wild rabbits and hares and making it highly likely that RHD will become endemic in the U.S. Vaccines are available for RHD; however, there is no specific treatment for this disease. Lagoviruses encode a 3C-like protease (3CLpro), which is essential for virus replication and a promising target for antiviral drug development. We have previously generated focused small-molecule libraries of 3CLpro inhibitors and demonstrated the in vitro potency and in vivo efficacy of some protease inhibitors against viruses encoding 3CLpro, including caliciviruses and coronaviruses. Here, we report the development of the enzyme and cell-based assays for the 3CLpro of GI.1c/RHDV, recombinant GI.3P-GI.2 (RHDV2/b), and GII.1/European brown hare syndrome virus (EBHSV) as well as the identification of potent lagovirus 3CLpro inhibitors, including GC376, a protease inhibitor being developed for feline infectious peritonitis. In addition, structure-activity relationship study and homology modeling of the 3CLpro and inhibitors revealed that lagovirus 3CLpro share similar structural requirements for inhibition with other calicivirus 3CLpro. IMPORTANCE Rabbit hemorrhagic disease (RHD) and European brown hare syndrome (EBHS) are viral diseases that affect lagomorphs with significant economic and ecological impacts. RHD vaccines are available, but specific antiviral treatment for these viral infections would be a valuable addition to the current control measures. Lagoviruses encode 3C-like protease (3CLpro), which is essential for virus replication and an attractive target for antiviral drug discovery. We have screened and identified potent small-molecule inhibitors that block lagovirus 3CLpro in the enzyme- and cell-based assays. Our results suggest that these compounds have the potential for further development as antiviral drugs for lagoviruses.

Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening.

The emergence of several zoonotic viruses in the last twenty years, especially the pandemic outbreak of SARS-CoV-2, has exposed a dearth of antiviral drug therapies for viruses with pandemic potential. Developing a diverse drug portfolio will be critical to rapidly respond to novel coronaviruses (CoVs) and other viruses with pandemic potential. Here we focus on the SARS-CoV-2 conserved macrodomain (Mac1), a small domain of non-structural protein 3 (nsp3). Mac1 is an ADP-ribosylhydrolase that cleaves mono-ADP-ribose (MAR) from target proteins, protects the virus from the anti-viral effects of host ADP-ribosyltransferases, and is critical for the replication and pathogenesis of CoVs. In this study, a luminescent-based high-throughput assay was used to screen ∼38,000 small molecules for those that could inhibit Mac1-ADP-ribose binding. We identified 5 compounds amongst 3 chemotypes that inhibit SARS-CoV-2 Mac1-ADP-ribose binding in multiple assays with IC50 values less than 100 µM, inhibit ADP-ribosylhydrolase activity, and have evidence of direct Mac1 binding. These chemotypes are strong candidates for further derivatization into highly effective Mac1 inhibitors.

The case for increased peritoneal dialysis utilization in low- and lower-middle-income countries.

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.

Impact of COVID-19 on the worsening crisis of chronic kidney disease: the imperative to fund early detection is now.

The number of Australians affected by kidney disease will increase as the impacts of COVID-19 infection on kidney health are realised. Chronic kidney disease (CKD) imposes significant health and economic burdens from dialysis costs, loss of employment, premature death and increased admissions to hospital. Screening for kidney disease must be integrated into post-COVID-19 care; however, currently there is no reimbursement for kidney health checks in primary care. Early detection can reduce the progression of CKD by as much as 50% and thus the imperative to fund the Kidney Health Check is now.

The Influence of Public Health Faculty on College and University Plans During the COVID-19 Pandemic.

The purpose of this study was to explore whether the institutional presence of public health expertise within colleges and universities was associated with operational plans for the fall semester of 2020. Using cross-sectional data collected by the College Crisis Initiative of Davidson College, six levels of instructional modalities (ranked from least to most restrictive) were compared between Council on Education of Public Health (CEPH)-accredited and non-CEPH-accredited 4-year institutions. Institutions with CEPH-accredited schools and programs were more likely to select some restrictive teaching modalities: 63.8% more likely to use hybrid/hyflex or more restrictive and 66.9% more likely to be primarily online (with some in person) or more restrictive. However, having CEPH-accredited programs did not push institutions to the most restrictive modalities. COVID-19 cases in county, enrollment, and political affiliation of the state governor were also found to be associated with instructional modality selection. While any ecological study has certain limitations, this study suggests that college and university fall plans may have been influenced by the presence of CEPH-accredited schools and programs of public health, and/or the input of their faculty. The influence of relevant faculty expertise on institutional decision-making can help inform college and university responses to future crises.