A spatio-temporal framework for modelling wastewater concentration during the COVID-19 pandemic

The potential utility of wastewater-based epidemiology as an early warning tool has been explored widely across the globe during the current COVID-19 pandemic. Methods to detect the presence of SARS-CoV-2 RNA in wastewater were developed early in the pandemic, and extensive work has been conducted to evaluate the relationship between viral concentration and COVID-19 case numbers at the catchment areas of sewage treatment works (STWs) over time. However, no attempt has been made to develop a model that predicts wastewater concentration at fine spatio-temporal resolutions covering an entire country, a necessary step towards using wastewater monitoring for the early detection of local outbreaks. We consider weekly averages of flow-normalised viral concentration, reported as the number of SARS-CoV-2N1 gene copies per litre (gc/L) of wastewater available at 303 STWs over the period between 1 June 2021 and 30 March 2022. We specify a spatially continuous statistical model that quantifies the relationship between weekly viral concentration and a collection of covariates covering socio-demographics, land cover and virus associated genomic characteristics at STW catchment areas while accounting for spatial and temporal correlation. We evaluate the model's predictive performance at the catchment level through 10-fold cross-validation. We predict the weekly viral concentration at the population-weighted centroid of the 32,844 lower super output areas (LSOAs) in England, then aggregate these LSOA predictions to the Lower Tier Local Authority level (LTLA), a geography that is more relevant to public health policy-making. We also use the model outputs to quantify the probability of local changes of direction (increases or decreases) in viral concentration over short periods (e.g. two consecutive weeks). The proposed statistical framework can predict SARS-CoV-2 viral concentration in wastewater at high spatio-temporal resolution across England. Additionally, the probabilistic quantification of local changes can be used as an early warning tool for public health surveillance. © 2023

Oxygen and Ventilator Logistics During California's COVID-19 Surge: When Oxygen Becomes a Scarce Resource

The state of California, in the United States of America, has a population of nearly 40 million people and is the 5th largest economy in the world. During the coronavirus disease 2019 (COVID-19) pandemic in 2020-2021, the state experienced a medical surge that stressed its sophisticated health-care and public health system. During this period, ventilators, oxygen, and other equipment necessary for providing ventilatory support became a scarce resource in many health-care settings. When demand overwhelms supply, creative solutions are required at all levels of disaster management and health care. This study describes the disaster response by the state of California to mitigate the emergency demands for oxygen delivery resources. © The Author(s), 2021. Published by Cambridge University Press on behalf of Society for Disaster Medicine and Public Health, Inc.

Virtual Reality for Anatomy and Surgical Teaching

The COVID-19 pandemic has led to significant challenges when it comes to the delivery of education across multiple domains. There has been a shift in paradigm towards the use of new innovative methods for the delivery of training within medicine and surgery. In this chapter, there is an outline of one such innovative method, the use of virtual reality for anatomy and surgical teaching. At all levels of training, undergraduate through to postgraduate specialty-based training, conventional methods of learning anatomy have had to be adapted due to difficulties encountered during the pandemic. The importance of hands-on cadaveric anatomy experience in surgical training cannot be understated. The decline in face-to-face sessions, as well as a reduction in bedside training due to the prioritisation of service provision and diminishing time spent in theatre have meant less exposure for trainees when it comes to learning procedural skills. Virtual Reality in Medicine and Surgery, a free for trainee resource utilising virtual reality technology, delivered 51-week courses with the aim to ensure high-quality training still occurred. The authors believe there is immense potential for immersive technology when it comes to the future of training within medicine and surgery. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Chicago's Citywide COVID-19 Vaccine Equity Program: Protect Chicago Plus.

Vaccination is one of the most effective strategies to control the spread of COVID-19 and reduce morbidity and mortality; however, rapid and equitable vaccine distribution is required to achieve such outcomes. We conducted a basic interrupted time-series analysis to examine the short-term impacts of a citywide vaccine equity plan, the Protect Chicago Plus (PCP) plan. We compared vaccine coverage in zip codes in Chicago with high COVID-19 vulnerability, as identified from the Chicago COVID-19 Community Vulnerability Index, with coverage in all other zip codes in Chicago. From our analysis, we observed that implementation of PCP coincided with reduced vaccination disparities between Chicago communities with low and high vulnerability indexes over time. In our analysis of vaccination coverage before program implementation, vaccination coverage climbed nearly twice as fast among non-PCP zip codes (0.19% per day) than among PCP zip codes (0.10% per day) or by 0.09 percentage points (P < .001). In model analysis after program implementation, zip codes prioritized for the program had 0.42% additional coverage per day as compared with 0.27% per day for non-PCP zip codes. Our findings suggest that such programs may improve vaccine equity, but additional research is needed to better understand the longer-term effects of citywide vaccination strategies on vaccine uptake.

Impact of COVID-19 & Response Measures on HIV-HCV Prevention Services and Social Determinants in People Who Inject Drugs in 13 Sites with Recent HIV Outbreaks in Europe, North America and Israel.

HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011-2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.

RESUMEN: La prevención del VIH/VHC entre las personas que se inyectan drogas (PWID) es de vital importancia para la salud pública. Nuestro objetivo fue evaluar el impacto de COVID-19 y las medidas de respuesta asociadas en los servicios de prevención del VIH/VHC y el estado socioeconómico de las PWID en sitios de alto riesgo de VIH. Se contactó con sitios con brotes recientes (2011­2019) de VIH entre PWID en Europa, América del Norte e Israel, que habían sido previamente identificados, a principios de mayo de 2020. De los 17 sitios invitados a participar, 13 aceptaron. Se prepararon informes cualitativos semiestructurados del sitio que cubrían los datos de marzo a mayo de 2020, analizados/codificados y confirmados con un cuestionario estructurado, en el que todos los sitios respondieron explícitamente a los 103 asuntos reportados en los informes cualitativos. El tratamiento de mantenimiento con opiáceos, los programas de agujas/jeringas y el tratamiento antirretroviral/tratamiento de la hepatitis C continuaron, pero con importantes reducciones y cambios operativos. Se reportaron aumentos en las sobredosis, dificultades generalizadas con las necesidades alimentarias y de higiene, interrupciones en el suministro de medicamentos y aumento de personas sin hogar. Los programas de servicios reformaron rápidamente las políticas restrictivas de prestación de servicios, establecidas desde hace mucho tiempo y políticamente arraigadas. Las futuras medidas de control de epidemias deben incluir la mitigación de los efectos secundarios negativos en la prestación de servicios y los determinantes socioeconómicos en las PWID.

Suprascapular nerve blockage for painful shoulder pathology - a systematic review and meta-analysis of treatment techniques.

BACKGROUND: Suprascapular nerve blockade (SSNB) through injection (SSNBi) and/or pulsed radiofrequency (PRF) provide options for the management of painful shoulder pathology. Multiple techniques for delivery of SSNB are described but no consensus on optimal symptom control is available. This systematic review and meta-analysis aims to assess patient-focussed outcomes in SSNB and explore the impact of variation in the technical application of this treatment modality. METHODS: MEDLINE, Embase and CINAHL were searched for case series, cohort studies and randomised control trials published from database inception until 28 January 2021. Articles reporting use of SSNBi or PRF for treatment of shoulder pain with a minimum 3 months follow-up were included. Patient-reported outcome measures (PROMs) were extracted and the pooled standardised mean difference (SMD), weighted by study size, was reported. Quality of methodology was assessed using Wylde's nonsummative four-point system. FINDINGS: Of 758 references, 18 studies were included, totalling 704 SSNB. Average pain improvement at 3 months was 52.3%, with meta-analysis demonstrating a SMD of 2.37. Whereas SSNBi combined with PRF shows the greatest SMD of 2.75, this did not differ significantly from SSNBi or PRF when used as monotherapy. Location of treatment and the guidance technique used did not influence outcome. CONCLUSION: SSNBi and PRF provide safe and effective treatment for shoulder pain, as judged by PROMs. This may be of particular value in aging or comorbid patients and with surgical restrictions during the Covid-19 pandemic. Regardless of technique, patients experience a marked improvement in pain that is maintained beyond 3 months.

Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency.

Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-ß. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-ß and compensatory adaptive immunity.

MAIT cell compartment characteristics are associated with the immune response magnitude to the BNT162b2 mRNA anti-SARS-CoV-2 vaccine.

Mucosa-associated invariant T (MAIT) cells are unconventional T cells with innate-like capacity to rapidly respond to microbial infection via MR1-restricted antigen recognition. Emerging evidence indicate that they can also act as rapid sensors of viral infection via innate cytokine activation. However, their possible role in the immune response to mRNA vaccination is unknown. Here, we evaluated the involvement of MAIT cells in individuals vaccinated with the BNT162b2 mRNA SARS-CoV-2 vaccine. MAIT cell levels, phenotype and function in circulation were preserved and unperturbed through day 35 post-vaccination in healthy donor (HD) vaccinees, as well as people living with HIV (PLWH) or with primary immunodeficiency (PID). Unexpectedly, pre-vaccination and post-vaccination levels of MAIT cells correlated positively with the magnitude of the SARS-CoV-2 spike protein-specific CD4 T cell and antibody responses in the HD vaccinees. This pattern was largely preserved in the PID group, but less so in the PLWH group. Furthermore, in the HD vaccinees levels of MAIT cell activation and cytolytic potential correlated negatively to the adaptive antigen-specific immune responses. These findings indicate an unexpected association between MAIT cell compartment characteristics and the immune response magnitude to the BNT162b2 mRNA vaccine.

Examining American Adult's Mental Well and Ill-Being During the 2020 COVID-19 Pandemic Using a Self-Determination Theory Perspective.

Objectives: The COVID-19 pandemic is an international health crisis that has caused unprecedented shifts in people's environments and has threatened people's wellbeing. The current study uses self-determination theory (SDT: 10) to understand how people were handling the pandemic, which proposes three basic psychological needs (autonomy, competence, and relatedness) are vital for human growth and thriving. Furthermore, we examined how people's wellbeing and ill-being changed over the course of the pandemic. Methods: A sample of 193 American adults from around the country reported on their need satisfaction and frustration as well as well and ill-being at three time periods during the pandemic (April 2020, late July/early August 2020, and late January/early February 2021). Results: There was much variability in how people were handling the pandemic, but on average, wellbeing increased, and ill-being decreased over time. Consistent with SDT, the basic needs significantly predicted well and ill-being even during such unprecedented times of disruption. Conclusion: Our results suggest that public health officials should help individuals to focus on autonomy, competence, and relatedness behaviors during times of upheaval.

Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant.

Immunodeficient individuals often rely on donor-derived immunoglobulin (Ig) replacement therapy (IGRT) to prevent infections. The passive immunity obtained by IGRT is limited and reflects the state of immunity in the plasma donor population at the time of donation. The objective of the current study was to describe how the potential of passive immunity to SARS-CoV-2 in commercial off-the-shelf Ig products used for IGRT has evolved during the pandemic. Samples were collected from all consecutive Ig batches (n = 60) from three Ig producers used at the Immunodeficiency Unit at Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until January 2022. SARS-CoV-2 antibody concentrations and neutralizing capacity were assessed in all samples. In vivo relevance was assessed by sampling patients with XLA (n = 4), lacking endogenous immunoglobulin synthesis and on continuous Ig substitution, for plasma SARS-CoV-2 antibody concentration. SARS-CoV-2 antibody concentrations in commercial Ig products increased over time but remained inconsistently present. Moreover, Ig batches with high neutralizing capacity towards the Wuhan-strain of SARS-CoV-2 had 32-fold lower activity against the Omicron variant. Despite increasing SARS-CoV-2 antibody concentrations in commercial Ig products, four XLA patients on IGRT had relatively low plasma concentrations of SARS-CoV-2 antibodies with no potential to neutralize the Omicron variant in vitro. In line with this observation, three out the four XLA patients had symptomatic COVID-19 during the Omicron wave. In conclusion, 2 years into the pandemic the amounts of antibodies to SARS-CoV-2 vary considerably among commercial Ig batches obtained from three commercial producers. Importantly, in batches with high concentrations of antibodies directed against the original virus strain, protective passive immunity to the Omicron variant appears to be insufficient.

Cognitive Walkthrough of Multiple Drone Delivery Operations

Advances of early twenty-first century aviation and transportation technologies provide opportunities for enhanced aerial projects, and the overall integration of unmanned aircraft systems (UAS) into the National Airspace System (NAS) has applications across a wide range of operations. Through these, remote operators have learned to manage several UAS at the same time in a variety of operational environments. The present work details a component piece of an ongoing body of research into multi-UAS operations. Beginning in early 2020, NASA has collaborated with Uber Technologies to design and develop concepts of operations, roles and responsibilities, and ground control station (GCS) concepts to enable food delivery operations via multiple, small UAS (sUAS). A cognitive walkthrough was chosen as the method for data collection. This allowed information to be gathered from UAS subject matter experts (SMEs) that could further mature designs for future human-in-the-loop (HITL) simulations;in addition, it allowed information to be collected remotely during the stringent restrictions of the COVID-19 pandemic. Consequently, the described cognitive walkthrough activity utilized remote data collection protocols mediated through the usage of programs designed for presentation and telecommunications. Scenarios were designed, complete with airspace, contingencies, and remedial actions, to be presented to the SMEs. Information was collected using a combination of rating scales and open-ended questions. Results received from the SMEs revealed expected hazards, workloads, and information concerns inherent in the contingency scenarios. SMEs also provided insight into the design of GCS tools and displays as well as the duties and relationships of human operators (i.e., monitors) and automation (i.e., informers and flight managers). Implications of these findings are discussed.

Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV 2 Spike Glycoprotein

SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease-COVID-19-within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronaviruss surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 . We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the closed prefusion S structure, but is accessible in open conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Suspected appendicitis and COVID-19, a change in investigation and management-a multicentre cohort study.

PURPOSE: The COVID-19 pandemic has reformed global healthcare delivery. On 25 March 2020, Intercollegiate guidelines were published in the UK to promote safe surgical provision during the COVID-19 outbreak advocating non-operative management or avoidance of laparoscopy when surgery is essential. The effects of this on the investigation and management of appendicitis remain unknown. METHODS: We performed a multicentre, prospective, observational study from the start of the new guidelines to the 6th of May 2020. We included all patients referred to surgical teams with suspected appendicitis. A recent historical cohort was identified for comparison. The primary outcome was the impact of the COVID-19 pandemic on the use of non-operative management in appendicitis. Secondary outcomes included imaging, negative appendicectomy rate (NAR), length of stay (LOS) and 30-day complications. RESULTS: A total of 63/164 (38%) patients compared to 79/191 (41%) were diagnosed with appendicitis before and after the guidelines were introduced (p = 0.589). CT scanning increased (71/164 vs 105/191; p = 0.033) while ultrasound scanning decreased (71/164 vs 62/191; p = 0.037). Appendicitis was more likely to be managed non-operatively (11/63 vs 51/79; p < 0.001) and, of those managed surgically, with an open approach (3/52 vs 26/28 p < 0.001). The NAR also reduced (5/52 vs 0/28; p = 0.157). LOS was shorter in non-operatively managed patients (1 day vs 3 days; p < 0.001) without a difference in complications (10/51 vs 4/28; p = 0.760). CONCLUSION: Introduction of the guidelines was associated with changes in practice. Despite these changes, short-term complications did not increase and LOS decreased. Questions remain on the longer-term complication rates in non-operatively managed patients.

Neuropathological findings in two patients with fatal COVID-19.

AIMS: To describe the neuropathological findings in two cases of fatal Coronavirus Disease 2019 (COVID-19) with neurological decline. METHODS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection was confirmed in both patients by reverse transcription polymerase chain reaction (RT-PCR) from nasopharyngeal swabs antemortem. Coronial autopsies were performed on both patients and histological sampling of the brain was undertaken with a variety of histochemical and immunohistochemical stains. RNAscope® in situ hybridization (ISH) using the V-nCoV2019-S probe and RT-PCR SARS-CoV-2 ribonucleic acid (RNA) was performed in paraffin-embedded brain tissue sampled from areas of pathology. RESULTS: Case 1 demonstrated severe multifocal cortical infarction with extensive perivascular calcification and numerous megakaryocytes, consistent with a severe multi-territorial cerebral vascular injury. There was associated cerebral thrombotic microangiopathy. Case 2 demonstrated a brainstem encephalitis centred on the dorsal medulla and a subacute regional infarct involving the cerebellar cortex. In both cases, ISH and RT-PCR for SARS-CoV-2 RNA were negative in tissue sampled from the area of pathology. CONCLUSIONS: Our case series adds calcifying cerebral cortical infarction with associated megakaryocytes and brainstem encephalitis to the spectrum of neuropathological findings that may contribute to the neurological decompensation seen in some COVID-19 patients. Viral RNA was not detected in post-mortem brain tissue, suggesting that these pathologies may not be a direct consequence of viral neuroinvasion and may represent para-infectious phenomena, relating to the systemic hyperinflammatory and hypercoagulable syndromes that both patients suffered.

Five Questions for Residency Leadership in the Time of COVID-19: Reflections of Chief Medical Residents From an Internal Medicine Program.

The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program's response to the demands of COVID-19 during this uncertain time in health care.