Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.

Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection.

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.

Efficacy of Bromhexine versus Standard of Care in Reducing Viral Load in Patients with Mild-to-Moderate COVID-19 Disease Attended in Primary Care: A Randomized Open-Label Trial.

A 28-day randomized open-label multicenter study was conducted to assess the efficacy of bromhexine plus standard of care (SOC) (n = 98) vs. SOC alone (n = 93) in 191 outpatients with mild-to-moderate COVID-19 in the primary health care setting. Bromhexine three daily doses of 10 mL (48 mg/day) were administered for seven days. The primary efficacy endpoint was the reduction of viral load estimated as the cycle thresholds (Ct) to detect ORF1ab, N Protein, and S Protein genes by RT-qPCR in saliva samples on day 4 as compared with baseline. Ct values of the three genes increased from baseline throughout days 4 to 14 (p < 0.001) but significant differences between the study groups were not found. Differences in the percentages of patients with low, medium, and high viral loads at 4, 7, and 14 days were not found either. In summary, treatment with bromhexine plus SCO was associated with a viral load reduction of ORF1ab, N Protein, and S Protein genes at day 4, which was not significantly different than similar viral load reductions observed with SOC alone. The present findings do not seem to favor the use of bromhexine as an antiviral in patients with COVID-19.

Adoption of measures to mitigate the impact of COVID-19: In search of a Hofstedian explanation for patterns among individual countries and country clusters.

We consider multiple safety measures in relation to the COVID-19 virus and look at their adoption levels for a variety of 15 individual countries, based on data from Yougov.co.uk. Subsequently, we establish correlation coefficients between measure-specific uptake levels and Hofstede dimension scores for all countries considered. We notably find that Power Distance Index (PDI) and Individualism (IDV) have a considerable explanatory power. In addition, we carried out a Principal Components Analysis (PCA) and a cluster analysis to see whether the behavioural patterns across countries can be grouped, and which Hofstede dimensions correlate strongest with the two main components that follow from the PCA. The PCA provides further confirmation of PDI and IDV being the most important explanatory factors for the uptake of measures across countries. The cluster analysis, in turn, reveals four broad groups, which only partly coincide with the way that the mental image clustering scheme by Wursten (2019) allots countries into its respective clusters. Hence, this provides a basis to suggest that data-driven exercises like the ones from our paper can serve to adjust Wursten's intuitive scheme.

Comparison of Acute Kidney Failure in Patients With SARS-COV-2 Infection During the First and Second Waves in a Third-Level Hospital in Andalusia

BACKGROUND AND AIMS The incidence of acute renal failure (ARF) is frequent and has an implication in the morbidity and mortality of SARS-CoV-2 infection. METHOD A retrospective descriptive study of patients admitted for SARS-CoV-2 infection during the first (G1) and second (G2) waves who presented with ARF. They correspond to the period from March to May 2020 (G1) and from August to December 2020 (G2). We compare populations, outcomes and treatments. RESULTS A total of 73 patients in the first wave (G1), with a cumulative incidence (CI) of 28.3% (G1), compared with 58 patients in the second wave (G2), with a CI of 8% (G2). The mean age was higher in G2 [65.8 ± 15 years (G1);75.3 ± 14 (G2);P <.05], with no difference regarding sex [63% (G1);54% (G2)]. In G2, there was a higher proportion of patients with cardiovascular disease [23% (G1);57% (G2)], hypertension [56% (G1);83% (G2)]. The baseline glomerular filtration rate (GFR) being similar for both groups (CKD EPI: 69 mL/min/1.73² (G1);P = .27). In the first wave, the mean days from admission to ARF was 3.1 days ± 4.2, and 42% of the patients were diagnosed at admission (31 patients). In the second, it was 2.9 days ± 5.7, of which 60% at admission (35 patients). The most prevalent cause was prerenal in both. Higher proportion in G1 of KDIGO stage 3 (G1: 30% versus G2: 17%) and renal replacement therapy (RRT) (G1: 9 versusG2: 2 patients). Only 3 patients remained in RRT in G1 and 1 patient in G2. In G1, 64% recovered their GFR [mean time (MT): 7.5 ± 8 days], and the percentage of deaths was 34%. In G2, 72% recovered GFR (MT: 16 ± 25 days), and 19% of patients died. CONCLUSION Despite a lower age and comorbidity of the first wave patients, the severity and lethality was higher. There were no differences in the proportion of patients who recovered their baseline renal function, although the recovery time was longer in the second wave.Table 1.Characteristics of kidney failure and treatmentsGroup 1Group 2Baseline CKD G1-240 (61%)36 (63%)P = .245 G316 (26%)18 (32%) G4-59 (14%)3 (5%)ARF severity (KDIGO) KDIGO 1 and 251 (70%)48 (83%)P = 0.08 KDIGO 322 (30%)10 (17%)Cause of ARF Prerenal38 (52%)39 (67%)P = 0.121 Sepsis25 (25%) 11 (19%) Obstructive2 (3%)4 (7%) Others8 (11%)4 (7%) Haematuria8 (11%)16 (27%)P = 0.74 ICU18 (25%)3 (5%)P = 0.03 OTI16 (22%)3 (5%)P = 0.007 RRT9 (12%)2 (3%)P = 0.069 ARF recovery time7.5 ± 816 ± 25P = 0.04 Total Patients7358 Group 1: ARF patients on first wave of SARS CoV2. Group 2: ARF patients on the second wave of SARS CoV2. Baseline CKD, baseline chronic kidney disease;ICU, intensive care unit;OTI, orotracheal intubation;and RRT, renal replacement therapy. ARF recovery time: days from renal failure to recovery of baseline renal function.

Acute Kidney Injury in COVID-19 Patients: Medium-Term Evolution of Renal Function

BACKGROUND AND AIMS Acute kidney injury (AKI) is a common complication among patients hospitalized with COVID-19. The incidence of AKI is estimated to be around 5%–80%, according to the series, but data on renal function evolution is limited. Our main objective was to describe the incidence of AKI in patients with SARS-CoV-2 infection;secondarily, we analysed the severity of AKI and medium-term renal function evolution in these patients. METHOD A retrospective observational study that included patients hospitalized a single hospital, diagnosed with SARS-CoV-2 infection, who developed AKI (March-May 2020). We register clinical and demographic characteristics, creatinine upon admission and prior to discharge, as well as creatinine and CKD-EPI glomerular filtration rate (eGFR) after at least 3 months after discharge. CKD was defined according to KDIGO stages based on the eGFR (G3-G5). The KDIGO classification was used to define and classify AKI. Recovery of kidney function was defined as difference in at discharge or post-hospitalization creatinine < 0.3 mg/dL with respect basal creatinine. The clinical follow-up ranged from admission to death or end of study. RESULTS Of 258 patients hospitalized with SARS-CoV-2 infection, AKI occurred in 73 (28.3%). 63% (n = 46) were men;the mean of age was 69 years (57–76). DRA severity: 35 (48%) KDIGO-1, 15 (21%) KDIGO-2 and 23 (31%) KDIGO-3. The mean stay was associated with the severity of AKI: 7 days (3–11) for KDIGO-1, 11 days for KDIGO-2 (5–22) and 12 days (8–35) for KDIGO-3 (P = .02). The stage of CKD established differences in the severity of AKI: 66.6% (n = 6) of the patients with CKD G4–G5 presented AKI-KDIGO 3 versus only 25.0% (n = 4) in the CKD-G3 patients (P = .02). Admission to the ICU was more frequent in KDIGO 2–3 versus KDIGO-1 [39% (n = 15) versus 9% (n = 3);P < .01]. Of the 48 patients discharged, 30 (62.5%) had recovered their baseline renal function upon discharge. Only 2 are still on RRT after 8 months (2.7% of all patients). Of the 25 patients died (34% of patients with AKI) with a median time of 3 days from DRA diagnosis (1–8). Renal function of 35 patients was monitored, which correspond to 19 (54%) KDIGO-1, 8 (23%) KDIGO-2, 8 (23%) KDIGO-3 stages. In these patients, analytical control starting 3 months after hospitalization revealed FG 66 (SD 30;56–76) mL/min/1.73 m2. We have not found differences in renal function between pre- and post-hospitalization in related test. A total of 77% (n = 37) of discharged patients recovered their baseline renal function in the post-hospitalization control. CONCLUSION The incidence of AKI in the context of COVID-19 in our series was 28.3%, with an associated mortality of 34.2%. Most of the patients presented with AKI KDIGO 1 (47.9%). The severity of AKI is associated with a longer hospital stay, admission to the ICU and the requirement for RRT. The advanced stages of CKD pre-admission showed more severity of AKI. The maintenance in TRS in our series has been 2.7%. Patients who were discharged for recovery/improvement of COVID-19 had normalized kidney function during subsequent follow-up, regardless of the severity of the AKI developed on admission for COVID-19.

Update on COVID-19 and histophysiology of the male reproductive system / Actualización sobre COVID-19 e histofisiología del sistema reproductor masculino

RESUMEN: La reciente pandemia de la COVID-19 ha sacudido a la sociedad teniendo una importante repercusión en el campo de la salud y de la investigación. Dada su relevancia, se han llevado a cabo estudios sobre los efectos del SARS-CoV-2 en la fisiología humana. En concreto, sobre la posible presencia y transmisión del virus a través del sistema reproductor masculino y su posible efecto en el éxito reproductivo. Conocer si la presencia del virus altera los órganos responsables del desarrollo y maduración de las células de la serie espermatogénica podría revelarnos su implicación en la calidad seminal. Por ello, nos planteamos esta revisión, con el fin de analizar las principales evidencias científicas sobre los efectos del SARS-CoV-2 en la histofisiología del sistema reproductor masculino y sobre la capacidad fecundante de los espermatozoides.

SUMMARY: The recent COVID-19 pandemic has shaken up society, having a significant impact on the field of health and research. Given its relevance, studies have been performed on the effects of SARS-CoV-2 on human physiology. In particular, the possible presence and transmission of the virus through the male reproductive system could affect reproductive success. Knowing if the presence of the virus disrupts the organs responsible for the development and maturation of the cell lines involved in spermatogenesis could reveal its implications in sperm quality. For that reason, we proposed this review, in order to analyze the main scientific evidence on the effects of SARS-CoV-2 on the histophysiology of the male reproductive system and sperm fertilizing capacity.

Fulminant myocarditis in a patient with a lung adenocarcinoma after the third dose of modern COVID-19 vaccine. A case report and literature review.

Introduction COVID-19 disease has caused a global health and economic crisis. The introduction of the different COVID-19 vaccines has resulted in a significant decrease in the morbidity and mortality associated with this disease. Adverse effects have been reported, including cardiological ones such as myocarditis or pericarditis after administration. Likewise, tyrosine kinase inhibitor drugs such as osimertinib used in lung cancer patients with epidermal growth factor receptor (EGFR) mutation are associated with heart failure or prolongation of the QT interval. Case report 62-year-old woman diagnosed in September 2019 of lung adenocarcinoma stage IV with bilateral lung and lymph node involvement, carrier of an EGFR mutation (Ex19Del) on treatment with osimertinib. She attended emergency department for fever and hypotension 24 h after administration of the third dose of Moderna® COVID-19 vaccine in the context of acute myocarditis with evidence of severe left ventricular (LV) dysfunction in cardiogenic shock. She required vasoactive support, non-invasive mechanical ventilation, corticotherapy, immunoglobulins and subsequent ventricular support with Impella, with improvement of the clinical picture after 3 days. Cardiac magnetic resonance imaging (MRI) showed evidence of global myocardial oedema compatible with acute myocarditis. Coronary CT showed a lesion in the anterior descending coronary artery requiring revascularization. A few days later, she presented febrile symptoms with isolation of Staphylococcus aureus in the central line catheter and antibiotherapy with cloxacillin was started, with subsequent resolution of the infectious symptoms. Conclusion This is an exceptional and controversial case of fulminant myocarditis probably related to the Modern COVID-19 vaccine in a patient diagnosed with metastatic lung adenocarcinoma on treatment with osimertinib. An increasing number of cases of myocarditis and pericarditis have been reported following vaccination with COVID-19 mRNA vaccines. In addition, retrospective data have shown an increased risk of QT prolongation and heart failure in patients treated with tyrosine kinase inhibitors. Hence, the need for close monitoring of cardiac function during treatment of these patients. Future studies will be necessary to evaluate unknown adverse reactions of these vaccines and their possible interaction with other antineoplastic drugs.

Detection of Enterovirus D68 in Wastewater Samples from the UK between July and November 2021.

Infection with enterovirus D68 (EV-D68) has been linked with severe neurological disease such as acute flaccid myelitis (AFM) in recent years. However, active surveillance for EV-D68 is lacking, which makes full assessment of this association difficult. Although a high number of EV-D68 infections were expected in 2020 based on the EV-D68's known biannual circulation patterns, no apparent increase in EV-D68 detections or AFM cases was observed during 2020. We describe an upsurge of EV-D68 detections in wastewater samples from the United Kingdom between July and November 2021 mirroring the recently reported rise in EV-D68 detections in clinical samples from various European countries. We provide the first publicly available 2021 EV-D68 sequences showing co-circulation of EV-D68 strains from genetic clade D and sub-clade B3 as in previous years. Our results show the value of environmental surveillance (ES) for the early detection of circulating and clinically relevant human viruses. The use of a next-generation sequencing (NGS) approach helped us to estimate the prevalence of EV-D68 viruses among EV strains from other EV serotypes and to detect EV-D68 minor variants. The utility of ES at reducing gaps in virus surveillance for EV-D68 and the possible impact of nonpharmaceutical interventions introduced to control the COVID-19 pandemic on EV-D68 transmission dynamics are discussed.

Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance.

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

Oriented immobilization of antibodies onto sensing platforms - A critical review.

The immunosensor has been proven a versatile tool to detect various analytes, such as food contaminants, pathogenic bacteria, antibiotics and biomarkers related to cancer. To fabricate robust and reproducible immunosensors with high sensitivity, the covalent immobilization of immunoglobulins (IgGs) in a site-specific manner contributes to better performance. Instead of the random IgG orientations result from the direct yet non-selective immobilization techniques, this review for the first time introduces the advances of stepwise yet site-selective conjugation strategies to give better biosensing efficiency. Noncovalently adsorbing IgGs is the first but decisive step to interact specifically with the Fc fragment, then following covalent conjugate can fix this uniform and antigens-favorable orientation irreversibly. In this review, we first categorized this stepwise strategy into two parts based on the different noncovalent interactions, namely adhesive layer-mediated interaction onto homofunctional support and layer-free interaction onto heterofunctional support (which displays several different functionalities on its surface that are capable to interact with IgGs). Further, the influence of ligands characteristics (synthesis strategies, spacer requirements and matrices selection) on the heterofunctional support has also been discussed. Finally, conclusions and future perspectives for the real-world application of stepwise covalent conjugation are discussed. This review provides more insights into the fabrication of high-efficiency immunosensor, and special attention has been devoted to the well-orientation of full-length IgGs onto the sensing platform.

Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England.

BACKGROUND: Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. METHODS: We examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021. FINDINGS: Across data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May. INTERPRETATION: The outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts. FUNDING: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy, Academy of Medical Sciences Bill,Melinda Gates Foundation, Imperial College Healthcare NHS Trust, The Novo Nordisk Foundation, MRC Centre for Global Infectious Disease Analysis, Community Jameel, Cancer Research UK, Imperial College COVID-19 Research Fund, Medical Research Council, Wellcome Sanger Institute.

University Virtual Learning in Covid Times

Online training is demanded in the ubiquitous society we live in, and this is especially true if we consider the current situation at universities due to the Government issuing a state of alarm decree which requests all citizens to remain at home. The goal of this study is to determine the opinion of university students from different Spanish campuses on e-learning platforms, by the means of a descriptive and correlational study design, with N = 431. The results reveal that there is still a long road ahead to ensure that these tools work optimally to enable professors to fully exert their teaching profession. We can conclude that the online teaching system needs to be improved regarding the technical service that the university offers.

Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021.

SARS-CoV-2 variants with multiple amino acid mutations in the spike protein are emerging in different parts of the world, raising concerns regarding their possible impact on human immune response and vaccine efficacy against the virus. Recently, a variant named lineage B.1.1.7 was detected and shown to be rapidly spreading across the UK since November 2020. As surveillance for these SARS-CoV-2 variants of concern (VOCs) becomes critical, we have investigated the use of environmental surveillance (ES) for the rapid detection and quantification of B.1.1.7 viruses in sewage as a way of monitoring its expansion that is independent on the investigation of identified clinical cases. Next-generation sequencing analysis of amplicons synthesized from sewage concentrates revealed the presence of B.1.1.7 mutations in viral sequences, first identified in a sample collected in London on 10 November 2020 and shown to rapidly increase in frequency to >95% in January 2021, in agreement with clinical data over the same period. We show that ES can provide an early warning of VOCs becoming prevalent in the population and that, as well as B.1.1.7, our method can detect VOCs B.1.351 and P.1, first identified in South Africa and Brazil, respectively, and other viruses carrying critical spike mutation E484K, known to have an effect on virus antigenicity. Although we did not detect such mutation in viral RNAs from sewage, we did detect mutations at amino acids 478, 490, and 494, located close to amino acid 484 in the spike protein structure and known to also have an effect on antigenicity. IMPORTANCE The recent appearance and growth of new SARS-CoV-2 variants represent a major challenge for the control of the COVID-19 pandemic. These variants of concern contain mutations affecting antigenicity, which raises concerns on their possible impact on human immune response to the virus and vaccine efficacy against them. Here, we show how environmental surveillance for SARS-CoV-2 can be used to help us understand virus transmission patterns and provide an early warning of variants becoming prevalent in the population. We describe the detection and quantification of variant B.1.1.7, first identified in southeast England in sewage samples from London (UK) before widespread transmission of this variant was obvious from clinical cases. Variant B.1.1.7 was first detected in a sample from early November 2020, with the frequency of B.1.1.7 mutations detected in sewage rapidly increasing to >95% in January 2021, in agreement with increasing SARS-CoV-2 infections associated with B.1.1.7 viruses.

Conceptual evolution of 3D printing in orthopedic surgery and traumatology: from "do it yourself" to "point of care manufacturing".

BACKGROUND: 3D printing technology in hospitals facilitates production models such as point-of-care manufacturing. Orthopedic Surgery and Traumatology is the specialty that can most benefit from the advantages of these tools. The purpose of this study is to present the results of the integration of 3D printing technology in a Department of Orthopedic Surgery and Traumatology and to identify the productive model of the point-of-care manufacturing as a paradigm of personalized medicine. METHODS: Observational, descriptive, retrospective and monocentric study of a total of 623 additive manufacturing processes carried out in a Department of Orthopedic Surgery and Traumatology from November 2015 to March 2020. Variables such as product type, utility, time or materials for manufacture were analyzed. RESULTS: The areas of expertise that have performed more processes are Traumatology, Reconstructive and Orthopedic Oncology. Pre-operative planning is their primary use. Working and 3D printing hours, as well as the amount of 3D printing material used, vary according to the type of product or material delivered to perform the process. The most commonly used 3D printing material for manufacturing is polylactic acid, although biocompatible resin has been used to produce surgical guides. In addition, the hospital has worked on the co-design of customized implants with manufacturing companies. CONCLUSIONS: The integration of 3D printing in a Department of Orthopedic Surgery and Traumatology allows identifying the conceptual evolution from "Do-It-Yourself" to "POC manufacturing".

Application of 3D printing and distributed manufacturing during the first-wave of COVID-19 pandemic. Our experience at a third-level university hospital.

BACKGROUND: 3D printing and distributed manufacturing represent a paradigm shift in the health system that is becoming critical during the COVID-19 pandemic. University hospitals are also taking on the role of manufacturers of custom-made solutions thanks to 3D printing technology. CASE PRESENTATION: We present a monocentric observational case study regarding the distributed manufacturing of three groups of products during the period of the COVID-19 pandemic from 14 March to 10 May 2020: personal protective equipment, ventilatory support, and diagnostic and consumable products. Networking during this period has enabled the delivery of a total of 17,276 units of products manufactured using 3D printing technology. The most manufactured product was the face shields and ear savers, while the one that achieved the greatest clinical impact was the mechanical ventilation adapters and swabs. The products were manufactured by individuals in 57.3% of the cases, and our hospital acted as the main delivery node in a hub with 10 other hospitals. The main advantage of this production model is the fast response to stock needs, being able to adapt almost in real time. CONCLUSIONS: The role of 3D printing in the hospital environment allows the reconciliation of in-house and distributed manufacturing with traditional production, providing custom-made adaptation of the specifications, as well as maximum efficiency in the working and availability of resources, which is of special importance at critical times for health systems such as the current COVID-19 pandemic.

Music as a factor associated with emotional self-regulation: A study on its relationship to age during COVID-19 lockdown in Spain.

The purpose of this research is to reveal the possible relational influence of age on frequency and form of music consumption, its use, and value as a factor associated with emotional self-regulation in pandemic contexts. With this objective, this study applied a transversal, descriptive and analytical design in a sample of 1377 Spaniards during the confinement of COVID-19 from March 14 to June 20, 2020. The results report that music has been an essential generalized support for living with isolation and a powerful instrument for emotional self-regulation and relief from loneliness. Although an increase of 56% in the daily use of music for self-regulation of emotions was detected, higher frequencies of consumption, mainly in solitude, and a better conception of this artistic expression are identified in the population over 51 years old. However, young people between 18 and 40 years old stood out in the use of music as a resource to alleviate loneliness. These results confirm that music seems to have arisen as one of the most used artistic expressions to cope with loneliness, to relate to the outside or as a tool to endure psychological and emotional states catalogued as negative such as anxiety, anguish and depression, among others. Likewise, they evidence its role in personal and social wellbeing in distant age ranges, and the relational influence of music and age in contexts of isolation and loneliness.

Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations.

Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.

BACKGROUND: Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. METHODS: In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. RESULTS: Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60-79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17-10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). CONCLUSIONS: In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.