Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Kinetics in Symptomatic Children, Adolescents, and Adults.

SARS-CoV-2 viral load (VL) can serve as a correlate for infectious virus presence and transmission. Viral shedding kinetics over the first week of illness for symptomatic children (n = 279), adolescents (n = 639), and adults (n = 7109) show VLs compatible with infectious virus presence, with slightly lower VL in children than adults.

Partnerships in global health and collaborative governance: lessons learnt from the Division of Tropical and Humanitarian Medicine at the Geneva University Hospitals.

BACKGROUND: In 2007 the "Crisp Report" on international partnerships increased interest in Northern countries on the way their links with Southern partners operated. Since its establishment in 2007 the Division of Tropical and Humanitarian Medicine at the Geneva University Hospitals has developed a variety of partnerships. Frameworks to assess these partnerships are needed and recent attention in the field of public management on collaborative governance may provide a useful approach for analyzing international collaborations. METHODS: Projects of the Division of Tropical and Humanitarian Medicine were analyzed by collaborators within the Division using the model proposed by Emerson and colleagues for collaborative governance, which comprises different components that assess the collaborative process. RESULTS: International projects within the Division of Tropical and Humanitarian Medicine can be divided into four categories: Human resource development; Humanitarian response; Neglected Tropical Diseases and Noncommunicable diseases. For each of these projects there was a clear leader from the Division of Tropical and Humanitarian Medicine as well as a local counterpart. These individuals were seen as leaders both due to their role in establishing the collaboration as well as their technical expertise. Across these projects the actual partners vary greatly. This diversity means a wide range of contributions to the collaboration, but also complexity in managing different interests. A common definition of the collaborative aims in each of the projects is both a formal and informal process. Legal, financial and administrative aspects of the collaboration are the formal elements. These can be a challenge based on different administrative requirements. Friendship is part of the informal aspects and helps contribute to a relationship that is not exclusively professional. CONCLUSION: Using collaborative governance allows the complexity of managing partnerships to be presented. The framework used highlights the process of establishing collaborations, which is an element often negated by other more traditional models used in international partnerships. Applying the framework to the projects of the Division of Tropical and Humanitarian Medicine highlights the importance of shared values and interests, credibility of partners, formal and informal methods of management as well as friendship.

Novel outpatient management of mild to moderate COVID-19 spares hospital capacity and safeguards patient outcome: The Geneva PneumoCoV-Ambu study.

BACKGROUND: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes coronavirus disease (COVID-19), is creating an unprecedented burden on health care systems across the world due to its high rate of pneumonia-related hospitalizations. This study presents recommendations for the outpatient management of moderate SARS-CoV-2 pneumonia implemented at the Geneva University Hospital, Switzerland, from April 4 to June 30, 2020 and evaluated the impact of these recommendations on patient safety, patient satisfaction, and overall hospital capacity. METHODS: Recommendations for the outpatient management of moderate pneumonia implemented in the Geneva University Hospital (PneumoCoV-Ambu) between April 4 and June 30, 2020, were evaluated prospectively. The primary endpoint was hospitalization. Secondary endpoints were: severity of COVID-19 disease based on a 7-points ordinal scale assessed at 1 and 2 months following SARS-CoV-2 infection; patient satisfaction using a satisfaction survey and the analysis of number of beds and costs potentially averted. RESULTS: A total of 36 patients with COVID-19-related pneumonia were followed between April 4 and May 5, 2020. Five patients (14%) were hospitalized and none died over a median of 30 days follow-up. The majority of patients (n = 31; 86%) were satisfied with the ambulatory care they received. These novel recommendations for outpatient management resulted in sparing an estimated potential 124 hospital bed-nights and CHF 6'826 per capita averted hospitalization costs over the three months period. CONCLUSIONS: Recommendations developed for the outpatient management of COVID-19-related pneumonia were able to spare hospital capacity without increasing adverse patient outcomes. Widely implementing such recommendations is crucial in preserving hospital capacity during this pandemic.

Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19.

The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient-provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.

Diagnostic accuracy of two commercial SARS-CoV-2 antigen-detecting rapid tests at the point of care in community-based testing centers.

OBJECTIVES: Determine the diagnostic accuracy of two antigen-detecting rapid diagnostic tests (Ag-RDT) for SARS-CoV-2 at the point of care and define individuals' characteristics providing best performance. METHODS: We performed a prospective, single-center, point of care validation of two Ag-RDT in comparison to RT-PCR on nasopharyngeal swabs. RESULTS: Between October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioTM Covid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. Lower sensitivity of 88.2% was seen on the same day of symptom development (day 0). CONCLUSIONS: We provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value.

Diagnostic accuracy of Panbio rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2.

BACKGROUND: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. METHODS: We conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS during the second pandemic wave in Switzerland. RESULTS: 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT clinical sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a clinical specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. INTERPRETATION: Based on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples, if taken by a trained person and high requirements regarding quality of the specimen, meet the criteria required by the WHO for Ag-RDTs (sensitivity ≥80% and specificity ≥97%) in a high incidence setting in symptomatic individuals.

A living WHO guideline on drugs to prevent covid-19.

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

A living WHO guideline on drugs for covid-19

Updates: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. Clinical question: What is the role of drugs in the treatment of patients with covid-19? Context: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics. What is new?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19. About this guideline: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.

Building Local Capacity in Hand-Rub Solution Production during the 2014-2016 Ebola Outbreak Disaster: The Case of Liberia and Guinea.

BACKGROUND: During the 2014-2015 Ebola outbreak in West Africa, the lack of infection prevention and control (IPC) measures in health care facilities amplified human-to-human transmission and contributed to the magnitude of this humanitarian disaster.Case ReportIn the summer of 2014, the Geneva University Hospitals (HUG; Geneva, Switzerland) conducted an IPC assessment and developed a project based on the local needs and their expertise with the support of the Swiss Agency for Development and Cooperation and the Humanitarian Aid Unit (SDC/HA; Bern, Switzerland). The project consisted of building local capacity in the production of alcohol-based hand-rub solution (ABHRS) based on the World Health Organization (WHO; Geneva, Switzerland) formula in non-Ebola health facilities at the peak of the outbreak in Liberia (Fall 2014) and during recovery in Guinea (September 2015) to promote safer care. Twenty-one pharmacists in Liberia and 22 in Guinea were trained and one years' worth of laboratory equipment, chemical products, containers for personal use, and bioethanol were delivered to 10 hospitals per country with more than 8,000 100 ml bottles of solution produced at the end of the project.DiscussionHand hygiene using hand-rub solution is a critical component of safer care, especially in health care settings lacking runnable water. Throughout the Ebola outbreak, it was a timely moment to promote hand-rub solution and to reinforce IPC measures in non-Ebola health facilities. During the project implementation, a substantial challenge was the unavailability of bioethanol in Liberia and Guinea. In the long run, sustainability of the production can become an issue as it depends heavily on the local government's financial and political commitment, the capacity to create an on-going demand for hand-rub solution in health facilities, the local purchase and replacement of the materials and chemical products, as well as the availability of continuous local partners' support. CONCLUSION: The project demonstrated that it was feasible to build local capacity in ABHRS production during an emergency and in limited-resource settings when materials and training are provided. Future programs in similar contexts should identify and address the factors of sustainability during the implementation phase and provide regular, long-term technical support. Jacquerioz BauschFA, HellerO, BengalyL, Matthey-KhouityB, BonnabryP, TouréY, KervillainGJ, BahEI, ChappuisF, HagonO. Building local capacity in hand-rub solution production during the 2014-2016 Ebola outbreak disaster: the case of Liberia and Guinea.. Prehosp Disaster Med. 2018;33(6):660-667.

A living WHO guideline on drugs to prevent COVID-19

Clinical question What is the role of drugs in preventing covid-19? Why does this matter?There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Understanding the new recommendation The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. Updates This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline.

A living WHO guideline on drugs for COVID-19

What is the role of drug interventions in the treatment of patients with covid-19? The latest version of this WHO living guidance focuses on remdesivir, following the 15 October 2020 preprint publication of results from the WHO SOLIDARITY trial. It contains a weak or conditional recommendation against the use of remdesivir in hospitalised patients with covid-19 The first version on this living guidance focused on corticosteroids. The strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19 are unchanged.