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ANH-Intl Covid-19 information tracker - Week 25

Science

Epidemiology

Hospital-Wide SARS-CoV-2 Antibody Screening in 3056 Staff in a Tertiary Center in Belgium

Authors: Steensels D PhD et al

Publication date: 15 June 2020

Journal: JAMA

DOI: 10.1001/jama.2020.11160

Belgium has a high burden of coronavirus disease 2019 (COVID-19), especially the region surrounding the Hospital East-Limburg, a tertiary care center.1 Infection prevention measures were instituted in the hospital beginning March 4, 2020, including testing and contact tracing of all symptomatic patients and staff, changes in hospital operations, and provision of personal protective equipment (PPE). The first case was detected March 13 (Figure 1). We investigated the prevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among hospital staff.

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Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study

Authors: Stinghini S PhD et al

Publication date: 11 June 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31304-0

Background: Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic.

Methods: The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Here we present results from the first 5 weeks of the study.

Findings: Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4–8·0, n=341). The estimate increased to 8·5% (5·9–11·4, n=469) in the second week, to 10·9% (7·9–14·4, n=577) in the third week, 6·6% (4·3–9·4, n=604) in the fourth week, and 10·8% (8·2–13·9, n=775) in the fifth week. Individuals aged 5–9 years (relative risk [RR] 0·32 [95% CI 0·11–0·63]) and those older than 65 years (RR 0·50 [0·28–0·78]) had a significantly lower risk of being seropositive than those aged 20–49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community.

Interpretation: These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over <2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5–9 years and adults older than 65 years, compared with those aged 10–64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission.

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Pathogenesis

Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system

Authors: Cantuti-Castelvetri L et al

Publication date: 10 June 2020

Journal: bioRXiv preprint

DOI: 10.1101/2020.06.07.137802

The causative agent of the current pandemic and coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Understanding how SARS-CoV-2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells2. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ3-5. Here, we found that the cellular receptor neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected NRP1-positive cells in the olfactory epithelium and bulb. In the olfactory bulb infection was detected particularly within NRP1-positive endothelial cells of small capillaries and medium-sized vessels. Studies in mice demonstrated, after intranasal application, NRP1-mediated transport of virus-sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS-CoV-2.

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COVID ‐19: a global threat to the nervous system

Authors: Igor J Koralnik MD and Kenneth L Tyler MD

Publication date: 07 June 2020

Journal: Annals of Neurology

DOI: 10.1002/ana.25807

In less than 6 months, the severe acute respiratory syndrome‐coronavirus type 2 (SARS‐CoV‐2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID‐19) also involves multiple other organs including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS‐CoV‐2 infection is rapidly accumulating. These may result from a variety of mechanisms including virus‐induced hyper‐inflammatory and hypercoagulable states, direct virus infection of the CNS, and post‐infectious immune mediated processes. Example of COVID‐19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis and endothelialitis. In the peripheral nervous system COVID‐19 is associated with dysfunction of smell and taste, muscle injury, the Guillain‐Barre syndrome and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID‐19 poses a global threat to the entire nervous system. While our understanding of SARS‐CoV‐2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID‐19.

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Transmission

The natural history and transmission potential of asymptomatic SARS-CoV-2 infection

Authors: Chau NVV et al

Publication date: 04 June 2020

Journal: Clinical Infectious Disease

DOI: 10.1093/cid/ciaa711

Background: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission.

Methods: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals.

Results: Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts.

Conclusions: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.

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Prevalence of Asymptomatic SARS-CoV-2 Infection

Authors: Daniel P Oran and Eric J Topol MD

Publication date: 03 June 2020

Journal: Annals of Internal Medicine

DOI: 10.7326/M20-3012

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful.

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Covid-19 patients

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

Authors: Clark A PhD et al

Publication date: 15 June 2020

Journal: The Lancet Global Health

DOI: 10.1016/S2214-109X(20)30264-3

Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies.

Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease.

Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds.

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UK report on 9777 patients critically ill with COVID-19

Institution: Intensive Care National Audit & Research Centre (ICNARC)

Publication date: 12 June 2020

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New-Onset Diabetes in Covid-19

Authors: Rubinoc F et al

Publication date: 12 June 2020

Journal: New England Journal of Medicine

DOI: 10.1056/NEJMc2018688

There is a bidirectional relationship between Covid-19 and diabetes. On the one hand, diabetes is associated with an increased risk of severe Covid-19. On the other hand, new-onset diabetes and severe metabolic complications of preexisting diabetes, including diabetic ketoacidosis and hyperosmolarity for which exceptionally high doses of insulin are warranted, have been observed in patients with Covid-19.1-3 These manifestations of diabetes pose challenges in clinical management and suggest a complex pathophysiology of Covid-19–related diabetes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19, binds to angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys.4 Thus, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism that could complicate the pathophysiology of preexisting diabetes or lead to new mechanisms of disease.

There are also several precedents for a viral cause of ketosis-prone diabetes, including other coronaviruses that bind to ACE2 receptors.5 Greater incidences of fasting glycemia and acute-onset diabetes have been reported among patients with SARS coronavirus 1 pneumonia than among those with non-SARS pneumonia.

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Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China

Authors: Rongron Yang PhD, Xien Gui and Yong Xiong PhD

Publication date: 27 May 2020

Journal: JAMA

DOI: 10.1001/jamanetworkopen.2020.10182

Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.1,2 To control the spread of COVID-19 and isolate patients as early as possible, the Chinese government requested that close contacts of individuals with COVID-19 must be screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the screening process, we found some patients whose test results were positive for SARS-CoV-2 but who had no symptoms or signs throughout the course of the disease. Considering that little is known about the differences of clinical features and prognosis between patients who were asymptomatic vs those who were symptomatic,3,4 this case series aimed to describe the clinical characteristics of patients with SARS-CoV-2 infection confirmed by reverse transcription–polymerase chain reaction (RT-PCR) from 26 transmission cluster series in Wuhan, China, from December 24, 2019, to February 24, 2020.

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Mortality

Have deaths from COVID-19 in Europe plateaued due to herd immunity?

Authors: Okell CL et al

Publication date: 11 June 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31357-X

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently in marked decline in many countries in Europe, North America, and parts of Asia, following unprecedented governmental interventions aiming to substantially reduce travel and physical contact between individuals. There are two possible and very different explanations for this decline.

First, the observed declines in cases and deaths could be due to lockdowns (taken to include public orders to stay at home, bans on public gatherings with less than ten people, and curfew of all age groups), social distancing, and other interventions. This would imply that the epidemic is still at a relatively early stage and that a large proportion of the population therefore remain susceptible. Under such a scenario, there is a high risk of renewed transmission if interventions or behavioural modifications are completely relaxed. This first explanation also is consistent with a high infection fatality ratio (IFR) in order to explain the number of deaths that have occurred to date.

Second, the observed declines in cases and deaths could be due to the achievement of herd immunity. This would imply that a large proportion of the population are now protected from infection, either through acquisition of immunity following previous infection or through other natural means (such as cross protection from other coronaviruses). Under such a scenario, further declines in cases and deaths are to be expected even in the absence of interventions or behavioural modifications. If one assumes that a large proportion of the population has been infected, this explanation implies a very low IFR to explain the number of deaths that have occurred to date.

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Between-centre differences for COVID-19 ICU mortality from early data in England

Authors: Qian Z et al

Publication date: 29 May 2020

Journal: medRXiv preprint

DOI: 10.1101/2020.04.19.20070722

The high numbers of COVID-19 patients developing severe respiratory failure has placed exceptional demands on ICU capacity around the world. Understanding the determinants of ICU mortality is important for surge planning and shared decision making. We used early data from the COVID-19 Hospitalisation in England Surveillance System (from the start of data collection 8th February -22nd May 2020) to look for factors associated with ICU outcome in the hope that information from such timely analysis may be actionable before the outbreak peak. Immunosuppressive disease, chronic cardiorespiratory/renal disease and age were key determinants of ICU mortality in a proportional hazards mixed effects model. However variation in site-stratified random effects were comparable in magnitude suggesting substantial between-centre variability in mortality. Notwithstanding possible ascertainment and lead-time effects, these early results motivate comparative effectiveness research to understand the origin of such differences and optimise surge ICU provision.

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Testing

Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure

Authors: Cukirka LM et al

Publication date: 13 May 2020

Journal: Annals of Internal Medicine

DOI: 10.7326/M20-1495

Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse transcriptase polymerase chain reaction (RT-PCR) are being used to “rule out” infection among high-risk persons, such as exposed inpatients and health care workers. It is critical to understand how the predictive value of the test varies with time from exposure and symptom onset to avoid being falsely reassured by negative test results.

Conclusion: Care must be taken in interpreting RT-PCR tests for SARS-CoV-2 infection—particularly early in the course of infection—when using these results as a basis for removing precautions intended to prevent onward transmission. If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered.

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Diet and nutrition

Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005–2016 NHANES

Authors: Reider CA et al

Publication date: 10 June 2020

Journal: Nutrients

DOI: 10.3390/nu12061735

A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005–2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.—specifically in critical nutrients that support immune health—public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.

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Children and covid

The effects of social deprivation on adolescent development and mental health

Authors: Orben A PhD et al

Publication date: 12 June 2020

Journal: The Lancet Child & Adolescent Health

DOI: 10.1016/S2352-4642(20)30186-3

Adolescence (the stage between 10 and 24 years) is a period of life characterised by heightened sensitivity to social stimuli and the increased need for peer interaction. The physical distancing measures mandated globally to contain the spread of COVID-19 are radically reducing adolescents' opportunities to engage in face-to-face social contact outside their household. In this interdisciplinary Viewpoint, we describe literature from a variety of domains that highlight how social deprivation in adolescence might have far-reaching consequences. Human studies have shown the importance of peer acceptance and peer influence in adolescence. Animal research has shown that social deprivation and isolation have unique effects on brain and behaviour in adolescence compared with other stages of life. However, the decrease in adolescent face-to-face contact might be less detrimental due to widespread access to digital forms of social interaction through technologies such as social media. The findings reviewed highlight how physical distancing might have a disproportionate effect on an age group for whom peer interaction is a vital aspect of development.

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Kawasaki-like syndrome linked to COVID-19 in children is a new condition

Authors: Whittaker E MD et al

Publication date: 08 June 2020

Journal: JAMA

DOI: 10.1001/jama.2020.10369

Design, Setting, and Participants: Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019.

Results: Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 33 girls [57%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including vomiting (26/58 [45%]), abdominal pain (31/58 [53%]), and diarrhea (30/58 [52%]). Rash was present in 30 of 58 (52%), and conjunctival injection in 26 of 58 (45%) cases. Laboratory evaluation was consistent with marked inflammation, for example, C-reactive protein (229 mg/L [IQR, 156-338], assessed in 58 of 58) and ferritin (610 μg/L [IQR, 359-1280], assessed in 53 of 58). Of the 58 children, 29 developed shock (with biochemical evidence of myocardial dysfunction) and required inotropic support and fluid resuscitation (including 23/29 [79%] who received mechanical ventilation); 13 met the American Heart Association definition of KD, and 23 had fever and inflammation without features of shock or KD. Eight patients (14%) developed coronary artery dilatation or aneurysm. Comparison of PIMS-TS with KD and with KD shock syndrome showed differences in clinical and laboratory features, including older age (median age, 9 years [IQR, 5.7-14] vs 2.7 years [IQR, 1.4-4.7] and 3.8 years [IQR, 0.2-18], respectively), and greater elevation of inflammatory markers such as C-reactive protein (median, 229 mg/L [IQR 156-338] vs 67 mg/L [IQR, 40-150 mg/L] and 193 mg/L [IQR, 83-237], respectively).

Conclusions and Relevance: In this case series of hospitalized children who met criteria for PIMS-TS, there was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms. The comparison with patients with KD and KD shock syndrome provides insights into this syndrome, and suggests this disorder differs from other pediatric inflammatory entities.

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Media – Science related

Therapeutics

UK public health bodies reviewing vitamin D's effects on coronavirus

Author: Mattha Busby

Publication date: 17 June 2020

Source: The Guardian

Public health officials are urgently reviewing the potential ability of vitamin D to reduce the risk of coronavirus.

It comes amid growing concern over the disproportionate number of black, Asian and minority ethnic people contracting and dying from the disease, including a reported 94% of all doctors killed by the virus.

A delayed Public Health England review into the reasons why BAME people are disproportionately affected, which pointed to historical racism, did not review the role of diet and vitamin D.

The Scientific Advisory Committee on Nutrition (SACN) began this work last month and is considering recent evidence on vitamin D and acute respiratory tract infection in the general population. Evidence will be considered on specific population groups, including those of different ages and BAME groups.

In a parallel development, the National Institute for Health and Care Excellence (Nice) is conducting a “rapid” evidence review on vitamin D “in the context of Covid-19” with support from Public Health England (PHE).

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Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19

Publication date: 16 June 2020

Source: RECOVERY Trial

In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK.

On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit.

A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).

Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone.

Given the public health importance of these results, we are now working to publish the full details as soon as possible.

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FDA revoke emergency authorisation for use of chloroquine phosphate and hydroxychloroquine

Publication date: 15 June 2020

Source: US Food and Drug Administration

Dear Dr. Disbrow:

This letter is in response to your request, dated today, that the Food and Drug Administration (FDA) revoke the Emergency Use Authorization (EUA) for emergency use of oral formulations of chloroquine phosphate (CQ) and hydroxychloroquine sulfate (HCQ) to be distributed from the Strategic National Stockpile (SNS) issued on March 28, 2020. Like BARDA’s earlier request to FDA to issue the EUA, BARDA’s request to revoke the EUA is part of a collaborative, USG- interagency effort to rapidly respond to this continuously evolving public health emergency. Today’s request to revoke is based on new information, including clinical trial data results, that have led BARDA to conclude that this drug may not be effective to treat COVID-19 [Coronavirus Disease 2019] and that the drug’s potential benefits for such use do not outweigh its known and potential risks.

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Social impact

NHS Confederation: ‘Unseen impact’ of coronavirus revealed in data

Publication date: 12 June 2020

Source: National Health Executive

NHS Confederation have warned about the potential unseen impacts of coronavirus on the population’s health which have been revealed in the latest NHS England performance figures, including significant backlog to treatments, delays in referrals and reduced numbers of A&E attendances.

Among the statistics released in the most recently-published report, A&E attendances in May 2020 had fallen 41.9% based on a year previously. Emergency admissions were also recorded as being 27.2% lower than in 2019, suggesting people had shown significant hesitancy in attending A&E, potentially causing diagnoses and necessary treatments to be missed.

An increased number of those who did attend A&E were seen within the targeted four hour window, though this is likely to have been largely the result of the reduced capacity.

At the end of April 2020, 71.3% of patients waiting to start treatment were facing a wait of up to 18 weeks according to the statistics, with 3.9 million patients awaiting a referral to treatment (RTT). Similar delays had also been seen in cancer referrals, partly impacted by reduced capacity and strict restrictions relating to coronavirus risk.

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The mental health effects of the first two months of lockdown and social distancing during the Covid-19 pandemic in the UK

Authors: James Banks and Xiaowei Xu

Publication date: 10 June 2020

Source: Institute for Fiscal Studies

Using longitudinal microdata for the UK over the period 2009-2020 we control for pre-existing previous trends in mental health in order to isolate and quantify the effects of the Covid-19 pandemic. Mental health in the UK worsened by 8.1% on average as a result of the pandemic and by much more for young adults and for women which are groups that already had lower levels of mental health before Covid- 19. Hence inequalities in mental health have been increased by the pandemic. Even larger effects are observed for measures of mental health that capture the number of problems reported or the fraction of the population reporting any frequent or severe problems, which more than doubled.

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Media – Reporting

Mortality

School age children more likely to be hit by lightning than die of coronavirus

Author: Sarah Knapton and Christopher Hope

Publication date: 09 June 2020

Source: The Telegraph

Schoolchildren under the age of 15 are more likely to be hit by lightning than die from coronavirus, new figures suggest, amid mounting pressure on the Government to get more to get pupils back into classrooms as quickly as possible.

Scientists from the universities of Cambridge and Oxford have called for "rational debate" based on the "tiny" risk to children, suggesting that if no vaccine is found in future it may be better for younger people to continue with their lives while the more vulnerable are shielded.

It comes as the Government was accused of "losing the plot" after Gavin Williamson, the Education Secretary,  scrapped the target of getting all primary school pupils back in the classroom before the summer holidays.

Mr Williamson told the Commons that the Government would instead like to see schools which "have the capacity" bring back more pupils where possible before the summer break.

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