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ANH-Intl Covid-19 information tracker - Week 23

Science

Pathogenesis

Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses

Authors: Gussow AB et al

Publication date: 10 June 2020

Journal: PNAS

DOI: 10.1073/pnas.2008176117

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions.

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SARS-CoV-2 strategically mimics proteolytic activation of human ENaC

Authors: Anand P et al

Publication date: 26 May 2020

Journal: eLife

DOI: 10.7554/eLife.58603

Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 65 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.

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Transmission

A modelling framework to assess the likely effectiveness of facemasks in combination with ‘lock-down’ in managing the COVID-19 pandemic

Authors: Stutt ROJH et al

Publication date: 10 June 2020

Journal: Proceedings of the Royal Society A

DOI: 10.1098/rspa.2020.0376

COVID-19 is characterized by an infectious pre-symptomatic period, when newly infected individuals can unwittingly infect others. We are interested in what benefits facemasks could offer as a non-pharmaceutical intervention, especially in the settings where high-technology interventions, such as contact tracing using mobile apps or rapid case detection via molecular tests, are not sustainable. Here, we report the results of two mathematical models and show that facemask use by the public could make a major contribution to reducing the impact of the COVID-19 pandemic. Our intention is to provide a simple modelling framework to examine the dynamics of COVID-19 epidemics when facemasks are worn by the public, with or without imposed ‘lock-down’ periods. Our results are illustrated for a number of plausible values for parameter ranges describing epidemiological processes and mechanistic properties of facemasks, in the absence of current measurements for these values. We show that, when facemasks are used by the public all the time (not just from when symptoms first appear), the effective reproduction number, Re, can be decreased below 1, leading to the mitigation of epidemic spread. Under certain conditions, when lock-down periods are implemented in combination with 100% facemask use, there is vastly less disease spread, secondary and tertiary waves are flattened and the epidemic is brought under control. The effect occurs even when it is assumed that facemasks are only 50% effective at capturing exhaled virus inoculum with an equal or lower efficiency on inhalation. Facemask use by the public has been suggested to be ineffective because wearers may touch their faces more often, thus increasing the probability of contracting COVID-19. For completeness, our models show that facemask adoption provides population-level benefits, even in circumstances where wearers are placed at increased risk. At the time of writing, facemask use by the public has not been recommended in many countries, but a recommendation for wearing face-coverings has just been announced for Scotland. Even if facemask use began after the start of the first lock-down period, our results show that benefits could still accrue by reducing the risk of the occurrence of further COVID-19 waves. We examine the effects of different rates of facemask adoption without lock-down periods and show that, even at lower levels of adoption, benefits accrue to the facemask wearers. These analyses may explain why some countries, where adoption of facemask use by the public is around 100%, have experienced significantly lower rates of COVID-19 spread and associated deaths. We conclude that facemask use by the public, when used in combination with physical distancing or periods of lock-down, may provide an acceptable way of managing the COVID-19 pandemic and re-opening economic activity. These results are relevant to the developed as well as the developing world, where large numbers of people are resource poor, but fabrication of home-made, effective facemasks is possible. A key message from our analyses to aid the widespread adoption of facemasks would be: ‘my mask protects you, your mask protects me’.

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Report 26 - Reduction in mobility and COVID-19 transmission

Publication date: 08 June 2020

Source: MRC Centre for Global Infectious Disease Analysis

In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2 by restricting population movement through social distancing interventions, reducing the number of contacts.

Mobility data represent an important proxy measure of social distancing. Here, we develop a framework to infer the relationship between mobility and the key measure of population-level disease transmission, the reproduction number (R). The framework is applied to 53 countries with sustained SARS-CoV-2 transmission based on two distinct country-specific automated measures of human mobility, Apple and Google mobility data.

For both datasets, the relationship between mobility and transmission was consistent within and across countries and explained more than 85% of the variance in the observed variation in transmissibility. We quantified country-specific mobility thresholds defined as the reduction in mobility necessary to expect a decline in new infections (R<1).

While social contacts were sufficiently reduced in France, Spain and the United Kingdom to control COVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for the majority of countries. We found encouraging early evidence of some decoupling of transmission and mobility in 10 countries, a key indicator of successful easing of social-distancing restrictions.

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Covid-19 patients

UK report on 9623 patients critically ill with COVID-19

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

Publication date: 06 June 2020

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Prevalence and Mortality of COVID-19 patients with Gastrointestinal Symptoms: A Systematic Review and Meta-analysis

Authors: Tariq R et al

Publication date: 02 June 2020

Journal: Mayo Clinic Proceedings

DOI: 10.1016/j.mayocp.2020.06.003

Objectives: To perform a systematic review and meta-analysis evaluating the prevalence of gastrointestinal (GI) symptoms and mortality in patients diagnosed with coronavirus disease 2019 (COVID-19).

Methods: A systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus was performed from 2019 to May 7th, 2020. Observational studies including adults with COVID-19 infection and reporting GI symptoms were included. Primary outcome was assessing weighted pooled prevalence (WPP) of GI symptoms in patients with COVID-19. Secondary outcomes were WPP of overall mortality, and mortality in COVID-19 patients with GI symptoms.

Results: A total of 78 studies with 12797 patients were included. Among GI symptoms (at onset of illness in 6, at admission in 17, data given separately for both in 3, data unavailable in 52 studies), WPP of diarrhea was 12% (95% CI, 8%-17%), I2=94%, nausea and/or vomiting was 9.0% (95% CI, 5.5%-12.9%). I2=93%, loss of appetite was 22.3% (95% CI, 11.2%-34.6%, I2=94%, and that of abdominal pain was 6.2% (95% CI, 2.6%-10.3%, I2=92%. Mortality among patients with GI symptoms [0.4% (95% CI, 0%-1.1%), I2=74%] was similar to overall mortality [2.1% (95% CI, 0.2%-4.7%), I2=94%], p=0.15. Majority of studies had high risk of bias and overall quality of evidence was low to very low for all outcomes.

Conclusions: Gastrointestinal symptoms are seen in up to one in five patients with COVID-19. More high quality evidence is needed to confirm these findings and to explore factors causing mortality in these patients.

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Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank

Authors: Niedzwiedz et al

Publication date: 29 May 2020

Journal: BMC Medicine

DOI: 10.1186/s12916-020-01640-8

Results: Amongst 392,116 participants in England, 2658 had been tested for SARS-CoV-2 and 948 tested positive (726 in hospital) between 16 March and 3 May 2020. Black and south Asian groups were more likely to test positive (RR 3.35 (95% CI 2.48–4.53) and RR 2.42 (95% CI 1.75–3.36) respectively), with Pakistani ethnicity at highest risk within the south Asian group (RR 3.24 (95% CI 1.73–6.07)). These ethnic groups were more likely to be hospital cases compared to the white British. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.19 for most deprived quartile vs least (95% CI 1.80–2.66) and RR 2.00 for no qualifications vs degree (95% CI 1.66–2.42)).

Conclusions: Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study, which was not accounted for by differences in socioeconomic conditions, baseline self-reported health or behavioural risk factors. An urgent response to addressing these elevated risks is required.

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Relationship between the ABO Blood Group and the COVID-19 Susceptibility

Authors: Zhao J et al

Publication date: 27 March 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.03.11.20031096

The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility.

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Mortality

The Importance of Proper Death Certification During the COVID-19 Pandemic

Authors: James R Gill, MD and Maura E DeJoseph, DO

Publication date: 10 June 2020

Journal: JAMA

DOI: 10.1001/jama.2020.9536

Death certificate data are used to monitor local, regional, and national mortality trends to improve public health and public safety. Accurate death certification related to coronavirus disease 2019 (COVID-19) is vital to understand the extent and progression of the pandemic. Death certificate data can inform the public and policy makers on the progress of the COVID-19 pandemic and provide important information about who is dying, where they are from, and what were their associated medical conditions. Public health mortality data are only as good as the quality of the death certificates, but proper death certification has been a long-standing challenge in the US.1-3 The COVID-19 pandemic has highlighted shortcomings that may compromise an accurate count of COVID-19 deaths.

COVID-19 death certificates are typically completed by treating physicians. There is a known training gap regarding proper death certification,1,2,4 which leads to improperly completed death certificates. This affects the quality of the public health data, which in turn limits the ability to track the evolving COVID-19 pandemic. Death certificate data can be used locally to guide disease surveillance and quarantine measures and optimize medical resources. These data are transmitted to the National Center for Health Statistics (NCHS) so the US can initiate broader responses to the pandemic. If the death certificates are inaccurate, local and national responses may be adversely affected.

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Therapeutics

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19

Authors: Ling Li, Wei Zhang and Yu Hu et al

Publication date: 03 June 2020

Journal: JAMA

DOI: 10.1001/jama.2020.10044

Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.

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Vaccines

SARS-CoV-2 Vaccines: ‘Warp Speed’ Needs Mind Melds not Warped Minds

Authors: John P Moore and P J Klasse

Publication date: 07 June 2020

Journal: Preprints

DOI: 202006.0079.v1

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not represented in the “Warp Speed” program. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program.

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Biovacc-19: A Candidate Vaccine for Covid-19 (SARS-CoV-2) Developed from Analysis of its General Method of Action for Infectivity

Authors: B Sørenson, A Susrud and A G Dalgleish

Publication date: 02 June 2020

Journal: Cambridge University Press

DOI: 10.1017/qrd.2020.8

This study presents the background, rationale and Method of Action of Biovacc-19, a candidate vaccine for Covid-19, now in advanced pre-clinical development, which has already passed the first acute toxicity testing. Unlike conventionally developed vaccines, Biovacc-19's Method of Operation is upon non human-like (NHL) epitopes in 21.6% of the composition of SARS-CoV-2's Spike protein, which displays distinct distributed charge including the presence of a charged furin-like cleavage site. The logic of the design of the vaccine is explained, which starts with empirical analysis of the aetiology of SARS-CoV-2. Mistaken assumptions about SARS-CoV-2's aetiology risk creating ineffective or actively harmful vaccines, including the risk of Antibody-Dependent Enhancement (ADE). Such problems in vaccine design are illustrated from past experience in the HIV domain. We propose that the dual effect general method of action of this chimeric virus’s spike, including receptor binding domain, includes membrane components other than the ACE2 receptor, which explains clinical evidence of its infectivity and pathogenicity. We show the non-receptor dependent phagocytic general method of action to be specifically related to cumulative charge from inserted sections placed on the SARS-CoV-2 Spike surface in positions to bind efficiently by salt bridge formations; and from blasting the Spike we display the non human-like epitopes from which Biovacc-19 has been down-selected.

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Climate and covid

The role of climate during the COVID‐19 epidemic in New South Wales, Australia

Authors: Michael P Ward, Shuang Xiao and Zhijie Zhang

Publication date: 21May 2020

Journal: Transboundary and Emerging Diseases

DOI: 10.1111/tbed.13631

Previous research has identified a relationship between climate and occurrence of SARS‐CoV and MERS‐CoV cases, information that can be used to reduce the risk of infection. Using COVID‐19 notification and postcode data from New South Wales, Australia during the exponential phase of the epidemic in 2020, we used time series analysis to investigate the relationship between 749 cases of locally acquired COVID‐19 and daily rainfall, 9 a.m. and 3 p.m. temperature, and 9 a.m. and 3 p.m. relative humidity. Lower 9 a.m. relative humidity (but not rainfall or temperature) was associated with increased case occurrence; a reduction in relative humidity of 1% was predicted to be associated with an increase of COVID‐19 cases by 6.11%. During periods of low relative humidity, the public health system should anticipate an increased number of COVID‐19 cases.

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Pregnancy and covid

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

Authors: Knight M et al

Publication date: 27 May 2020

Journal: The BMJ

DOI: 10.1136/bmj.m2107

Objectives: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants.

Participants: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020.

Main outcome measures: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission.

Results: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.

Conclusions Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation.

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Vitamin D and covid

Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship?

Author: Hand K Biesalski

Publication date: 07 June 2020

Journal: NFS Journal

DOI: 10.1016/j.nfs.2020.06.001

An inadequate supply of vitamin D has a variety of skeletal and non-skeletal effects. There is ample evidence that various non-communicable diseases (hypertension, diabetes, CVD, metabolic syndrome) are associated with low vitamin D plasma levels. These comorbidities, together with the often concomitant vitamin D deficiency, increase the risk of severe COVID-19 events. Much more attention should be paid to the importance of vitamin D status for the development and course of the disease. Particularly in the methods used to control the pandemic (lockdown), the skin's natural vitamin D synthesis is reduced when people have few opportunities to be exposed to the sun. The short half-lives of the vitamin therefore make an increasing vitamin D deficiency more likely. Specific dietary advice, moderate supplementation or fortified foods can help prevent this deficiency. In the event of hospitalisation, the status should be urgently reviewed and, if possible, improved.

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Vitamin D Levels and COVID-19 Susceptibility: Is there any Correlation?

Authors: Karan Razdan, Kuldeep Singh and Dilpreet Singh

Publication date: 02 June 2020

Journal: Medicine in Drug Discovery

DOI: 10.1016/j.medidd.2020.100051

Coronavirus disease (COVID-19) is a major pandemic and now a leading cause of death worldwide. Currently, no drugs/vaccine is available for the treatment of this disease. Future preventions and social distancing are the only ways to prevent this disease from community transmission. Vitamin D is an important micronutrient and has been reported to improve immunity and protect against respiratory illness. This short review highlights the important scientific link between Vitamin D levels and susceptibility to COVID-19 in patients. This review also discusses recommendations for Vitamin D dose required for healthy as well as COVID-19 susceptible patients for protection and prevention.

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SARS‐CoV‐2 pandemic and Vitamin D deficiency—A double trouble

Authors: Miguel Alpahlhão and Paulo Filipe

Publication date: 01 June 2020

Journal: Photodermatiology, Photoimmunology & Photomedicine

DOI: 10.1111/phpp.12579

The current SARS‐CoV‐2 pandemic has mandated significant isolation measures. Streets in affected countries are mostly empty, and many individuals spend several consecutive days at home to reduce the risk of infection. While determinant for pandemic control, home reclusion may have a significant toll on the health of individuals.

One relevant area where we are yet to see proper discussion and strategies pertains to vitamin D deficiency.

Vitamin D is a fat‐soluble hormone that plays a significant role in calcium‐phosphate metabolism, in addition to intervening in cell metabolic activity, immune regulation, among other functions.

Vitamin D is synthesized in skin epithelium under ultraviolet B (UVB) radiation. It then undergoes two successive hydroxylations in the 25‐ and 1‐ carbons, in the liver and in the kidney, respectively, to yield the active form, calcitriol. A minor portion of vitamin D is obtained from alimentary sources.

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Vitamin D Deficiency and COVID-19 Pandemic

Authors: Zemb P et al

Publication date: 28 May 2020

Journal: Journal of Global Antimicrobial Resistance

DOI: 10.1016/j.jgar.2020.05.006

In conclusion, despite a lack of direct evidence of an effect of vitamin D status on COVID-19 infection, we believe that vitamin D deficiency is an easily modifiable risk factor of ARIs and should be actively corrected, through inexpensive, safe, and readily-available vitamin D supplements. Even a small decrease in COVID-19 infections would easily justify this intervention. Nevertheless, we acknowledge that specific high-quality data are needed to demonstrate the efficacy of vitamin D supplementation in the prevention of COVID-19.

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Diet and nutrition

Is Diet Partly Responsible for Differences in COVID-19 Death Rates Between and Within Countries?

Authors: Bousquet J et al

Publication date: 27 May 2020

Journal: Clinical and Translational Allergy

DOI: 10.1186/s13601-020-00323-0

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

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Children and covid

Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2

Authors: Whittaker E, MD et al

Publication date: 08 June 2020

Journal: JAMA

DOI: 10.1001/jama.2020.10369

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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Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19

Authors: Loades ME et al

Publication date: 03 June 2020

Journal: Journal of the American Academy of Child & Adolescent Psychiatry

DOI: 10.1016/j.jaac.2020.05.009

Objective: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents.

Method: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance.

Results: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness.

Conclusion: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems.

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Effects of COVID‐19 Lockdown on Lifestyle Behaviors in Children with Obesity Living in Verona, Italy: A Longitudinal Study

Authors: Pietrobellie A et al

Publication date: 30 April 2020

Journal: Obesity

DOI: 10.1002/oby.22861

Objective: To test the hypothesis that youths with obesity, when removed from structured school activities and confined to their homes during the COVID‐19 pandemic, will display unfavorable trends in lifestyle behaviors.

Methods: The sample included 41 children and adolescents with obesity participating in a longitudinal observational study located in Verona, Italy. Lifestyle information including diet, activity, and sleep behaviors were collected at baseline and three weeks into the national lockdown during which home confinement was mandatory. Changes in outcomes over the two study time points were evaluated for significance using paired t‐tests.

Results: There were no changes in reported vegetable intake; fruit intake increased (p=0.055) during the lockdown. By contrast, potato chip, red meat, and sugary drink intakes increased significantly during the lockdown (p‐value range, 0.005 to <0.001). Time spent in sports activities decreased (X±SD) by 2.30±4.60 hours/week (p=0.003) and sleep time increased by 0.65±1.29 hours/day (p=0.003). Screen time increased by 4.85±2.40 hours/day (p<0.001).

Conclusions: Recognizing these adverse collateral effects of the COVID‐19 pandemic lockdown is critical in avoiding depreciation of weight control efforts among youths afflicted with excess adiposity. Depending on duration, these untoward lockdown effects may have a lasting impact on a child’s or adolescent’s adult adiposity level.

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Social Impact

The Neurobiology of Social Distance

Authors: Danil Bzdok and Robin IM Dunbar

Publication date: 02 June 2020

Journal: Trends in Cognitive Sciences

DOI: 10.1016/j.tics.2020.05.016

Never before have we experienced social isolation on such a massive scale as we have in response to COVID-19. Yet we know that the social environment has a dramatic impact on our sense of life satisfaction and well-being. In times of distress, crisis, or disaster, human resilience depends on the richness and strength of social connections, as well as active engagement in groups and communities. Over recent years, evidence emerging from various disciplines has made it abundantly clear: loneliness may be the most potent threat to survival and longevity. Here, we highlight the benefits of social bonds, choreographies of bond creation and maintenance, as well as the neurocognitive basis of social isolation and its deep consequences for mental and physical health.

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For the Greater Good? The Devastating Ripple Effects of the Covid-19 Crisis

Authors: Michaéla Schippers and Erwin Kompanje

Publication date: 28 May 2020

Source: SSRN preprint

DOI: 10.2139/ssrn.3612622

As the crisis around Covid-19 evolves, it becomes clear that there are numerous negative side-effects of the lockdown strategies implemented by many countries. At the same time, more evidence becomes available that the lockdowns may have more negative effects than positive effects. For instance, many measures taken in a lockdown aimed at protecting human life may compromise the immune system, especially of vulnerable groups. This leads to the paradoxical situation of compromising the immune system of many people, including the ones we aim to protect. Other side effects include financial insecurity of billions of people, excess mortality, and increased inequalities. As the virus outbreak and media coverage spread fear and anxiety, superstition, cognitive dissonance reduction and conspiracy theories are ways to find meaning and reduce anxiety. This may play a role in the continuance of lockdown behaviors even as it becomes clear that this strategy in some ways seems to do more harm than good. Based on theories regarding social influence, superstition and stress and coping, we seek to explain the social and behavioral science behind the human behavior in times of crises. We present a model of drivers and outcomes of lockdown behaviors and offer suggestions to counteract the negative psychological effects by means of online life crafting therapeutic writing interventions.

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Government/Health authorities

Mortality

Disparities in the risk and outcomes of COVID-19

Publication date: 02 June 2020

Source: Public Health England

This is a descriptive review of data on disparities in the risk and outcomes from COVID- 19. This review presents findings based on surveillance data available to PHE at the time of its publication, including through linkage to broader health data sets. It confirms that the impact of COVID-19 has replicated existing health inequalities and, in some cases, has increased them. These results improve our understanding of the pandemic and will help in formulating the future public health response to it.

The largest disparity found was by age. Among people already diagnosed with COVID- 19, people who were 80 or older were seventy times more likely to die than those under 40. Risk of dying among those diagnosed with COVID-19 was also higher in males than females; higher in those living in the more deprived areas than those living in the least deprived; and higher in those in Black, Asian and Minority Ethnic (BAME) groups than in White ethnic groups. These inequalities largely replicate existing inequalities in mortality rates in previous years, except for BAME groups, as mortality was previously higher in White ethnic groups. These analyses take into account age, sex, deprivation, region and ethnicity, but they do not take into account the existence of comorbidities, which are strongly associated with the risk of death from COVID-19 and are likely to explain some of the differences.

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Media – Science related

Origins

The Case Is Building That COVID-19 Had a Lab Origin

Authors: Jonathan Latham, PhD and Allison Wilson PhD

Publication date: 02 June 2020

Source: Independent Science News

If the public has learned a lesson from the COVID-19 pandemic it is that science does not generate certainty. Do homemade face masks work? What is the death rate of COVID-19? How accurate are the tests? How many people have no symptoms? And so on. Practically the lone undisputed assertion made so far is that all the nearest known genetic relatives of its cause, the Sars-CoV-2 virus, are found in horseshoe bats (Zhou et al., 2020). Therefore, the likely viral reservoir was a bat.

However, most of these ancestor-like bat coronaviruses cannot infect humans (Ge et al., 2013). In consequence, from its beginning, a key question hanging over the pandemic has been: How did a bat RNA virus evolve into a human pathogen that is both virulent and deadly?

The answer almost universally seized upon is that there was an intermediate species. Some animal, perhaps a snake, perhaps a palm civet, perhaps a pangolin, served as a temporary host. This bridging animal would probably have had an ACE2 cellular receptor (the molecule which allows cellular entry of the virus) intermediate in protein sequence (or at least structure) between the bat and the human one (Wan et al., 2020).

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Covd-19 patients

23andMe finds evidence that blood type plays a role in COVID-19

Publication date: 08 June 2020

Source: 23andMe

Preliminary data from 23andMe’s ongoing genetic study of COVID-19 appears to lend more evidence for the importance of a person’s blood type — determined by the ABO gene — in differences in the susceptibility to the virus.

23andMe is still recruiting for its massive study, most recently seeking 10,000 participants outside of 23andMe who have been hospitalized and diagnosed with COVID-19. 23andMe researchers have yet to finish looking at what the genetic data indicate.

But a first blush look at the information from the more than 750,000 participants in the study shows the following:

  • The preliminary data suggest that O blood type appears to be protective against the virus when compared to all other blood types.
  • Individuals with O blood type are between 9-18% percent less likely than individuals with other blood types to have tested positive for COVID-19, according to the data.
  • There appeared to be little differences in susceptibility among the other blood types.
  • These findings hold when adjusted for age, sex, body mass index, ethnicity, and co-morbidities.
  • Although one study found the blood group O only to be protective across rhesus positive blood types, differences in rhesus factor (blood type + or -) were not significant in 23andMe data. Nor was this a factor in susceptibility or severity in cases.
  • Among those exposed to the virus — healthcare and other front line workers — 23andMe found that blood type O is similarly protective, but the proportion of cases within strata is higher.

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Covid infections

SARS-CoV-2 COVID-19: Assessing Infection Severity

Publication date: June 2020

Source: Physicians for Informed Consent

1. HOW CAN THE SEVERITY OF COVID-19 BE CALCULATED?

COVID-19 (coronavirus disease 2019) is caused by the SARS-CoV-2 virus, the newest strain among seven coronaviruses known to infect humans.1 Although more than 99% of people infected with SARS-CoV-2 fully recover, some cases involve severe complications and could be fatal.2 The severity of COVID-19 can be measured by calculating a case-fatality rate (CFR): dividing the number of people who died from the infection by the total number of people who were infected.3 In the context of COVID-19 epidemiological studies, the CFR is sometimes expressed as an infection-fatality rate (IFR).

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Therapeutics

Preliminary results from RECOVERY trial on the use of hydroxychloroquine in hospitalised patients with COVID-19

Publication date: 08/06/2020

Source: UK Research and Innovation

The ‘RECOVERY’ trial has released preliminary results showing no effect on mortality from the use of hydroxychloroquine in patients admitted to hospital with COVID-19. The RECOVERY trial (which stands for ‘Randomised Evaluation of COVid-19 thERapY’) was funded by UKRI as part of the UKRI/DHSC/NIHR COVID-19 rapid research response.

To provide real-time information in the pandemic, the results have been announced as quickly as possible, so it should be noted that the findings have not yet been peer-reviewed and accepted in a journal.

A range of potential treatments have been suggested for COVID-19 but nobody knows if any of them will turn out to be more effective in improving survival than the usual standard of hospital care which all patients will receive.

The RECOVERY trial is a large, randomised controlled trial of possible treatments for patients admitted to hospital with COVID-19. Over 11,000 patients have been randomised to several treatment arms, or no additional treatment - find out more on the RECOVERY website.

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This cow’s antibodies could be the newest weapon against COVID-19

Author: Mitch Leslie

Publication date: 05 June 2020

Source: Science

The latest recruits in the fight against COVID-19 are munching hay in a South Dakota barn. A biotech company has coaxed genetically modified cows to pump out human antibodies that subdue SARS-CoV-2, the pathogen causing the deadly disease, and it plans to start clinical trials of them this summer.

“This is promising,” says Amesh Adalja, an infectious disease physician at the Johns Hopkins University Center for Health Security. “We want to have as many countermeasures as we can.”

To manufacture antibodies for treating or preventing diseases, companies typically turn to sources such as cultured cells or tobacco plants. But almost 20 years ago, researchers began to develop the approach now pursued by SAb Biotherapeutics of Sioux Falls, South Dakota, to produce antibodies on the hoof. The company genetically alters dairy cows so that certain immune cells carry the DNA that allows people to make antibodies. That upgrade enables the animals to manufacture large quantities of human antibodies against a pathogen protein injected into them, such as the “spike” surface protein of the new coronavirus. “Essentially, the cows are used as a giant bioreactor,” says viral immunologist William Klimstra of the University of Pittsburgh, who has been analyzing the bovinemade antibodies’ potency against SARS-CoV-2.

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Social impact

Getting the NHS back on track: planning for the next phase of COVID-19

Publication date: 10 June 2020

Source: NHS Confederation

As part of our NHS Reset campaign, this report outlines the key challenges that local organisations will face over the coming months. It also suggests some changes in policy and practice that will be required as the NHS prepares to restart a wide range of services either paused or stopped when the pandemic struck.

It is based on in-depth engagement with our members and is published to support and influence forthcoming guidance from NHS England and NHS Improvement on how the next phase of the NHS’ response to the pandemic will be managed.

The key challenges we identify are: funding; capacity; rehabilitation; health inequalities; regulation and inspections; system working; and managing public expectations.

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The potential impact of COVID-19 on cancer mortality in the UK

Author: Prof Karol Sikora

Publication date: 06 May 2020

Source: Oncology Central

Coronavirus has meant that cancer diagnostics and treatment have been put on hold. This pandemic has thrown our already stretched cancer services into disarray. Many patients have had their treatment rightly stopped because of the immunosuppressive impact, but we are seeing a wider scale rationing of cancer services.

Every day I receive dozens of tweets and emails from cancer patients who have had their treatment or check-ups delayed. Good friends of mine have had their chemotherapy delayed with no good reason, or even stopped altogether. Receiving a templated email telling you not to come for further treatment is not the best way to communicate such a bombshell. I have managed to help a few patients, but there is only so much anybody can do.

Our health system has come to a shuddering halt. Hospitals have become mostly coronavirus-receiving stations and cancer patients are no longer a priority. I have been one of the loudest voices in favor of a measured lockdown; it was absolutely required to get control of the virus. But now that we are past the peak, and the data suggests, we have to get the system moving again.

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Media – Reporting

Origins

Exclusive: Coronavirus began 'as an accident' in Chinese lab, says former MI6 boss

Author: Bill Gardner

Publication date: 03 June 2020

Source: The Telegraph

A former head of MI6 has said he believes the coronavirus pandemic "started as an accident" when the virus escaped from a laboratory in China. 

In an interview with The Telegraph, Sir Richard Dearlove said he had seen an "important" new scientific report suggesting the virus did not emerge naturally but was man-made by Chinese scientists.

The apparent discovery will raise the prospect of China paying "reparations" for the death and economic catastrophe wreaked upon the world, the former intelligence chief said. It comes as Beijing faces growing pressure to explain precisely how coronavirus first began to spread late last year.

International scientists have reached a near-unanimous consensus, however, that the virus emerged in animals – most likely bats or pangolins – before jumping to the human population.

But Sir Richard, 75, pointed to a scientific paper published this week by a Norwegian-British research team who claim to have discovered clues within Covid-19's genetic sequence suggesting key elements were "inserted" and may not have evolved naturally.

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Transmission

China delayed releasing coronavirus info, frustrating WHO

Publication date: 03 June 2020

Source: The Associated Press

Throughout January, the World Health Organization publicly praised China for what it called a speedy response to the new coronavirus. It repeatedly thanked the Chinese government for sharing the genetic map of the virus “immediately,” and said its work and commitment to transparency were “very impressive, and beyond words.”

But behind the scenes, it was a much different story, one of significant delays by China and considerable frustration among WHO officials over not getting the information they needed to fight the spread of the deadly virus, The Associated Press has found.

Despite the plaudits, China in fact sat on releasing the genetic map, or genome, of the virus for more than a week after three different government labs had fully decoded the information. Tight controls on information and competition within the Chinese public health system were to blame, according to dozens of interviews and internal documents.

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Second wave

Second more deadly wave of coronavirus expected 'to hit Europe this winter'

Author: Anne Gulland

Publication date: 08 June 2020

Source: The Telegraph

European countries should brace themselves for a deadly second wave of coronavirus infections because the pandemic is not over, the World Health Organisation’s top official in Europe has said.

In an exclusive interview with The Telegraph, Dr Hans Kluge, director for the WHO European region, delivered a stark warning to countries beginning to ease their lockdown restrictions, saying that now is the "time for preparation, not celebration".

Dr Kluge stressed that, as the number of cases of Covid-19 in countries such as the UK, France and Italy was beginning to fall, it did not mean the pandemic was coming to an end. The epicentre of the European outbreak is now in the east, with the number of cases rising in Russia, Ukraine, Belarus and Kazakhstan, he warned.

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Covd-19 patients

COVID-19 Can Last for Several Months

Author: Ed Yong

Publication date: 04 June 2020

Source: The Atlantic

For vonny leclerc, day one was March 16.

Hours after British Prime Minister Boris Johnson instated stringent social-distancing measures to halt the SARS-CoV-2 coronavirus, LeClerc, a Glasgow-based journalist, arrived home feeling shivery and flushed. Over the next few days, she developed a cough, chest pain, aching joints, and a prickling sensation on her skin. After a week of bed rest, she started improving. But on day 12, every old symptom returned, amplified and with reinforcements: She spiked an intermittent fever, lost her sense of taste and smell, and struggled to breathe.

When I spoke with LeClerc on day 66, she was still experiencing waves of symptoms. “Before this, I was a fit, healthy 32-year-old,” she said. “Now I’ve been reduced to not being able to stand up in the shower without feeling fatigued. I’ve tried going to the supermarket and I’m in bed for days afterwards. It’s like nothing I’ve ever experienced before.” Despite her best efforts, LeClerc has not been able to get a test, but “every doctor I’ve spoken to says there’s no shadow of a doubt that this has been COVID,” she said. Today is day 80.

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Mortality

Antibody Tests Point To Lower Death Rate For The Coronavirus Than First Thought

Author: Jon Hamilton

Publication date: 28 May 2020

Source: NPR

Mounting evidence suggests the coronavirus is more common and less deadly than it first appeared.

The evidence comes from tests that detect antibodies to the coronavirus in a person's blood rather than the virus itself.

The tests are finding large numbers of people in the U.S. who were infected but never became seriously ill. And when these mild infections are included in coronavirus statistics, the virus appears less dangerous.

"The current best estimates for the infection fatality risk are between 0.5% and 1%," says Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security.

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Vaccines

Philippines students face distance learning until COVID-19 vaccine found

Publication date: 09 June 2020

Source: Reuters

MANILA (Reuters) - With schools in the Philippines only due to reopen when a vaccine for COVID-19 has been found, educational authorities are racing to devise a distance learning regime for 27 million children by August, when the summer holidays end.

That poses a huge challenge in a archipelago nation of 107 million, where many households have no access to the internet or a computer, and teachers fear they will not be ready to roll out remote learning in two months.

Duterte last month said resuming face-to-face classes without a vaccine for COVID-19 “spells disaster”.

Elsewhere in the world, schools are starting to reopen for students with social distancing regimes to keep infection rates down, and amid fears about children missing out on weeks of their education.

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Social Impacts

UK coronavirus victims have lain undetected at home for two weeks

Author: Denis Campbell

Publication date: 07 Jun 2020

Source: The Guardian

People have died at home alone of Covid-19 during the pandemic and not been found for up to two weeks, doctors who have investigated such deaths have said.

They have only been discovered after a relative, friend or neighbour raised the alarm and have in many cases gone undetected for so long that their body has started to decompose.

‘It was profoundly sad work, and challenging’

Campaigners for the elderly said the phenomenon highlighted the vulnerability of isolated older people living on their own with little family support and the risks being run by the large numbers of patients who have avoided hospitals and GP surgeries in recent months through fear of coronavirus.

“People have lain undiscovered during the pandemic for seven to 14 days,” said Dr Mike Osborn, a senior pathologist in London and the chair of the death investigation committee at the Royal College of Pathologists.

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Extra 10,000 dementia deaths in England and Wales in April

Author: Hannah Devlin

Publication date: 05 June 2020

Source: The Guardian

There were almost 10,000 unexplained extra deaths among people with dementia in England and Wales in April, according to official figures that have prompted alarm about the severe impact of social isolation on people with the condition.

The data, from the Office for National Statistics, reveals that, beyond deaths directly linked to Covid-19, there were 83% more deaths from dementia than usual in April, with charities warning that a reduction in essential medical care and family visits were taking a devastating toll.

“It’s horrendous that people with dementia have been dying in their thousands,” said Kate Lee, chief executive officer at Alzheimer’s Society. “We’ve already seen the devastating effect of coronavirus on people with dementia who catch it, but our [research] reveals that the threat of the virus extends far beyond that.”

A survey of 128 care homes by Alzheimer’s Society reveals that 79% report that lack of social contact is causing a deterioration in the health and wellbeing of their residents with dementia. Relatives of those with dementia in care homes have spoken of their loved ones feeling confused and abandoned, stopping eating and losing the ability to speak.

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