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Infection rate

Prevalence of suspected COVID-19 infection in patients from ethnic minority populations: a cross-sectional study in primary care

Authors: Sally A Hull, Crystal Williams, Mark Ashworth, Chris Carvalho and Kambiz Boomla

Publication date: 07 September 2020

Journal: British Journal of General Practice

DOI: 10.3399/bjgp20X712601

Background: The first wave of the London COVID-19 epidemic peaked in April 2020. Attention initially focused on severe presentations, intensive care capacity, and the timely supply of equipment. While general practice has seen a rapid uptake of technology to allow for virtual consultations, little is known about the pattern of suspected COVID-19 presentations in primary care.

Aim: To quantify the prevalence and time course of clinically suspected COVID-19 presenting to general practices, to report the risk of suspected COVID-19 by ethnic group, and to identify whether differences by ethnicity can be explained by clinical data in the GP record.

Design and setting: Cross-sectional study using anonymised data from the primary care records of approximately 1.2 million adults registered with 157 practices in four adjacent east London clinical commissioning groups. The study population includes 55% of people from ethnic minorities and is in the top decile of social deprivation in England.

Method: Suspected COVID-19 cases were identified clinically and recorded using SNOMED codes. Explanatory variables included age, sex, self-reported ethnicity, and measures of social deprivation. Clinical factors included data on 16 long-term conditions, body mass index, and smoking status.

Results: GPs recorded 8985 suspected COVID-19 cases between 10 February and 30 April 2020.Univariate analysis showed a two-fold increase in the odds of suspected COVID-19 for South Asian and black adults compared with white adults. In a fully adjusted analysis that included clinical factors, South Asian patients had nearly twice the odds of suspected infection (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.83 to 2.04). The OR for black patients was 1.47 (95% CI = 1.38 to 1.57).

Conclusion: Using data from GP records, black and South Asian ethnicity remain as predictors of suspected COVID-19, with levels of risk similar to hospital admission reports. Further understanding of these differences requires social and occupational data.

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Italy's first wave of the COVID-19 pandemic has ended: no excess mortality in May, 2020

Authors: Gianfranco Alicandro, Giuseppe Remuzzi and Carlo La Vecchia

Publication date: 03 September 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31865-1

In response to the urgent need for data on the effect of the COVID-19 pandemic, the National Institute of Statistics, in collaboration with the Italian National Institute of Health, published preliminary data on the daily number of deaths in Italy from any cause occurring during the pandemic, up to May 31, 2020.1 The total number of deaths was obtained through integration of the Population Registers and the Tax Register, and these data were released for 7357 municipalities, with validated data from 7904 municipalities, covering 95% of the Italian resident population. Total mortality is a key indicator of the real effect of COVID-19 since it is not subject to errors in the certification of the causes of death.

The total number of deaths recorded in all municipalities with validated data, and in the municipalities located in the Lombardy region only (the Italian region most severely hit by the pandemic) were compared with the mean number of deaths occurring in the period 2015–19 (appendix). Also shown in the appendix are the number of deceased patients registered in the surveillance system of the Ministry of Health and the Civil Protection Department as having had COVID-19 in the same period (in all Italian municipalities).2

In Italy, the first death due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was observed on Feb 21, 2020,3 and in mid-March, 2020, the number of deaths rapidly increased, resulting in almost 50% of excess deaths from any causes in March, 2020. In April, 2020, excess mortality was still 36%. In the first 2 weeks of May, 2020, excess mortality decreased to 3%, and in the last 2 weeks of May, 2020, the number of deaths was lower than that observed in the previous years (−7%). Lombardy, the most widely hit region, lagged behind: in the first 2 weeks of May, 2020, the excess mortality was still 20%, corresponding to more than 700 excess deaths. In the last 2 weeks of May, 2020, mortality was also lower than that observed in the previous years in Lombardy.


Public health lessons learned from biases in coronavirus mortality overestimation

Author: Ronald B Brown

Publication date: 12 August 2020

Journal: Cambridge Core

DOI: 10.1017/dmp.2020.298

In testimony before U.S. Congress on March 11, 2020, members of the House Oversight and Reform Committee were informed that estimated mortality for the novel coronavirus was ten-times higher than for seasonal influenza. Additional evidence, however, suggests the validity of this estimation could benefit from vetting for biases and miscalculations. The main objective of this article is to critically appraise the coronavirus mortality estimation presented to Congress. Informational texts from the World Health Organization and the Centers for Disease Control and Prevention are compared with coronavirus mortality calculations in Congressional testimony. Results of this critical appraisal reveal information bias and selection bias in coronavirus mortality overestimation, most likely caused by misclassifying an influenza infection fatality rate as a case fatality rate. Public health lessons learned for future infectious disease pandemics include: safeguarding against research biases that may underestimate or overestimate an associated risk of disease and mortality; reassessing the ethics of fear-based public health campaigns; and providing full public disclosure of adverse effects from severe mitigation measures to contain viral transmission.

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Viral load of SARS-CoV-2 across patients and compare to other respiratory viruses

Authors: Jacot D et al

Publication date: 03 September 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.07.15.20154518

RT-PCTs to detect SARS-CoV-2 RNA is key to manage the COVID-19 pandemic. We analyzed SARS-CoV-2 viral loads from 22’323 RT-PCR results according to samples types, gender, age and health units. Viral load did not show any difference across age and appears to be a poor predictor of disease outcome. SARS-CoV-2 viral load similar high viral loads than the one observed for RSV and influenza B. The importance of viral load to predict contagiousness and to assess disease progression is discussed.

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Covid-19 patients

UK report on 10834 patients critically ill with COVID-19

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

Publication date: 07 September 2020


The Collision of Meta-Inflammation and SARS-CoV-2 Pandemic Infection

Authors: Huizubga GP et al

Publication date: 03 September 2020

Journal: Endocrinology

DOI: 10.1210/endocr/bqaa154

The COVID-19 pandemic has forced us to consider the physiologic role of obesity in the response to infectious disease. There are significant disparities in morbidity and mortality by sex, weight and diabetes status. Numerous endocrine changes might drive these varied responses to SARS-CoV-2 infection including hormone and immune mediators, hyperglycemia, leukocyte responses, cytokine secretion, and tissue dysfunction. Studies of patients with severe COVID-19 disease have revealed the importance of innate immune responses in driving immunopathology and tissue injury. In this review we will describe the impact of the metabolically induced inflammation (meta-inflammation) that characterizes obesity on innate immunity. We consider that obesity-driven dysregulation of innate immune responses may drive organ injury in development of severe COVID-19 and impair viral clearance.

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Covid-19 and children

Covid-19: UK studies find gastrointestinal symptoms are common in children

Author: Susan Mayor

Publication date: 07 September 2020

Journal: The BMJ

DOI: 10.1136/bmj.m3484

Gastrointestinal symptoms are common in children infected with SARS-CoV-2 and should trigger tests for the virus, researchers have said.

A prospective study of 992 healthy children (median age 10.1 years) of healthcare workers from across the UK found that 68 (6.9%) tested positive for SARS-CoV-2 antibodies.1 Half of the children testing positive reported no symptoms, but for those that did the commonest were fever (21 of 68, 31%); gastrointestinal symptoms, including diarrhoea, vomiting, and abdominal cramps (13 of 68, 19%); and headache (12 of 68, 18%).

Latest findings from the Covid-19 Symptom Study app,2 which was launched in late March to track people’s symptoms, also show that gastrointestinal symptoms occur frequently in children with positive swab tests.3

Tom Waterfield, lead author of the antibodies study, told The BMJ, “Based on our findings I think that gastrointestinal symptoms should be added to the current list—high temperature, cough, and loss or change in sense of smell or taste—that trigger testing for coronavirus.” He added, “Diarrhoea and vomiting in children should trigger a test.”

Modelling showed that gastrointestinal symptoms were significantly associated with the presence of SARS-CoV-2 antibodies, in addition to known household contact with confirmed SARS-CoV-2, fatigue, and changes in sense of smell or taste.

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Multisystem inflammatory syndrome in children: A systematic review

Authors: Ahmed M et al

Publication date: 04 September 2020

Journal: EClinicalMedicine

DOI: 10.1016/j.eclinm.2020.100527

Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (COVID-19). We aimed to describe the typical presentation and outcomes of children diagnosed with this hyperinflammatory condition.

Methods: We conducted a systematic review to communicate the clinical signs and symptoms, laboratory findings, imaging results, and outcomes of individuals with MIS-C. We searched four medical databases to encompass studies characterizing MIS-C from January 1st, 2020 to July 25th, 2020. Two independent authors screened articles, extracted data, and assessed risk of bias. This review was registered with PROSPERO CRD42020191515.

Findings: Our search yielded 39 observational studies (n = 662 patients). While 71·0% of children (n = 470) were admitted to the intensive care unit, only 11 deaths (1·7%) were reported. Average length of hospital stay was 7·9 ± 0·6 days. Fever (100%, n = 662), abdominal pain or diarrhea (73·7%, n = 488), and vomiting (68·3%, n = 452) were the most common clinical presentation. Serum inflammatory, coagulative, and cardiac markers were considerably abnormal. Mechanical ventilation and extracorporeal membrane oxygenation were necessary in 22·2% (n = 147) and 4·4% (n = 29) of patients, respectively. An abnormal echocardiograph was observed in 314 of 581 individuals (54·0%) with depressed ejection fraction (45·1%, n = 262 of 581) comprising the most common aberrancy.

Interpretation: Multisystem inflammatory syndrome is a new pediatric disease associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is dangerous and potentially lethal. With prompt recognition and medical attention, most children will survive but the long-term outcomes from this condition are presently unknown.

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Seroprevalence of SARS-CoV-2 antibodies in children - A prospective multicentre cohort study

Authors: Waterfield T et al

Publication date: 02 September 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.08.31.20183095

Background Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity and timing of testing. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection, and to report the symptomatology of infection in children. Design This multicentre observational cohort study, conducted between 16th April - 3rd July 2020 at 5 UK sites, aimed to recruit 900 children aged 2 to 15 years of age. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. Results 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10.1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariate analysis 4 independent variables were identified as significantly associated with SARS-CoV-2 infection. These were: known infected household contact; fatigue; gastrointestinal symptoms; and changes in sense of smell or taste. Discussion In this study children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. The symptoms of SARS-CoV-2 infection in children were subtle but of those reported, fatigue, gastrointestinal symptoms and changes in sense of smell or taste were most strongly associated with antibody positivity.

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Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results

Authors: Meltzer DO PhD et al

Publication date: 03 September 2020

Journal: JAMA Network Open

DOI: 10.1001/jamanetworkopen.2020.19722

Importance: Vitamin D treatment has been found to decrease the incidence of viral respiratory tract infection, especially in patients with vitamin D deficiency. Whether vitamin D is associated with coronavirus disease 2019 (COVID-19) incidence is unknown.

Design, Setting, and Participants: This retrospective cohort study at an urban academic medical center included patients with a 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol level measured within 1 year before being tested for COVID-19 from March 3 to April 10, 2020.

Exposures: Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL or 1,25-dihydroxycholecalciferol less than 18 pg/mL before COVID-19 testing. Treatment changes were defined by changes in vitamin D type and dose between the date of the last vitamin D level measurement and the date of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize the most recent vitamin D status before COVID-19 testing as likely deficient (last level deficient and treatment not increased), likely sufficient (last level not deficient and treatment not decreased), and 2 groups with uncertain deficiency (last level deficient and treatment increased, and last level not deficient and treatment decreased).

Main Outcomes and Measures: The outcome was a positive COVID-19 polymerase chain reaction test result. Multivariable analysis tested whether vitamin D status before COVID-19 testing was associated with testing positive for COVID-19, controlling for demographic and comorbidity indicators.

Results: A total of 489 patients (mean [SD] age, 49.2 [18.4] years; 366 [75%] women; and 331 [68%] race other than White) had a vitamin D level measured in the year before COVID-19 testing. Vitamin D status before COVID-19 testing was categorized as likely deficient for 124 participants (25%), likely sufficient for 287 (59%), and uncertain for 78 (16%). Overall, 71 participants (15%) tested positive for COVID-19. In multivariate analysis, testing positive for COVID-19 was associated with increasing age up to age 50 years (relative risk, 1.06; 95% CI, 1.01-1.09; P = .02); non-White race (relative risk, 2.54; 95% CI, 1.26-5.12; P = .009), and likely deficient vitamin D status (relative risk, 1.77; 95% CI, 1.12-2.81; P = .02) compared with likely sufficient vitamin D status. Predicted COVID-19 rates in the deficient group were 21.6% (95% CI, 14.0%-29.2%) vs 12.2%(95% CI, 8.9%-15.4%) in the sufficient group.

Conclusions and Relevance: In this single-center, retrospective cohort study, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that suggests that randomized trials may be needed to determine whether vitamin D affects COVID-19 risk.

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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Authors: The Writing Committee for the REMAP-CAP Investigators

Publication date: 02 September 2020

Journal: JAMA

DOI: 10.1001/jama.2020.17022

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes and Measures: The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

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"Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study"

Authors: Castillo ME et al

Publication date: 29 August 2020

Journal: The Journal of Steroid Biochemistry and Molecular Biology

DOI: 10.1016/j.jsbmb.2020.105751

Objective: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.

Participants: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).

Procedures: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 hours on the first day, and 200 mg every 12 hours for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths.

Results: Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95%CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95%CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.

Conclusion: Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

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Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Authors: The COVID-19 RISK and Treatments (CORIST) Collaboration members

Publication date: 25 August 2020

Journal: European Journal of Internal Medicine

DOI: 10.1016/j.ejim.2020.08.019

Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality.

Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses.

Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry.

Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

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Are we underestimating seroprevalence of SARS-CoV-2?

Authors: Stephen Burgess, Mark J Ponsford and Dipender Gill

Publication date: 03 September 2020

Journal: The BMJ

DOI: 10.1136/bmj.m3364

Current antibody tests fail to identify people who had mild infections

Testing for severe acute respiratory coronavirus 2 (SARS-CoV-2), which causes covid-19, is complex and politically sensitive. Seroprevalence studies use antibodies as markers of pathogen exposure to estimate the proportion of the population that has been infected.

Considerable variation has been observed in the results of SARS-CoV-2 seroprevalence studies.1 A recent survey in Spain suggested that a small fraction of the population was seropositive, despite the country being severely affected by the virus.2 However, within-individual variation has been observed in immune responses to viral exposure, particularly in those with mild or asymptomatic disease. For example, a pilot study from the Karolinska Institute found the percentage of people mounting T cell responses after mild covid-19, asymptomatic disease, or exposure to infected family members, consistently exceeded the percentage mounting detectable IgG serological responses against the virus.3 Such discordant results could have major implications for epidemiological modelling of disease transmission and herd immunity.

Seroepidemiological studies may underestimate the true seroprevalence of SARS-CoV-2 for several reasons. Accuracy demands the use of an assay sensitive enough to reliably detect antibody responses to mild infection across different post-exposure scenarios. The selection of target antigen is critical, with recent data showing that the trimeric spike glycoprotein offers superior detection to the nucleocapsid in people with low level antibody responses.4 Of the 24 serological diagnostic tests that the FDA initially authorised for emergency use, six consider only the nucleocapsid, including high throughput tests in widespread use.

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Seroprevalence of anti-SARS-CoV-2 antibodies in COVID-19 patients and healthy volunteers

Authors: Figueiredo-Campos P et al

Publication date: 02 September 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.08.30.20184309

SARS-CoV-2 has emerged as a novel human pathogen, causing clinical signs, from fever to pneumonia - COVID-19 - but may remain mild or even asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed and have been setup around the world. We quantified immunoglobulin M (IgM), IgG and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of five months following COVID-19 disease onset or in previously SARS-CoV-2 PCR-positive volunteers. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff and 187 post-COVID19 volunteers, and assessing titres for IgM, IgG and IgA. Anti-SARS-CoV-2 antibody responses followed a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce from approximately four weeks, the ability to detect SARS-CoV-2 antibodies remained robust for five months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Moreover, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2, at least up to five months after infection.

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Humoral Immune Response to SARS-CoV-2 in Iceland

Authors: Gudbjartsson DF et al

Publication date: 01 September 2020

Journal: The New England Journal of Medicine

DOI: 10.1056/NEJMoa2026116

Background: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed.

Results: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR.

Conclusions: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

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High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19; a prospective cohort study in England

Authors: Ladhani SN et al

Publication date: 12 August 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.08.10.20171413

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found very high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up serological analysis in these care homes five weeks later. Methods: Residents and staff had a convalescent blood sample for SARS-CoV-2 antibody levels and neutralising antibodies by SARS-COV-2 RT-PCR five weeks after the primary COVID-19 outbreak investigation. Results: Of the 518 residents and staff in the initial investigation, 208/241 (86.3%) surviving residents and 186/254 (73.2%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were antibody positive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.1%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 62/92, 67.3%; staff 95/143, 66.4%). Neutralising antibody was present in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/108, 9.3%) remained RT-PCR positive, but with lower RT-PCR cycle threshold values; all 7 tested were seropositive. New infections were detected in three residents and one staff member. Conclusions: RT-PCR testing for SARS-CoV-2 significantly underestimates the true extent of an outbreak in institutional settings. Elderly frail residents and younger healthier staff were equally able to mount robust and neutralizing antibody responses to SARS-CoV-2. More than two-thirds of residents and staff members had detectable antibodies against SARS-CoV-2 irrespective of their nasal swab RT-PCR positivity or symptoms status.

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Viral cultures for COVID-19 infectivity assessment – a systematic review (Update 3)

Authors: Jefferson T, Spencer EA, Brassey J and Heneghan C

Publication date: 03 September 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.08.04.20167932

Objective: to review of the evidence from studies comparing SARS-CoV-2 culture, the best indicator of current infection and infectiousness with the results of reverse transcriptase polymerase chain reaction (RT-PCR).

Methods: We searched LitCovid, medRxiv, Google Scholar and Google for Covid-19 for 'viral culture' or 'viral replication' and associated synonyms up to 31st August 2020. We carried out citation matching and included studies reporting attempts to culture or observe SARS-CoV-2 matching the with cutoffs for RT-PCR positivity. One reviewer extracted data for each study and a second reviewer checked end edited the extraction and summarised the narratively by sample: fecal, respiratory, environment or mixed.

Where necessary we wrote to corresponding authors of the included or background papers for additional information. We assessed quality using a modified QUADAS 2 risk of bias tool.

This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. Summaries of the included studies and the protocol (v1) are available at: https://www.cebm.net/evidence-synthesis/transmission-dynamics-of-covid-19/. Searches are updated every 2 weeks. This is the third version of this review that was fist published on the 4th of August and updated on the 21St of August. https://www.medrxiv.org/content/10.1101/2020.08.04.20167932v2Results We included 25 studies reporting culturing or observing tissue invasion by SARS-CoV in sputum,

naso or oropharyngeal, urine, stool, blood and environmental samples from patients diagnosed with Covid-19. The data are suggestive of a relation between the time from collection of a specimen to test, cycle threshold (as a proxy for viral load) and symptom severity. The quality of the studies was moderate with lack of standardised reporting. Ten studies reported that Ct values were significantly lower and log copies higher in those with live virus culture. Nine studies reported no growth in samples based on a Ct cut-off value. These values ranged from CT > 24 for no growth to Ct ≥ 34. Two studies report a strong relationship between Ct value and ability to recover infectious virus and that the odds of live virus culture reduced by 33% for every one unit increase in Ct. A cut-off RT-PCR Ct > 30 was associated with non-infectious samples. One study that analysed the NSP, N and E gene fragments of the PCR result reported different cut-off thresholds depending on the gene fragment analysed. The duration of RNA shedding detected by PCR was far longer compared to detection of live culture. Six out of eight studies reported RNA shedding for longer than 14 days. Yet, Infectivity declines after day 8 even among cases with ongoing high viral loads. A very small proportion of people re-testing positive after hospital discharge or with high Ct are likely to be infectious.

Conclusion: Prospective routine testing of reference and culture specimens are necessary for each country involved in the pandemic to establish the usefulness and reliability of PCR for Covid-19 and its relation to patients’ factors. Infectivity is related to the date of onset of symptoms and cycle threshold level. A binary Yes/No approach to the interpretation RT-PCR unvalidated against viral culture will result in false positives with segregation of large numbers of people who are no longer infectious and hence not a threat to public health.

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Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia

Authors: Loguno DY et al

Publication date: 04 September 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31866-3

Background: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine.

Methods: We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18–60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875.

Findings: Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation, and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised formulation.

Interpretation: The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19.

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Evolution of the COVID-19 vaccine development landscape

Author: Le Thanh T et al

Publication date: 04 September 2020

Journal: Nature Reviews Drug Discovery

DOI: 10.1038/d41573-020-00151-8

The COVID-19 vaccine R&D landscape has developed at unprecedented scale and speed since our initial analysis in April identified 115 candidates in the pipeline (Nat. Rev. Drug Discov. 19, 305–306; 2020). In this updated overview, we focus on candidates in clinical trials and provide some initial perspectives on their clinical development.

Evolution of the R&D landscapeAs of 3 September 2020, the global COVID-19 vaccine R&D landscape includes 321 vaccine candidates, an increase of more than 2.5 fold compared with our previous report. Of these, 33 vaccine candidates are in clinical trials (Supplementary Table 1), with plans to enrol more than 280,000 participants from at least 470 sites in 34 different countries. The most advanced clinical candidates are now in phase III trials, and data to support licensure are anticipated to be available later this year. For the leading candidates, large-scale manufacturing of vaccine has already been initiated to enable rapid distribution if approval is obtained.

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Social Impacts

Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic

Authors: Ettman CK et al

Publication date: 02 September 2020

Journal: JAMA Network Open

DOI: 10.1001/jamanetworkopen.2020.19686

Objective: To estimate the prevalence of and risk factors associated with depression symptoms among US adults during vs before the COVID-19 pandemic.

Design, Setting, and Participants: This nationally representative survey study used 2 population-based surveys of US adults aged 18 or older. During COVID-19, estimates were derived from the COVID-19 and Life Stressors Impact on Mental Health and Well-being study, conducted from March 31, 2020, to April 13, 2020. Before COVID-19 estimates were derived from the National Health and Nutrition Examination Survey, conducted from 2017 to 2018. Data were analyzed from April 15 to 20, 2020.

Main Outcomes and Measures: Depression symptoms, defined using the Patient Health Questionnaire-9 cutoff of 10 or higher. Categories of depression symptoms were defined as none (score, 0-4), mild (score, 5-9), moderate (score, 10-14), moderately severe (score, 15-19), and severe (score, ≥20).

Results: A total of 1470 participants completed the COVID-19 and Life Stressors Impact on Mental Health and Well-being survey (completion rate, 64.3%), and after removing those with missing data, the final during–COVID-19 sample included 1441 participants (619 participants [43.0%] aged 18-39 years; 723 [50.2%] men; 933 [64.7%] non-Hispanic White). The pre–COVID-19 sample included 5065 participants (1704 participants [37.8%] aged 18-39 years; 2588 [51.4%] women; 1790 [62.9%] non-Hispanic White). Depression symptom prevalence was higher in every category during COVID-19 compared with before (mild: 24.6% [95% CI, 21.8%-27.7%] vs 16.2% [95% CI, 15.1%-17.4%]; moderate: 14.8% [95% CI, 12.6%-17.4%] vs 5.7% [95% CI, 4.8%-6.9%]; moderately severe: 7.9% [95% CI, 6.3%-9.8%] vs 2.1% [95% CI, 1.6%-2.8%]; severe: 5.1% [95% CI, 3.8%-6.9%] vs 0.7% [95% CI, 0.5%-0.9%]). Higher risk of depression symptoms during COVID-19 was associated with having lower income (odds ratio, 2.37 [95% CI, 1.26-4.43]), having less than $5000 in savings (odds ratio, 1.52 [95% CI, 1.02-2.26]), and exposure to more stressors (odds ratio, 3.05 [95% CI, 1.95-4.77]).

Conclusions and Relevance: These findings suggest that prevalence of depression symptoms in the US was more than 3-fold higher during COVID-19 compared with before the COVID-19 pandemic. Individuals with lower social resources, lower economic resources, and greater exposure to stressors (eg, job loss) reported a greater burden of depression symptoms. Post–COVID-19 plans should account for the probable increase in mental illness to come, particularly among at-risk populations.

Read more[https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770146]


Government and Health Authorities

Coronavirus Infections

Coronavirus (COVID-19) Infection Survey pilot: England and Wales, 4 September 2020

Publication date: 04 September 2020

Source: Office for National Statistics (UK)

In this bulletin, we refer to the number of current COVID-19 infections within the community population; community in this instance refers to private residential households and it excludes those in hospitals, care homes or other institutional settings.

We use current COVID-19 infections to mean testing positive for SARS-CoV-2, with or without having symptoms, on a swab taken from the nose and throat.

All analysis was produced with our research partners at the University of Oxford.

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Covid-19 and children

Children and COVID-19: State Data Report

Publication date: 03 September 2020

Source: American Academy of Pediatrics

A joint report from the American Academy of Pediatrics and the Children’s Hospital Association

Summary of publicly reported data from 49 states, NYC, DC, PR, and GU

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Multidisciplinary Task and Finish Group on Mass Testing. Consensus Statement for SAGE

Publication date: 31 August 2020

Source: UK Government

This consensus statement presents the findings and recommendations of the SAGE Task and Finish Group on Mass Screening (TFMS). The TFMS is a multidisciplinary group established to examine, from technological, epidemiological, and behavioural perspectives, the benefits and challenges of mass testing for SARS-CoV-2.

TFMS adopts the terminology ‘mass testing’, or ‘population-level case detection’ (PCD), which refers to regular and/or large-scale testing of whole populations defined by area or sector regardless of whether or not they have symptoms. Mass testing is a distinct strategy and set of technologies to NHS Test and Trace (NHSTT). Rather than testing self-reported, symptomatic individuals, mass testing involves pro-active asymptomatic testing of a defined group; either through universal provision of accessible testing to that group or as a requirement before entering a particular setting.

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Media – Science related


Renowned European scientist: COVID-19 was engineered in China lab, effective vaccine ‘unlikely’

Author: Steven Mosher

Publication date: 10 August 2020

Source: LifeSite

August 10, 2020 (LifeSiteNews) – It will not be possible for the Dr. Faucis of the world to dismiss Professor Giuseppe Tritto as a crank.  Not only is he an internationally known expert in biotechnology and nanotechnology who has had a stellar academic career, but he is also the president of the World Academy of Biomedical Sciences and Technologies (WABT), an institution founded under the aegis of UNESCO in 1997.

In other words, he is a man of considerable stature in the global scientific community.  Equally important, one of the goals of WABT is to analyze the effect of biotechnologies—like genetic engineering—on humanity. 

In his new book, this world-class scientist does exactly that.  And what he says is that the China Virus definitely wasn’t a freak of nature that happened to cross the species barrier from bat to man.  It was genetically engineered in the Wuhan Institute of Virology’s P4 (high-containment) lab in a program supervised by the Chinese military.

Prof. Tritto’s book, which at present is available only in Italian, is called Cina COVID 19: La Chimera che ha cambiato il Mondo (China COVID 19: The chimera that changed the world).  It was published on August 4 by a major Italian press, Edizioni Cantagalli, which coincidently also published the Italian edition of one of my books, Population Control (Controllo Demografico in Italian) several years ago.

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How Likely is a Second wave?

Authors: Paul Kirkham, Dr Mike Yeadon and Barry Thomas

Publication date: 07 September 2020

Source: Lockdown Sceptics

Evidence presented in this paper indicates that the severe acute respiratory syndrome coronavirus 2 pandemic as an event in the UK is essentially complete, with ongoing and anticipated challenges well within the capacity of a normalised NHS to cope. The virus infection has passed through the bulk of the population as a result of wholly natural processes and evidence indicates that in the UK and other heavily infected European countries the spread of the virus has been all but halted by a substantial reduction in the susceptible population. This has occurred because the level of infection required to introduce enough immunity into the population to reduce the reproduction number (R) permanently below 1 occurred at markedly lower infection rates and loss of life than had been initially anticipated. The evidence presented in this paper indicates that there should be no expectation of a large scale ‘second wave’ with smaller localised outbreaks when the virus contacts pockets of previously uninfected populations.

Current mass testing using the PCR test is inappropriate in its current form. If it is to continue, then results and reporting should be refined to meet the gold standard of testing methodology to give clinicians improved information so that they are able to make appropriate clinical decisions. Positive tests should be confirmed by testing a second sample and all positive tests should be reported along with the Cycle Threshold (Ct) obtained during the test to aid assessment of a patient’s viral load.

It is recommended that a greater focus be placed on evidence-based medicine rather than highly sensitive theoretical modelling based on assumptions and unknowns. Current evidence allows for a greatly improved understanding of positive infectious patients and using the evidence to improve measurements and understanding can lead to sensitive measurements of active cases to give a more accurate warning of escalating cases and potential issues and outbreaks.

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Should we be worried about the uptick in Covid cases? Almost certainly not

Author: Toby Young

Publication date: 07 September 2020

Source: The Telegraph

Yesterday, Matt Hancock said he was “concerned” about the number of new cases of coronavirus which  jumped to 2,988, the highest number on a single day since 22 May. According to the Health Secretary, this means we have to be extra vigilant to avoid being engulfed by a “second wave”.

“It's so important that everybody does their bit and follows the social distancing,” he told the BBC.

Should we be worried about the uptick in cases? Almost certainly not. It’s due to recent increases in testing capacity, with many more tests being done now than ever before. As Professor Carl Heneghan and others have pointed out, the problem with the PCR test currently being used in Pillar 2 community testing – which accounts for the lion’s share of the 2,988 new cases detected – is that it yields numerous false positives, so the more tests you do, the more positives you get.

In a preprint published on Friday, Prof Heneghan and his team at Oxford’s Centre for Evidence-Based Medicine analysed the data from 25 studies and found that the PCR tests being used by Public Health England are often over-sensitive and detect fragments of the virus in patients who’ve made a complete recovery. He told the BBC that people are only infectious for about a week, but in some cases the test is so sensitive that anyone who’s had the virus will get a positive result for weeks afterwards.

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The 1% blunder: How a simple but fatal math mistake by US Covid-19 experts caused the world to panic and order lockdowns

Author: Malcolm Kendrick

Publication date: 06 September 2020

Source: RT

In February, US Covid guru Anthony Fauci predicted the virus was ‘akin to a severe flu’ and would therefore kill around 0.1 percent of people. Then fatality rate predictions were somehow mixed up to make it look ten times WORSE.

When you strip everything else out, the reason for lockdown comes from a single figure: one percent. This was the prediction that Covid, if left unchecked, would kill around one percent of us.

You may not think that percentage is enormous, but one percent of the population of the world is 70 million people – and that’s a lot. It would mean 3.2 million Americans dead, and 670,000 Britons.

But where did this one percent figure come from? You may find this hard to believe, but this figure emerged by mistake. A pretty major thing to make a mistake about, but that’s what happened.

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Covid-19 patients

Independent role of morbid obesity as a risk factor for COVID‐19 hospitalization: a Spanish population‐based cohort study

Authors: Fresán U et al

Publication date: 04 September 2020

Journal: Obesity

DOI: 10.1002/oby.23029

Objectives: To analyze the association between morbid obesity and COVID‐19 hospitalization and severe disease.

Methods: We evaluated the incidence of hospitalization for laboratory‐confirmed COVID‐19 in a prospective population‐based cohort of 433,995 persons aged 25‐79 years in Spain during March and April 2020. Persons with and without morbid obesity were compared using Poisson regression to estimate the adjusted relative risk (aRR) of morbid obesity for COVID‐19 hospitalization and for severe disease (intensive care unit admission or death). Differences in the effect by age, sex and chronic conditions were evaluated.

Results: Individuals with morbid obesity had higher risk of hospitalization (aRR=2.20; 95% confidence interval (CI) 1.66‐2.93) and severe COVID‐19 (aRR=2.30; 95%CI 1.20‐4.40). In people younger than 50 years, these effects were more pronounced (aRR=5.02, 95%CI 3.19‐7.90; and aRR=13.80, 95%CI 3.11‐61.17, respectively), while no significant effects were observed in those aged 65‐79 years (aRR=1.22, 95%CI 0.70‐2.12; and aRR=1.42, 95%CI 0.52‐3.88, respectively). Sex and chronic conditions did not modify the effect of morbid in any of the outcomes.

Conclusions: Morbid obesity is a relevant risk factor for COVID‐19 hospitalization and severity in young adults, of a similar magnitude as aging. Tackling current obesity pandemic could alleviate impact of chronic and infectious diseases.

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Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions

Authors: Kox M PhD et al

Publication date: 03 September 2020

Journal: JAMA

DOI: 10.1001/jama.2020.17052

An abnormally strong proinflammatory response known as “cytokine storm” may play an important role in the pathophysiology of coronavirus disease 2019 (COVID-19), although cytokine storm remains ill defined.1 Sinha and colleagues2 reported that although IL-6 levels are elevated in severe COVID-19, they are lower than levels usually observed in (non–COVID-19) acute respiratory distress syndrome (ARDS). However, this comparison is limited by the use of different assays, which are not well standardized.3 We compared cytokine levels in critically ill patients with COVID-19 vs levels in patients with other critical illnesses.

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Covariation of Zinc Deficiency with COVID-19 Infections and Mortality in European Countries: Is Zinc Deficiency a Risk Factor for COVID-19?

Author: Samer Singh

Publication date: 02 September 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.06.12.20105676

Variables responsible for the differential COVID-19 pandemic severity among countries remain undefined. Zinc, a micronutrient required for immunocompetence, is found deficient in populations. We hypothesized the differential COVID-19 severity observed among European countries could be associated with the Zn-deficiency prevalence. The COVID-19 data from different stages of pandemic, i.e., 8 April, 12 and 26 May 2020, were analyzed for covariation with the estimated Zn-deficiency. A significant, relatively stable, but negative correlation of Zn-deficiency with cases per million for the time period [r(20): -0.4930 to -0.5335, p-value: 0.02720 to 0.0154] and a steady improvement of covariation with deaths per million [r(20): -0.4056; p-value: 0.0760 on 26 May 2020] was observed. Considering, Zinc′s key immunomodulatory role, widespread deficiency along with the self- and prescribed intervention in different target groups, e.g., children, women, elderly, carefully planned dedicated exploratory studies to understand the basis of the observed association are advisable.

Read more… 

Is a Bradykinin Storm Brewing in COVID-19?

Author: Alakananda Dasgupta

Publication date: 26 August 2020

Source: The Scientist

On a Sunday afternoon in mid-April this year, Daniel Jacobson, a computational systems biologist at Oak Ridge National Laboratory in Tennessee, was looking at gene expression data from the lung fluid of COVID-19 patients on his computer screen when he spotted something striking—the expression of genes for key enzymes in the renin-angiotensin system (RAS), involved in blood pressure regulation and fluid balance, was askew.

Jacobson followed this abnormal RAS in the lung fluid samples to the kinin cascade, an inflammatory pathway that is tightly regulated by the RAS. He found that the kinin system—in which a key peptide, bradykinin, causes blood vessels to leak and fluid to accumulate in tissues and organs—was thrown out of balance as well in COVID-19 patients. Infected individuals showed heightened expression of genes for the bradykinin receptors, as well as for enzymes called kallikreins that activate the kinin pathway, compared with controls.

The results, published July 7 in eLife, could perhaps explain the abnormal accumulation of fluid in the lungs that is so common in COVID-19 patients, the authors say.

Unbeknownst to Jacobson, Frank van de Veerdonk, an infectious disease specialist at the Radboud University Medical Center in the Netherlands, was heading down the same molecular pathway in mid-March. He had noticed two features in COVID-19 patients in his clinic—fluid in the lungs and inflammation. Because other labs had pegged angiotensin-converting enzyme-2 (ACE2), a key enzyme in the RAS, as being the SARS-CoV-2 receptor, and because he knew that ACE2 regulates the kinin system, van de Veerdonk began connecting the dots. In April, he and his group hypothesized that a dysregulated bradykinin system was leading to leaky blood vessels in the lungs and perhaps causing excess fluid to build up

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Covid-19 and children

Damage of the lockdown for children and young people – let’s choose a different path

Authors: Sunil Bhopal and Delan Devakumar

Publication date: 07 September 2020

Source: Reachwell

Children are fortunately minimally affected by COVID-19. Despite early reports of a new inflammatory syndrome, children are much more likely to be severely unwell or die from illnesses that we consider ‘normal’, including influenza and pneumonia. This applies to most children with chronic medical conditions such as asthma and type I diabetes.1 This became clearer and clearer as the pandemic progressed, and calls for UK schools to reopen were made by experts as early as April 2020 based on data from around the world. School closures were based on the risk of transmission but current reviews and modelling have questioned the overall benefit.2

During lockdown there is clear evidence of massive reduction of children being brought for emergency medical treatment,3 child protection investigations have decreased in number despite the increased risk of abuse and neglect,4 health visiting services have reduced in many areas despite the importance of the earliest moments of a child’s life on their health and development,5 and vaccination services were stopped and have been slow to recover.6 This was coupled with the closure of playgroups, nurseries, breastfeeding support groups and numerous other child health and wellbeing organisations and activities.

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The Londoner: Let children be exposed to viruses, says Professor Gupta

Publication date: 02 September 2020

Source: Evening Standard

Professor Sunetra Gupta, who has been a leading critic of the cost of lockdown, says she welcomes the return of schools as children “if anything... would benefit from being exposed to this and other seasonal coronaviruses”.

Gupta, who is a professor of theoretical epidemiology at Oxford, told The Londoner that alongside huge social and educational benefits, the “evidence is mounting that early exposure to these various coronaviruses is what enables people to survive them”.

Professor Gupta came to prominence earlier this year when she questioned the government’s reliance on the Imperial College London modelling of the coronavirus epidemic. Professor Gupta and her team produced modelling that posited a greater number of Britons could have immunity to the virus than thought. She has been a longstanding critic of the wider impacts of lockdown on the poorest in society and across the world.

Read more… 


Sweden Now Has a Lower COVID-19 Death Rate Than the US. Here’s Why It Matters

Author: Jon Miltimore

Publication date: 04 September 2020

Source: Foundation for Economic Education

For months, Sweden was the punching bag of the world’s media and politicians.

For foregoing a lockdown, Sweden was declared a “cautionary tale” by The New York Times.

“Sweden is paying heavily for its decision not to lockdown,” President Trump tweeted.

“They are leading us to catastrophe,” said The Guardian in March, quoting a virus immunology researcher.

Experts and media around the world all seemed to agree, with a few notable exceptions, that lockdowns were the sound approach to the COVID-19 pandemic.

There’s been much less talk about Sweden of late. The reason, it would seem, is that Sweden’s strategy appears to have tamed the virus. While countries around the world are experiencing a resurgence of COVID-19 outbreaks, Sweden’s COVID-19 deaths have slowed to a crawl.

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How many people has the coronavirus killed?

Author: Giuliana Viglione

Publication date: 01 September 2020

Source: Nature

Researchers are struggling to tally mortality statistics as the pandemic rages. Here’s how they gauge the true toll of the coronavirus outbreak.

At the beginning of March, Andrew Noymer felt a familiar twinge of doubt. He was watching countries across Europe and North America begin to record their first deaths from COVID-19, and he knew there could be problems with the data. Even in a normal winter, some deaths caused by influenza get misclassified as pneumonia. If that can happen with a well-known disease, there were bound to be deaths from COVID-19 going unreported, thought Noymer, a demographer at the University of California, Irvine. “I just remember thinking, ‘this is going to be really difficult to explain to people’,” he recalls.

And in March and April, when national statistics offices began to release tallies of the number of deaths, it confirmed his suspicions: the pandemic was killing a lot more people than the COVID-19 figures alone would suggest.

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Finally Confirmed! Vitamin D Nearly Abolishes ICU Risk in COVID-19

Author: Chris Masterjohn

Publication date: 03 September 2020

Source: Chris Masterjohn PhD

The first randomized controlled trial (RCT) of vitamin D in COVID-19 has just been published. The results are astounding: vitamin D nearly abolished the odds of requiring treatment in ICU. Although the number of deaths was too small to say for sure, vitamin D may actually abolish the risk of death from COVID-19.

The First Randomized Controlled Trial on Vitamin D and COVID-19

The trial was conducted at the Reina Sofía University Hospital in Córdoba, Spain. The trial included 76 patients with COVID-19 pneumonia. Although this is no longer the standard of care, all patients were treated with hydroxychloroquine and azithromycin and, when needed, a broad-spectrum antibiotic. Admission to the ICU was determined by a multidisciplinary committee consisting of intensive care specialists, pulmonologists, internal medicine specialists, and members of the ethics committee.

The patients were randomly allocated to receive or not receive vitamin D in a 2:1 ratio. This resulted in 50 patients in the vitamin D group and 26 patients in the control group.

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What the immune response to the coronavirus says about the prospects for a vaccine

Author: Heidi Ledford

Publication date: 17 August 2020

Source: Nature

In the late 1980s, 15 healthy people moved into new apartments in Salisbury, UK. On their third day, each was asked to snort a nostrilful of solution containing a coronavirus — one of several viruses that causes the common cold. Then the volunteers spent three weeks quarantined at the Common Cold Unit, part of the Medical Research Council, where researchers monitored a range of symptoms. Some study participants likened stays at the Common Cold Unit to a vacation — if so, it was a holiday complete with blood draws and nasal washes.

About a year later, 14 of the volunteers came back to do it again. This time, researchers were keen to know if the participants’ exposure to the virus had made them immune. The answer: sort of. Although they showed no symptoms, analyses revealed that nearly all of them became infected before their immune systems could launch an effective defence1.

It was an early hint to the answer for a question that now keeps researchers, physicians and politicians alike awake at night: can the human immune system mount a lasting defence against the pandemic virus SARS-CoV-2? The answer is crucial to understanding whether a vaccine will provide adequate protection, whether those who have recovered from COVID-19 can return to pre-pandemic behaviours, and how readily the world can reduce the threat posed by the disease.

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COVID-19 antibody testing ‘the only safe pathway’

Publication date: 03 September 2020

Source: Health Europa

UK company Testing For All has launched a large scale finger-prick COVID-19 antibody testing kit aimed at providing accessibility and affordability for UK workers.

Testing For All, which describes itself as ‘proudly not-for-profit’, says: ‘The challenge that COVID-19 poses for communities and businesses across the country is immense. We believe that the only safe pathway out of the crisis is through large scale, affordable testing.’ The testing kit, a capillary blood-based home test which is fully compliant with current Medicines and Healthcare products Regulatory Agency (MHRA) guidelines, is priced at £39, in line with Testing For All’s key goals of affordability and transparent pricing. The kits are suitable for individuals at home and for large scale workplace testing, which can be conducted on site by a registered nurse.

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Toward COVID-19 Testing Any Time, Anywhere

Author: Abby Olena

Publication date: 02 September 2020

Source: The Scientist

In late January, as the COVID-19 pandemic was gaining steam, Charles Chiu, a researcher at the University of California, San Francisco, reached out to colleagues at San Francisco–based biotech Mammoth Biosciences. Chiu’s group and the team at Mammoth had already collaborated on developing a CRISPR-based diagnostic test for Lyme disease, which they thought would easily translate to SARS-CoV-2 detection, he says.

“The CRISPR system allows you to target pathogens very precisely,” Chiu, who is part of Mammoth’s scientific advisory board, tells The Scientist. “Within two to three weeks, we were able to go from just designing the assay to actually getting it to work and demonstrating that we can use it to rapidly identify or potentially diagnose SARS-CoV-2 from clinical samples.”

The gold standard for detecting a virus such as SARS-CoV-2 is reverse transcription PCR, which requires isolation of RNA from a sample followed by the conversion of RNA to DNA and subsequent PCR to amplify any viral nucleic acids. While sensitive, this type of test requires collection of a specimen, such as saliva or a nasal swab, and the transport of that sample to a clinical lab for processing. Earlier in the year, reagents for this type of test were in short supply.

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Do Medical Complications and Lingering Effects Make COVID-19 an Unusually Dangerous Diseases?

Publication date: 06 September 2020

Source: Lockdown Sceptics

COVID-19 death rates have fallen across much of Europe since a peak in early April, irrespective of governments’ responses to the virus. Even in those countries at lower latitudes – Brazil, India and the southern United States – death rates also appear to be falling, following a flatter trajectory. These patterns are akin to those of another seasonal respiratory virus – influenza, where declining fatality rates reflect a natural seasonal waning of the disease.

In the absence of a high seroprevalence of anti-SARS-CoV-2 antibodies, the evidence of natural immunity – including innate and T-cell mediated immunity and cross-immunity conferred by exposure to other coronaviruses – offers an explanation at the community, cellular and molecular level for how immunity to COVID-19 may be leading to a decline in infection rates across the world.

Nonetheless, acute complications of COVID-19 in children, and the persistence of symptoms following serious and, as noted in the media, mild illness may be seen as posing sufficient risk to justify attempts to maximally suppress SARS-CoV-2 through ongoing or intensified Non-Pharmaceutical Interventions.

But how substantial are the complications of COVID-19 in children? What are the connotations of symptom persistence? And are these conditions unique to COVID-19, or more generally true of influenza? Therefore, are maximum suppression (i.e. Zero-COVID) measures warranted for COVID-19?

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AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction in participant in the U.K.

Author: Rebecca Robins, Adam Feuerstein and Helen Branswell

Publication date: 08 September 2020

Source: STAT

A large, Phase 3 study testing a Covid-19 vaccine being developed by AstraZeneca and the University of Oxford at dozens of sites across the U.S. has been put on hold due to a suspected serious adverse reaction in a participant in the United Kingdom.

A spokesperson for AstraZeneca, a frontrunner in the race for a Covid-19 vaccine, said in a statement that the company’s “standard review process triggered a pause to vaccination to allow review of safety data.”

In a follow-up statement, AstraZeneca said it initiated the study hold. The nature of the adverse reaction and when it happened were not immediately known, though the participant is expected to recover, according to an individual familiar with the matter.

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Media – Reporting

COVID-19 patients

Lungs damaged by coronavirus can repair themselves in three months

Author: Henry Bodkin

Publication date: 06 September 2020

Source: The Telegraph

Lungs can repair themselves in just three months after a serious bout of coronavirus, a new study has revealed, raising hope that patients will not be living with debilitating symptoms for years on end.

Doctors said trials revealed that nearly half of patients showed no evidence of lung damage at 12 weeks.

Although they confirm long-standing fears that Covid patients can suffer serious effects weeks after recovering from the virus, the results are the first to show that these tend to heal over time.

Eighty-six patients from an outbreak hotspot in the Tyrolean region of Austria were hospitalised between April 29 and June 9, then followed up at six, 12 and 24 weeks after discharge.

At the six-week visit, 88 per cent of patients showed evidence of lung damage, but this dropped to 56 per cent at the 12-week check-up. The results from the 24-week visits are not yet ready to be published.

Meanwhile, 65 per cent of the cohort showed general symptoms of lung problems at the six-week visit, with breathlessness the most common symptom – at 47 per cent – followed by coughing at 15 per cent.

By 12 weeks, breathlessness had improved and was present in 39 per cent of patients. The proportion of patients coughing at this stage did not improve as markedly, however, only dropping to 13 per cent.

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COVID-19 vaccine makers issue rare safety pledge as fears of political pressures swirl

Author: Catherine Thorbecke

Publication date: 08 September 2020

Source: ABC News

A coalition of nine pharmaceutical chief executives issued a joint pledge Tuesday that they will not rush the development of a COVID-19 vaccination for political purposes and will not seek approvals until the vaccines have gone through Phase 3 clinical trials.

The unusual joint move from nine industry leaders comes after the U.S. Centers for Disease Control and Prevention notified states to be ready to distribute a vaccine to certain groups just two days before the presidential election, stoking concerns that the Trump administration may be putting political pressure on companies and health officials to fast-track vaccine approvals ahead of the November vote.

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Overwhelmingly strong results could end COVID-19 vaccine trials early, Fauci says

Author: Liz Szabo

Publication date: 02 September 2020

Source: Los Angeles Times

A COVID-19 vaccine could be available earlier than expected if ongoing clinical trials produce overwhelmingly positive results, Dr. Anthony Fauci, the nation’s top infectious disease official, said this week.

Although two ongoing clinical trials of 30,000 volunteers are expected to conclude by the end of the year, Fauci said an independent board has the authority to end the trials weeks early if interim results are overwhelmingly positive or negative.

The Data and Safety Monitoring Board could say, “The data is so good right now that you can say it’s safe and effective,” Fauci said Tuesday. In that case, researchers would have “a moral obligation” to end the trial early and make the active vaccine available to everyone in the study, he said, including those who had been given placebos — and accelerate the process to give the vaccine to millions.

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‘Urgent’ request sent to states in push for coronavirus vaccine delivery by Nov. 1

Author: Michael Wilner

Publication date: 02 September 2020

Source: Impact2020

Dr. Robert Redfield, director of the Centers for Disease Control and Prevention, sent a letter last week to the nation’s governors with an urgent request. The Trump administration wanted them to do everything in their power to eliminate hurdles for vaccine distribution sites to be fully operational by Nov. 1.

The Aug. 27 letter, obtained by McClatchy, asked governors to fast-track permits and licenses for new distribution sites. “The normal time required to obtain these permits presents a significant barrier to the success of this urgent public health program,” Redfield wrote.

“CDC urgently requests your assistance in expediting applications for these distribution facilities,” he continued, “and, if necessary, asks that you consider waiving requirements that would prevent these facilities from becoming fully operational by November 1, 2020.”

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Covid death rates dropped as doctors rejected ventilators

Author: Henry Bodkin

Publication date: 03 September 2020

Source: The Telegraph

Death rates among seriously ill Covid-19 patients dropped sharply as doctors rejected the use of mechanical ventilators, analysis has found.

The chances of dying in an intensive care unit (ICU) went from 43 per cent before the pandemic peaked to 34 per cent in the period after.

In a report yesterday, the Intensive Care National Audit & Research Centre said that no new drugs nor changes to clinical guidelines were introduced in that period that could account for the improvement. However, the use of mechanical ventilators fell dramatically.

Before the peak in admissions on April 1, 75.9 per cent of Covid-19 patients were intubated within 24 hours of getting to an ICU, a proportion which fell to 44.1 per cent after the peak.

Meanwhile, the proportion of ICU patients put on a ventilator at any point dropped 22 percentage points to 61 per cent either side of the peak.

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Coronavirus: gatherings of more than six to be banned in England

Authors: Peter Walker and Simon Murphy

Publication date: 08 September 2020

Source: The Guardian

The government has announced emergency action to try to stem a feared autumn resurgence of coronavirus, tightening laws to ban virtually all gatherings of more than six people in England.

Amid concerns that the current rules are both widely misunderstood and too difficult for police to implement, Boris Johnson will hold a hastily arranged Downing Street press conference on Wednesday to outline the new restrictions.

The dramatic change of approach by No 10 follows a sudden rise in the number of people being infected with the virus, with almost 8,500 positive tests being recorded in England in the last three days.

On Tuesday, ministers added Bolton to the number of cities and towns under local lockdowns, restricting restaurants and pubs to takeaways and forcing all venues to close from 10pm to 5am.

Bottlenecks in laboratories processing Covid tests have hampered the government’s attempts to keep on top of the pandemic. The Labour leader, Keir Starmer, warned that the test-and-trace system is “on the verge of collapse”.

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It’s now looking like the lockdowns may have been a huge mistake

Author: Michael Barone

Publication date: 06 September 2020

Source: New York Post

Were lockdowns a mistake? To that nagging question, the answer increasingly seems to be yes.

Certainly, they were a novelty. As novelist Lionel Shriver writes, “We’ve never before responded to a contagion by closing down whole countries.” As I’ve noted, the 1957-58 Asian flu killed between 70,000 and 116,000 Americans, between 0.04 percent and 0.07 percent of the nation’s population. The 1968-70 Hong Kong flu killed about 100,000, 0.05 percent of the population.

The US coronavirus death toll of 186,000 is 0.055 percent of the current population. It will go higher, but it’s about the same magnitude as those two flus, and it has been less deadly to those under 65 than the flus were. Yet there were no statewide lockdowns; no massive school closings; no closings of office buildings and factories, restaurants and museums. No one considered shutting down Woodstock.

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The Covid trap: will society ever open up again?

Author: Johan Norberg

Publication date: 05 September 2020

Source: The Spectator

The great pandemic of 2020 has led to an extraordinary expansion of government power. Countries rushed to close their borders and half of the world’s population were forced into some sort of curfew. Millions of companies, from micropubs to mega corporations, were prohibited from carrying on business. In supposedly free and liberal societies, peaceful strollers and joggers were tracked by drones and stopped by policemen asking for their papers. It’s all in the name of defeating coronavirus; all temporary, we’re told. But it’s time to ask, just how temporary? As Milton Friedman used to warn: ‘Nothing is so permanent as a temporary government programme.’

Measures that seemed unthinkable a few months ago have been implemented in haste and without debate. In the UK, as in many other countries, the rationale changed. First, lockdown was designed to ‘buy time’ so the health service could prepare. Next, it was needed to ‘flatten the curve’. But when the curve peaked a few weeks later, the restrictions didn’t merely stay in place, they were reinforced.

Is the science on face masks weak? No matter, let’s make them mandatory anyway. Is there any evidence that closing borders has any meaningful effect on slowing the spread of the virus? With parliamentary debate suspended, no one will really ask. It was always a certainty that Putin or Xi would use any kind of Reichstag fire to grab more power, but it is very worrying to see similar behaviour in liberal democracies.

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'There is no sign of a second wave': Experts rubbish Matt Hancock's warning a surge in Covid-19 hospitalisations is coming - as they put UK's rise in cases down to better testing finding 'young, healthy, symptomless people' who are unlikely to die

Authors: Vanessa Chalmers and Sam Blanchard

Publication date: 02 September 2020

Source: Mail Online

Britain is not entering a second wave of coronavirus infections and the young, mildly-affected people being diagnosed in rising case numbers are not likely to trigger a rise in hospitalisations, experts say.

Health Secretary Matt Hancock yesterday warned that the UK 'must do everything in our power' to stop a second surge of people going into hospital with the coronavirus, which he said was starting to happen in Europe.

But experts told MailOnline Mr Hancock's comments were 'alarmist' and that there is currently 'no sign' of a second wave coming over the horizon. The data shows hospital cases are also not rising by much in Europe, contrary to the Health Secretary's claim.

As of yesterday there were only 764 people in hospital with Covid-19 in the UK, just 60 of whom are in intensive care. This is a sharp drop from a peak of 19,872 hospitalised patients on April 12.

The falling number of hospital cases comes despite infections having been on the rise since lockdown restrictions were lifted at the start of July. Experts say this is because the groups getting infected and diagnosed now are completely different to those at the start of the pandemic.

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Social distancing

Hack Partners Developed Social Distancing App Mind The Gap For Network Rail

Author: Natasha Meisel

Publication date: 07 September 2020

Source: Tech Round

With businesses under mounting pressure to demonstrate how they are making their workplaces socially-distanced and Covid-19-secure, technology startup Hack Partners has developed Mind The Gap social-distancing app. After a successful pilot with Britain’s railway infrastructure owner Network Rail, the app is ready for industry-wide deployment.

Mind The Gap uses inaudible ultra high frequency sounds and Bluetooth to calculate the distance between mobile phones. The technology does not require an active internet connection, making it ideal for use in various environments, outdoors and indoors. It also has the option to customise the distance that triggers the alert so it can be adapted for any change in government guidelines.

Built with user-privacy in mind, Mind The Gap has no user-tracking in place: no sensitive data is collected, stored or shared. This means employers will not have the capability to monitor employees’ movement either past or present.

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Social Impacts

Dozens of arrests as Melbourne's anti-lockdown protest turns violent with more than 1,000 angry locals defying attempt to cancel event - while demonstrators gather in huge numbers in Byron Bay

Author: Eliza McPhee

Publication date: 05 September 2020

Source: MailOnline

A swarm of more than 1,000 anti-lockdown protesters have descended on Melbourne and clashed with police officers in wild scenes as the 'Freedom Day' rally threatens to spiral out of control.

Frustrated activists, furious with Daniel Andrew's Stage Four lockdown, turned out in their droves to demand the restrictions come to an end, with new coronavirus cases now in the double digits.

Shocking footage shows the horde of protesters, many refusing to wear masks and battling with police, as the city's CBD was brought to a standstill as traffic was diverted from the area.

Dramatic scenes saw demonstrators tackled to the ground while officers struggled to detain them. 

The protests kicked off at the Shrine of Remembrance but coronavirus-deniers have since taken to the streets, stopping traffic near Albert Park.

One crowd faced off with police on horseback as the chant 'freedom' rang out across the city while 15 people were arrested and more than 150 fines given out.

Of those arrests, 14 were for breaching COVID-19 restrictions and one was for assaulting a police officer after a cop was hit round the head as the protests turned violent.

Meanwhile protests have erupted in Byron Bay with one onlooker telling Daily Mail Australia crowds were chanting 'free Victoria'. 

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Downing Street plans new digital ID cards for British citizens as Dominic Cummings bids to transform Government's use of data despite privacy fears

Author: James Gant

Publication date: 02 September 2020

Source: Daily Mail

Downing Street is planning new digital ID cards for British citizens as Dominic Cummings bids to transform the Government's use of data despite privacy fears.

People will get an online identity that can be used for daily activities such as proving ones age, registering with a GP and buying properties from a different location.

It comes after issues emerged in identifying people during the Covid-19 pandemic, such as during the self-employment income support scheme.

The government did not have any details on half of the 2.6million who applied for support at the start of the crisis.

Some - such as Tony Blair - called for new digital ID cards to prove their 'disease status' as the world relaxed lockdown measures.

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Telehealth grew wildly popular amid Covid-19. Now visits are plunging, forcing providers to recalibrate

Author: Casey Ross

Publication date: 01 September 2020

Source: STAT

A nationwide dropoff in telemedicine visits is forcing providers who raced to ramp up virtual care in the face of the pandemic to quickly recalibrate their offerings as more patients turn back to in-person appointments.

Telemedicine visits accounted for just 21% of total encounters by the middle of July, down from 69% at the early peak of the public health crisis in April, according to national data from Epic, the electronic health record company.

While telemedicine use largely remains well above pre-pandemic levels — and many still say telemedicine’s popularity is here to stay — the recent downturn in visits has created an undeniable whiplash effect. Hospitals that rushed to retrain their staff to deliver most types of care virtually in March are now trying to strike a new balance based on shifting patient preferences and needs.

“We’re trying to right-size, but it’s really hard because during the pandemic we switched to nearly 100% virtual in some clinical areas, and we know that’s not realistic or sustainable,” said Jessie DeVito, director of virtual care at Michigan Medicine, the health system affiliated with the University of Michigan. She said the health system will end up with some empty virtual appointment slots before it finds the right mix between office and telemedicine visits in the coming weeks.

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