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ANH-Intl Covid-19 information tracker - Week 28



Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

Authors: Korber B et al

Publication date: 26 June 2020

Journal: Cell

DOI: 10.1016/j.cell.2020.06.043

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT- PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

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SARS-CoV-2 seroprevalence in COVID-19 hotspots

Authors: Isabella Eckerle and Benjamin Meyer

Publication date: 06 July 2020

Source: The Lancet

DOI: 10.1016/S0140-6736(20)31482-3

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has surprised the world with its range of disease manifestations, from asymptomatic infection to critical illness leading to hospital admission and death.1,  2 Due to the high proportion of asymptomatic or mild infections (approximately 80%), data restricted to laboratory-confirmed cases do not capture the true extent of the spread or burden of the virus, or its infection-fatality ratio.2 Therefore, serological detection of specific antibodies against SARS-CoV-2 can better estimate the true number of infections. Due to co-circulation of other human coronaviruses, serology for SARS-CoV-2 is not trivial. Antibody cross-reactivity with other human coronaviruses has been largely overcome by using selected viral antigens, and several commercial assays are now available for SARS-CoV-2 serology. However, despite high sensitivity and specificity, a setting with a low pretest probability, such as current population-based seroprevalence studies, warrants careful validation of results.3 Extensive previous assay validation in well characterised serum samples and confirmation of positive results are thus necessary to prevent false-positive findings from confounding seroprevalence rates.

The first SARS-CoV-2 seroprevalence studies from cohorts representing the general population have become available from COVID-19 hotspots such as China, the USA, Switzerland, and Spain.4,  5,  6,  7,  8 In The Lancet, Marina Pollán and colleagues6 and Silvia Stringhini and colleagues7 separately report representative population-based seroprevalence data from Spain and Switzerland collected from April to early May this year. Studies were done in both the severely affected urban area of Geneva, Switzerland, and the whole of Spain, capturing both strongly and less affected provinces. Both studies recruited randomly selected participants but excluded institutionalised populations (ie, permanent residents of institutions such as prisons or care homes, as well as hospitalised residents), which is a clear limitation. They relied on IgG as a marker for previous exposure, which was detected by two assays for confirmation of positive results.

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Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

Authors: Pollan M Prof et al

Publication date: 06 July 2020

Journal: The Lancet

DOI: 10.1016/S0140-6736(20)31483-5

Background: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.

Methods: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test).

Findings: Seroprevalence was 5·0% (95% CI 4·7–5·4) by the point-of-care test and 4·6% (4·3–5·0) by immunoassay, with a specificity–sensitivity range of 3·7% (3·3–4·0; both tests positive) to 6·2% (5·8–6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1–92·1; both tests positive) to 91·8% (86·3–95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8–16·8) to 19·3% (17·7–21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1–24·9) to 35·8% (33·1–38·5). Only 19·5% (16·3–23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test.

Interpretation: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave.

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It is Time to Address Airborne Transmission of COVID-19

Authors: Lidia Morawska and Donald K Milton

Publication date: 06 July 2020

Journal: Clinical Infectious Diseases

DOI: 10.1093/cid/ciaa939

We appeal to the medical community and to the relevant national and international bodies to recognize the potential for airborne spread of COVID-19. There is significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale), and we are advocating for the use of preventive measures to mitigate this route of airborne transmission.

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Association of country-wide coronavirus mortality with demographics, testing, lockdowns, and public wearing of masks. Update July 2, 2020

Authors: Leffler CT et al

Publication date: 07 July 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.05.22.20109231

Background. There is wide variation between countries in per-capita mortality from COVID-19 (caused by the SARS-CoV-2 virus). Determinants of this variation are not fully understood. Methods. Potential predictors of per-capita coronavirus-related mortality in 198 countries were examined, including age, sex ratio, obesity prevalence, temperature, urbanization, smoking, duration of infection, lockdowns, viral testing, contact tracing policies, and public mask-wearing norms and policies. Multivariable linear regression analysis was performed. Results. In univariate analyses, the prevalence of smoking, per-capita gross domestic product, urbanization, and colder average country temperature were positively associated with coronavirus-related mortality. In a multivariable analysis of 194 countries, the duration of infection in the country, and the proportion of the population 60 years of age or older were positively associated with per-capita mortality, while duration of mask-wearing by the public was negatively associated with mortality (all p<0.001). The prevalence of obesity was independently associated with mortality in models which controlled for testing levels or policy. International travel restrictions were independently associated with lower per-capita mortality, but other containment measures and viral testing and tracing policies were not. In countries with cultural norms or government policies supporting public mask-wearing, per-capita coronavirus mortality increased on average by just 7.2% each week, as compared with 55.0% each week in remaining countries. On multivariable analysis, lockdowns tended to be associated with less mortality (p=0.41), and increased per-capita testing with higher reported mortality (p=0.55), though neither association was statistically significant. Conclusions. Societal norms and government policies supporting the wearing of masks by the public, as well as international travel controls, are independently associated with lower per-capita mortality from COVID-19.

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Filtration Efficiencies of Nanoscale Aerosol by Cloth Mask Materials Used to Slow the Spread of SARS-CoV-2

Authors: Zangmeister CD et al

Publication date: 25 June 2020

Journal: ACS Publications

DOI: 10.1021/acsnano.0c05025

Filtration efficiency (FE), differential pressure (ΔP), quality factor (QF), and construction parameters were measured for 32 cloth materials (14 cotton, 1 wool, 9 synthetic, 4 synthetic blends, and 4 synthetic/cotton blends) used in cloth masks intended for protection from the SARS-CoV-2 virus (diameter 100 ± 10 nm). Seven polypropylene-based fiber filter materials were also measured including surgical masks and N95 respirators. Additional measurements were performed on both multilayered and mixed-material samples of natural, synthetic, or natural-synthetic blends to mimic cloth mask construction methods. Materials were microimaged and tested against size selected NaCl aerosol with particle mobility diameters between 50 and 825 nm. Three of the top five best performing samples were woven 100% cotton with high to moderate yarn counts, and the other two were woven synthetics of moderate yarn counts. In contrast to recently published studies, samples utilizing mixed materials did not exhibit a significant difference in the measured FE when compared to the product of the individual FE for the components. The FE and ΔP increased monotonically with the number of cloth layers for a lightweight flannel, suggesting that multilayered cloth masks may offer increased protection from nanometer-sized aerosol with a maximum FE dictated by breathability (i.e., ΔP).

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Covid-19 patients

A Novel Approach to Treating COVID-19 Using Nutritional and Oxidative Therapies

Authors: Brownstein D MD et al

Publication date: July 2020

Journal: Science, Public Health Policy and the Law

Objective: This report is a case series of consecutive patients diagnosed with COVID-19 treated with a nutritional and oxidative medical approach. We describe the treatment program and report the response of the 107 COVID-19 patients.

Setting: A family practice office in a suburb of Detroit, Michigan.

Patients: All patients seen in the office from February through May 2020 diagnosed with COVID-19 were included in the study. COVID-19 was either diagnosed via PCR or antibody testing as well as those not tested diagnosed via symptomology.

Interventions: Oral Vitamins A, C, D, and iodine were given to 107 subjects (99%). Intravenous solutions of hydrogen peroxide and Vitamin C were given to 32 (30%) and 37 (35%) subjects. Thirty-seven (35%) of the cohort was treated with intramuscular ozone. A dilute, nebulized hydrogen peroxide/saline mixture, with Lugol’s iodine, was used by 91 (85%).

Main Outcome Measures: History and physical exam were reviewed for COVID-19 symptoms including cough, fever, shortness of breath, and gastrointestinal complaints. Laboratory reports were examined for SARS-CoV-2 results. Symptomatic improvement after treatment was reported for each patient consisting of first improvement, mostly better, and completely better.

Results: There were a total of 107 pa- tients diagnosed with COVID-19. Thirty- four were tested for SARS-CoV-2(32%) and twenty-seven (25%) tested positive. Three were hospitalized (3%) with two of the three hospitalized before instituting treatment and only one requiring hospitalization after begin- ning treatment. There were no deaths. The most common symptoms in the cohort were fever (81%), shortness of breath (68%), URI which included cough (69%), and gastroin- testinal distress symptoms (27%). For the entire cohort, first improvement was noted in 2.4 days. The cohort reported symptoms mostly better after 4.4 days and completely better 6.9 days after starting the program. For the SARS-CoV-2 test positive patients, fever was present in 25 (93%), shortness of breath in 20 (74%) and upper respiratory symptoms including cough in 21 (78%) while gastroin- testinal symptoms were present in 9 (33%). The time to improvement in the SARS-CoV- 2 test positive group was slightly longer than the entire cohort.

Conclusion: At present, there is no pub- lished cure, treatment, or preventive for COVID-19 except for a recent report on dex- amethasone for seriously ill patients. A novel treatment program combining nutritional and oxidative therapies was shown to success- fully treat the signs and symptoms of 100% of 107 patients diagnosed with COVID-19. Each patient was treated with an individual- ized plan consisting of a combination of oral, IV, IM, and nebulized nutritional and oxida- tive therapies which resulted in zero deaths and recovery from COVID-19. Keywords: SARS-CoV-2, COVID-19, ozone therapy, hydrogen peroxide therapy, Vitamin A, iodine, Vitamin C, Vitamin D, immune system, antiviral.


The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings

Authors: Paterson RW et al

Publication date: 08 July 2020

Journal: Brain

DOI: 10.1093/brain/awaa240

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

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UK report on 10,287 patients critically ill with COVID-19

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

Publication date: 03 July 2020


COVID‐19 rise in Younger adults with Obesity: Visceral Adiposity can predict the Risk

Authors: Gianluca Lacobellis, Alexis Elias Malavazos and Tanira Ferreira

Publication date: 03 July 2020

Journal: Obesity

DOI: 10.1002/oby.22951

A concerning rise in coronavirus disease 2019 (COVID‐19) cases has been recently reported, particularly in the USA. The causes of this increase are likely multifactorial and the object of an ongoing health and socio‐economic debate. However, preliminary data indicate that the new COVID‐19 cases are increasing among younger and obese adults. Considering this recent spike, the timing of the paper by Deng et al is of particular importance (1). Deng et al not only confirmed that obesity is a major and independent risk factor for COVID‐19 complications in young adults (2), they pointed out ectopic and visceral fat depots as new markers of that risk. The authors found that computed tomography (CT) imaging of fatty liver and epicardial adipose tissue (EAT) were significantly higher in severely and critically ill COVID‐19 patients under 40 years old as compared to those with milder disease.

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Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome

Authors: Weiskopf D et al

Publication date: 26 June 2020

Journal: Science Immunology

DOI: 10.1126/sciimmunol.abd2071

SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a ‘cytokine storm’ have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with ‘common cold’ coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.

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Excess Deaths From COVID-19 and Other Causes, March-April 2020

Authors: Steven H Woolf MD, Derek A Chapmen PhD and Roy T Sabo PhD

Publication date: 01 July 2020

The number of publicly reported deaths from coronavirus disease 2019 (COVID-19) may underestimate the pandemic’s death toll. Such estimates rely on provisional data that are often incomplete and may omit undocumented deaths from COVID-19. Moreover, restrictions imposed by the pandemic (eg, stay-at-home orders) could claim lives indirectly through delayed care for acute emergencies, exacerbations of chronic diseases, and psychological distress (eg, drug overdoses). This study estimated excess deaths in the early weeks of the pandemic and the relative contribution of COVID-19 and other causes.

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Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020

Authors: Daniel M Weinberger PhD, Jenny Chen and Ted Cohen MD

Publication date: 01 July 2020

Journal: JAMA Internal Medicine

DOI: 10.1001/jamainternmed.2020.3391

Importance:  Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19.

Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020.

Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data.

Results: There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19–reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths.

Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

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Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Authors: Bastos ML et al

Publication date: 01 July 2020

Journal: The BMJ

DOI: 10.1136/bmj.m2516

Objective: To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).

Main outcome measures: The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.

Results: 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).

Conclusion: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.

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Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance

Authors: Larremore DB et al

Publication date: 27 June 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.06.22.20136309

The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.

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Prognostic Value of Leukocytosis and Lymphopenia for Coronavirus Disease Severity

Authors: Glen Huang, Alex J Kovalic and Christopher J Graber

Publication date: 08 May 2020

Source: Centers for Disease Control and Prevention

To evaluate lymphopenia as a marker for coronavirus disease severity, we conducted a meta-analysis of 10 studies. Severe illness was associated with lower lymphocyte and higher leukocyte counts. Using these markers for early identification of patients with severe disease may help healthcare providers prioritize the need to obtain therapy.

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Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein

Authors: Kulkarni SA

Publication date: 04 July 2020

Journal: Journal of Molecular Structure

DOI: 10.1016/j.molstruc.2020.128823

COVID-19, caused by SARS-CoV-2 has recently emerged as a global pandemic. Intense efforts are ongoing to find a vaccine or a drug to control the disease across the globe. Meanwhile, alternative therapies are also being explored to manage the disease. Phytochemicals present in essential oils are promising candidates which have been known to possess wide range of therapeutic activities. In this study, major components of several essential oils which are known for their antimicrobial properties have been docked against the S1 receptor binding domain of the spike (S) glycoprotein, which is the key target for novel antiviral drugs, to ascertain their inhibitory effects based on their binding affinities. It has been found that some monoterpenes, terpenoid phenols and phenyl propanoids such as anethole, cinna- maldehyde, carvacrol, geraniol, cinnamyl acetate, L-4-terpineol, thymol and pulegone from essential oils extracted from plants belonging to families such as Lamiaceae, Lauraceae, Myrtaceae, Apiaceae, Ger- aniaceae and Fabaceae are effective antiviral agents that have potential to inhibit the viral spikeprotein.

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Effective and safe global public health strategy to fight the COVID-19 pandemic: Specific micronutrient composition inhibits Coronavirus cell-entry receptor (ACE2) expression

Authors: Ivanov V, Ivanova S, Niedzwiecki A, Rath M

Publication date: 03 July 2020

Journal: Cellular Medicine and Natural Health Journal

Optimum micronutrient intake is the only scientifically proven way to improve general immune resistance against infections, a fact documented in every leading textbook of biology.  This study provides scientific evidence that, in addition, specific micronutrient compositions are powerful tools in the fight against the COVID-19 pandemic.

Both, SARS-CoV-2 – the virus that causes the current pandemic – and other coronaviruses enter body cells via a specific receptor, the Angiotensin-Converting-Enzyme 2 (ACE2). The ACE2 receptor is expressed by many cell types, including lung epithelial cells as well as endothelial cells of the vascular system.

Based on our earlier research that demonstrated that specific micronutrients can block several mechanisms of viral infections, we tested the efficacy of these natural compounds in suppressing the expression of the ACE2 receptor on human endothelial cells and small airway epithelial cells.

Our results show that a micronutrient composition comprising vitamin C as well as certain amino acids, polyphenols, and trace elements is able to suppress this viral ‘entry door’ into the body under both normal and inflammatory conditions, which are associated with infections.

Thus, vitamin-rich nutrition and micronutrient supplementation should be implemented as effective, safe and affordable public health strategies to fight the COVID-19 pandemic and help prevent future outbreaks.  Optimizing the micronutrient status of the entire population should form the basis for any global strategy to help prevent future pandemics across the world, including the developing nations.



Developing a SARS-CoV-2 Vaccine at Warp Speed

Authors: Kevin P O’Callaghan, Allison M Blatz and Paul A Offit

Publication date: 06 July 2020

Journal: JAMA

DOI: 10.1001/jama.2020.12190

The coronavirus disease 2019 (COVID-19) pandemic has unleashed major and substantial changes in the provision of health care, including public health policy and the practice of medicine, and in the ways most individuals live their lives.1 Significant changes also have occurred in vaccine development, with shortening the usual 15- to 20-year timeline to one that might be as short as 1 to 1.5 years.2 COVID-19, the acute illness due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei province, China, in December 2019, and rapidly progressed to a global pandemic. By June 27, 2020, a total of 9.76 million people had been infected with this virus and 492 000 had died. Although widespread quarantine, isolation, and social distancing measures have, to some extent, countered the spread of SARS-CoV-2 and “flattened the curve,” countries now face a multitude of challenges to the “re-opening” of society. Yet, it is clear the only way to provide effective herd immunity is with a safe and effective vaccine.

With this background, the US Department of Health and Human Services (HHS) launched Operation Warp Speed—a partnership between government and industry—with the goal of delivering 300 million doses of a safe and effective vaccine by January 2021.3 This ambitious plan initially focused on 125 potential vaccine candidates, but was rapidly narrowed to 14 candidates in May 2020, and, as reported in June 2020, the current administration plans to narrow this list to 5 core candidates (Table).4 In this Viewpoint, we describe the proposed mechanisms and current status of each of these leading candidates, all of which are aimed at inducing antibodies directed against the receptor-binding domain of the surface spike (S) protein of SARS-CoV-2.

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The Development of COVID-19 Vaccines: Safeguards Needed

Authors: Nicole Lurie, Joshua M Sharfstein and Jesse L Goodman

Publication date: 06 July 2020

Journal: JAMA

DOI: 10.1001/jama.2020.12461

A safe and effective vaccine against coronavirus disease 2019 (COVID-19) is the best way to control and ultimately end the pandemic. Vaccine development is moving at unprecedented speed, with more than 200 candidates, billions of dollars committed, and manufacturing often proceeding before even knowing whether a given vaccine candidate will succeed. To date, the US federal government has rapidly advanced 5 vaccine candidates through Operation Warp Speed.1 At the same time, a growing movement of skeptics has raised doubt about future COVID-19 vaccines.2 A poll of 1056 individuals in the US found that only 49% reported that they currently are planning to receive a COVID-19 vaccine, 31% are uncertain, and 20% are not, with safety a major concern.3

The best response to such concerns is a transparent and rigorous approach to vaccine development and regulation, including for licensure or any prelicensure use permitted by the US Food and Drug Administration (FDA). For this effort to be successful, it is critical that the independence of the agency be respected, standards maintained, and politicians kept from pronouncements that create the appearance of interference such as that engendered by the emergency use authorization of antimalarial drugs to treat COVID-19.4,5 To help ensure the best possible decision-making and increase public confidence, regulators should be transparent about plans for 4 needed safeguards in COVID-19 vaccine development.

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Ensuring Uptake of Vaccines against SARS-CoV-2

Authors: Mello MM et al

Publication date: 26 June 2020

Journal: New England Journal of Medicine

DOI: 10.1056/NEJMp2020926

As Covid-19 continues to exact a heavy toll, development of a vaccine appears the most promising means of restoring normalcy to civil life. Perhaps no scientific breakthrough is more eagerly anticipated. But bringing a vaccine to market is only half the challenge; also critical is ensuring a high enough vaccination rate to achieve herd immunity. Concerningly, a recent poll found that only 49% of Americans planned to get vaccinated against SARS-CoV-2.

One option for increasing vaccine uptake is to require it. Mandatory vaccination has proven effective in ensuring high childhood immunization rates in many high-income countries. However, except for influenza vaccination of health care workers, mandates have not been widely used for adults.

Although a vaccine remains months to years away, developing a policy strategy to ensure uptake takes time. We offer a framework that states can apply now to help ensure uptake of the vaccine when it becomes available — including consideration of when a mandate might become appropriate. Our approach is guided by lessons from U.S. experiences with vaccines for the 1976 “swine flu,” H1N1 influenza, smallpox, and human papillomavirus (HPV).



Government/Health authorities

Covid-19 and pregnancy

Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020

Publication date: 26 June 2020

Source: Centers for Disease Control and Prevention

As of June 16, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in 2,104,346 cases and 116,140 deaths in the United States.* During pregnancy, women experience immunologic and physiologic changes that could increase their risk for more severe illness from espire- tory infections (1,2). To date, data to assess the prevalence and severity of COVID-19 among pregnant U.S. women and determine whether signs and symptoms differ among pregnant and nonpregnant women are limited. During January 22– June 7, as part of COVID-19 surveillance, CDC received reports of 326,335 women of reproductive age (15–44 years) who had positive test results for SARS-CoV-2, the virus that causes COVID-19. Data on pregnancy status were available for 91,412 (28.0%) women with laboratory-confirmed infections; among these, 8,207 (9.0%) were pregnant.

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Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry

Publication date: 30 June 2020

Source: U.S. Department of Health and Human Services

This guidance is being issued to address the coronavirus disease 2019 (COVID-19) public health emergency. This guidance is being implemented without prior public comment because the Food and Drug Administration (FDA or Agency) has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 371(h)(1)(C)) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices.

Comments may be submitted at any time for Agency consideration. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov. All comments should be identified with the docket FDA-2020-D-1137 and complete title of the guidance in the request.

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Trump Administration Secures New Supplies of Remdesivir for the United States

Publication date: 29 June 2020

Source: U.S. Department of Health & Human Services

On Monday, the Department of Health and Human Services announced an agreement to secure large supplies of the drug remdesivir for the United States from Gilead Sciences through September, allowing American hospitals to purchase the drug in amounts allocated by HHS and state health departments.

“President Trump has struck an amazing deal to ensure Americans have access to the first authorized therapeutic for COVID-19,” said HHS Secretary Alex Azar. “To the extent possible, we want to ensure that any American patient who needs remdesivir can get it. The Trump Administration is doing everything in our power to learn more about life-saving therapeutics for COVID-19 and secure access to these options for the American people.”

HHS has secured more than 500,000 treatment courses of the drug for American hospitals through September. This represents 100 percent of Gilead’s projected production for July (94,200 treatment courses), 90 percent of production in August (174,900 treatment courses), and 90 percent of production in September (232,800 treatment courses), in addition to an allocation for clinical trials. A treatment course of remdesivir is, on average, 6.25 vials.

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Media – Science related

Covd-19 patients

SARS-CoV-2-Reactive T Cells Found in Patients with Severe COVID-19

Author: Abby Olena

Publication date: 03 July 2020

Source: The Scientist

In May, researchers showed that people with mild forms of COVID-19, the disease caused by the SARS-CoV-2 virus, have circulating T cells that respond to the virus. Now, in a Science Immunology study published last week (June 26), a collaborating research team has determined that people who are sick enough with COVID-19 to be hospitalized in the intensive care unit also make SARS-CoV-2-reactive T cells. In both studies, the researchers found that a subset of healthy, unexposed people also had some of these T cells that react to the virus, perhaps due to previous exposures to other coronaviruses that cause symptoms of the common cold.

The latest study provides more solid evidence that there are SARS-CoV-2-specific T cells that are induced by the infection, says Antonio Bertoletti, who studies T cells at Duke-NUS Medical School in Singapore and was not involved in the work. This is important because researchers have put a lot of emphasis on antibodies, he adds, but it’s still not clear whether antibodies or T cells are more important for protection from the virus.

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Why hasn't the UK seen a second wave of the coronavirus?

Author: Clare Wilson

Publication date: 07 July 2020

Source: New Scientist

Pubs, restaurants and cafes in England welcomed customers back through their doors on 4 July, sparking warnings of a second wave of covid-19 infections. Yet there have been warnings of another wave since the country began easing restrictions, and one hasn’t materialised. Will this time be different?

Scientists on an independent advisory panel on coronavirus called Independent SAGE have repeatedly warned that the relatively swift easing of lockdown restrictions in England risks cases rising again.

On 11 May, people in England were allowed to go outside to exercise multiple times a day and certain groups were encouraged to return to work. June saw the reopening of non-essential shops, certain year groups returning to school and households mixing outside. On Saturday, social distancing guidelines were reduced and numerous indoor hospitality venues reopened.

Speaking at a press briefing last Thursday, England’s deputy chief medical officer, Jenny Harries, said a new spike in cases in the UK was a possibility: “A second peak, as in an epidemic peak, another one, is also not ruled out.”

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President of the Royal Society urges everyone to wear a face covering

Publication date: 07 July 2020

Source: The Royal Society

Everyone should have a face covering to help tackle the COVID-19 pandemic and they should not leave home without having one in their possession according to the President of the Royal Society.

Venki Ramakrishnan’s call comes as a new review of evidence reinforces the benefits of face coverings and even suggests they may protect the wearer as well as those around them. However, the British public remain much less likely to wear face coverings in public compared to other countries, including the United States.

Venki Ramakrishnan said: “The virus has not been eliminated, so as we lift lockdown and people increasingly interact with each other we need to use every tool we have to reduce the risk of a second wave of infection.  There are no silver bullets but alongside hand washing and physical distancing, we also need everyone to start wearing face coverings, particularly indoors in enclosed public spaces where physical distancing is often not possible.

“The UK is way behind many countries in terms of wearing masks and clear policies and guidelines about mask wearing for the public.  The public have taken to handwashing and distancing but remain sceptical about face coverings.  You only need to go on public transport, where they are supposed to be mandatory, to see how many people are ignoring this new rule based on the growing body of evidence that wearing a mask will help protect others – and might even protect you.

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Face Masks for the General Public

Publication date: 04 May 2020

Source: Royal Society DELVE Initiative

Face masks could offer an important tool for contributing to the management of community transmission of Covid19 within the general population. Evidence supporting their potential effectiveness comes from analysis of: (1) the incidence of asymptomatic and pre-symptomatic transmission; (2) the role of respiratory droplets in transmission, which can travel as far as 1-2 meters; and (3) studies of the use of homemade and surgical masks to reduce droplet spread. Our analysis suggests that their use could reduce onward transmission by asymptomatic and pre-symptomatic wearers if widely used in situations where physical distancing is not possible or predictable, contrasting to the standard use of masks for the protection of wearers. If correctly used on this basis, face masks, including homemade cloth masks, can contribute to reducing viral transmission.

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In the pipeline

Author: Derek Lowe

Publication date: 07 July 2020

Source: Science Translational Medicine

I wrote here about the reports of rather short antibody persistence in recovering coronavirus patients, and what’s been coming out in the two weeks since then has only made this issue more important. In that post, I was emphasizing that although we can measure antibody levels, we don’t know how well that correlates with exposure to the virus nor to later immunity from it, and that T cells are surely a big part of this picture that we don’t have much insight into.

This Twitter thread by Eric Topol is exactly what I mean, and this article that he references is an important read. Its schematic at right (see also here) will help make clear that antibody levels are only one aspect of the immune response to the infection – it’s an important one, but we’re making it look even more important than it is because it’s by far the easiest part of the process to measure. The T-cell response (much harder to get good data on) is known to be a key player in viral infections, and is also known to be highly variable, both between different types of pathogens and among individuals themselves. The latter variations are also beginning to be characterized among patients in the current pandemic. We have to get more data on it across a broader population of patients in order to make sense of what we’re seeing.

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Operation Warp Speed’s opaque choices of COVID-19 vaccines draw Senate scrutiny

Author: Jon Cohen

Publication date: 02 July 2020

Source: Science

The leaders of Operation Warp Speed, the Trump administration’s well-funded project to develop COVID-19 vaccines at record speed, have said they are running a transparent project. They have bristled at critics who say they make major decisions behind closed doors. But at a Senate subcommittee hearing today that focused on Warp Speed, scientists at the front of the effort, after repeated questioning, gave limited answers about the vaccine candidates they have chosen as frontrunners in the race and their selection criteria. At the opening of the hearing—held by the Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies—Senator Patty Murray (D–WA) put the witnesses on notice that she wanted straightforward answers on many issues. “We’re going to need to hold this administration accountable to avoid repeating mistakes and delays,” Murray said. “The administration still has not provided any explanation of how it is selecting vaccine candidates, what the risks are of narrowing down that shortlist or addressed concerns about potential conflicts in contracts that predate this crisis.”


FDA to Require 50 Percent Efficacy for COVID-19 Vaccines

Author: Amanda Heidt

Publication date: 01 July 2020

Source: The Scientist

The US Food and Drug Administration has released a set of guidelines outlining the approval process for future COVID-19 vaccines, stating that any product will need to prevent or decrease the severity of the disease by at least 50 percent.

The new guidelines were released during a June 30 briefing with the Senate Health, Education, Labor and Pensions Committee during which senators sought assurances from FDA Commissioner Stephen Hahn, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, and other high-ranking health officials that the expedited speed of development wouldn’t compromise the integrity of the final product.

“I want the American people to hear me when I say we will use the science and data from those trials, and will ensure that our high levels of standards for safety and efficacy are met,” Hahn said during the briefing.

Currently, more than 145 vaccines are being tested worldwide, The New York Times reports, and a leading US candidate developed by the biotech company Moderna is slated to begin Phase III clinical trials this month.

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Media – Reporting

Second wave

Beijing reports zero virus cases for first time since new outbreak

Publication date: 07 July 2020

Source: MedicalXpress

Beijing on Tuesday reported zero new coronavirus cases for the first time since the emergence of a cluster in the Chinese capital in June that prompted fears of a domestic second wave.

A total of 335 people have been infected since a cluster emerged at the city's massive Xinfadi wholesale market in early June.

Beijing's health commission said on Tuesday it detected only one asymptomatic case the previous day, which China does not include in its confirmed cases counts.

While Chinese authorities are still investigating the cause of the latest outbreak, the virus was detected on chopping boards used to handle imported salmon at Xinfadi market, prompting a ban on certain imports and increased scrutiny of foreign food suppliers.

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What makes a 'wave' of disease? An epidemiologist explains

Author: Abram L Wagner

Publication date: 06 July 2020

Source: The Conversation

Panic about a second wave of coronavirus cases is “overblown,” Vice President Mike Pence wrote in June, implying the U.S. has COVID-19 under control. On the other hand, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, warns that the U.S. is still firmly within a first wave of cases.

As media broadcast information about daily increases in the number of cases, it’s hard not to wonder which way the country is headed. Have the weeks and months of lockdown really helped? What do the trends in diagnoses and deaths mean for the course of the pandemic? Is the U.S. stuck in a first wave? Through the worst of it? Headed for a second round?

Six months into the pandemic, people are looking for ways to make sense of what’s happening. Talking about waves of disease, with the implication of predictable rises and falls, is part of that. As an epidemiologist, I know that disease waves aren’t scientifically defined. But looking to the history of previous epidemics and other countries’ current COVID-19 outbreaks can be useful.

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Coronavirus: Majority testing positive have no symptoms

Author: Rachel Schraer

Publication date: 07 July 2020

Source: BBC News

Only 22% of people testing positive for coronavirus reported having symptoms on the day of their test, according to the Office for National Statistics.

This hammers home the role of people who aren't aware they're carrying the virus in spreading it onwards.

Health and social care staff appeared to be more likely to test positive.

This comes as deaths from all causes in the UK fell to below the average for the second week in a row.

Between the end of March and June, there were 59,000 more deaths than the five-year average.

Meanwhile, the UK government's daily figures released on Tuesday showed another 155 people have died after testing positive for the virus. This takes the total number of deaths to 44,391.

It comes after 16 new deaths were reported on Monday, but there are often reporting lags over the weekend.

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Up to ONE-THIRD of all coronavirus antibody tests may come back as false negatives, study finds

Author: Mary Kakatos

Publication date: 02 July 2020

Source: The Daily Mail

There is little to no evidence proving the accuracy of coronavirus antibody blood tests, a new report suggests.

Researchers reviewed dozens of studies looking at antibody kits, which determine whether or not someone has previously been infected by the virus and has built up an immune response. 

Specificity rates ranged from 66 percent to 97.8 percent, meaning the test may return false negative up to one-third of the time.

Nearly two-thirds of people in the UK have been sleeping badly since lockdown

What's more, commercial test kits were more likely to miss cases than those conducted in a lab.

The international team, led by McGill University Health Center in Montreal, Quebec, Canada, says the findings should make governments rethink about issuing 'immunity passports' to get people back to work and shore up the economy.

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LancetGate: “Scientific Corona Lies” and Big Pharma Corruption. Hydroxychloroquine versus Gilead’s Remdesivir

Author: Prof Michael Chossudovsky

Publication date: 05 July 2020

Source: GlobalResearch


There is an ongoing battle to suppress Hydroxychloroquine (HCQ), a cheap and effective drug for the treatment of Covid-19. The campaign against HCQ is carried out through slanderous political statements, media smears, not to mention an authoritative peer reviewed “evaluation” published on May 22nd by The Lancet, which was based on fake figures and test trials.

The study was allegedly based on data analysis of 96,032 patients hospitalized with COVID-19 between Dec 20, 2019, and April 14, 2020 from 671 hospitals Worldwide. The database had been fabricated. The objective was to kill the Hydroxychloroquine (HCQ) cure on behalf of Big Pharma.

While The Lancet article was retracted, the media casually blamed “a tiny US based company” named Surgisphere whose employees included “a sci-fi writer and an adult content model” for spreading “flawed data” (Guardian). This Chicago based outfit was accused of having misled both the WHO and national governments, inciting them to ban HCQ. None of those trial tests actually took place.

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Diet and lifestyle

COVID-19: A Pandemic Within a Pandemic

Author: Jeffrey Bland PhD

Publication date: 27 June 2020

Source: Medium

COVID-19 officially became a pandemic on March 11, 2020. The World Health Organization (WHO) had been closely monitoring this novel coronavirus since early January, when a cluster of pneumonia cases in Wuhan, Hubei Province, China was reported. Past experiences with infectious respiratory viruses such as SARS and MERS informed decision-making in the weeks that preceded the declaration of a public health emergency. Two factors were of high concern: spread and severity. These concerns proved to be more than justified.

As of June 17, 2020, more than 8,000,000 cases of COVID-19 infection have been confirmed globally, and at least 440,000 deaths have been reported. COVID-19 has provided us with the opportunity to examine emerging data in real time. By tracking the history of the infection, it quickly became clear that there are significant differences among people in terms of both risk to infection and — if infected — severity of disease.

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“No one has died from the coronavirus”

Authors: Rosemary Frei and Patrick Corbett

Publication date: 02 July 2020

Source: Off Guardian

A high-profile European pathologist is reporting that he and his colleagues across Europe have not found any evidence of any deaths from the novel coronavirus on that continent.

Dr. Stoian Alexov called the World Health Organization (WHO) a “criminal medical organization” for creating worldwide fear and chaos without providing objectively verifiable proof of a pandemic.

Another stunning revelation from Bulgarian Pathology Association (BPA) president Dr. Alexov is that he believes it’s currently “impossible” to create a vaccine against the virus.

He also revealed that European pathologists haven’t identified any antibodies that are specific for SARS-CoV-2.

These stunning statements raise major questions, including about officials’ and scientists’ claims regarding the many vaccines they’re rushing into clinical trials around the world.

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U.S. government awards Novavax $1.6 billion for coronavirus vaccine

Author: Julie Steenhuysen

Publication date: 07 July 2020

Source: Reuters

The U.S. government has awarded Novavax Inc $1.6 billion to cover testing and manufacturing of a potential vaccine for the novel coronavirus in the United States, with the aim of delivering 100 million doses by January.

The award announced by the U.S. Department of Health and Human Services is the biggest yet from “Operation Warp Speed,” the White House initiative aimed at accelerating access to vaccines and treatments to fight COVID-19, the respiratory disease caused by the coronavirus.

Shares in Gaithersburg, Maryland-based Novavax rose 29% to $102 in morning trading.

“What this Warp Speed award does is it pays for production of 100 million doses, which would be delivered starting in the fourth quarter of this year, and may be completed by January or February of next year,” Novavax Chief Executive Stanley Erck told Reuters.

It will also cover the cost of running a large Phase III trial, the final stage of human testing.

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Social Impacts

New £8.4m study launched into long-term impacts of Covid-19

Publication date: 07 July 2020

Source: National Health Executive

The National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI) have launched a major new research study into the long-term impacts of Covid-19 on hospitalised patients, with £8.4m of funding awarded to the research.

The PHOSP-COVID study is set to be led by the NIHR Leicester Biomedical Research Centre – a partnership between the University of Leicester and the University Hospitals of Leicester NHS Trust.

The expertise of a consortium of leading researchers and clinicians from across the UK will be drawn on to assess the impact of coronavirus on patient health and their recovery.

Around 10,000 patients are expected to take part in the study, making it one of the largest comprehensive studies in the world to understand and improve the health of survivors following hospitalisation from Covid-19.

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Coronavirus could cause 35,000 extra UK cancer deaths, experts warn

Publication date: 06 July 2020

Source: BBC News

Delays to cancer diagnosis and treatment due to coronavirus could cause thousands of excess deaths in the UK within a year, research suggests.

Scientists suggest there could be at least 7,000 additional deaths - but in a worst case scenario that number could be as high as 35,000.

There are concerns routine screenings, urgent referrals and treatments have been delayed or cancelled.

NHS England said it was working hard to restore services.

Scientists examined data from eight hospital trusts and shared their findings exclusively with BBC Panorama.

The study, conducted by DATA-CAN, the Health Care Research Hub (HDR UK) for Cancer, modelled different outcomes depending on how long services take to get back to normal levels.

In a worst case scenario, if delays continue, there could be 35,000 additional cancer deaths within a year.

Prof Mark Lawler, Scientific Lead of DATA-CAN, told BBC Panorama: "Initial data that we got was very worrying to us.

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