• Find related articles, information and videos in our Covid Zone

ANH-Intl Covid-19 information tracker - Week 18

Science

Pathogenesis

SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

Authors: Ziegler CGK et al

Publication date: 22 April 2020

Journal: Cell

DOI: 10.1016/j.cell.2020.04.035

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARS-CoV- 2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is a human interferon- stimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Read more

Epidemiology

Epidemiological characteristics and incubation period of 7,015 confirmed cases with Coronavirus Disease 2019 outside Hubei Province in China

Authors: Nie X et al

Publication date: 27 April 2020

Journal: The Journal of Infectious Diseases

DOI: 10.1093/infdis/jiaa211

Method: Information on 7,015 confirmed cases from January 19 to February 8, 2020, in all provinces outside Hubei was collected from the national and local health commissions in China. Incubation period and interval times were calculated using dates of the following events: contact with an infected person, onset, first visit and diagnosis. We evaluated changes in incubation period and interval times.

Results: The average age of all cases was 44.24 years old. The median incubation period was 5 days and extended from 2 days on January 23 to 15 days on February 8. The proportion of imported cases decreased from 85.71% to 33.19% after January 23. In addition, the lengths of the intervals between onset and diagnosis, onset and first visit, and first visit and diagnosis decreased over time.

Conclusion: Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurs among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.

Read more


Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study

Authors: Qifang Bi et al

Publication date: 27 April 2020

Journal: The Lancet Infectious Diseases

DOI: 10.1016/S1473-3099(20)30287-5

Findings: Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6).

Interpretation: Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control.

Read more


The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak

Authors: Chinazzi M et al

Publication date: 24 April 2020

Journal: Science

DOI: 10.1126/science.aba9757

Motivated by the rapid spread of coronavirus disease 2019 (COVID-19) in mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated on the basis of internationally reported cases and shows that, at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in mainland China but had a more marked effect on the international scale, where case importations were reduced by nearly 80% until mid-February. Modeling results also indicate that sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.

Read more


Effect of changing case definitions for COVID-19 on the epidemic curve and transmission parameters in mainland China: a modelling study

Authors: Tsanh TK, PhD et al

Publication date: 21 April 2020

Journal: The Lancet Public Health

DOI: 10.1016/S2468-2667(20)30089-X

Background: When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and for public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. We aimed to assess whether changes in case definitions affected inferences on the transmission dynamics of coronavirus disease 2019 (COVID-19) in China.

Methods: We examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used exponential growth models to estimate how changes in the case definitions affected the number of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic.

Findings: From Jan 15 to March 3, 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. We estimated that when the case definitions were changed, the proportion of infections being detected as cases increased by 7·1 times (95% credible interval [CrI] 4·8–10·9) from version 1 to 2, 2·8 times (1·9–4·2) from version 2 to 4, and 4·2 times (2·6–7·3) from version 4 to 5. If the fifth version of the case definition had been applied throughout the outbreak with sufficient testing capacity, we estimated that by Feb 20, 2020, there would have been 232 000 (95% CrI 161 000–359 000) confirmed cases in China as opposed to the 55 508 confirmed cases reported.

Read more

Covid-19 patients

Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol

Authors: Docherty AB et al

Publication date: 28 April 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.04.23.20076042

Objective: To characterize the clinical features of patients with severe COVID-19 in the UK. Design: Prospective observational cohort study with rapid data gathering and near real-time analysis, using a pre-approved questionnaire adopted by the WHO. Setting: 166 UK hospitals between 6th February and 18th April 2020. Participants: 16,749 people with COVID-19. Interventions: No interventions were performed, but with consent samples were taken for research purposes. Many participants were co-enrolled in other interventional studies and clinical trials. Results: The median age was 72 years [IQR 57, 82; range 0, 104], the median duration of symptoms before admission was 4 days [IQR 1,8] and the median duration of hospital stay was 7 days [IQR 4,12]. The commonest comorbidities were chronic cardiac disease (29%), uncomplicated diabetes (19%), non-asthmatic chronic pulmonary disease (19%) and asthma (14%); 47% had no documented reported comorbidity. Increased age and comorbidities including obesity were associated with a higher probability of mortality. Distinct clusters of symptoms were found: 1. respiratory (cough, sputum, sore throat, runny nose, ear pain, wheeze, and chest pain); 2. systemic (myalgia, joint pain and fatigue); 3. enteric (abdominal pain, vomiting and diarrhoea). Overall, 49% of patients were discharged alive, 33% have died and 17% continued to receive care at date of reporting. 17% required admission to High Dependency or Intensive Care Units; of these, 31% were discharged alive, 45% died and 24% continued to receive care at the reporting date. Of those receiving mechanical ventilation, 20% were discharged alive, 53% died and 27% remained in hospital. Conclusions: We present the largest detailed description of COVID-19 in Europe, demonstrating the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks.

Read more


UK report on 6720 patients critically ill with COVID-19

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

Publication date: 24 April 2020

Read more...


Neutrophil extracellular traps in COVID-19

Authors: Zuo Y et al

Publication date: 24 April 2020

Journal: JCI Insight

DOI: 10.1172/jci.insight.138999

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have potential to propagate inflammation and microvascular thrombosis — including in the lungs of patients with acute respiratory distress syndrome. While elevated levels of blood neutrophils predict worse outcomes in COVID-19, the role of NETs has not been investigated. We now report that sera from patients with COVID-19 (n = 50 patients, n = 84 samples) have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute phase reactants including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. In summary, these data reveal high levels of NETs in many patients with COVID-19, where they may contribute to cytokine release and respiratory failure. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts, and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.

Read more


Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

Authors: Richardson S MD, MPH et al

Publication date: 22 April 2020

Journal: JAMA

DOI: 10.1001/jama.2020.6775

Objective: To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.

Results: A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. Mortality for those requiring mechanical ventilation was 88.1%. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1).

Read more

Co-morbidities

The role of adipocytes and adipocyte‐like cells in the severity of COVID‐19 infections

Authors: Ilja L Kruglikov and Phillipp E Scherer

Publication date: 27 April 2020

Journal: Obesity

DOI: 10.1002/oby.22856

Coronavirus disease‐2019 (COVID‐19), caused by the highly pathogenic virus SARS‐CoV‐2, demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis (PF). In this Perspective, we argue that adipocytes and adipocyte‐like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to COVID‐19. Expression of angiotensin‐converting enzyme 2 (ACE2 ‐ the functional receptor for SARS‐CoV) ‐ is upregulated in adipocytes of obese and diabetic patients, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID‐19 infections. Similar to the recently established adipocyte‐myofibroblast transition (AMT), pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes, demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of PF. This may significantly increase the severity of the local response to COVID‐19 in the lung. To reduce the severity and mortality with COVID‐19, we propose to probe for the clinical response to thiazolidinediones (TZDs), PPARγ agonists, that are the well‐known anti‐diabetic drugs. TZDs are able to stabilize lipofibroblasts in their “inactive” state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.

Read more… 

Therapeutics

Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019)

Author: Mark Alipio

Publication date: 23 April 2020

Journal: SSRN

DOI: 10.2139/ssrn.3571484

The rapid spread of COVID-2019 in many areas of the world calls for preventive health measures. Although basic guidelines on infection control are recommended, treatment has remained the best choice to avert mortality. However, for the time being, there are no known vaccines for the disease. In this paper, I used multinomial logistic regression to predict clinical outcomes of patients infected with COVID-2019 based on 25-hydroxyvitamin D [25(OH)D] levels, the barometer for Vitamin D status. Using the database of three hospitals in Southern Asian countries, I conducted a retrospective multicentre study of 212 cases with laboratory-confirmed infection of SARS-CoV-2. Data pertaining to clinical features and serum 25(OH)D levels were extracted from the medical records. For statistical analysis, I used Mann-Whitney U and χ² tests to compare differences in the clinical outcomes. Multinomial logistic regression was used to explore the association between serum 25(OH)D level and clinical outcomes of the cases. Frequency and percentage were used for categorical variables. Mean was used for continuous variables. A p-value below 0.01 was considered statistically significant. Of the 212 cases of COVID-2019, majority had ordinary clinical outcome. Mean serum 25(OH)D level was 23.8 ng/ml. Serum 25(OH)D level was lowest in critical cases, but highest in mild cases. Serum 25(OH)D levels were statistically significant among clinical outcomes. Majority had insufficient Vitamin D status, most of them were not severe. Vitamin D status is significantly associated with clinical outcomes. A multinomial logistic regression analysis reported that for each standard deviation increase in serum 25(OH)D, the odds of having a mild clinical outcome rather than a severe outcome were approximately 7.94 times (OR=0.126, p<0.001) while interestingly, the odds of having a mild clinical outcome rather than a critical outcome were approximately 19.61 times (OR=0.051, p<0.001). The results suggest that an increase in serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while a decrease in serum 25(OH)D level in the body could worsen clinical outcomes of COVID-2019 patients. In conclusion, this study provides substantial information to clinicians and health policy-makers. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with COVID-2019. Further research should conduct randomized controlled trials and large population studies to evaluate this recommendation.

Read more

Nutrition

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Authors: Dofferhoff ASM et al

Publication date: 24 April 2020

Journal: Preprints

DOI: 10.20944/preprints202004.0457.v1

Introduction: Coronavirus 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2. The majority of patients have at most mild symptoms, however, a significant proportion develops respiratory failure. COVID-19 may also progress beyond the lungs. Coagulopathy and thromboembolism are prevalent in severe COVID-19 and relate to decreased survival. Coagulation is an intricate balance between clot promoting and dissolving processes in which vitamin K plays a well-known role. We hypothesized that vitamin K status is reduced in patients with severe COVID-19. Methods: Vitamin K status was assessed by measuring desphospho-uncarboxylated matrix Gla protein (dp-ucMGP; inversely related to vitamin K status) and the rate of elastin degradation by measuring desmosine. We included 123 patients who were admitted with COVID-19 and 184 controls. Results: Dp-ucMGP levels were significantly elevated in COVID-19 patients (1,673Å}1,584 pmol/L) compared to controls (536±291 pmol/L; p<0.0005). Dp-ucMGP levels were significantly higher in COVID-19 patients with unfavorable outcome compared to those with less severe disease. Furthermore, dp-ucMGP and desmosine levels were significantly associated (r=0.65; p<0.0005). Conclusions: Vitamin K status was reduced in patients with COVID-19 and related to poor prognosis. Also, low vitamin K status seems to be associated with accelerated elastin degradation. An intervention trial is now needed to assess whether vitamin K administration improves outcome in patients with COVID-19.

Read more


Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections

Authors: Calder PC et al

Publication date: 23 April 2020

Journal: Nutrition

DOI: 10.3390/nu12041181

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, were responsible for approximately 2.38 million deaths worldwide in 2016. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

Read more


Enhancing immunity in viral infections, with special emphasis on COVID-19: A review

Authors: Jayawardena R et al

Publication date: 16 April 2020

Journal: Diabetes & Metabolic Syndrome: Clinical Research & Reviews

DOI: 10.1016/j.dsx.2020.04.015

We summaries possible benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections. Nutrition principles based on these data could be useful in possible prevention and management of COVID-19.

Read more

Social distancing

Optimal control of the COVID-19 pandemic with non-pharmaceutical interventions

Authors: T Alex Perkins and Guido España

Publication date: 23 April 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.04.22.20076018

The COVID-19 pandemic has forced societies across the world to resort to social distancing to slow the spread of the SARS-CoV-2 virus. Due to the economic impacts of social distancing, there is growing desire to relax these measures. To characterize a range of possible strategies for control and to understand their consequences, we performed an optimal control analysis of a mathematical model of SARS-CoV-2 transmission. Given that the pandemic is already underway and controls have already been initiated, we calibrated our model to data from the US and focused our analysis on optimal controls from May 2020 through December 2021. We found that a major factor that differentiates strategies that prioritize lives saved versus reduced time under control is how quickly control is relaxed once social distancing restrictions expire in May 2020. Strategies that maintain control at a high level until summer 2020 allow for tapering of control thereafter and minimal deaths, whereas strategies that relax control in the short term lead to fewer options for control later and a higher likelihood of exceeding hospital capacity. Our results also highlight that the potential scope for controlling COVID-19 until a vaccine is available depends on epidemiological parameters about which there is still considerable uncertainty, including the basic reproduction number and the effectiveness of social distancing. In light of those uncertainties, our results do not constitute a quantitative forecast and instead provide a qualitative portrayal of possible outcomes from alternative approaches to control.

Read more


Forecasting the Impacts of Weather and Social Distancing on COVID-19 Transmission Across the U.S.

Publication date: 22 April 2020

Institution: Children’s Hospital of Philadelphia Policy Lab

As the nation mobilizes to respond to the once-in-a-century challenge of the COVID-19 pandemic, there is an urgent need to project how the virus will spread in the coming months. This information is critical to help local, state, and federal leadership make informed decisions about public policy solutions to manage the crisis.

As the crisis has unfolded, society has largely shut down through a variety of social distancing interventions that vary in magnitude and timing, and are designed to help slow the rate of infection, or flatten the curve. Flattening the curve is essential to prevent overwhelming health care systems, particularly with increased demands for ICU beds and ventilators, as well as to improve access to rapid and serologic testing for public health surveillance.

As the pandemic spreads in varied ways among our cities, it will be critical to provide more robust and reliable data models to guide decision-making about when and how to relax social distancing interventions in a way that allows Americans to safely transition back to work and school.

Read more

Personal protection

Masks for the public: laying straw men to rest

Author: Trisha Greenhalgh

Publication date: 28 April 2020

Journal: Authorea

DOI: 10.22541/au.158809415.52483068

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

Read more

Clinical trials

As at 29/04/20 997 clinical trials have been registered with the National Institutes of Health (NIH) ClinicalTrials.gov website: Covid-19 related trials

Of those 33 (3%) are related to natural health interventions

Vaccines

A SARS-CoV-2 vaccine candidate would likely match all currently circulating strains

Authors: Dearlove B et al

Publication date: 27 April 2020

Journal: bioRxiv preprint

DOI: 10.1101/2020.04.27.064774

The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective

vaccine. Here we analyzed SARS-CoV-2 sequence diversity across 5,700 sequences sampled 5 since December 2019. The Spike protein, which is the target immunogen of most vaccine candidates, showed 93 sites with shared polymorphisms; only one of these mutations was found in more than 1% of currently circulating sequences. The minimal diversity found among SARS- CoV-2 sequences can be explained by drift and bottleneck events as the virus spread away from its original epicenter in Wuhan, China. Importantly, there is little evidence that the virus has 10 adapted to its human host since December 2019. Our findings suggest that a single vaccine should be efficacious against current global strains.

Read more


Rapid development of an inactivated vaccine for SARS-CoV-2

Authors: Gao Q et al

Publication date: 19 April 2020

Journal: bioRxiv

DOI: 10.1101/2020.04.17.046375

A purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology

Read more

Herd immunity

Controlled Avalanche – A Regulated Voluntary Exposure Approach for Addressing

Authors: Klement E et al

Publication date: 22 April 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.04.12.20062687

Methods:

Using a compartmental model we examine the implications of the controlled avalanche (CA) strategy over the population in Israel. We compare four scenarios: in two scenarios the CA program is applied to the low-risk population (with the rest of the population subject to mitigation measures), followed by mitigation for the entire population or by uncontrolled spread. These are compared to mitigated and uncontrolled scenarios without the CA program. We discuss the economic, ethical and public health implications of the CA strategy.

Findings: We show that compared to mitigation of the entire population, the CA strategy reduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62% and decreases the time required for release of 50% of the low-risk population by more than 2 months.

Interpretation: This study suggests an ethically acceptable practice, that enables reaching herd immunity faster than the current alternatives, with low mortality and minimal economic damage.

Read more

Environmental factors

Links between air pollution and COVID-19 in England

Authors: Travaglio M et al

Publication date: 20 April 2020

Journal: medRxiv preprint

DOI: 10.1101/2020.04.16.20067405

In December 2019 a novel disease [coronavirus disease 19 (COVID-19) emerged in the Wuhan province of the People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) thought to have jumped species, from another mammal to humans. A pandemic caused by this virus is running rampant throughout the world. Thousands of cases of COVID-19 are reported in England and over 10,000 patients have died. Whilst there has been progress in managing this disease, it is not clear which factors, besides age, affect the severity and mortality of COVID-19. A recent analysis of COVID-19 in Italy identified links between air pollution and death rates. Here, we explored the correlation between three major air pollutants linked to fossil fuels and SARS-CoV-2 lethality in England. We compare up-to-date, real-time SARS-CoV-2 cases and death measurements from public databases to air pollution data monitored across over 120 sites in different regions. We found that the levels of some markers of poor air quality, nitrogen oxides and ozone, are associated with COVID-19 lethality in different English regions. We conclude that the levels of some air pollutants are linked to COVID-19 cases and morbidity. We suggest that our study provides a useful framework to guide health policy in countries affected by this pandemic.

Read more

 

Media – Science related

Origins

Another expert challenges assertions that SARS-CoV-2 was not genetically engineered

Publication date: 27 April 2020

Source: GMWatch

Another expert on biotechnology has attacked the evidence being used to quash suggestions that SARS-CoV-2, the virus strain that causes COVID-19, might have been genetically engineered. Professor Stuart Newman, professor of cell biology and anatomy at New York Medical College, says that a key argument used to deny that it could be a genetically engineered strain that escaped from a laboratory actually points to the exact opposite. In other words, it indicates that SARS-CoV-2 could well be genetically engineered and that it could have escaped from a lab.

The evidence that is being cited as proving that SARS-CoV-2 is “not a laboratory construct or a purposefully manipulated virus” is a paper published by the immunologist Kristian Andersen and colleagues in Nature Medicine. As Adam Lauring, an associate professor of microbiology, immunology and infectious diseases at the University of Michigan Medical School, has noted, Andersen’s paper argues that, "the SARS-CoV-2 virus has some key differences in specific genes relative to previously identified coronaviruses – the ones a laboratory would be working with. This constellation of changes makes it unlikely that it is the result of a laboratory 'escape’.”

Read more

Therapeutics

Covid-19 drugs & vaccines tracker

Source: Stat

In the months since the novel coronavirus rose from a regional crisis to a global threat, drug makers large and small have scrambled to advance their best ideas for thwarting a pandemic.

Some are taking a cue from older antivirals. Some are tapping tried-and-true technologies, and others are pressing forward with futuristic approaches to human medicine.

Here’s a guide to some of the most talked-about efforts to treat or prevent coronavirus infection, with details on the science, history, and timeline for each endeavor. We’re looking at novel medicines, not repurposed drugs. (For more on some of the efforts to repurpose drugs, read this.) The below therapies and vaccines are sorted in order of how close they could be to approval, starting with a treatment in Phase 3 trials, followed by others in Phase 1 studies and then preclinical development. Approval, of course, would only come if they are proven safe and effective.

Read more

Perspectives on the Pandemic

Professor Knut Wittkowski Update Interview | Episode 5

Publication date: 28 April 2020

Source: Journeyman Pictures (YouTube)

Perspectives on the Pandemic Episode 5: In this highly-charged follow-up interview, Knut Wittkowski says his initial claim has been vindicated:  The lockdowns - always a dubious proposition for a respiratory virus - came too late in the U.S. and elsewhere, and were therefore even worse than useless. By turns emotional and darkly comic, Wittkowski ranges across all the essential topics of the crisis, and gives answers you are unlikely to see in the major media. Not to be missed.

Watch the video

Covid-19 patients

There is no relationship between covid-19 and altitude illness

Authors: Basnyat B et al

Publication date: 28 April 2020

Source: The BMJ Opinion

There have recently been suggestions that covid-19 lung disease is similar to high altitude pulmonary oedema (HAPE). There have been proposals to treat covid-19 with medications that are used for HAPE. [1] Although innovative treatment measures may be required for the treatment of covid-19 it is vital to examine the differences in pathophysiology before proposing similar treatments.

HAPE is a hypobaric hypoxic phenomenon, but covid-19 occurs in normobaric conditions. Both HAPE and covid-19 can cause non-cardiogenic pulmonary oedema with extreme hypoxaemia, fluffy patches on chest x-ray and a ground glass appearance on chest computed tomography (CT). [2,3] However the pathophysiologies are vastly different.

Read more

Testing

Abbott obtains CE mark for COVID-19 laboratory-based antibody test

Publication date: 29 April 2020

Source: SelectScience

Abbott has announced it received CE Mark to the IVD Directive (98/79/EC) for its laboratory-based serology blood test for the detection of the antibody, IgG, that identifies if a person has had the novel coronavirus (COVID-19). Antibody testing is an important next step to tell if someone has been previously infected. It will provide more understanding of the virus including how long antibodies stay in the body and if they provide immunity. This type of knowledge could help support the development of treatments and vaccines.

This antibody test adds to Abbott's existing COVID-19 tests in the UK that are already being used on its m2000™ molecular laboratory system, which is already in use across NHS laboratories.

Read more

Environmental impact

IPBES Guest Article: COVID-19 Stimulus Measures Must Save Lives, Protect Livelihoods, and Safeguard Nature to Reduce the Risk of Future Pandemics

Authors: Professors Josef Settele, Sandra Díaz and Eduardo Brondizio and Dr Peter Daszak

Publication date: 27 april 2020

Source: The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES)

There is a single species that is responsible for the COVID-19 pandemic - us. As with the climate and biodiversity crises, recent pandemics are a direct consequence of human activity – particularly our global financial and economic systems, based on a limited paradigm that prizes economic growth at any cost. We have a small window of opportunity, in overcoming the challenges of the current crisis, to avoid sowing the seeds of future ones.  

Diseases like COVID-19 are caused by microorganisms that infect our bodies – with more than 70% of all emerging diseases affecting people having originated in wildlife and domesticated animals. Pandemics, however, are caused by activities that bring increasing numbers of people into direct contact and often conflict with the animals that carry these pathogens.

Read more

Vaccines

Oxford COVID-19 vaccine begins human trial stage

Publication date: 23 April 2020

Source: University of Oxford

University of Oxford researchers have begun testing a COVID-19 vaccine in human volunteers in Oxford today. Around 1,110 people will take part in the trial, half receiving the vaccine and the other half (the control group) receiving a widely available meningitis vaccine.

Of the first two volunteers to take part today, one will likewise receive the vaccine and the other the control.

The researchers started screening healthy volunteers (aged 18-55) in March for their upcoming ChAdOx1 nCoV-19 vaccine trial in the Thames Valley Region. The vaccine is based on an adenovirus vaccine vector and the SARS-CoV-2 spike protein, and has been produced in Oxford.

Read more

 

Media – Reporting

Coronavirus research

Trump cuts U.S. research on bat-human virus transmission over China ties

Author: Sarah Owemohle

Publication date: 27 April 2020

Source: Politico

The Trump administration abruptly cut off funding for a project studying how coronaviruses spread from bats to people after reports linked the work to a lab in Wuhan, China, at the center of conspiracy theories about the Covid-19 pandemic’s origins.

The National Institutes of Health on Friday told EcoHealth Alliance, the study’s sponsor for the past five years, that all future funding was cut. The agency also demanded that the New York-based research nonprofit stop spending the $369,819 remaining from its 2020 grant, according to emails obtained by POLITICO.

“At this time, NIH does not believe that the current project outcomes align with the program goals and agency priorities,” Michael Lauer, the agency’s deputy director for extramural research, wrote in a letter to EcoHealth Alliance officials.

Read more

Therapeutics

New data on Gilead’s remdesivir, released by accident, show no benefit for coronavirus patients. Company still sees reason for hope

Authors: Ed Silverman, Adam Feuerstein and Matthew Herper

Publication date: 23 April 2020

Source: Stat

The antiviral medicine remdesivir from Gilead Sciences failed to speed the improvement of patients with Covid-19 or prevent them from dying, according to results from a long-awaited clinical trial conducted in China. Gilead, however, said the data suggest a “potential benefit.”

A summary of the study results was inadvertently posted to the website of the World Health Organization and seen by STAT on Thursday, but then removed.

“A draft manuscript was provided by the authors to WHO and inadvertently posted on the website and taken down as soon as the mistake was noticed. The manuscript is now undergoing peer review and we are waiting for a final version before WHO comments on it,” said WHO spokesperson Daniela Bagozzi.

Read more


Coronavirus: the miracle remedy touted by Madagascar’s Rajoelina

Author: Emre Sari

Publication date: 22 April 2020

Source: The Africa Report

Madagascar’s president surprised many observers when he announced that certain traditional plants grown on the large island country have the potential to cure Covid-19. Was his mention of this African remedy based on the healing properties of traditional medicine premature given that it is still being studied?

Could traditional African medicine “change the course of history” in the combat against COVID-19? Madagascar President Andry Rajoelina believes so, and he is also convinced that the island country has a special role to play in stemming the pandemic.

On the evening of 8 April, the head of state made a surprising revelation to his fellow citizens on national television: “I received a letter on 24 March indicating that Madagascar possesses a remedy that could – and I say could because it has not yet been proven – cure the coronavirus.”

Read more

Trials

Upasi studying tea’s efficacy against Covid-19

Publication date: 23 April 2020

Source: The Hindu Business Line

The United Planters’ Association of Southern India (Upasi) has announced that its Tea Research Institute is exploring the possibility of using tea as a defence against the Coronavirus.

“The Upasi Tea Research Institute is exploring the possibility of investigating the antiviral property of Theaflavins-3, a compound abundantly found in black tea and catechins from green tea to ward off Coronavirus in collaboration with the Tea Board of India through ICMR,” Chairman of Upasi Tea Committee C Shreedharan said.

This follows a recent study by a research group from Indonesia and Thailand that explored the secondary metabolites secreted by plants in tropical regions that can be developed as medicines. This group investigated a number of compounds for their potential to inhibit Covid-19.

Read more

Second wave infections

Coronavirus: Immunity passports 'could increase virus spread'

Publication date: 25 April 2020

Source: BBC

Governments should not issue so-called "immunity passports" or "risk-free certificates" as a way of easing lockdowns, the World Health Organization (WHO) says.

It said there was "no evidence" that people who had developed antibodies after recovering from the virus were protected against a second infection.

Such a move could actually increase virus transmission, it warned.

People who assumed they were immune might stop taking precautions, it said.

Some governments have considered permitting people who have recovered to travel or return to work.

Read more

Reverse zoonotic transmission

Two cats in New York are first pets known to have coronavirus in the US

Author: Arman Azad

Publication date: 23 April 2020

Source: CNN

Two cats in New York have been infected with the novel coronavirus, federal officials announced Wednesday. Both had mild respiratory symptoms and are expected to make a full recovery.

"These are the first pets in the United States to test positive," the US Department of Agriculture said Wednesday in a joint statement with the US Centers for Disease Control and Prevention.

Coronavirus pandemic in the US

Coronavirus pandemic in the US

The agencies emphasized that there is no evidence pets play a role in spreading coronavirus in the United States. "There is no justification in taking measures against companion animals that may compromise their welfare," they said.

Read more