President Donald Trump, who has previously touted antimalarial drugs as unproven treatments for Covid-19, is now reportedly seeking approval from the Food and Drug Administration for an extract from the oleander plant—another remedy with weak scientific backing—to be used to treat the coronavirus after being endorsed by a member of his cabinet and Trump-supporting MyPillow CEO, Mike Lindell

After Hydroxychloroquine, Trump Is Now Seeking To Get Another Unproven Drug Approved By The FDA: Report

An essential mechanism for SARS-CoV-1 and -2 infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human Fc domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2 pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50) in the 10-100 ng/ml range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-utilizing coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be pre-designed for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated or generated from convalescent patients.

10.1101/2020.07.31.231746

Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

Background: Unprecedented demand for N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic has led to a global shortage of these masks. We validated a rapidly applicable, lowcost decontamination protocol in compliance with regulatory standards to enable the safe reuse of N95 respirators. Methods: We inoculated 4 common models of N95 respirators with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and evaluated viral inactivation after disinfection for 60 minutes at 70°C and 0% relative humidity. Similarly, we evaluated thermal disinfection at 0% to 70% relative humidity for masks inoculated with Escherichia coli. We assessed masks subjected to multiple cycles of thermal disinfection for structural integrity using scanning electron microscopy and for protective functions using standards of the United States National Institute for Occupational Safety and Health for particle filtration efficiency, breathing resistance and respirator fit.Results: A single heat treatment rendered SARS-CoV-2 undetectable in all mask samples. Compared with untreated inoculated control masks, E. coli cultures at 24 hours were virtually undetectable from masks treated at 70°C and 50% relative humidity (optical density at 600 nm wavelength, 0.02 ± 0.02 v. 2.77 ± 0.09, p < 0.001), but contamination persisted for masks treated at lower relative humidity. After 10 disinfection cycles, masks maintained fibre diameters similar to untreated masks and continued to meet standards for fit, filtration efficiency and breathing resistance.Interpretation: Thermal disinfection successfully decontaminated N95 respirators without impairing structural integrity or function. This process could be used in hospitals and long-term care facilities with commonly available equipment to mitigate the depletion of N95 masks..

10.1503/cmaj.201203

Effect of moist heat reprocessing of N95 respirators on SARS-CoV-2 inactivation and respirator function

BackgroundThe accurate detection of SARS-CoV-2 through respiratory sampling is critical for the prevention of further transmission and the timely initiation of treatment for COVID-19. There is a diverse range of SARS-CoV-2 detection rates in reported studies, with uncertainty as to the optimal sampling strategy for COVID-19 diagnosis and monitoring.MethodsWe performed a systematic review and meta-analysis of studies comparing respiratory sampling strategies for the detection of SARS-CoV-2 RNA. The inclusion criteria were studies that assessed at least two respiratory sampling sites (oropharyngeal swab, nasopharyngeal swab, and sputum) in participants with COVID-19. The percentage positive tests were compared between sampling modalities by constructing a Z-test assuming independence and using the standard errors obtained from the random effects meta-analysis.• View related content for this articleFindingsFrom 1039 total studies, we identified 11 studies that met our inclusion criteria, with SARS-CoV-2 testing results from a total of 3442 respiratory tract specimens. Compared to nasopharyngeal swab sampling, sputum testing resulted in significantly higher rates of SARS-CoV-2 RNA detection while oropharyngeal swab testing had lower rates of viral RNA detection. Earlier sampling after symptom onset was associated with improved detection rates, but the differences in SARS-CoV-2 RNA detection by sampling method was consistent regardless of the duration of symptoms.InterpretationThe results support sputum sampling as a valuable method of COVID-19 diagnosis and monitoring, and highlight the importance of early testing after symptom onset to increase the rates of COVID-19 diagnosis.

10.1016/j.ebiom.2020.102903

SARS-CoV-2 detection in different respiratory sites: A systematic review and meta-analysis

Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding of the natural immune response to SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology, termed T-Scan, to identify specific epitopes in SARS-CoV-2 that are recognized by the memory CD8+ T cells of 25 COVID-19 convalescent patients, focusing on epitopes presented by the six most prevalent Human Leukocyte Antigen (HLA) types: A*02:01, A*01:01, A*03:01, A*11:01, A*24:02, and B*07:02. For each HLA type, the patients' T cells recognized 3-8 immunodominant epitopes that are broadly shared among patients. Remarkably, 94% of screened patients had T cells that recognized at least one of the three most dominant epitopes for a given HLA, and 53% of patients had T cells that recognized all three. Subsequent validation studies in 18 additional A*02:01 patients confirmed the presence of memory CD8+ T cells specific for the top six identified A*02:01 epitopes, and single-cell sequencing revealed that patients often have many different T cell clones targeting each epitope, but that the same T cell receptor Valpha regions are predominantly used to recognize these epitopes, even across patients. In total, we identified 29 shared epitopes across the six HLA types studied. T cells that target most of these immunodominant epitopes (27 of 29) do not cross-react with the endemic coronaviruses that cause the common cold, and the epitopes do not occur in regions with high mutational variation. Notably, only 3 of the 29 epitopes we identified reside in the spike protein, highlighting the need to design new classes of vaccines that recapitulate natural CD8+ T cell responses to SARS-CoV-2.

10.1101/2020.07.24.20161653

COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 “apical-out” organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.

10.1101/2020.07.27.212076

Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

10.1101/2020.07.30.229120

A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.

10.1101/2020.07.25.20162107

SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness: a living systematic review and meta-analysis

Background: A significant number of infectious diseases display seasonal patterns in their incidence, including human coronaviruses. Betacoronaviruses such as MERS-CoV and SARS-CoV are not thought to be seasonal. Methods: We examined climate data from cities with significant community spread of COVID-19 using ERA-5 reanalysis, and compared to areas that are either not affected, or do not have significant community spread.Findings: To date, Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, has established significant community spread in cities and regions along a narrow east west distribution roughly along the 30-50o N’ corridor at consistently similar weather patterns consisting of average temperatures of 5-11oC, combined with low specific (3-6 g/kg) and absolute humidity (4-7 g/m3). There has been a lack of significant community establishment in expected locations that are based only on population proximity and extensive population interaction through travel. Interpretation: The distribution of significant community outbreaks along restricted latitude, temperature, and humidity are consistent with the behavior of a seasonal respiratory virus. Additionally, we have proposed a simplified model that shows a zone at increased risk for COVID-19 spread. Using weather modeling, it may be possible to predict the regions most likely to be at higher risk of significant community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

Temperature, Humidity and Latitude Analysis to Predict Potential Spread and Seasonality for COVID-19

Although unmeasured confounding remains the most likely explanation for the discrepancies, a robust meta-analysis is still lacking, and we believe that hydroxychloroquine should be further tested in randomised trials. When best to start treatment is also a question that needs to be addressed in ad-hoc randomized studies.

10.1016/j.ijid.2020.07.056

Effectiveness of hydroxychloroquine in COVID-19 disease: A done and dusted deal?

A computer model of the cruise-ship outbreak found that the virus spread most readily in microscopic droplets light enough to linger in the air.

Aboard the Diamond Princess, a Case Study in Aerosol Transmission

Grim jobless and economic growth data on Thursday underscored how badly the coronavirus pandemic has damaged the world’s largest economy, as still rising COVID-19 diagnoses in the Sun Belt region amplify concerns for the recovery, and America’s ability to contain the fallout.The U.S. continues a concerning upward trend in cases and deaths, with Texas, California and Florida all surpassing New York as states with the highest cases in the past week, surpassing 4.4 million cases. The Empire State, a former hotspot, continues to see hospitalizations and casualties decline amid slowly spreading cases.Meanwhile, the political world was jolted by news that former GOP presidential candidate Herman Cain lost his battle with COVID-19 Thursday, making him the latest victim among the more than 150,000 in the U.S. that have now died from the virus. In recent weeks, high profile politicians like Atlanta’s Mayor and Oklahoma’s governor have tested positive for the virus

Coronavirus update: Sun Belt surge fans recovery fears; Trump ally Herman Cain dies

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17F, and vascular endothelial growth factor (VEGF) in tissue culture models. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and previously established favorable pharmacokinetic and human safety profiles render PTC299 a promising therapeutic for COVID-19.

10.1101/2020.08.05.238394

The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines

BackgroundThe epidemic of COVID-19 presents a special threat to older adults. However, information on kidney damage in older patients with COVID-19 is limited. Acute kidney injury (AKI) is common in hospitalized adults and associated with poor prognosis. We sought to explore the association between AKI and mortality in older patients with COVID-19.MethodsWe conducted a retrospective, observational cohort study in a large tertiary care university hospital in Wuhan, China. All consecutive inpatients older than 65 years with COVID-19 were enrolled in this cohort. Demographic data, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between patients with AKI and without AKI. The association between AKI and mortality was analyzed.ResultsOf 1764 in-hospital patients, 882 older adult cases were included in this cohort. The median age was 71 years (interquartile range: 68–77), 440 (49.9%) were men. The most presented comorbidity was cardiovascular diseases (58.2%), followed by diabetes (31.4%). Of 882 older patients, 115 (13%) developed AKI and 128 (14.5%) died. Patients with AKI had higher mortality than those without AKI (68 [59.1%] vs 60 [7.8%]; p < .001). Multivariable Cox regression analysis showed that increasing odds of in-hospital mortality are associated with higher interleukin-6 on admission, myocardial injury, and AKI.ConclusionsAcute kidney injury is not an uncommon complication in older patients with COVID-19 but is associated with a high risk of death. Physicians should be aware of the risk of AKI in older patients with COVID-19.

10.1093/gerona/glaa181

Acute Kidney Injury Is Associated With In-hospital Mortality in Older Patients With COVID-19

Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. Interestingly, we also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.

10.1101/2020.08.06.234674

Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate

10.1038/s41586-020-2622-0

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the global coronavirus infectious disease (COVID-19) public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved the expression and immunogenicity of betacoronavirus spike proteins1. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant2 SARS-CoV-2 and CD8 T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in Phase 3 efficacy evaluation.

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

Current bottlenecks for improving accessibility and scalability of SARS-CoV-2 testing include diagnostic assay costs, complexity, and supply chain shortages. To resolve these issues, we developed SalivaDirect. The critical component of our approach is to use saliva instead of respiratory swabs, which enables non-invasive frequent sampling and reduces the need for trained healthcare professionals during collection. Furthermore, we simplified our diagnostic test by (1) not requiring nucleic acid preservatives at sample collection, (2) replacing nucleic acid extraction with a simple proteinase K and heat treatment step, and (3) testing specimens with a dualplex quantitative reverse transcription PCR (RT-qPCR) assay. We validated SalivaDirect with reagents and instruments from multiple vendors to minimize the risk for supply chain issues. Regardless of our tested combination of reagents and instruments from different vendors, we found that SalivaDirect is highly sensitive with a limit of detection of 6-12 SARS-CoV-2 copies/μL. When comparing paired nasopharyngeal swabs and saliva specimens using the authorized ThermoFisher Scientific TaqPath COVID-19 combo kit and our SalivaDirect protocol, we found high agreement in testing outcomes (>94%). Being flexible and inexpensive ($1.29-$4.37/sample), SalivaDirect is a viable and accessible option to help alleviate SARS-CoV-2 testing demands. We submitted SalivaDirect as a laboratory developed test to the US Food and Drug Administration for Emergency Use Authorization on July 14th, 2020, and current details can be found on our website (covidtrackerct.com/about-salivadirect/).

10.1101/2020.08.03.20167791

SalivaDirect: Simple and sensitive molecular diagnostic test for SARS-CoV-2 surveillance

This study characterized a genetically adapted Pseudomonas aeruginosa small colony variant isolated from a COVID-19 patient who suffered persistent bacterial coinfection and eventually recovered from critical illness. Specification and modification of the isolates discovered at genomic and transcriptomic levels with aligned phenotypic observations indicated that these isolates formed excessive biofilm with elevated quorum sensing systems.

10.1101/2020.08.05.238998

Persistent bacterial coinfection of a COVID-19 patient caused by a genetically adapted Pseudomonas aeruginosa chronic colonizer

10.1101/2020.08.03.20167395

Background - There currently is substantial controversy about the role played by SARS-CoV-2 in aerosols in disease transmission, due in part to detections of viral RNA but failures to isolate viable virus from clinically generated aerosols. Methods - Air samples were collected in the room of two COVID-19 patients, one of whom had an active respiratory infection with a nasopharyngeal (NP) swab positive for SARS-CoV-2 by RT-qPCR. By using VIVAS air samplers that operate on a gentle water-vapor condensation principle, material was collected from room air and subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and of virus isolated in cell culture from air sampling and from a NP swab from a newly admitted patient in the room were sequenced. Findings - Viable virus was isolated from air samples collected 2 to 4.8m away from the patients. The genome sequence of the SARS-CoV-2 strain isolated from the material collected by the air samplers was identical to that isolated from the NP swab from the patient with an active infection. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. Interpretation - Patients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus.

Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients

Our analyses suggest children younger than 5 years with mild to moderate COVID-19 have high amounts of SARS-CoV-2 viral RNA in their nasopharynx compared with older children and adults. Our study is limited to detection of viral nucleic acid, rather than infectious virus, although SARS-CoV-2 pediatric studies reported a correlation between higher nucleic acid levels and the ability to culture infectious virus.5 Thus, young children can potentially be important drivers of SARS-CoV-2 spread in the general population, as has been demonstrated with respiratory syncytial virus, where children with high viral loads are more likely to transmit.

10.1001/jamapediatrics.2020.3651

Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19)

10.1038/s41591-020-1025-y

The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising1. In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-22,3. Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed4. Advances in malaria control this century have been largely due to distribution of long-lasting insecticidal nets (LLINs)5, with many SSA countries having planned campaigns for 2020. In the present study, we use COVID-19 and malaria transmission models to estimate the impact of disruption of malaria prevention activities and other core health services under four different COVID-19 epidemic scenarios. If activities are halted, the malaria burden in 2020 could be more than double that of 2019. In Nigeria alone, reducing case management for 6 months and delaying LLIN campaigns could result in 81,000 (44,000–119,000) additional deaths. Mitigating these negative impacts is achievable, and LLIN distributions in particular should be prioritized alongside access to antimalarial treatments to prevent substantial malaria epidemics.

The potential public health consequences of COVID-19 on malaria in Africa

Researchers at the George Washington University (GW) discovered five biomarkers (medical indicators found in the blood) associated with higher odds of clinical deterioration and death in Covid-19 patients.

Scientists find five blood molecules linked to severe Covid-19 outcome in patients

While most children who catch the coronavirus have either no symptoms or mild ones, they are still at risk of developing "severe" symptoms requiring admission to an intensive care unit, the Centers for Disease Control and Prevention said in a new report released Friday.

Children Can Get Severe COVID-19, CDC Says — Especially Black And Hispanic Children

10.1038/d41586-020-02416-z

The United Kingdom’s RECOVERY trial shows a way to benefit patients faster.

How we accelerated clinical trials in the age of coronavirus

10.31234/osf.io/7cvdm

Close relationships will play a crucial role in protecting health and well-being during the COVID-19 pandemic. Yet, the pandemic and quarantines to contain COVID-19 present acute, ongoing demands that put couples at risk of relationship problems. The current research tested how (1) couples’ pre-existing vulnerabilities assessed prior to the pandemic (attachment insecurity) and (2) stress during a mandated quarantine predicted residual changes in relationship problems, satisfaction and commitment. When people experienced high levels of stress, greater own and partner attachment anxiety (assessed prior to the quarantine) predicted residual increases in relationship problems, and in turn, residual decreases in satisfaction and commitment (controlling for pre-quarantine problems, satisfaction and commitment). These vulnerability x stress patterns demonstrate that key models in relationship science can identify which couples are at most risk of relationship problems in the unprecedented context of a global pandemic and mandated quarantine.

Relationship Functioning During COVID-19 Quarantine

10.31234/osf.io/ag2r7

Early work indicates the significant impact of the COVID-19 pandemic on the mental health of children. The current study investigated associations between family factors, and children’s mental health during the early phase of COVID-19. Parents (N = 385) across a number of countries reported on their mental health, distress, and parenting behaviors, in addition to mental health changes in their 5-17 year old children (N = 481) during April/May 2020. Analyses revealed significant associations between family factors (perceived impact of COVID-19, parent mental health, parenting behaviors, family cohesion, and parent-child COVID-19 communication) and changes in child mental health. Further, some associations were more pronounced for disadvantaged and single parent families.

Parenting and child and adolescent mental health during the COVID-19 pandemic

Schaake offered a hopeful vision for the new values that could animate Silicon Valley—values that were democratic, incremental, and even traditional. Many talented software engineers, she said, “are looking for more value than the value of money. They also see the homeless people in the streets in the areas where they live, and they can’t afford homes themselves.” If tech companies could be regulated by voters, she said, then laws could be passed that limited the civic and economic damage those platforms caused. Legislation could protect privacy and increase transparency about how companies use data; revised liability laws could hold companies accountable for what they disseminate, and improve public debate; antitrust actions could check the flow of wealth to the small number of companies that control platforms, aggregators, and algorithms. Stronger taxation might fund a more effective and comprehensive social safety net. There might be less homelessness in the Bay Area. Possibly, people at Silicon Valley cocktail parties would no longer introduce each other by referencing their net worth. The world would be a bit more sane.

What Can America Learn from Europe About Regulating Big Tech?

The perils of preprints

Preprints—manuscripts that have not undergone peerreview—were first embraced in physics, catalysed bythe creation in the early 1990s of arXiv.org, an openonline repository for scholarly papers.1It was notuntil 2013 that similar initiatives were embraced bythe biological and then medical sciences,2and novelpublishing platforms continue to emerge. Somecommentators believe the potential for harm isoutweighed by the benefits,1 3 4but others have raisedspecific concerns regarding medical preprints andmitigating the risk of harm to the public.2Thesediscussions need to be revisited in the context of thecovid-19 pandemic, which has been accompanied byan explosion of preprint publications.

10.1136/bmj.m3111

Social distancing is the core policy response to coronavirus disease 2019 (COVID-19). But, as federal, state and local governments begin opening businesses and relaxing shelter-in-place orders worldwide, we lack quantitative evidence on how policies in one region affect mobility and social distancing in other regions and the consequences of uncoordinated regional policies adopted in the presence of such spillovers. To investigate this concern, we combined daily, county-level data on shelter-in-place policies with movement data from over 27 million mobile devices, social network connections among over 220 million Facebook users, daily temperature and precipitation data from 62,000 weather stations, and county-level census data on population demographics to estimate the geographic and social network spillovers created by regional policies across the United States. Our analysis shows that the contact patterns of people in a given region are significantly influenced by the policies and behaviors of people in other, sometimes distant, regions. When just one-third of a state’s social and geographic peer states adopt shelter-in-place policies, it creates a reduction in mobility equal to the state’s own policy decisions. These spillovers are mediated by peer travel and distancing behaviors in those states. A simple analytical model calibrated with our empirical estimates demonstrated that the “loss from anarchy” in uncoordinated state policies is increasing in the number of noncooperating states and the size of social and geographic spillovers. These results suggest a substantial cost of uncoordinated government responses to COVID-19 when people, ideas, and media move across borders.

10.1073/pnas.2009522117

Interdependence and the cost of uncoordinated responses to COVID-19

What are we doing? And why?The ProblemIt is difficult for people new to open scholarship ideas and practices to find and apply existing materials.It is difficult for educators to bring open scholarship concepts and exercises into their courses.The open scholarship landscape changes quickly, so materials can become outdated. Our SolutionOur Project Roadmap outlines our approach: Build a knowledge base platform and a community of contributors to organize information on the what, why, and how of open scholarship so it is easy to find and apply. Contributors keep the information up-to-date and curate modules for self-learning or teaching.

Open Scholarship Knowledge Base

10.31234/osf.io/5bz3f

Mediation analysis empirically investigates the process underlying the effect of an experimental manipulation on a dependent variable of interest. In the simplest mediation setting, the experimental treatment can affect the dependent variable through the mediator (indirect effect) and/or directly (direct effect). Recent methodological advances made in the field of mediation analysis aim at developing statistically reliable estimates of the indirect effect of the treatment on the outcome. However, what appears to be an indirect effect through the mediator may reflect a data generating process without mediation, regardless of the statistical properties of the estimate. To overcome this indeterminacy where possible, we develop the insight that a statistically reliable indirect effect combined with strong evidence for conditional independence of treatment and outcome given the mediator is unequivocal evidence for mediation (as the underlying causal model generating the data) into an operational procedure. Our procedure combines Bayes factors as principled measures of the degree of support for conditional independence, i.e., the degree of support for a Null hypothesis, with latent variable modeling to account for measurement error and discretization in a fully Bayesian framework. We illustrate how our approach facilitates stronger conclusions by re-analzing a set of published mediation studies.

Measuring evidence for mediation in the presence of measurement error

10.1038/d41586-020-02403-4

Masks, class sizes and hygiene are important, but low community spread is key.

How schools can reopen safely during the pandemic

10.1038/d41586-020-02400-7

Viral immunologists say that results so far have been predictable — here’s why that’s good news.

What the immune response to COVID-19 says about the prospects for a vaccine

Russian president Vladimir Putin announced yesterday that the country has approved a vaccine against SARS-CoV-2, the coronavirus that causes covid-19. Putin said that the vaccine is safe and effective. Russia apparently plans to start mass vaccinations in October. However, the announcement has caused global concern. Immunologists say there is no way to be sure that the vaccine is safe, let alone effective, and that Russia seems to be cutting corners.

Everything you need to know about Russia's coronavirus vaccine claims

In the last decade Open Science principles, such as Open Access, study preregistration, use of preprints, making available data and code, and open peer review, have been successfully advocated for and are being slowly adopted in many different research communities. In response to the COVID-19 pandemic many publishers and researchers have sped up their adoption of some of these Open Science practices, sometimes embracing them fully and sometimes partially or in a sub-optimal manner. In this article, we express concerns about the violation of some of the Open Science principles and its potential impact on the quality of research output. We provide evidence of the misuses of these principles at different stages of the scientific process. We call for a wider adoption of Open Science practices in the hope that this work will encourage a broader endorsement of Open Science principles and serve as a reminder that science should always be a rigorous process, reliable and transparent, especially in the context of a pandemic where research findings are being translated into practice even more rapidly. We provide all data and scripts at https://osf.io/renxy/.

10.1101/2020.08.13.249847

Open Science Saves Lives: Lessons from the COVID-19 Pandemic