Showing papers by "Fred Hutchinson Cancer Research Center published in 2020"
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
7,219 citations
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Icahn School of Medicine at Mount Sinai1, University of Michigan2, Pasteur Institute3, University of California, San Francisco4, European Bioinformatics Institute5, University of California, San Diego6, University of North Carolina at Chapel Hill7, Fred Hutchinson Cancer Research Center8, Gladstone Institutes9, Buck Institute for Research on Aging10
TL;DR: A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
Abstract: A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
3,319 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin2 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
TL;DR: The results suggest that early detection, hand washing, self-isolation, and household quarantine will likely be more effective than travel restrictions at mitigating this pandemic, and 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.
Abstract: 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.
2,949 citations
TL;DR: ‘weighted-nearest neighbor’ analysis is introduced, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Abstract: The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce ‘weighted-nearest neighbor’ analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity. Availability Installation instructions, documentation, tutorials, and CITE-seq datasets are available at http://www.satijalab.org/seurat
2,924 citations
TL;DR: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both.
Abstract: Background Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. Methods We identified patients from nine Seattle-area hospitals w...
2,119 citations
University of KwaZulu-Natal1, University of Massachusetts Medical School2, Ragon Institute of MGH, MIT and Harvard3, Harvard University4, Broad Institute5, Massachusetts Institute of Technology6, Boston Children's Hospital7, Aix-Marseille University8, Centre national de la recherche scientifique9, Vanderbilt University Medical Center10, Brigham and Women's Hospital11, University of California, Berkeley12, University of Washington13, Fred Hutchinson Cancer Research Center14, Seattle Children's15, University of Pittsburgh16, University of Sheffield17, United States Department of Veterans Affairs18, University College London19, Scripps Research Institute20
TL;DR: The 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.
1,911 citations
Francis Crick Institute1, Fox Chase Cancer Center2, Washington University in St. Louis3, Cold Spring Harbor Laboratory4, Salk Institute for Biological Studies5, Howard Hughes Medical Institute6, Cornell University7, Goethe University Frankfurt8, Fred Hutchinson Cancer Research Center9, Massachusetts Institute of Technology10, Harvard University11, University of Manchester12, New York University13, University of Texas Health Science Center at Houston14, University of Pennsylvania15, Stony Brook University16, Hofstra University17, Weizmann Institute of Science18, Oregon Health & Science University19, University of California, San Francisco20, King's College London21, Johns Hopkins University22
TL;DR: This Consensus Statement issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance the understanding of this important cell type in the tumour microenvironment.
Abstract: Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.
1,616 citations
TL;DR: It is found that a substantial number of mutations to the RBD are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses.
1,517 citations
TL;DR: The outcomes of a cohort of patients with cancer and COVID-19 are characterised and potential prognostic factors for mortality and severe illness are identified and race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.
Harvard University1, Memorial Sloan Kettering Cancer Center2, Northwestern University3, University of Nebraska Medical Center4, University of Texas MD Anderson Cancer Center5, Beth Israel Deaconess Medical Center6, University of Alabama at Birmingham7, University of Colorado Denver8, Fred Hutchinson Cancer Research Center9, University of California, San Francisco10, University of Pittsburgh11, Northside Hospital12, Bristol-Myers Squibb13, City of Hope National Medical Center14
TL;DR: Overall safety and activity of liso-cel did not differ by dose level, with a high objective response rate, and a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas.
University of North Carolina at Chapel Hill1, Cleveland Clinic2, University of Washington3, American Society of Clinical Oncology4, BC Cancer Agency5, University of Granada6, Dartmouth–Hitchcock Medical Center7, Penn State Cancer Institute8, Emory University9, University of Rochester10, University College London11, McMaster University12, University of Southern California13, University of California, San Francisco14, Fred Hutchinson Cancer Research Center15, University of Milan16
TL;DR: An Expert Panel convened an Expert Panel to review the evidence and revise previous recommendations as needed to provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.
Abstract: PURPOSETo provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.METHODSPubMed and the Cochrane Library were searched for randomized...
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TL;DR: A large number of head and neck cancers are now related to human papillomavirus infection rather than tobacco and alcohol, and the number of cases is expected to increase in the coming years.
Abstract: Head and Neck Cancer Most head and neck cancers (73% in the United States) are now related to human papillomavirus infection rather than tobacco and alcohol. Primary cancers are largely squamous-ce...
University of Jena1, University of Bologna2, Cornell University3, Wayne State University4, Imperial College London5, University of Liverpool6, Georgia Regents University7, Huntsman Cancer Institute8, Norwegian University of Science and Technology9, University of South Australia10, University of Amsterdam11, University of Texas MD Anderson Cancer Center12, Catholic University of Korea13, University of Chicago14, University of Toronto15, University of Bordeaux16, Masaryk University17, Leipzig University18, University of Naples Federico II19, Fred Hutchinson Cancer Research Center20, Lund University21, University of Turin22, Heidelberg University23, Russian Academy24
TL;DR: An expert panel to critically evaluate and update the evidence to achieve goals to achieve a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR) in chronic myeloid leukemia.
Abstract: The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
TL;DR: The findings question the role of a cytokine storm in COVID-19-induced organ dysfunction and the potential role of anti-cytokine and immune-modulating treatments in patients with the disease.
TL;DR: It is demonstrated that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus and indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
Abstract: SUMMARY The recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
TL;DR: An agent-based model of SARS-CoV-2 transmission shows that testing, contact tracing and household quarantine could keep new COVID-19 waves under control while allowing the reopening of the economy with minimal social-distancing interventions.
Abstract: While severe social-distancing measures have proven effective in slowing the coronavirus disease 2019 (COVID-19) pandemic, second-wave scenarios are likely to emerge as restrictions are lifted. Here we integrate anonymized, geolocalized mobility data with census and demographic data to build a detailed agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in the Boston metropolitan area. We find that a period of strict social distancing followed by a robust level of testing, contact-tracing and household quarantine could keep the disease within the capacity of the healthcare system while enabling the reopening of economic activities. Our results show that a response system based on enhanced testing and contact tracing can have a major role in relaxing social-distancing interventions in the absence of herd immunity against SARS-CoV-2.
Eugene Applebaum College of Pharmacy and Health Sciences1, University of Montana2, Albany College of Pharmacy and Health Sciences3, Wayne State University4, University of California, San Diego5, Fred Hutchinson Cancer Research Center6, University of Michigan7, University of Southern California8, University of Minnesota9, University of Illinois at Urbana–Champaign10, Arkansas Children's Hospital11, Albany Medical College12
TL;DR: The primary recommendations consisted of eliminating routine monitoring of serum peak concentrations, emphasizing a ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC/ MIC) of ≥400 as the primary PK/ PD predictor of vancomycin activity, and promoting serum trough concentrations of 15 to 20 mg/L as a surrogate marker for the optimal vancomYcin AUC/MIC if the MIC was ≤1mg/L in patients with normal renal function.
Abstract: Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.
TL;DR: It is demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.
Abstract: SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.
TL;DR: The findings indicate that strict containment, movement restrictions, and increased awareness of the population have contributed to interrupt transmission of SARS-CoV-2 outside Hubei, and an early peak of infectiousness, with possible transmission before the onset of symptoms is suggested.
Abstract: Summary Background The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. Methods We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. Findings We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, Interpretation Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. Funding National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.
Memorial Sloan Kettering Cancer Center1, University Hospitals of Cleveland2, Washington University in St. Louis3, University of Utah4, Duke University5, University of Wisconsin-Madison6, Harvard University7, Moffitt Cancer Center8, Vanderbilt University9, Stanford University10, Johns Hopkins University11, University of Tennessee Health Science Center12, Mayo Clinic13, Fox Chase Cancer Center14, University of Texas MD Anderson Cancer Center15, Brigham and Women's Hospital16, Roswell Park Cancer Institute17, University of Colorado Boulder18, City of Hope National Medical Center19, University of California, San Diego20, Northwestern University21, Ohio State University22, Fred Hutchinson Cancer Research Center23, University of Pennsylvania24, University of Michigan25, University of California, San Francisco26, National Comprehensive Cancer Network27
TL;DR: The NCCN Guidelines for Head and Neck Cancers as mentioned in this paper describe supportive care recommendations for patients with H&N cancers and the rationale supporting a new section on imaging recommendations for head and neck cancers.
Abstract: Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
Cornell University1, Tokyo Institute of Technology2, Yonsei University3, Linköping University4, Uppsala University5, National Institutes of Health6, Memorial Sloan Kettering Cancer Center7, University of Porto8, Rockefeller University9, École Polytechnique Fédérale de Lausanne10, Carlos III Health Institute11, University of Tokyo12, Ohio State University13, Princeton University14, University of Oviedo15, Icahn School of Medicine at Mount Sinai16, Weizmann Institute of Science17, Lucile Packard Children's Hospital18, New York University19, Champalimaud Foundation20, University of Nebraska Medical Center21, Fred Hutchinson Cancer Research Center22, University of Pennsylvania23, University of California, San Diego24, University of Vermont25, University of Southern California26, City of Hope National Medical Center27, Lawrence Berkeley National Laboratory28
TL;DR: EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type, and a panel of tumor-type-specific EVP proteins in TEs and plasma are defined, which can classify tumors of unknown primary origin.
TL;DR: It is expected that the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2 as the limited circulation of the virus in the western United States.
Abstract: Coronavirus disease 2019 (COVID-19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020 and necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested reverse transcription-PCR (RT-PCR) positive for SARS-CoV-2 for whom 689 excess serum specimens were available and found that sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested specimens from 4,856 individuals from Boise, ID, collected over 1 week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect that the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.
01 Dec 2020
TL;DR: The findings suggest that households are and will continue to be important venues for transmission, even in areas where community transmission is reduced.
Abstract: Importance Crowded indoor environments, such as households, are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives To examine evidence for household transmission of SARS-CoV-2, disaggregated by several covariates, and to compare it with other coronaviruses. Data Source PubMed, searched through October 19, 2020. Search terms includedSARS-CoV-2orCOVID-19withsecondary attack rate,household,close contacts,contact transmission,contact attack rate, orfamily transmission. Study Selection All articles with original data for estimating household secondary attack rate were included. Case reports focusing on individual households and studies of close contacts that did not report secondary attack rates for household members were excluded. Data Extraction and Synthesis Meta-analyses were done using a restricted maximum-likelihood estimator model to yield a point estimate and 95% CI for secondary attack rate for each subgroup analyzed, with a random effect for each study. To make comparisons across exposure types, study was treated as a random effect, and exposure type was a fixed moderator. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Main Outcomes and Measures Secondary attack rate for SARS-CoV-2, disaggregated by covariates (ie, household or family contact, index case symptom status, adult or child contacts, contact sex, relationship to index case, adult or child index cases, index case sex, number of contacts in household) and for other coronaviruses. Results A total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI, 4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95% CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) than in households with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%). Conclusions and Relevance The findings of this study suggest that given that individuals with suspected or confirmed infections are being referred to isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.
TL;DR: The authors identified shared biology and host-directed drug targets to prioritize therapeutics with potential for rapid deployment against current and future coronavirus outbreaks, and found that individuals with genotypes corresponding to higher soluble IL17RA levels in plasma are at decreased risk of COVID-19 hospitalization.
Abstract: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
TL;DR: The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans, as the presence of neutralizing antibodies from prior infection was significantly associated with protection against reinfection.
Abstract: The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have been performed only in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral reverse transcription-PCR (RT-PCR) testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.5 days (range, 18.8 to 50.5 days). A total of 104 individuals had an RT-PCR-positive viral test with a cycle threshold (CT ) of <35 or seroconverted during the follow-up period, yielding an attack rate on board of 85.2% (104/122 individuals). Metagenomic sequencing of 39 viral genomes suggested that the outbreak originated largely from a single viral clade. Only three crew members tested seropositive prior to the boat's departure in initial serological screening and also had neutralizing and spike-reactive antibodies in follow-up assays. None of the crew members with neutralizing antibody titers showed evidence of bona fide viral infection or experienced any symptoms during the viral outbreak. Therefore, the presence of neutralizing antibodies from prior infection was significantly associated with protection against reinfection (Fisher's exact test, P = 0.002).
TL;DR: This Special Feature highlights the unique circumstances and challenges of cancer treatment amidst this global pandemic, and the importance of organizational structure, preparation, agility, and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.
Abstract: The first confirmed case of coronavirus disease 2019 (COVID-19) in the United States was reported on January 20, 2020, in Snohomish County, Washington. At the epicenter of COVID-19 in the United States, the Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, and University of Washington are at the forefront of delivering care to patients with cancer during this public health crisis. This Special Feature highlights the unique circumstances and challenges of cancer treatment amidst this global pandemic, and the importance of organizational structure, preparation, agility, and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.
TL;DR: A new method for the detection of SARS-CoV-2 combines simplified extraction of RNA with isothermal amplification and CRISPR (clustered regularly int…) with a CRISpr-Based Test.
Abstract: Detection of SARS-CoV-2 with a CRISPR-Based Test A new method for the detection of SARS-CoV-2 combines simplified extraction of RNA with isothermal amplification and CRISPR (clustered regularly int...
New York University1, Johns Hopkins University2, University of Washington3, University of North Carolina at Chapel Hill4, Duke University5, Scripps Research Institute6, Hebrew University of Jerusalem7, Ohio State University8, University of California, San Francisco9, Baylor College of Medicine10, École Polytechnique Fédérale de Lausanne11, Vanderbilt University12, Rutgers University13, Swiss Institute of Bioinformatics14, Fred Hutchinson Cancer Research Center15, Rensselaer Polytechnic Institute16, Northeastern University17, Stanford University18, DSM19, Fox Chase Cancer Center20, University of Maryland, College Park21, University of Warsaw22, University of Denver23, Australian National University24, University of Kansas25, University of Zurich26, University of Massachusetts Dartmouth27, University of Tokyo28, Franklin & Marshall College29, Weizmann Institute of Science30, Lund University31, University of California, Santa Cruz32, University of California, Davis33
TL;DR: This Perspective reviews tools developed over the past five years in the Rosetta software, including over 80 methods, and discusses improvements to the score function, user interfaces and usability.
Abstract: The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.