Publications

@article{10.2147/rmi.s292314,

title = {Artificial Intelligence in Predicting Clinical Outcome in COVID-19 Patients from Clinical, Biochemical and a Qualitative Chest X-Ray Scoring System},

author = {Andrea Esposito and Elena Casiraghi and Francesca Chiaraviglio and Alice Scarabelli and Elvira Stellato and Guido Plensich and Giulia Lastella and Letizia Di Meglio and Stefano Fusco and Emanuele Avola and Alessandro Jachetti and Caterina Giannitto and Dario Malchiodi and Marco Frasca and Afshin Beheshti and Peter N Robinson and Giorgio Valentini and Laura Forzenigo and Gianpaolo Carrafiello},

doi = {10.2147/rmi.s292314},

year  = {2021},

date = {2021-01-01},

journal = {Reports in Medical Imaging},

volume = {Volume 14},

pages = {27--39},

keywords = {Publications from COV-IRT},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/2021.07.02.450920,

title = {Betacoronavirus-specific alternate splicing},

author = {Guy Karlebach and Bruce Aronow and Stephen B Baylin and Daniel Butler and Jonathan Foox and Shawn Levy and Cem Meydan and Christopher Mozsary and Amanda M Saravia-Butler and Deanne M Taylor and Eve Wurtele and Christopher E Mason and Afshin Beheshti and Peter N Robinson},

doi = {10.1101/2021.07.02.450920},

year  = {2021},

date = {2021-01-01},

journal = {bioRxiv},

pages = {2021.07.02.450920},

abstract = {Viruses can subvert a number of cellular processes in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection as well as datasets from the betacoronaviruses SARS-CoV and MERS as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification and a smaller number of exons than differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by DAS and DGE in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS, potentially modifying a broad range of cellular functions and affecting a diverse set of genes and biological functions.},

keywords = {Publications from COV-IRT},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/gr.268961.120,

title = {Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission},

author = {Nicolae Sapoval and Medhat Mahmoud and Michael Jochum and Yunxi Liu and Leo R A Elworth and Qi Wang and Dreycey Albin and Huw Ogilvie and Michael D Lee and Sonia Villapol and Kyle Hernandez and Irina Maljkovic Berry and Jonathan Foox and Afshin Beheshti and Krista Ternus and Kjersti Aagaard and David Posada and Christopher Mason and Fritz J Sedlazeck and Todd J Treangen},

doi = {10.1101/gr.268961.120},

issn = {1088-9051},

year  = {2021},

date = {2021-01-01},

journal = {Genome Research},

volume = {31},

number = {4},

pages = {gr.268961.120},

abstract = {The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq datasets and 6,928 consensus genomes to contrast the intrahost and interhost diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with differences in C>U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.},

keywords = {Publications from COV-IRT},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/2021.03.08.434433,

title = {Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps},

author = {Jiwoon Park and Jonathan Foox and Tyler Hether and David Danko and Sarah Warren and Youngmi Kim and Jason Reeves and Daniel J Butler and Christopher Mozsary and Joel Rosiene and Alon Shaiber and Ebrahim Afshinnekoo and Matthew MacKay and Yaron Bram and Vasuretha Chandar and Heather Geiger and Arryn Craney and Priya Velu and Ari M Melnick and Iman Hajirasouliha and Afshin Beheshti and Deanne Taylor and Amanda Saravia-Butler and Urminder Singh and Eve Syrkin Wurtele and Jonathan Schisler and Samantha Fennessey and André Corvelo and Michael C Zody and Soren Germer and Steven Salvatore and Shawn Levy and Shixiu Wu and Nicholas Tatonetti and Sagi Shapira and Mirella Salvatore and Massimo Loda and Lars F Westblade and Melissa Cushing and Hanna Rennert and Alison J Kriegel and Olivier Elemento and Marcin Imielinski and Alain C Borczuk and Cem Meydan and Robert E Schwartz and Christopher E Mason},

doi = {10.1101/2021.03.08.434433},

year  = {2021},

date = {2021-01-01},

journal = {bioRxiv},

pages = {2021.03.08.434433},

abstract = {The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.},

keywords = {Publications from COV-IRT},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/2021.04.23.441024,

title = {The Great Deceiver: miR-2392’s Hidden Role in Driving SARS-CoV-2 Infection},

author = {Tyson J McDonald and Francisco Javier Enguita and Deanne Taylor and Robert J Griffin and Waldemar Priebe and Mark R Emmett and Marisa McGrath and Mohammad M Sajadi and Anthony D Harris and Jean Clement and Joseph M Dybas and Nukhet Aykin-Burns and Joseph W Guarnieri and Larry N Singh and Peter Grabham and Stephen B Baylin and Aliza Yousey and Andrea N Pearson and Peter M Corry and Amanda Saravia-Butler and Thomas R Aunins and Prashant Nagpal and Cem Meydan and Jonathan Foox and Christopher Mozsary and Bianca Cerqueira and Viktorija Zaksas and Urminder Singh and Eve Syrkin Wurtele and Sylvain V Costes and Diego Galeano and Alberto Paccanaro and Suzanne L Meinig and Robert S Hagan and Natalie M Bowman and UNC COVID-19 Pathobiology Consortium and Matthew C Wolfgang and Selin Altinok and Nicolae Sapoval and Todd J Treangen and Matthew Frieman and Charles Vanderburg and Douglas C Wallace and Jonathan Schisler and Christopher E Mason and Anushree Chatterjee and Robert Meller and Afshin Beheshti},

doi = {10.1101/2021.04.23.441024},

year  = {2021},

date = {2021-01-01},

journal = {bioRxiv},

pages = {2021.04.23.441024},

abstract = {MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we found that miR-2392 was key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 patients tested, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using both in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic targeting miR-2392 that significantly reduces SARS-CoV-2 viability and may potentially inhibit a COVID-19 disease state in the host.},

keywords = {Publications from COV-IRT},

pubstate = {published},

tppubtype = {article}

}

@article{10.1007/s11302-021-09771-0,

title = {Cystic fibrosis improves COVID-19 survival and provides clues for treatment of SARS-CoV-2},

author = {Edward H Abraham and Guido Guidotti and Eliezer Rapaport and David Bower and Jack Brown and Robert J Griffin and Andrew Donnelly and Ellen D Waitzkin and Kenon Qamar and Mark A Thompson and Sukumar Ethirajan and Kent Robinson},

doi = {10.1007/s11302-021-09771-0},

issn = {1573-9538},

year  = {2021},

date = {2021-01-01},

journal = {Purinergic Signalling},

pages = {1--12},

abstract = {Systemic pools of ATP are elevated in individuals homozygous for cystic fibrosis (CF) as evidenced by elevated blood and plasma ATP levels. This elevated ATP level seems to provide benefit in the presence of advanced solid tumors (Abraham et al., Nature Medicine 2(5):593–596, 1996). We published in this journal a paper showing that IV ATP can elevate the depleted ATP pools of advanced cancer patients up to levels found in CF patients with subsequent clinical, biochemical, and quality of life (QOL) improvements (Rapaport et al., Purinergic Signalling 11(2): 251–262, 2015). We hypothesize that the elevated ATP levels seen in CF patients may be benefiting CF patients in another way: by improving their survival after contracting COVID-19. We discuss here the reasoning behind this hypothesis and suggest how these findings might be applied clinically in the general population.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1016/j.cell.2021.03.061,

title = {Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States},

author = {Tara Alpert and Anderson F Brito and Erica Lasek-Nesselquist and Jessica Rothman and Andrew L Valesano and Matthew J MacKay and Mary E Petrone and Mallery I Breban and Anne E Watkins and Chantal B F Vogels and Chaney C Kalinich and Simon Dellicour and Alexis Russell and John P Kelly and Matthew Shudt and Jonathan Plitnick and Erasmus Schneider and William J Fitzsimmons and Gaurav Khullar and Jessica Metti and Joel T Dudley and Megan Nash and Nike Beaubier and Jianhui Wang and Chen Liu and Pei Hui and Anthony Muyombwe and Randy Downing and Jafar Razeq and Stephen M Bart and Ardath Grills and Stephanie M Morrison and Steven Murphy and Caleb Neal and Eva Laszlo and Hanna Rennert and Melissa Cushing and Lars Westblade and Priya Velu and Arryn Craney and Lin Cong and David R Peaper and Marie L Landry and Peter W Cook and Joseph R Fauver and Christopher E Mason and Adam S Lauring and Kirsten St. George and Duncan R MacCannell and Nathan D Grubaugh},

doi = {10.1016/j.cell.2021.03.061},

issn = {0092-8674},

year  = {2021},

date = {2021-01-01},

journal = {Cell},

volume = {184},

number = {10},

pages = {2595--2604.e13},

abstract = {The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/2021.05.17.21257341,

title = {Epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa},

author = {Olayinka Sunday Okoh and Nicholas Israel Nii-Trebi and Abdulrokeeb Jakkari and Tosin Titus Olaniran and Tosin Yetunde Senbadejo and Anna Aba Kafintu-kwashie and Emmanuel Oluwatobi Dairo and Tajudeen Oladunni Ganiyu and Ifiokakaninyene Ekpo Akaninyene and Louis Odinakaose Ezediuno and Idowu Jesulayomi Adeosun and Michael Asebake Ockiya and Esther Moradeyo Jimah and David J Spiro and Elijah Kolawole Oladipo and Nídia S Trovão},

doi = {10.1101/2021.05.17.21257341},

year  = {2021},

date = {2021-01-01},

journal = {medRxiv},

pages = {2021.05.17.21257341},

abstract = {COVID-19 disease dynamics have been widely studied in different settings around the globe, but little is known about these patterns in the African continent. To investigate the epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa, more than 2400 complete genomes from 33 African countries were retrieved from the GISAID database and analyzed. We investigated their diversity using various clade and lineage nomenclature systems, reconstructed their evolutionary divergence and history using maximum likelihood inference methods, and studied the case and death trends in the continent. We also examined potential repeat patterns and motifs across the sequences. In this study, we show that after almost one year of the COVID-19 pandemic, only 143 out of the 782 Pango lineages found worldwide circulated in Africa, with five different lineages dominating in distinct periods of the pandemic. Analysis of the number of reported deaths in Africa also revealed large heterogeneity across the continent. Phylogenetic analysis revealed that African viruses cluster closely with those from all continents but more notably with viruses from Europe. However, the extent of viral diversity observed among African genomes is closest to that of the Oceania outbreak, most likely due to genomic under-surveillance in Africa. We also identified two motifs that could function as integrin-binding sites and N-glycosylation domains. These results shed light on the evolutionary dynamics of the circulating viral strains in Africa, elucidate the functions of protein motifs present in the genome sequences, and emphasize the need to expand genomic surveillance efforts in the continent to better understand the molecular, evolutionary, epidemiological, and spatiotemporal dynamics of the COVID-19 pandemic in Africa.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1177/2150135120975771,

title = {Fulminant Enteroviral Myocarditis in a Newborn Accompanying Maternal SARS-CoV-2 Infection},

author = {Tyler A Fick and Shaine A Morris and Sebastian C Tume and Tiffany D Stafford and Kjersti Aagaard and Deborah Schady and Silvana Molossi},

doi = {10.1177/2150135120975771},

issn = {2150-1351},

year  = {2021},

date = {2021-01-01},

journal = {World Journal for Pediatric and Congenital Heart Surgery},

pages = {215013512097577},

abstract = {We present a case of fulminant myocarditis in a preterm neonate born to a SARS-CoV-2-infected mother with COVID-19 disease. Despite complete separation after birth, cardiogenic decompensation initiated on day of life 7. Although the neonate tested negative for SARS-CoV-2, enterovirus viremia accompanied cardiac dysfunction, multiorgan failure, and neonatal death within 36 hours.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1172/jci.insight.144350,

title = {Genomic diversity of SARS-CoV-2 during early introduction into the Baltimore–Washington metropolitan area},

author = {Peter M Thielen and Shirlee Wohl and Thomas Mehoke and Srividya Ramakrishnan and Melanie Kirsche and Oluwaseun Falade-Nwulia and Nídia S Trovão and Amanda Ernlund and Craig Howser and Norah Sadowski and Paul C Morris and Mark Hopkins and Matthew Schwartz and Yunfan Fan and Victoria Gniazdowski and Justin Lessler and Lauren Sauer and Michael C Schatz and Jared D Evans and Stuart C Ray and Winston Timp and Heba H Mostafa},

doi = {10.1172/jci.insight.144350},

year  = {2021},

date = {2021-01-01},

journal = {JCI Insight},

volume = {6},

number = {6},

pages = {e144350},

abstract = {The early COVID-19 pandemic was characterized by rapid global spread. In Maryland and Washington, DC, United States, more than 2500 cases were reported within 3 weeks of the first COVID-19 detection in March 2020. We aimed to use genomic sequencing to understand the initial spread of SARS-CoV-2 — the virus that causes COVID-19 — in the region. We analyzed 620 samples collected from the Johns Hopkins Health System during March 11–31, 2020, comprising 28.6% of the total cases in Maryland and Washington, DC. From these samples, we generated 114 complete viral genomes. Analysis of these genomes alongside a subsampling of over 1000 previously published sequences showed that the diversity in this region rivaled global SARS-CoV-2 genetic diversity at that time and that the sequences belong to all of the major globally circulating lineages, suggesting multiple introductions into the region. We also analyzed these regional SARS-CoV-2 genomes alongside detailed clinical metadata and found that clinically severe cases had viral genomes belonging to all major viral lineages. We conclude that efforts to control local spread of the virus were likely confounded by the number of introductions into the region early in the epidemic and the interconnectedness of the region as a whole.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/2021.01.28.21250486,

title = {PCR assay to enhance global surveillance for SARS-CoV-2 variants of concern},

author = {Chantal B F Vogels and Mallery I Breban and Tara Alpert and Mary E Petrone and Anne E Watkins and Isabel M Ott and Jaqueline Goes de Jesus and Ingra Morales Claro and Giulia Magalhães Ferreira and Myuki A E Crispim and Brazil-UK CADDE Genomic Network and Lavanya Singh and Houriiyah Tegally and Ugochukwu J Anyaneji and NGS-SA and Emma B Hodcroft and Christopher E Mason and Gaurav Khullar and Jessica Metti and Joel T Dudley and Matthew J MacKay and Megan Nash and Jianhui Wang and Chen Liu and Pei Hui and Steven Murphy and Caleb Neal and Eva Laszlo and Marie L Landry and Anthony Muyombwe and Randy Downing and Jafar Razeq and Tulio de Oliveira and Nuno R Faria and Ester C Sabino and Richard A Neher and Joseph R Fauver and Nathan D Grubaugh},

doi = {10.1101/2021.01.28.21250486},

year  = {2021},

date = {2021-01-01},

journal = {medRxiv},

pages = {2021.01.28.21250486},

abstract = {With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses1–3, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike Δ69-70, such as B.1.351 (also 501Y.V2) detected in South Africa6 and P.1 (also 501Y.V3) recently detected in Brazil7. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern8. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1038/s41467-021-21361-7,

title = {Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions},

author = {Daniel Butler and Christopher Mozsary and Cem Meydan and Jonathan Foox and Joel Rosiene and Alon Shaiber and David Danko and Ebrahim Afshinnekoo and Matthew MacKay and Fritz J Sedlazeck and Nikolay A Ivanov and Maria Sierra and Diana Pohle and Michael Zietz and Undina Gisladottir and Vijendra Ramlall and Evan T Sholle and Edward J Schenck and Craig D Westover and Ciaran Hassan and Krista Ryon and Benjamin Young and Chandrima Bhattacharya and Dianna L Ng and Andrea C Granados and Yale A Santos and Venice Servellita and Scot Federman and Phyllis Ruggiero and Arkarachai Fungtammasan and Chen-Shan Chin and Nathaniel M Pearson and Bradley W Langhorst and Nathan A Tanner and Youngmi Kim and Jason W Reeves and Tyler D Hether and Sarah E Warren and Michael Bailey and Justyna Gawrys and Dmitry Meleshko and Dong Xu and Mara Couto-Rodriguez and Dorottya Nagy-Szakal and Joseph Barrows and Heather Wells and Niamh B O’Hara and Jeffrey A Rosenfeld and Ying Chen and Peter A D Steel and Amos J Shemesh and Jenny Xiang and Jean Thierry-Mieg and Danielle Thierry-Mieg and Angelika Iftner and Daniela Bezdan and Elizabeth Sanchez and Thomas R Campion and John Sipley and Lin Cong and Arryn Craney and Priya Velu and Ari M Melnick and Sagi Shapira and Iman Hajirasouliha and Alain Borczuk and Thomas Iftner and Mirella Salvatore and Massimo Loda and Lars F Westblade and Melissa Cushing and Shixiu Wu and Shawn Levy and Charles Chiu and Robert E Schwartz and Nicholas Tatonetti and Hanna Rennert and Marcin Imielinski and Christopher E Mason},

doi = {10.1038/s41467-021-21361-7},

year  = {2021},

date = {2021-01-01},

journal = {Nature Communications},

volume = {12},

number = {1},

pages = {1660},

abstract = {In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin–angiotensin–aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies. Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1038/s41586-021-03475-6,

title = {The spatial landscape of lung pathology during COVID-19 progression},

author = {André F Rendeiro and Hiranmayi Ravichandran and Yaron Bram and Vasuretha Chandar and Junbum Kim and Cem Meydan and Jiwoon Park and Jonathan Foox and Tyler Hether and Sarah Warren and Youngmi Kim and Jason Reeves and Steven Salvatore and Christopher E Mason and Eric C Swanson and Alain C Borczuk and Olivier Elemento and Robert E Schwartz},

doi = {10.1038/s41586-021-03475-6},

issn = {0028-0836},

year  = {2021},

date = {2021-01-01},

journal = {Nature},

volume = {593},

number = {7860},

pages = {564--569},

abstract = {Recent studies have provided insights into the pathology of and immune response to COVID-191–8. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Here we use high-parameter imaging mass cytometry9 that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution. These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyperinflammatory cell state that is associated with lung damage. We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses—possibly as a result of attempts to repair the damaged lung tissue. Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general. Imaging mass cytometry of the human lung reveals the cellular composition and spatial architecture during COVID-19 and other acute injuries, enabling the characterization of lung pathophysiology from structural, immunological and clinical perspectives.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1101/2020.08.29.20184176,

title = {Estimating Unreported Deaths from Natural Causes during COVID-19},

author = {Benjamin Stear and Kyle M Hernandez and Vidya Manian and Deanne Taylor and Catharine A Conley},

doi = {10.1101/2020.08.29.20184176},

year  = {2020},

date = {2020-01-01},

journal = {medRxiv},

pages = {2020.08.29.20184176},

abstract = {Efforts to mitigate the spread of coronavirus disease 2019 (COVID-19) in the United States require an accurate understanding of how the epidemic is progressing. The National Center for Health Statistics (NCHS) releases weekly numbers of deaths attributed to a set of ‘select causes’, including deaths from COVID-19 in the entire United States (US), by state, and cumulatively for individual counties. Comparing US and state level deaths from select causes recorded in 2020 with values from 2014-2019 identifies a number of differences that exceeded 95% confidence limits on historical mean values, including three states with deaths possibly from COVID-19 in December 2019. Comparing county-level NCHS datasets with county-level data on deaths from COVID-19 compiled by four public pandemic tracking sites suggests that a large number of COVID-19 deaths have not yet been reported to the NCHS. Dividing the numbers of COVID-19 deaths counted by the public tracking sites by the percentage of COVID-19 deaths reported to the NCHS suggests that approximately 20% of all US deaths from Natural Causes, as many as 200,000, may not yet have been reported to the NCHS. Evaluating changes in the fractions of deaths attributed to COVID-19 and other specific causes or nonspecific outcomes during the epidemic, relative to 2020 totals or historical mean values, can provide a valuable perspective on the public health consequences of COVID-19. Estimating total deaths from natural causes using the percentage of natural cause deaths from COVID-19 reported to the CDC and the number of COVID-19 deaths counted by public tracking sites suggests that up to 200,000 deaths from natural causes between 22 April and 15 August, 2020, around 20% of the total recorded as of 26 August, have not yet been reported to the CDC.},

keywords = {Publications from COV-IRT},

pubstate = {published},

tppubtype = {article}

}

@article{10.7759/cureus.7343,

title = {Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19)},

author = {Solaimanzadeh I},

doi = {10.7759/cureus.7343},

issn = {2168-8184},

year  = {2020},

date = {2020-01-01},

journal = {Cureus},

volume = {12},

number = {3},

pages = {e7343},

abstract = {Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed. While anti-viral approaches and vaccines are being considered immediate countermeasures are unavailable. The aim of this article is to outline a perspective on the pathophysiology of COVID-19 in the context of the currently available clinical data published in the literature. This article appreciates clinical data published on COVID-19 in the context of another respiratory illness - high altitude pulmonary edema (HAPE). Both conditions have significant similarities that portend pathophysiologic trajectories. Following this potential treatment options emerge. Both COVID-19 and HAPE exhibit a decreased ratio of arterial oxygen partial pressure to fractional inspired oxygen with concomitant hypoxia and tachypnea. There also appears to be a tendency for low carbon dioxide levels in both as well. Radiologic findings of ground glass opacities are present in up to 86% of patients with COVID-19 in addition to patchy infiltrates. Patients with HAPE also exhibit patchy infiltrates throughout the pulmonary fields, often in an asymmetric pattern and CT findings reveal increased lung markings and ground glass-like changes as well. Widespread ground-glass opacities are most commonly a manifestation of hydrostatic pulmonary edema. Similarly, elevated fibrinogen levels in both conditions are likely an epiphenomenon of edema formation rather than coagulation activation. Autopsy results of a COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS). HAPE itself is initially caused by an increase in pulmonary capillary pressure and induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema. It appears that COVID-19 and HAPE both discretely converge on ARDS. In light of this, a countermeasure that has been shown to be effective in the analogous condition of HAPE is Acetazolamide. Acetazolamide has a myriad of effects on different organ systems, potently reduces hypoxic pulmonary vasoconstriction, improves minute ventilation and expired vital capacity. Other therapeutics to consider that are also directed towards decreased pulmonary pressure include Nifedipine and Phosphodiesterase inhibitors. This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are present in both conditions are highlighted. The utilization of medications found to be effective in HAPE, for the treatment of COVID-19, is proposed. Given the medical emergency of a growing contagion and the thousands of lives at stake, expedient attempts to improve survival are needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may be potential countermeasures.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1152/ajpcell.00224.2020,

title = {Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis},

author = {Keshav K Singh and Gyaneshwer Chaubey and Jake Y Chen and Prashanth Suravajhala},

doi = {10.1152/ajpcell.00224.2020},

issn = {0363-6143},

year  = {2020},

date = {2020-01-01},

journal = {American Journal of Physiology-Cell Physiology},

volume = {319},

number = {2},

pages = {C258--C267},

abstract = {Because of the ongoing pandemic around the world, the mechanisms underlying the SARS-CoV-2-induced COVID-19 are subject to intense investigation. Based on available data for the SARS-CoV-1 virus, we suggest how CoV-2 localization of RNA transcripts in mitochondria hijacks the host cell’s mitochondrial function to viral advantage. Besides viral RNA transcripts, RNA also localizes to mitochondria. SARS-CoV-2 may manipulate mitochondrial function indirectly, first by ACE2 regulation of mitochondrial function, and once it enters the host cell, open-reading frames (ORFs) such as ORF-9b can directly manipulate mitochondrial function to evade host cell immunity and facilitate virus replication and COVID-19 disease. Manipulations of host mitochondria by viral ORFs can release mitochondrial DNA (mtDNA) in the cytoplasm and activate mtDNA-induced inflammasome and suppress innate and adaptive immunity. We argue that a decline in ACE2 function in aged individuals, coupled with the age-associated decline in mitochondrial functions resulting in chronic metabolic disorders like diabetes or cancer, may make the host more vulnerable to infection and health complications to mortality. These observations suggest that distinct localization of viral RNA and proteins in mitochondria must play essential roles in SARS-CoV-2 pathogenesis. Understanding the mechanisms underlying virus communication with host mitochondria may provide critical insights into COVID-19 pathologies. An investigation into the SARS-CoV-2 hijacking of mitochondria should lead to novel approaches to prevent and treat COVID-19.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1016/j.cmet.2020.07.015,

title = {Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis},

author = {Ana Campos Codo and Gustavo Gastão Davanzo and Lauar Brito de Monteiro and Gabriela Fabiano de Souza and Stéfanie Primon Muraro and João Victor Virgilio-da-Silva and Juliana Silveira Prodonoff and Victor Corasolla Carregari and Carlos Alberto Oliveira Biagi de Junior and Fernanda Crunfli and Jeffersson Leandro Jimenez Restrepo and Pedro Henrique Vendramini and Guilherme Reis-de-Oliveira and Karina Bispo dos Santos and Daniel A Toledo-Teixeira and Pierina Lorencini Parise and Matheus Cavalheiro Martini and Rafael Elias Marques and Helison R Carmo and Alexandre Borin and Laís Durço Coimbra and Vinícius O Boldrini and Natalia S Brunetti and Andre S Vieira and Eli Mansour and Raisa G Ulaf and Ana F Bernardes and Thyago A Nunes and Luciana C Ribeiro and Andre C Palma and Marcus V Agrela and Maria Luiza Moretti and Andrei C Sposito and Fabrício Bíscaro Pereira and Licio Augusto Velloso and Marco Aurélio Ramirez Vinolo and André Damasio and José Luiz Proença-Módena and Robson Francisco Carvalho and Marcelo A Mori and Daniel Martins-de-Souza and Helder I Nakaya and Alessandro S Farias and Pedro M Moraes-Vieira},

doi = {10.1016/j.cmet.2020.07.015},

issn = {1550-4131},

year  = {2020},

date = {2020-01-01},

journal = {Cell Metabolism},

volume = {32},

number = {3},

pages = {498--499},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.7759/cureus.10230,

title = {Heterogeneous Perfusion in COVID-19 and High Altitude Pulmonary Edema: A Review of Two Cases Followed by Implications for Hypoxic Pulmonary Vasoconstriction, Thrombosis Development, Ventilation Perfusion Mismatch and Emergence of Treatment Approaches},

author = {Solaimanzadeh I},

doi = {10.7759/cureus.10230},

issn = {2168-8184},

year  = {2020},

date = {2020-01-01},

journal = {Cureus},

volume = {12},

number = {9},

pages = {e10230},

abstract = {Coronavirus disease 2019 (COVID-19) has been compared to high altitude pulmonary edema (HAPE). Multiple similarities between the two conditions were drawn in the past. This article seeks to further clarify potential underlying mechanisms related to hypoxia and pulmonary vascular responses. It does so by looking at perfusion imaging of patients with COVID-19 and comparing them with patterns observed in HAPE and hypoxic exposure. Two separate clinical cases are reviewed. The salient aspect of each case that is emphasized is the perfusion scintigraphy results that revealed heterogeneous perfusion patterns in both patients. Heterogeneous or non-homogeneous perfusion is also observed in HAPE. A detailed clinical course of each patient is described. Medications utilized to treat the conditions are outlined as well as laboratory parameters and clinical findings. Interestingly, both of these patients were treated with calcium channel blockers and this class of medications is utilized to prevent HAPE as well. Discussion following the case presentations attempts to contextualize possible implications of this and other studies on the broader pathophysiology of COVID-19 disease. Findings related to pathophysiologic patterns and treatment strategies are also described. Micro-thrombi formation has been reported in both COVID-19 and HAPE as well and may be an accessory complication of perfusion compromise. In a separate study, vasodilatation with calcium channel blocker (CCB) therapy has been associated with improved mortality in COVID-19 and potential pathophysiologic mechanisms were previously presented. This case report provides further clinical findings that support the notion that perfusion deficits are an integral component of hypoxia in COVID-19. It also advances the basis for use of vasodilator therapy as part of treatment regimens in COVID-19. Vasodilators may improve micro-perfusion. In this way, oxygenation may be promoted by decreasing impedance and improving flow via the alveolar-capillary unit.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1016/j.ajog.2020.04.030,

title = {Maternal death due to COVID-19},

author = {Sedigheh Hantoushzadeh and Alireza A Shamshirsaz and Ashraf Aleyasin and Maxim D Seferovic and Soudabeh Kazemi Aski and Sara E Arian and Parichehr Pooransari and Fahimeh Ghotbizadeh and Soroush Aalipour and Zahra Soleimani and Mahsa Naemi and Behnaz Molaei and Roghaye Ahangari and Mohammadreza Salehi and Atousa Dabiri Oskoei and Parisa Pirozan and Roya Faraji Darkhaneh and Mahboobeh Gharib Laki and Ali Karimi Farani and Shahla Atrak and Mir Mohammad Miri and Mehran Kouchek and Seyedpouzhia Shojaei and Fahimeh Hadavand and Fatemeh Keikha and Maryam Sadat Hosseini and Sedigheh Borna and Shideh Ariana and Mamak Shariat and Alireza Fatemi and Behnaz Nouri and Seyed Mojtaba Nekooghadam and Kjersti Aagaard},

doi = {10.1016/j.ajog.2020.04.030},

issn = {0002-9378},

year  = {2020},

date = {2020-01-01},

journal = {American Journal of Obstetrics and Gynecology},

volume = {223},

number = {1},

pages = {109.e1--109.e16},

abstract = {Background Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. Objective To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. Study Design We describe here a multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. Results Among 9 pregnant women with severe COVID-19 disease, at the time of reporting, 7 of 9 died, 1 of 9 remains critically ill and ventilator dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). Conclusion We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1016/j.mito.2020.06.008,

title = {Mitochondria and microbiota dysfunction in COVID-19 pathogenesis},

author = {Jumana Saleh and Carole Peyssonnaux and Keshav K Singh and Marvin Edeas},

doi = {10.1016/j.mito.2020.06.008},

issn = {1567-7249},

year  = {2020},

date = {2020-01-01},

journal = {Mitochondrion},

volume = {54},

pages = {1--7},

abstract = {The COVID-19 pandemic caused by the coronavirus (SARS-CoV-2) has taken the world by surprise into a major crisis of overwhelming morbidity and mortality. This highly infectious disease is associated with respiratory failure unusual in other coronavirus infections. Mounting evidence link the accelerated progression of the disease in COVID-19 patients to the hyper-inflammatory state termed as the “cytokine storm” involving major systemic perturbations. These include iron dysregulation manifested as hyperferritinemia associated with disease severity. Iron dysregulation induces reactive oxygen species (ROS) production and promotes oxidative stress. The mitochondria are the hub of cellular oxidative homeostasis. In addition, the mitochondria may circulate “cell-free” in non-nucleated platelets, in extracellular vesicles and mitochondrial DNA is found in the extracellular space. The heightened inflammatory/oxidative state may lead to mitochondrial dysfunction leading to platelet damage and apoptosis. The interaction of dysfunctional platelets with coagulation cascades aggravates clotting events and thrombus formation. Furthermore, mitochondrial oxidative stress may contribute to microbiota dysbiosis, altering coagulation pathways and fueling the inflammatory/oxidative response leading to the vicious cycle of events. Here, we discuss various cellular and systemic incidents caused by SARS-CoV-2 that may critically impact intra and extracellular mitochondrial function, and contribute to the progression and severity of the disease. It is crucial to understand how these key modulators impact COVID-19 pathogenesis in the quest to identify novel therapeutic targets that may reduce fatal outcomes of the disease.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.7759/cureus.8069,

title = {Nifedipine and Amlodipine Are Associated With Improved Mortality and Decreased Risk for Intubation and Mechanical Ventilation in Elderly Patients Hospitalized for COVID-19},

author = {Isaac Solaimanzadeh and Solaimanzadeh I},

doi = {10.7759/cureus.8069},

issn = {2168-8184},

year  = {2020},

date = {2020-01-01},

journal = {Cureus Journal of Medical Science},

volume = {12},

number = {5},

pages = {e8069},

abstract = {Dihydropyridine calcium channel blockers (CCB) are typically used agents in the clinical management of hypertension. Yet, they have also been utilized in the treatment of various pulmonary disorders with vasoconstriction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been implicated in the development of vasoconstrictive, proinflammatory, and pro-oxidative effects. A retrospective review was conducted on CCB use in hospitalized patients in search of any difference in outcomes related to specific endpoints: survival to discharge and progression of disease leading to intubation and mechanical ventilation. The electronic medical records for all patients that tested positive for SARS-CoV-2 that were at or above the age of 65 and that expired or survived to discharge from a community hospital in Brooklyn, NY, between the start of the public health crisis due to the viral disease up until April 13, 2020, were included. Of the 77 patients that were identified, 18 survived until discharge and 59 expired. Seven patients from the expired group were excluded since they died within one day of presentation to the hospital. Five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group (89 years old). With 65 patients left, 24 were found to have been administered either amlodipine or nifedipine (CCB group) and 41 were not (No-CCB group). Patients treated with a CCB were significantly more likely to survive than those not treated with a CCB: 12 (50%) survived and 12 expired in the CCB group vs. six (14.6%) that survived and 35 (85.4%) that expired in the No-CCB treatment group (P<.01; p=0.0036). CCB patients were also significantly less likely to undergo intubation and mechanical ventilation. Only one patient (4.2%) was intubated in the CCB group whereas 16 (39.0%) were intubated in the No-CCB treatment group (P<.01; p=0.0026). Nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with COVID-19. Further clinical studies are warranted. Including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for COVID-19 may be considered.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1080/14767058.2020.1849101,

title = {Perinatal COVID-19 outcomes: evaluating the strength of current evidence},

author = {Rose O Sulentic and Maxim D Seferovic and Kjersti M Aagaard and Gregory C Valentine},

doi = {10.1080/14767058.2020.1849101},

issn = {1476-7058},

year  = {2020},

date = {2020-01-01},

journal = {The Journal of Maternal-Fetal & Neonatal Medicine},

pages = {1--7},

abstract = {Purpose of the Study: Viral respiratory diseases, like those caused by novel strains of influenza and Coronaviridae, have historically disproportionately affected pregnant women and conferred increased risk of adverse perinatal outcomes. Initial reports published from Wuhan, China identified only limited symptoms in pregnant women and no cases of mortality, but more recent reports from other regions of the world have reported contrasting information. The purpose of the study was to evaluate initially published cases of SARS-CoV-2 infection in pregnant women in China and compare them to subsequently published studies from the remainder of the world. Materials and Methods: This review curates 199 maternal published cases of SARS-CoV-2 infection and COVID-19 initially reported in the literature from China and contrasts them to more recent literature reporting clinical findings and outcomes of 729 selected cases from the rest of the world, including the United States. Results: Overall, initial case reports and series from China reported no cases of maternal mortality, which contrasts with subsequent reports from other regions of the world demonstrating significant morbidity and mortality can and does occur in pregnant women infected with SARS-CoV-2. Conclusion: While initial reports suggest limited risks of infection in pregnancy with SARS-CoV-2, subsequent findings have demonstrated pregnant women are at risk for severe morbidity and mortality. Case studies and series that are imperative in the early stages of a pandemic to provide data on a novel pathogen cannot be used to provide generalizable information predicting group risks.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1073/pnas.2007295117,

title = {Sampling bias and incorrect rooting make phylogenetic network tracing of SARS-COV-2 infections unreliable},

author = {Carla Mavian and Sergei Kosakovsky Pond and Simone Marini and Brittany Rife Magalis and Anne-Mieke Vandamme and Simon Dellicour and Samuel V Scarpino and Charlotte Houldcroft and Julian Villabona-Arenas and Taylor K Paisie and Nídia S Trovão and Christina Boucher and Yun Zhang and Richard H Scheuermann and Olivier Gascuel and Tommy Tsan-Yuk Lam and Marc A Suchard and Ana Abecasis and Eduan Wilkinson and Tulio de Oliveira and Ana I Bento and Heiko A Schmidt and Darren Martin and James Hadfield and Nuno Faria and Nathan D Grubaugh and Richard A Neher and Guy Baele and Philippe Lemey and Tanja Stadler and Jan Albert and Keith A Crandall and Thomas Leitner and Alexandros Stamatakis and Mattia Prosperi and Marco Salemi},

doi = {10.1073/pnas.2007295117},

issn = {0027-8424},

year  = {2020},

date = {2020-01-01},

journal = {Proceedings of the National Academy of Sciences},

volume = {117},

number = {23},

pages = {12522--12523},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}

@article{10.1126/science.abd0827,

title = {Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail},

author = {Johanna Hansen and Alina Baum and Kristen E Pascal and Vincenzo Russo and Stephanie Giordano and Elzbieta Wloga and Benjamin O Fulton and Ying Yan and Katrina Koon and Krunal Patel and Kyung Min Chung and Aynur Hermann and Erica Ullman and Jonathan Cruz and Ashique Rafique and Tammy Huang and Jeanette Fairhurst and Christen Libertiny and Marine Malbec and Wen-yi Lee and Richard Welsh and Glen Farr and Seth Pennington and Dipali Deshpande and Jemmie Cheng and Anke Watty and Pascal Bouffard and Robert Babb and Natasha Levenkova and Calvin Chen and Bojie Zhang and Annabel Romero Hernandez and Kei Saotome and Yi Zhou and Matthew Franklin and Sumathi Sivapalasingam and David Chien Lye and Stuart Weston and James Logue and Robert Haupt and Matthew Frieman and Gang Chen and William Olson and Andrew J Murphy and Neil Stahl and George D Yancopoulos and Christos A Kyratsous},

doi = {10.1126/science.abd0827},

issn = {0036-8075},

year  = {2020},

date = {2020-01-01},

journal = {Science},

volume = {369},

number = {6506},

pages = {1010--1014},

abstract = {Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola—one from genetically humanized mice and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which yielded a large collection of fully human antibodies that were characterized for binding, neutralization, and three-dimensional structure. On the basis of these criteria, we selected pairs of highly potent individual antibodies that simultaneously bind the receptor binding domain of the spike protein, thereby providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single-antibody treatment.},

keywords = {Publications by specific COV-IRT members},

pubstate = {published},

tppubtype = {article}

}