Publications by authors named "Thomas Briese"

143 Publications

Detailed analysis of the pathologic hallmarks of Nipah virus (Malaysia) disease in the African green monkey infected by the intratracheal route.

PLoS One 2022 10;17(2):e0263834. Epub 2022 Feb 10.

Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.

Disease associated with Nipah virus infection causes a devastating and often fatal spectrum of syndromes predominated by both respiratory and neurologic conditions. Additionally, neurologic sequelae may manifest months to years later after virus exposure or apparent recovery. In the two decades since this disease emerged, much work has been completed in an attempt to understand the pathogenesis and facilitate development of medical countermeasures. Here we provide detailed organ system-specific pathologic findings following exposure of four African green monkeys to 2.41×105 pfu of the Malaysian strain of Nipah virus. Our results further substantiate the African green monkey as a model of human Nipah virus disease, by demonstrating both the respiratory and neurologic components of disease. Additionally, we demonstrate that a chronic phase of disease exists in this model, that may provide an important opportunity to study the enigmatic late onset and relapse encephalitis as it is described in human disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263834PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830707PMC
February 2022

Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study.

Diabetes Care 2022 03;45(3):624-633

Department of Pediatrics, University of Florida, Gainesville, FL.

Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA).

Research Design And Methods: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes.

Results: Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Twenty-three children (6.1%) had DKA at onset, only 1 (0.97%) of 103 with and 22 (8.0%) of 276 children without a first-degree relative (FDR) with type 1 diabetes (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001).

Conclusions: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.
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http://dx.doi.org/10.2337/dc21-0422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918232PMC
March 2022

Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case.

Front Immunol 2021 9;12:779026. Epub 2021 Dec 9.

Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States.

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.
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http://dx.doi.org/10.3389/fimmu.2021.779026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695925PMC
January 2022

SARS-CoV-2 Sequence Analysis during COVID-19 Case Surge, Liberia, 2021.

Emerg Infect Dis 2021 12 28;27(12):3185-3188. Epub 2021 Oct 28.

In June 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases surged in Liberia. SARS-CoV-2 sequences from patients hospitalized during March-July 2021 revealed the Delta variant was in Liberia in early March and was dominant in June, irrespective of geography. Mutations and deletions suggest multiple SARS-CoV-2 Delta variant introductions.
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http://dx.doi.org/10.3201/eid2712.211818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632187PMC
December 2021

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Arch Virol 2021 Dec;166(12):3513-3566

RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
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http://dx.doi.org/10.1007/s00705-021-05143-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627462PMC
December 2021

ICTV Virus Taxonomy Profile: .

J Gen Virol 2021 07;102(7)

Institute for Frontier Life and Medical Sciences (inFront), Kyoto University, Kyoto, Japan.

Members of the family produce enveloped virions containing a linear negative-sense non-segmented RNA genome of about 9 kb. Bornaviruses are found in mammals, birds, reptiles and fish. The most-studied viruses with public health and veterinary impact are Borna disease virus 1 and variegated squirrel bornavirus 1, both of which cause fatal encephalitis in humans. Several orthobornaviruses cause neurological and intestinal disorders in birds, mostly parrots. Endogenous bornavirus-like sequences occur in the genomes of various animals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family , which is available at ictv.global/report/bornaviridae.
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http://dx.doi.org/10.1099/jgv.0.001613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491894PMC
July 2021

Development of a capture sequencing assay for enhanced detection and genotyping of tick-borne pathogens.

Sci Rep 2021 06 11;11(1):12384. Epub 2021 Jun 11.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.

Inadequate sensitivity has been the primary limitation for implementing high-throughput sequencing for studies of tick-borne agents. Here we describe the development of TBDCapSeq, a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. We evaluated the performance of TBDCapSeq to surveil samples that included human whole blood, mouse tissues, and field-collected ticks. For Borrelia burgdorferi and Babesia microti, the sensitivity of TBDCapSeq was comparable and occasionally exceeded the performance of agent-specific quantitative PCR and resulted in 25 to > 10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. TBDCapSeq also enabled genome analyses directly within vertebrate and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches.
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http://dx.doi.org/10.1038/s41598-021-91956-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196166PMC
June 2021

Molecular Features of the Measles Virus Viral Fusion Complex That Favor Infection and Spread in the Brain.

mBio 2021 06 1;12(3):e0079921. Epub 2021 Jun 1.

Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.

Measles virus (MeV) bearing a single amino acid change in the fusion protein (F)-L454W-was isolated from two patients who died of MeV central nervous system (CNS) infection. This mutation in F confers an advantage over wild-type virus in the CNS, contributing to disease in these patients. Using murine organotypic brain cultures and human induced pluripotent stem cell-derived brain organoids, we show that CNS adaptive mutations in F enhance the spread of virus . The spread of virus in human brain organoids is blocked by an inhibitory peptide that targets F, confirming that dissemination in the brain tissue is attributable to F. A single mutation in MeV F thus alters the fusion complex to render MeV more neuropathogenic. Measles virus (MeV) infection can cause serious complications in immunocompromised individuals, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE), another severe central nervous system (CNS) complication, develop even in the face of a systemic immune response. Both MIBE and SSPE are relatively rare but lethal. It is unclear how MeV causes CNS infection. We introduced specific mutations that are found in MIBE or SSPE cases into the MeV fusion protein to test the hypothesis that dysregulation of the viral fusion complex-comprising F and the receptor binding protein, H-allows virus to spread in the CNS. Using metagenomic, structural, and biochemical approaches, we demonstrate that altered fusion properties of the MeV H-F fusion complex permit MeV to spread in brain tissue.
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http://dx.doi.org/10.1128/mBio.00799-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263006PMC
June 2021

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19.

J Clin Invest 2021 07;131(13)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83-2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, P = 0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.
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http://dx.doi.org/10.1172/JCI150646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245169PMC
July 2021

Immunoreactive peptide maps of SARS-CoV-2.

Commun Biol 2021 02 12;4(1):225. Epub 2021 Feb 12.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.

Serodiagnosis of SARS-CoV-2 infection is impeded by immunological cross-reactivity among the human coronaviruses (HCoVs): SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, 229E, HKU1, and NL63. Here we report the identification of humoral immune responses to SARS-CoV-2 peptides that may enable discrimination between exposure to SARS-CoV-2 and other HCoVs. We used a high-density peptide microarray and plasma samples collected at two time points from 50 subjects with SARS-CoV-2 infection confirmed by qPCR, samples collected in 2004-2005 from 11 subjects with IgG antibodies to SARS-CoV-1, 11 subjects with IgG antibodies to other seasonal human coronaviruses (HCoV), and 10 healthy human subjects. Through statistical modeling with linear regression and multidimensional scaling we identified specific peptides that were reassembled to identify 29 linear SARS-CoV-2 epitopes that were immunoreactive with plasma from individuals who had asymptomatic, mild or severe SARS-CoV-2 infections. Larger studies will be required to determine whether these peptides may be useful in serodiagnostics.
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http://dx.doi.org/10.1038/s42003-021-01743-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881038PMC
February 2021

Nipah virus dynamics in bats and implications for spillover to humans.

Proc Natl Acad Sci U S A 2020 11 2;117(46):29190-29201. Epub 2020 Nov 2.

EcoHealth Alliance, New York, NY 10018.

Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia-one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir, bats, in Bangladesh. We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than other species (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh. These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughout 's range.
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http://dx.doi.org/10.1073/pnas.2000429117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682340PMC
November 2020

2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Arch Virol 2020 Dec 4;165(12):3023-3072. Epub 2020 Sep 4.

Colorado State University, Fort Collins, CO, USA.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
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http://dx.doi.org/10.1007/s00705-020-04731-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606449PMC
December 2020

Virome Sequencing in Patients With Myocarditis.

Circ Heart Fail 2020 07 26;13(7):e007103. Epub 2020 Jun 26.

Royal Brompton and Harefield Hospitals and Imperial College, London, United Kingdom (T.F.L.).

Background: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood.

Methods: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13).

Results: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K.

Conclusions: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007103DOI Listing
July 2020

Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

Trials 2020 06 8;21(1):499. Epub 2020 Jun 8.

Columbia University Medical Center, New York, USA.

Objectives: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection.

Trial Design: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor.

Participants: Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for ≥ 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA.

Intervention And Comparator: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 - 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 - 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis.

Main Outcomes: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period.

Randomization: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability.

Blinding (masking): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment.

Numbers To Be Randomized (sample Size): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5.

Trial Status: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing.

Trial Registration: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-020-04422-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276974PMC
June 2020

Neurologic manifestations in an infant with COVID-19.

Neurology 2020 06 23;94(24):1100-1102. Epub 2020 Apr 23.

From the Department of Neurology (R.D., K.C.C.-M., K.T.T., D.K.M., J.M.B.), Columbia University Irving Medical Center; Center for Infection and Immunity (J.A.G., L.V.C., S.H.W., T.B., K.J., W.I.L., N.M.), Mailman School of Public Health, Columbia University; Department of Epidemiology (W.I.L., N.M.), Mailman School of Public Health, Columbia University; Department of Pediatric Infectious Disease (M.F.), Columbia University Irving Medical Center; and New York Presbyterian Hospital (R.D., K.C.C.-M., K.T.T., M.F., D.K.M., J.M.B.), Columbia University Medical Center, New York, NY.

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http://dx.doi.org/10.1212/WNL.0000000000009653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455334PMC
June 2020

Higher frequency of vertebrate-infecting viruses in the gut of infants born to mothers with type 1 diabetes.

Pediatr Diabetes 2020 03 7;21(2):271-279. Epub 2020 Jan 7.

School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Background: Microbial exposures in utero and early life shape the infant microbiome, which can profoundly impact on health. Compared to the bacterial microbiome, very little is known about the virome. We set out to characterize longitudinal changes in the gut virome of healthy infants born to mothers with or without type 1 diabetes using comprehensive virome capture sequencing.

Methods: Healthy infants were selected from Environmental Determinants of Islet Autoimmunity (ENDIA), a prospective cohort of Australian children with a first-degree relative with type 1 diabetes, followed from pregnancy. Fecal specimens were collected three-monthly in the first year of life.

Results: Among 25 infants (44% born to mothers with type 1 diabetes) at least one virus was detected in 65% (65/100) of samples and 96% (24/25) of infants during the first year of life. In total, 26 genera of viruses were identified and >150 viruses were differentially abundant between the gut of infants with a mother with type 1 diabetes vs without. Positivity for any virus was associated with maternal type 1 diabetes and older infant age. Enterovirus was associated with older infant age and maternal smoking.

Conclusions: We demonstrate a distinct gut virome profile in infants of mothers with type 1 diabetes, which may influence health outcomes later in life. Higher prevalence and greater number of viruses observed compared to previous studies suggests significant underrepresentation in existing virome datasets, arising most likely from less sensitive techniques used in data acquisition.
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http://dx.doi.org/10.1111/pedi.12952DOI Listing
March 2020

Immune Suppressive Extracellular Vesicle Proteins of Are Encoded in the Wasp Genome.

G3 (Bethesda) 2020 01 7;10(1):1-12. Epub 2020 Jan 7.

Biology Department, The City College of New York, 160 Convent Avenue, New York, 10031,

are obligate parasitoid wasps that develop in the body of their hosts. During oviposition, female wasps introduce venom into the larval hosts' body cavity. The venom contains discrete, 300 nm-wide, mixed-strategy extracellular vesicles (MSEVs), until recently referred to as virus-like particles. While the crucial immune suppressive functions of MSEVs have remained undisputed, their biotic nature and origin still remain controversial. In recent proteomics analyses of MSEVs, we identified 161 proteins in three classes: conserved eukaryotic proteins, infection and immunity related proteins, and proteins without clear annotation. Here we report 246 additional proteins from the MSEV proteome. An enrichment analysis of the entire proteome supports vesicular nature of these structures. Sequences for more than 90% of these proteins are present in the whole-body transcriptome. Sequencing and assembly of the 460 Mb-sized genome revealed 90% of MSEV proteins have coding regions within the genomic scaffolds. Altogether, these results explain the stable association of MSEVs with their wasps, and like other wasp structures, their vertical inheritance. While our results do not rule out a viral origin of MSEVs, they suggest that a similar strategy for co-opting cellular machinery for immune suppression may be shared by other wasps to gain advantage over their hosts. These results are relevant to our understanding of the evolution of figitid and related wasp species.
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http://dx.doi.org/10.1534/g3.119.400349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945029PMC
January 2020

One-step pentaplex real-time polymerase chain reaction assay for detection of zika, dengue, chikungunya, West nile viruses and a human housekeeping gene.

J Clin Virol 2019 11 16;120:44-50. Epub 2019 Sep 16.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.

Background: Recent emergence of Zika virus (ZIKV), and the global spread of dengue (DENV), chikungunya (CHIKV) and West Nile viruses (WNV) raised urgent need of accurate and affordable molecular diagnosis of these clinically indistinguishable arboviral infections.

Objectives: We established a pentaplex real-time reverse transcription PCR (rRT-PCR) assay (CII-ArboViroPlex rRT-PCR) for specific and sensitive detection of the African and American genotypes of ZIKV, all four serotypes of DENV, CHIKV, WNV and a housekeeping gene as internal control in single reaction.

Study Design: Specific primers and probe sets were designed for ZIKV, DENV, CHIKV, WNV and RNase P (housekeeping gene) and tested for in-vitro transcribed RNA standards, virus cultures, clinical samples positive for ZIKV, DENV, CHIKV and WNV and limit of detection (LOD) were determined for each. Results Using ten-fold serially diluted in-vitro transcribed RNA, CII- ArboViroPlex rRT-PCR assay has LOD of 100 RNA copies/reaction (Rn) for ZIKV in serum or urine, 100 RNA copies/Rn for DENV in serum, and 10 RNA copies/Rn for CHIKV and WNV in serum. LODs from sera spiked with quantitated viral stocks were 2.6 × 10 GEQ/Rn for ZIKV, 2.2 × 10 GEQ/Rn for DENV-1, 9.4 × 10 GEQ/Rn for DENV-2, 2.3 × 10 GEQ/Rn for DENV-3, 1.4 × 10 GEQ/Rn for DENV-4, 2.7 × 10 GEQ/Rn for CHIKV, and 1.05 × 10 GEQ/Rn for WNV.

Conclusions: The CII-ArboViroPlex rRT-PCR assay is a quantitative one-step pentaplex rRT-PCR assay for the molecular detection and differential diagnosis of ZIKV, DENV, CHIKV, WNV and a human housekeeping gene control in a single- PCR reaction.
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http://dx.doi.org/10.1016/j.jcv.2019.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032662PMC
November 2019

Discovery of two highly divergent negative-sense RNA viruses associated with the parasitic nematode, , in wild from New York City.

J Gen Virol 2019 10 12;100(10):1350-1362. Epub 2019 Sep 12.

Center for Infection and Immunity, Columbia University, New York, NY, USA.

Recent advances in high-throughput sequencing technology have led to a rapid expansion in the number of viral sequences associated with samples from vertebrates, invertebrates and environmental samples. Accurate host identification can be difficult in assays of complex samples that contain more than one potential host. Using unbiased metagenomic sequencing, we investigated wild house mice () and brown rats () from New York City to determine the aetiology of liver disease. Light microscopy was used to characterize liver disease, and fluorescent microscopy with hybridization was employed to identify viral cell tropism. Sequences representing two novel negative-sense RNA viruses were identified in homogenates of wild house mouse liver tissue: Amsterdam virus and Fulton virus. hybridization localized viral RNA to a parasitic nematode that had infected the mouse liver. RNA from either virus was found within nematode adults and unembryonated eggs. Expanded PCR screening identified brown rats as a second rodent host for as well as both nematode-associated viruses. Our findings indicate that the current diversity of nematode-associated viruses may be underappreciated and that anatomical imaging offers an alternative to computational host assignment approaches.
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http://dx.doi.org/10.1099/jgv.0.001315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363305PMC
October 2019

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

mBio 2019 08 13;10(4). Epub 2019 Aug 13.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) ( = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; = 0.139, 0.002, and 0.009, respectively). The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.
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http://dx.doi.org/10.1128/mBio.01903-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692520PMC
August 2019

Waterpipe smoking as a public health risk: Potential risk for transmission of MERS-CoV.

Saudi J Biol Sci 2019 Jul 3;26(5):938-941. Epub 2018 May 3.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.

The Middle East Respiratory Syndrome (MERS-CoV) emerged in the Kingdom of Saudi Arabia in 2012 causing a critical challenge to public health. The epidemiology of MERS-CoV remain enigmatic as human-to-human transmission is not fully understood. One possible scenario that might play a role in the virus transmission is the cultural waterpipe smoking. Cafés providing waterpipe smoking in cities within Saudi Arabia have been moved to areas outside city limits that frequently place them close to camels markets. We report results of a surveillance study wherein waterpipe hoses throughout several regions in Saudi Arabia were tested for the presence of MERS-CoV. A total of 2489 waterpipe samples were collected from cities where MERS-CoV cases were continuously recorded. MERS-CoV RNA wasn't detected in collected samples. Irrespective of the negative results of our survey, the public health risk of waterpipe smoking should not be underestimated. To avoid a possible transmission within country where MERS-CoV is prevalent, we recommend the replacement of resusable hoses with "one-time-use" hoses in addition to a close inspection of waterpipe components to assure the appropriate cleaning and sanitization.
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http://dx.doi.org/10.1016/j.sjbs.2018.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600605PMC
July 2019

Taxonomy of the order Mononegavirales: update 2019.

Arch Virol 2019 Jul;164(7):1967-1980

Public Health England, Porton Down, Wiltshire, Salisbury, UK.

In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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http://dx.doi.org/10.1007/s00705-019-04247-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641539PMC
July 2019

Taxonomy of the order Bunyavirales: update 2019.

Arch Virol 2019 Jul 7;164(7):1949-1965. Epub 2019 May 7.

United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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http://dx.doi.org/10.1007/s00705-019-04253-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641860PMC
July 2019

A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia.

PLoS One 2019 10;14(4):e0214227. Epub 2019 Apr 10.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, United States of America.

Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214227PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457491PMC
December 2019

A Novel Orthohepadnavirus Identified in a Dead Maxwell's Duiker () in Taï National Park, Côte d'Ivoire.

Viruses 2019 03 19;11(3). Epub 2019 Mar 19.

Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, 13353 Berlin, Germany.

New technologies enable viral discovery in a diversity of hosts, providing insights into viral evolution. We used one such approach, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform, on 21 samples originating from six dead Maxwell's duikers () from Taï National Park, Côte d'Ivoire. We detected the presence of an orthohepadnavirus in one animal and characterized its 3128 bp genome. The highest viral copy numbers were detected in the spleen, followed by the lung, blood, and liver, with the lowest copy numbers in the kidney and heart; the virus was not detected in the jejunum. Viral copy numbers in the blood were in the range known from humans with active chronic infections leading to liver histolytic damage, suggesting this virus could be pathogenic in duikers, though many orthohepadnaviruses appear to be apathogenic in other hosts, precluding a formal test of this hypothesis. The virus was not detected in 29 other dead duiker samples from the Côte d'Ivoire and Central African Republic, suggesting either a spillover event or a low prevalence in these populations. Phylogenetic analysis placed the virus as a divergent member of the mammalian clade of orthohepadnaviruses, though its relationship to other orthohepadnaviruses remains uncertain. This represents the first orthohepadnavirus described in an artiodactyl. We have tentatively named this new member of the genus (family ), Taï Forest hepadnavirus. Further studies are needed to determine whether it, or some close relatives, are present in a broader range of artiodactyls, including livestock.
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http://dx.doi.org/10.3390/v11030279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466360PMC
March 2019
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