2023
Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation
Farhadian S, Reisert H, McAlpine L, Chiarella J, Kosana P, Yoon J, Spudich S. Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation. JAMA Network Open 2023, 6: e2342741. PMID: 37948085, PMCID: PMC10638645, DOI: 10.1001/jamanetworkopen.2023.42741.Peer-Reviewed Original ResearchAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersA unique maternal and placental galectin signature upon SARS-CoV-2 infection suggests galectin-1 as a key alarmin at the maternal–fetal interface
Zhao F, Tallarek A, Wang Y, Xie Y, Diemert A, Lu-Culligan A, Vijayakumar P, Kittmann E, Urbschat C, Bayo J, Arck P, Farhadian S, Dveksler G, Garcia M, Blois S. A unique maternal and placental galectin signature upon SARS-CoV-2 infection suggests galectin-1 as a key alarmin at the maternal–fetal interface. Frontiers In Immunology 2023, 14: 1196395. PMID: 37475853, PMCID: PMC10354452, DOI: 10.3389/fimmu.2023.1196395.Peer-Reviewed Original ResearchMeSH KeywordsAlarminsCOVID-19FemaleGalectin 1GalectinsHumansInfant, NewbornPlacentaPregnancySARS-CoV-2ConceptsSARS-CoV-2 infectionPregnancy-specific glycoprotein 1SARS-CoV-2Maternal-fetal interfacePregnant womenSuccessful pregnancyGal-1Gal-3SARS-CoV-2-infected patientsAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicMaternal immune systemCoronavirus 2 pandemicMaternal immune adaptationRisk of infectionΒ-galactoside-binding proteinKey alarminUninfected womenHealthy pregnancyPregnancy parametersGal-9Inflammatory processVirus infectionImmune responseGalectin signature
2022
Anti-SARS-CoV-2 and Autoantibody Profiling of a COVID-19 Patient With Subacute Psychosis Who Remitted After Treatment With Intravenous Immunoglobulin
McAlpine L, Lifland B, Check J, Angarita G, Ngo T, Chen P, Dandekar R, Alvarenga B, Browne W, Pleasure S, Wilson M, Spudich S, Farhadian S, Bartley C. Anti-SARS-CoV-2 and Autoantibody Profiling of a COVID-19 Patient With Subacute Psychosis Who Remitted After Treatment With Intravenous Immunoglobulin. Biological Psychiatry 2022, 93: e25-e29. PMID: 36481066, PMCID: PMC9722219, DOI: 10.1016/j.biopsych.2022.09.007.Peer-Reviewed Original ResearchMultiscale PHATE identifies multimodal signatures of COVID-19
Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingTransposase-accessible chromatinSingle-cell sequencingRNA sequencingBiological insightsPopulation groupingsSophisticated computational toolsBiological featuresSequencingFlow cytometryComputational toolsChromatinBiomedical communityDifferent data typesCell responsesCellsPhateSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
Diverse functional autoantibodies in patients with COVID-19
Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE, Dela Cruz C, Farhadian S, Schulz W, Ma S, Grubaugh N, Ko A, Iwasaki A, Ring A. Diverse functional autoantibodies in patients with COVID-19. Nature 2021, 595: 283-288. PMID: 34010947, DOI: 10.1038/s41586-021-03631-y.Peer-Reviewed Original ResearchConceptsPeripheral immune cell compositionSARS-CoV-2 infectionCOVID-19Effects of autoantibodiesTissue-associated antigensSpecific clinical characteristicsInnate immune activationImmune cell compositionCOVID-19 exhibitCOVID-19 manifestsAnalysis of autoantibodiesSARS-CoV-2Functional autoantibodiesMouse surrogateClinical characteristicsVirological controlClinical outcomesImmune activationMild diseaseAsymptomatic infectionAutoantibody reactivityDisease progressionHealthcare workersHigh prevalenceAutoantibodiesDelayed production of neutralizing antibodies correlates with fatal COVID-19
Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.Peer-Reviewed Original ResearchConceptsDeceased patientsAntibody levelsAntibody responseDisease severityAnti-S IgG levelsCOVID-19 disease outcomesFatal COVID-19Impaired viral controlWorse clinical progressionWorse disease severitySevere COVID-19Length of hospitalizationImmunoglobulin G levelsHumoral immune responseCoronavirus disease 2019COVID-19 mortalityCOVID-19Domain (RBD) IgGSeroconversion kineticsDisease courseIgG levelsClinical parametersClinical progressionHumoral responseDisease onsetMaternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activation
2020
SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity
Vogels CBF, Watkins AE, Harden CA, Brackney DE, Shafer J, Wang J, Caraballo C, Kalinich CC, Ott IM, Fauver JR, Kudo E, Lu P, Venkataraman A, Tokuyama M, Moore AJ, Muenker MC, Casanovas-Massana A, Fournier J, Bermejo S, Campbell M, Datta R, Nelson A, Team Y, Anastasio K, Askenase M, Batsu M, Bickerton S, Brower K, Bucklin M, Cahill S, Cao Y, Courchaine E, DeIuliis G, Earnest R, Geng B, Goldman-Israelow B, Handoko R, Khoury-Hanold W, Kim D, Knaggs L, Kuang M, Lapidus S, Lim J, Linehan M, Lu-Culligan A, Martin A, Matos I, McDonald D, Minasyan M, Nakahata M, Naushad N, Nouws J, Obaid A, Odio C, Oh J, Omer S, Park A, Park H, Peng X, Petrone M, Prophet S, Rice T, Rose K, Sewanan L, Sharma L, Shaw A, Shepard D, Smolgovsky M, Sonnert N, Strong Y, Todeasa C, Valdez J, Velazquez S, Vijayakumar P, White E, Yang Y, Dela Cruz C, Ko A, Iwasaki A, Krumholz H, Matheus J, Hui P, Liu C, Farhadian S, Sikka R, Wyllie A, Grubaugh N. SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity. Med 2020, 2: 263-280.e6. PMID: 33521748, PMCID: PMC7836249, DOI: 10.1016/j.medj.2020.12.010.Peer-Reviewed Original ResearchConceptsEmergency use authorizationSARS-CoV-2 testingSARS-CoV-2 screeningSARS-CoV-2 testing capacitySupply chain shortagesHospital cohortNasopharyngeal swabsHealthy individualsDrug AdministrationHigh positive agreementQRT-PCR assaysDiagnostic testsU.S. FoodSafe reopeningTesting capacityGlobal healthPositive agreementFast GrantLower ratesSalivaNucleic acid extractionSwabsValid alternativeAssay costsCollection tubesNewborn Dried Blood Spots for Serologic Surveys of COVID-19
Liu F, Nguyen M, Vijayakumar P, Kaplan A, Meir A, Dai Y, Wang E, Walsh H, Ring AM, Omer SB, Farhadian SF. Newborn Dried Blood Spots for Serologic Surveys of COVID-19. The Pediatric Infectious Disease Journal 2020, 39: e454-e456. PMID: 33105339, PMCID: PMC7654948, DOI: 10.1097/inf.0000000000002918.Peer-Reviewed Original ResearchSex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesSARS-CoV-2 infection of the placenta
Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, Yasumoto Y, Vogels C, Casanovas-Massana A, Vijayakumar P, Geng B, Odio CD, Fournier J, Brito AF, Fauver JR, Liu F, Alpert T, Tal R, Szigeti-Buck K, Perincheri S, Larsen C, Gariepy AM, Aguilar G, Fardelmann KL, Harigopal M, Taylor HS, Pettker CM, Wyllie AL, Dela Cruz CS, Ring AM, Grubaugh ND, Ko AI, Horvath TL, Iwasaki A, Reddy UM, Lipkind HS. SARS-CoV-2 infection of the placenta. Journal Of Clinical Investigation 2020, 130: 4947-4953. PMID: 32573498, PMCID: PMC7456249, DOI: 10.1172/jci139569.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAbortion, TherapeuticAbruptio PlacentaeAdultBetacoronavirusCoronavirus InfectionsCOVID-19FemaleHumansMicroscopy, Electron, TransmissionPandemicsPhylogenyPlacentaPneumonia, ViralPre-EclampsiaPregnancyPregnancy Complications, InfectiousPregnancy Trimester, SecondRNA, ViralSARS-CoV-2Viral LoadConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 invasionMaternal antibody responseSymptomatic COVID-19Second trimester pregnancySyndrome coronavirus 2Coronavirus disease 2019Materno-fetal interfaceDense macrophage infiltratesPlacental abruptionSevere preeclampsiaMacrophage infiltratesSevere morbidityTrimester pregnancyPregnant womenCoronavirus 2Antibody responseBackgroundThe effectsDisease 2019Histological examinationImmunohistochemical assaysPlacentaLongitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19
Farhadian S, Glick LR, Vogels CBF, Thomas J, Chiarella J, Casanovas-Massana A, Zhou J, Odio C, Vijayakumar P, Geng B, Fournier J, Bermejo S, Fauver JR, Alpert T, Wyllie AL, Turcotte C, Steinle M, Paczkowski P, Dela Cruz C, Wilen C, Ko AI, MacKay S, Grubaugh ND, Spudich S, Barakat LA. Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. BMC Neurology 2020, 20: 248. PMID: 32552792, PMCID: PMC7301053, DOI: 10.1186/s12883-020-01812-2.Peer-Reviewed Original ResearchConceptsInitial presentationCentral nervous system inflammationSARS-CoV-2 infectionCSF inflammatory markersNervous system inflammationCerebrospinal fluid (CSF) cytokinesSeizure-like activityCOVID-19 infectionVirus SARS-CoV-2COVID-19SARS-CoV-2BackgroundCOVID-19Inflammatory markersNeurologic complicationsSystem inflammationImmunocompromised womanNeurologic manifestationsNeurologic symptomsViral neuroinvasionCase presentationWeInfected patientsMental statusRespiratory pathogensConclusionOur findingsInflammation