2024
Post-Acute sequelae of COVID-19 in pediatric patients within the United States: A Scoping Review
Miller C, Borre C, Green A, Funaro M, Oliveira C, Iwasaki A. Post-Acute sequelae of COVID-19 in pediatric patients within the United States: A Scoping Review. American Journal Of Medicine Open 2024, 100078. DOI: 10.1016/j.ajmo.2024.100078.Peer-Reviewed Original ResearchClinical epidemiologyPost-acute sequelae of COVID-19High risk of biasLack of standardized definitionsPost-acute sequelaeRisk of biasSequelae of COVID-19United StatesScoping reviewComprehensive literature searchUS childrenShort follow-up durationFollow-up durationInclusion criteriaFemale sexOlder ageRisk factorsSARS-CoV-2 infectionLiterature searchChest painHigh riskOptimal preventionPediatric patientsPersistent symptomsCOVID-19
2023
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Proal A, VanElzakker M, Aleman S, Bach K, Boribong B, Buggert M, Cherry S, Chertow D, Davies H, Dupont C, Deeks S, Eimer W, Ely E, Fasano A, Freire M, Geng L, Griffin D, Henrich T, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter M, Peluso M, Pretorius E, Price D, Putrino D, Scheuermann R, Tan G, Tanzi R, VanBrocklin H, Yonker L, Wherry E. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nature Immunology 2023, 24: 1616-1627. PMID: 37667052, DOI: 10.1038/s41590-023-01601-2.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 reservoirPost-acute sequelaeImmune responseHost immune responseCoronavirus SARS-CoV-2COVID-19SARS-CoV-2Neuroimmune abnormalitiesAcute infectionLong COVIDClinical trialsViral RNAMillions of peopleSequelaeFurther studiesViral proteinsPathologyResearch prioritiesRNA/proteinBiological factorsPASCAntiviralsInfectionAbnormalitiesTrialsAn 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 biomarkersSARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
Jaycox J, Lucas C, Yildirim I, Dai Y, Wang E, Monteiro V, Lord S, Carlin J, Kita M, Buckner J, Ma S, Campbell M, Ko A, Omer S, Lucas C, Speake C, Iwasaki A, Ring A. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nature Communications 2023, 14: 1299. PMID: 36894554, PMCID: PMC9996559, DOI: 10.1038/s41467-023-36686-8.Peer-Reviewed Original ResearchConceptsVaccine-associated myocarditisAutoimmune patientsAutoantibody reactivitySARS-CoV-2 mRNA vaccinationVaccine-related adverse effectsSARS-CoV-2 immunitySARS-CoV-2 infectionAcute COVID-19Development of autoantibodiesCOVID-19 patientsAnti-viral immunityVirus-specific antibodiesCOVID-19 vaccineCOVID-19Humoral autoimmunityMRNA vaccinationAutoantibody responsePost vaccinationAutoantibody developmentAutoimmune diseasesHumoral responseHealthy individualsPatientsAntigen profilingAdverse effects
2022
Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia
Bernard-Raichon L, Venzon M, Klein J, Axelrad J, Zhang C, Sullivan A, Hussey G, Casanovas-Massana A, Noval M, Valero-Jimenez A, Gago J, Putzel G, Pironti A, Wilder E, Thorpe L, Littman D, Dittmann M, Stapleford K, Shopsin B, Torres V, Ko A, Iwasaki A, Cadwell K, Schluter J. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nature Communications 2022, 13: 5926. PMID: 36319618, PMCID: PMC9626559, DOI: 10.1038/s41467-022-33395-6.Peer-Reviewed Original ResearchConceptsGut microbiome dysbiosisCOVID-19 patientsMicrobiome dysbiosisSecondary infectionSARS-CoV-2 infection inducesLife-threatening secondary infectionsTranslocation of bacteriaBlood culture resultsCOVID-19 severityAntimicrobial-resistant speciesCOVID-19Different clinical sitesMicrobial translocationBloodstream infectionsInfection inducesBarrier permeabilitySystemic circulationDysbiosisGoblet cellsPaneth cellsClinical sitesCulture resultsPatient healthGut microbiomePatientsOperation Nasal Vaccine—Lightning speed to counter COVID-19
Topol EJ, Iwasaki A. Operation Nasal Vaccine—Lightning speed to counter COVID-19. Science Immunology 2022, 7: eadd9947. PMID: 35862488, DOI: 10.1126/sciimmunol.add9947.Peer-Reviewed Original ResearchInflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1The immunology and immunopathology of COVID-19
Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science 2022, 375: 1122-1127. PMID: 35271343, DOI: 10.1126/science.abm8108.Peer-Reviewed Original ResearchConceptsImmune responseAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionFatal COVID-19Coronavirus 2 infectionPost-acute sequelaeCOVID-19 pathophysiologyProlongation of symptomsLong COVID syndromeMajor unmet needCOVID-19SARS-CoV-2COVID syndromeDisease resolutionInflammatory processChronic illnessUnmet needDefinitive findingsImmunology researchCOVID-19 researchImmunopathologySequelaePathophysiologySyndromeTargeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion
Vora SM, Fontana P, Mao T, Leger V, Zhang Y, Fu TM, Lieberman J, Gehrke L, Shi M, Wang L, Iwasaki A, Wu H. Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2117198119. PMID: 35149555, PMCID: PMC8892331, DOI: 10.1073/pnas.2117198119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 nonstructural protein 1Host protein synthesisSARS-CoV-2 5Nonstructural protein 1Viral translationNucleic acid antisenseAntiviral immunityProtein synthesisTherapeutic targetTransgenic miceViral protein synthesisViral replicationDrug resistanceHuman ACE2Infected cellsProtein 1COVID-19Virulence mechanismsNanomolar concentrationsHost translationPathogenic virusesEntry channelSuppressionTranslational suppressionHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19PatientsSingle-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
A humanized mouse model of chronic COVID-19
Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature Biotechnology 2021, 40: 906-920. PMID: 34921308, PMCID: PMC9203605, DOI: 10.1038/s41587-021-01155-4.Peer-Reviewed Original ResearchConceptsChronic COVID-19Humanized mouse modelImmune responseMouse modelAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCOVID-19Adaptive human immune responsesInterferon-stimulated gene signaturePersistent viral RNACoronavirus 2 infectionPatient-derived antibodiesT-cell lymphopeniaHuman immune responseHyperactive immune responseCoronavirus disease 2019Inflammatory macrophage responseImmunological injuryLung pathologyCell lymphopeniaDisease 2019Severe diseaseRodent modelsInflammatory macrophagesHigh-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19
Haynes WA, Kamath K, Bozekowski J, Baum-Jones E, Campbell M, Casanovas-Massana A, Daugherty PS, Dela Cruz CS, Dhal A, Farhadian SF, Fitzgibbons L, Fournier J, Jhatro M, Jordan G, Klein J, Lucas C, Kessler D, Luchsinger LL, Martinez B, Catherine Muenker M, Pischel L, Reifert J, Sawyer JR, Waitz R, Wunder EA, Zhang M, Iwasaki A, Ko A, Shon J. High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19. Communications Biology 2021, 4: 1317. PMID: 34811480, PMCID: PMC8608966, DOI: 10.1038/s42003-021-02835-2.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 antibodiesRespiratory syndrome coronavirus 2SARS-CoV-2 epitopesSyndrome coronavirus 2SARS-CoV-2 strainsHigh-resolution epitope mappingCOVID-19SARS-CoV-2SARS-CoV-2 mutantsCoronavirus 2Antibody responseEffective vaccineImmune responseNeutralization activitySevere diseaseLarge cohortEpitope regionsAntibody epitopesEpitope mappingRelated coronavirusesTherapyVaccineViral proteomePrevention of host-to-host transmission by SARS-CoV-2 vaccines
Mostaghimi D, Valdez CN, Larson HT, Kalinich CC, Iwasaki A. Prevention of host-to-host transmission by SARS-CoV-2 vaccines. The Lancet Infectious Diseases 2021, 22: e52-e58. PMID: 34534512, PMCID: PMC8439617, DOI: 10.1016/s1473-3099(21)00472-2.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 vaccinesSymptomatic COVID-19Population-level dataVaccine's abilityIntramuscular vaccineImmunological mechanismsVaccine strategiesVaccine capacityPrimary infectionNatural courseClinical trialsObservational studyRespiratory epitheliumReal-world settingViral titresViral replicationVaccineVaccine distributionInfectionCOVID-19Host transmissionTrialsPopulation-level effectsMucosaChallenges in interpreting cytokine data in COVID-19 affect patient care and management
Wang SY, Takahashi T, Pine AB, Damsky WE, Simonov M, Zhang Y, Kieras E, Price CC, King BA, Siegel MD, Desir GV, Lee AI, Iwasaki A, Chun HJ. Challenges in interpreting cytokine data in COVID-19 affect patient care and management. PLOS Biology 2021, 19: e3001373. PMID: 34358229, PMCID: PMC8372945, DOI: 10.1371/journal.pbio.3001373.Peer-Reviewed Original ResearchKynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesDiverse 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 onsetDivergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencingThe first 12 months of COVID-19: a timeline of immunological insights
Carvalho T, Krammer F, Iwasaki A. The first 12 months of COVID-19: a timeline of immunological insights. Nature Reviews Immunology 2021, 21: 245-256. PMID: 33723416, PMCID: PMC7958099, DOI: 10.1038/s41577-021-00522-1.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2Antibodies, ViralAutoantibodiesCOVID-19COVID-19 Drug TreatmentCOVID-19 SerotherapyCOVID-19 VaccinesDexamethasoneDrug DevelopmentGlucocorticoidsHumansImmunization, PassiveImmunologic FactorsInterferon Type IReceptors, CoronavirusSARS-CoV-2Systemic Inflammatory Response SyndromeConceptsSARS-CoV-2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Numerous candidate vaccinesSyndrome coronavirus 2Coronavirus disease 2019Peer-reviewed journalsCandidate vaccinesCoronavirus 2Pneumonia casesDisease 2019Immune responseViral infectionImmunological insightsNovel coronavirusInitial reportCOVID-19First yearMonthsHighlight gapsPreprint serversUnidentified originFuture investigationsVaccineInfection