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 factorsPASCAntiviralsInfectionAbnormalitiesTrialsEnhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.Peer-Reviewed Original ResearchConceptsMHC-I expressionBreakthrough infectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsMajor histocompatibility complex class I expressionCell-mediated immunityInfluenza virus infectionSARS-CoV-2 VOCsMHC-I upregulationClass I expressionSARS-CoV-2T cell recognitionVirus infectionMHC II expressionSpike proteinEnhanced inhibitionInfectionCell recognitionCommon mutationsReinfectionE proteinAntibodiesViral genesSubvariantsExpressionPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2022
Unexplained post-acute infection syndromes
Choutka J, Jansari V, Hornig M, Iwasaki A. Unexplained post-acute infection syndromes. Nature Medicine 2022, 28: 911-923. PMID: 35585196, DOI: 10.1038/s41591-022-01810-6.Peer-Reviewed Original ResearchConceptsPost-acute sequelaeMyalgic encephalomyelitis/chronic fatigue syndromeSARS-CoV-2 infectionCertain acute infectionsMinority of patientsChronic fatigue syndromeSubstantial healthcare burdenSimilar symptom profilesSARS-CoV-2Common etiopathogenesisAcute infectionInfection syndromeClinical featuresFatigue syndromeChronic disabilityHealthcare burdenChronic illnessSymptom profilesInfectious agentsInfectionPotential involvementSequelaeSyndromeField of medicinePatientsDe novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report
Gandhi S, Klein J, Robertson AJ, Peña-Hernández MA, Lin MJ, Roychoudhury P, Lu P, Fournier J, Ferguson D, Mohamed Bakhash SAK, Catherine Muenker M, Srivathsan A, Wunder EA, Kerantzas N, Wang W, Lindenbach B, Pyle A, Wilen CB, Ogbuagu O, Greninger AL, Iwasaki A, Schulz WL, Ko AI. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report. Nature Communications 2022, 13: 1547. PMID: 35301314, PMCID: PMC8930970, DOI: 10.1038/s41467-022-29104-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionVirologic responsePersistent SARS-CoV-2 infectionResistance mutationsPre-treatment specimensB-cell deficiencyRemdesivir resistanceRemdesivir therapyViral sheddingCase reportAntiviral agentsPatientsCombinatorial therapyInfectionTherapyWhole-genome sequencingTreatmentImportance of monitoringDe novo emergenceFold increaseRNA-dependent RNA polymeraseNovo emergencePotential benefitsMutationsIndolentLack of association between pandemic chilblains and SARS-CoV-2 infection
Gehlhausen JR, Little AJ, Ko CJ, Emmenegger M, Lucas C, Wong P, Klein J, Lu P, Mao T, Jaycox J, Wang E, Ugwu N, Muenker C, Mekael D, Klein R, Patrignelli R, Antaya R, McNiff J, Damsky W, Kamath K, Shon J, Ring A, Yildirim I, Omer S, Ko A, Aguzzi A, Iwasaki A, Obaid A, Lu-Culligan A, Nelson A, Brito A, Nunez A, Martin A, Watkins A, Geng B, Kalinich C, Harden C, Todeasa C, Jensen C, Kim D, McDonald D, Shepard D, Courchaine E, White E, Song E, Silva E, Kudo E, DeIuliis G, Rahming H, Park H, Matos I, Nouws J, Valdez J, Fauver J, Lim J, Rose K, Anastasio K, Brower K, Glick L, Sharma L, Sewanan L, Knaggs L, Minasyan M, Batsu M, Petrone M, Kuang M, Nakahata M, Campbell M, Linehan M, Askenase M, Simonov M, Smolgovsky M, Sonnert N, Naushad N, Vijayakumar P, Martinello R, Datta R, Handoko R, Bermejo S, Prophet S, Bickerton S, Velazquez S, Alpert T, Rice T, Khoury-Hanold W, Peng X, Yang Y, Cao Y, Strong Y. Lack of association between pandemic chilblains and SARS-CoV-2 infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122090119. PMID: 35217624, PMCID: PMC8892496, DOI: 10.1073/pnas.2122090119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionPrior SARS-CoV-2 infectionSARS-CoV-2PC biopsiesAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicT-cell receptor sequencingCell receptor sequencingT cell responsesCoronavirus 2 pandemicEnzyme-linked immunosorbent assayLack of associationCOVID toesSkin eruptionAntibody responseImmunohistochemistry studiesBackground seroprevalenceTissue microarrayViral infectionStimulation assaysCell responsesInfectionChilblainsImmunosorbent assayAbortive infectionHigh-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-19Patients
2021
Prevention 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 effectsMucosaAdaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, Iwasaki A. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Science Immunology 2021, 6: eabl4509. PMID: 34623900, PMCID: PMC9047536, DOI: 10.1126/sciimmunol.abl4509.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Viral clearanceImmune determinantsMouse modelSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Cellular adaptive immunitySyndrome coronavirus 2Vivo protective capacityVariants of concernMRNA vaccinationHomologous infectionCellular immunityConvalescent miceCoronavirus 2Antibody responsePrimary infectionEffective vaccineAdaptive immunityConfer protectionInfectionNatural infectionProtective capacityClearanceThe 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 investigationsVaccineInfectionNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
RUNX Binding Sites Are Enriched in Herpesvirus Genomes, and RUNX1 Overexpression Leads to Herpes Simplex Virus 1 Suppression
Kim DJ, Khoury-Hanold W, Jain PC, Klein J, Kong Y, Pope SD, Ge W, Medzhitov R, Iwasaki A. RUNX Binding Sites Are Enriched in Herpesvirus Genomes, and RUNX1 Overexpression Leads to Herpes Simplex Virus 1 Suppression. Journal Of Virology 2020, 94: 10.1128/jvi.00943-20. PMID: 32878886, PMCID: PMC7592204, DOI: 10.1128/jvi.00943-20.Peer-Reviewed Original ResearchConceptsDorsal root gangliaHSV-1 infectionNumerous viral genesHSV-2Sensory neuronsHost transcription factorsHSV-1 genomeHSV-1Dorsal root ganglion neuronsViral gene expressionMouse DRG neuronsLifelong latent infectionViral genesKnockdown of RUNX1Herpes simplex virus 1Simplex virus 1DRG neuronsGanglion neuronsRoot gangliaOverall infectionViral gene transcriptionLatent infectionHSV-2 genomeInfectionNeuroblastoma cellsSaliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2
Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M, Vijayakumar P, Warren JL, Geng B, Muenker MC, Moore AJ, Vogels CBF, Petrone ME, Ott IM, Lu P, Venkataraman A, Lu-Culligan A, Klein J, Earnest R, Simonov M, Datta R, Handoko R, Naushad N, Sewanan LR, Valdez J, White EB, Lapidus S, Kalinich CC, Jiang X, Kim DJ, Kudo E, Linehan M, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Weizman OE, Wong P, Yang Y, Bermejo S, Odio CD, Omer SB, Dela Cruz CS, Farhadian S, Martinello RA, Iwasaki A, Grubaugh ND, Ko AI. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. New England Journal Of Medicine 2020, 383: 1283-1286. PMID: 32857487, PMCID: PMC7484747, DOI: 10.1056/nejmc2016359.Peer-Reviewed Original ResearchContributions of maternal and fetal antiviral immunity in congenital disease
Yockey LJ, Lucas C, Iwasaki A. Contributions of maternal and fetal antiviral immunity in congenital disease. Science 2020, 368: 608-612. PMID: 32381717, DOI: 10.1126/science.aaz1960.Peer-Reviewed Original ResearchConceptsViral infectionCongenital diseaseDirect viral toxicityMaternal immune responseMaternal immune activationFetal developmental defectsFuture treatment strategiesImmune defense mechanismsPregnancy outcomesFetal demiseImmune activationUncontrolled inflammationMaternal healthChronic infectionTreatment strategiesImmune responseAntiviral immunityRange of syndromesFetal developmentTissue damagePathological effectsInfectionViral toxicityDevastating consequencesPregnancyWhy does Japan have so few cases of COVID‐19?
Iwasaki A, Grubaugh ND. Why does Japan have so few cases of COVID‐19? EMBO Molecular Medicine 2020, 12: emmm202012481. PMID: 32275804, PMCID: PMC7207161, DOI: 10.15252/emmm.202012481.Peer-Reviewed Original ResearchEnvironmental Conditioning and Aerosol Infection of Mice.
Kudo E, Iwasaki A. Environmental Conditioning and Aerosol Infection of Mice. Bio-protocol 2020, 10: e3592. PMID: 33659558, PMCID: PMC7842367, DOI: 10.21769/bioprotoc.3592.Peer-Reviewed Original ResearchCutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy.
Gopinath S, Lu P, Iwasaki A. Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy. The Journal Of Immunology 2020, 204: 1703-1707. PMID: 32122994, DOI: 10.4049/jimmunol.1900462.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsGenital herpes infectionMemory T cellsT cellsHerpes infectionVirus-specific effector T cellsVaginal applicationTopical vaginal applicationCD8 T cellsEffector T cellsProtective immune responseSingle topical applicationTopical aminoglycosidesGenital mucosaChemokine expressionVaccine strategiesImmune responseVaginal mucosaTopical applicationBarrier tissuesMiceRobust activationAminoglycoside antibioticsMucosaInfectionSeasonality of Respiratory Viral Infections
Moriyama M, Hugentobler WJ, Iwasaki A. Seasonality of Respiratory Viral Infections. Annual Review Of Virology 2020, 7: 1-19. PMID: 32196426, DOI: 10.1146/annurev-virology-012420-022445.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusCoronavirus InfectionsCOVID-19HumansHumidityInfectious Disease Incubation PeriodInfluenza, HumanOrthomyxoviridaePandemicsPicornaviridae InfectionsPneumonia, ViralRespiratory Tract InfectionsRhinovirusSARS-CoV-2SeasonsSevere Acute Respiratory SyndromeSevere acute respiratory syndrome-related coronavirusSeverity of Illness IndexTemperatureConceptsRespiratory viral infectionsViral infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusViral respiratory infectionsAdaptive immune responsesRespiratory viral diseasesRespiratory infectionsRespiratory virusesInfluenza diseaseRespiratory tractImmune responseAnnual epidemicsHost responseInfectionMajor contributing factorViral diseasesDiseaseContributing factorVirus stabilityVirusEpidemicRecent studiesYearsHuman population
2019
Ketogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietIAV infectionT cellsGlobal health care concernHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionHealth care concernHigh-carbohydrate dietInfluenza diseaseKD feedingVirus infectionNew therapiesAntiviral resistanceHepatic ketogenesisCare concernsCell responsesInfectionBarrier functionDietMetabolic adaptationKetogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg E, Molony R, Sidorov S, Kudo E, Dixit V, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. The Journal Of Immunology 2019, 202: 62.7-62.7. DOI: 10.4049/jimmunol.202.supp.62.7.Peer-Reviewed Original ResearchΓδ T cellsKetogenic dietIAV infectionT cellsHigh-fat high-carbohydrate dietHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionAnti-viral resistanceHigh-carbohydrate dietInfluenza diseaseKD feedingNovel therapiesVirus infectionGlobal healthcare concernHepatic ketogenesisAbstract InfluenzaCell responsesHealthcare concernInfectionBarrier functionDiet