2024
Sex differences in postacute infection syndromes
Silva J, Iwasaki A. Sex differences in postacute infection syndromes. Science Translational Medicine 2024, 16: eado2102. PMID: 39536120, DOI: 10.1126/scitranslmed.ado2102.Peer-Reviewed Original ResearchIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusRandomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
2022
Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.
Chow RD, Michaels T, Bellone S, Hartwich T, Bonazzoli E, Iwasaki A, Song E, Santin AD. Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery 2022, 13: 312-331. PMID: 36301137, PMCID: PMC9905265, DOI: 10.1158/2159-8290.cd-22-0686.Peer-Reviewed Original ResearchConceptsAnti-PD-1 immunotherapyImmune checkpoint blockadeMMRd tumorsNK cellsEndometrial carcinomaICB responseMutation burdenT-cell-driven immunityPhase II clinical trialMMRd endometrial cancersPD-1 inhibitorsMismatch repair-deficient cancersTumor-extrinsic factorsHigh response rateEffector CD8Antitumor immunityEndometrial cancerCancer immunotherapyImmune cellsLonger survivalClinical trialsPrimary resistanceT cellsResponse rateMMRdNo evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
Lu-Culligan A, Tabachnikova A, Pérez-Then E, Tokuyama M, Lee HJ, Lucas C, Monteiro V, Miric M, Brache V, Cochon L, Muenker MC, Mohanty S, Huang J, Kang I, Dela Cruz C, Farhadian S, Campbell M, Yildirim I, Shaw AC, Ma S, Vermund SH, Ko AI, Omer SB, Iwasaki A. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination. PLOS Biology 2022, 20: e3001506. PMID: 35609110, PMCID: PMC9129011, DOI: 10.1371/journal.pbio.3001506.Peer-Reviewed Original ResearchConceptsCOVID-19 mRNA vaccinationMRNA vaccinationEarly pregnancyFetal sizeCoronavirus disease 2019 (COVID-19) mRNA vaccinationSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Maternal antibody statusAdverse neonatal outcomesSyndrome coronavirus 2Birth defectsPolyinosinic-polycytidylic acidCrown-rump lengthGross birth defectsUnvaccinated adultsMaternal illnessNeonatal outcomesVaccinated adultsAntibody statusTLR3 agonistEarly immunizationMurine pregnancyAntibody inductionCoronavirus 2De 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 benefitsMutationsIndolentThe 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 researchImmunopathologySequelaePathophysiologySyndromeLack 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 infectionSingle-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 interactionsDevelopment and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses
Wisnewski AV, Liu J, Lucas C, Klein J, Iwasaki A, Cantley L, Fazen L, Luna J, Slade M, Redlich CA. Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses. PLOS ONE 2022, 17: e0262657. PMID: 35041700, PMCID: PMC8765639, DOI: 10.1371/journal.pone.0262657.Peer-Reviewed Original ResearchConceptsPlaque reduction neutralization testCOVID-19 patientsVaccine responsesRecovered COVID-19 patientsSARS-CoV-2 immunityBooster vaccine dosesMRNA vaccine responsePost-vaccine seraCompetitive ELISAEnzyme 2 (ACE2) receptorReduction neutralization testType of vaccineSARS-CoV-2 spike protein receptorSpike protein receptorVaccine seraVaccine recipientsPost vaccinationVaccinated individualsVaccine dosesViral culturePrior historyViral neutralizationNeutralization testBooster shotsPost vaccineEndogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease
Jayewickreme R, Mao T, Philbrick W, Kong Y, Treger RS, Lu P, Rakib T, Dong H, Dang-Lawson M, Guild WA, Lau TJ, Iwasaki A, Tokuyama M. Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease. Frontiers In Immunology 2022, 12: 758721. PMID: 35058919, PMCID: PMC8764156, DOI: 10.3389/fimmu.2021.758721.Peer-Reviewed Original ResearchConceptsHSV-2 infectionHSV-2 diseaseHerpes simplex virus type 2 infectionSimplex virus type 2 infectionEnhanced type I interferonIntravaginal HSV-2 infectionVaginal HSV-2 infectionVirus type 2 infectionEndogenous retrovirusesReceptor-deficient miceType 2 infectionHigh systemic levelsWildtype C57BL/6 miceType I interferonTLR7-/- miceC57BL/6 miceInfectious endogenous retrovirusDeficient miceIntravaginal applicationAntiviral immunityI interferonVaginal tissueDetrimental functionsTLR7Mice
2021
Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protectionA phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIImpact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsMRNA vaccine-induced immunityT-cell activation markersSARS-CoV-2 antibodiesSecond vaccine doseVaccine-induced immunityCell activation markersT cell responsesHigh antibody titresSARS-CoV-2Vaccine boosterVaccine doseActivation markersVaccine dosesHumoral immunityAntibody titresMRNA vaccinesVitro stimulationNeutralization capacityNeutralization responseCell responsesE484KNucleocapsid peptideAntibody-binding sitesGreater reductionAdaptive 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 capacityClearanceAssociations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel
Zell J, Wisnewski AV, Liu J, Klein J, Lucas C, Slade M, Iwasaki A, Redlich CA. Associations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel. PLOS ONE 2021, 16: e0251114. PMID: 34460832, PMCID: PMC8405017, DOI: 10.1371/journal.pone.0251114.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Live SARS-CoV-2Moderate SARS-CoV-2SARS-CoV-2 seroprevalenceWork-related risk factorsTransportation-related occupationsSerum IgG levelsAntigen-specific IgGIgG seropositivity rateBiomarkers of infectionSARS-CoV-2 spikeCOVID-19 exposureUS National Guard soldiersMilitary personnelIgG levelsSeropositivity rateHumoral responseSerum IgGViral exposureBlack raceRisk factorsOdds ratioStudy populationNational Guard soldiersDemographic dataKynurenic 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 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