2022
De 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 infectionEndogenous 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
Impact 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 reductionDelayed 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 onsetNeuroinvasion 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