2024
SARS-CoV-2 reprograms murine alveolar macrophages to dampen flu
Tabachnikova A, Iwasaki A. SARS-CoV-2 reprograms murine alveolar macrophages to dampen flu. Trends In Immunology 2024 PMID: 39580310, DOI: 10.1016/j.it.2024.11.002.Peer-Reviewed Original ResearchSARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity
Peña-Hernández M, Alfajaro M, Filler R, Moriyama M, Keeler E, Ranglin Z, Kong Y, Mao T, Menasche B, Mankowski M, Zhao Z, Vogels C, Hahn A, Kalinich C, Zhang S, Huston N, Wan H, Araujo-Tavares R, Lindenbach B, Homer R, Pyle A, Martinez D, Grubaugh N, Israelow B, Iwasaki A, Wilen C. SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity. Nature Microbiology 2024, 9: 2038-2050. PMID: 39075235, DOI: 10.1038/s41564-024-01765-z.Peer-Reviewed Original ResearchBat coronavirusesRelatives of SARS-CoV-2Upper airwayUpper airways of miceEpithelial cellsHuman nasal epithelial cellsAirways of miceMajor histocompatibility complex class I.SARS-CoV-2Nasal epithelial cellsHistocompatibility complex class I.Human bronchial epithelial cellsGenetic similarityBronchial epithelial cellsInnate immune restrictionCoronavirus replicationFunctional characterizationMolecular cloningReduced pathogenesisImpaired replicationBat virusCoronavirus pathogenesisPandemic potentialHigh-risk familiesImmune restrictionInflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2
Martin-Lopez E, Brennan B, Mao T, Spence N, Meller S, Han K, Yahiaoui N, Wang C, Iwasaki A, Greer C. Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2. ENeuro 2024, 11: eneuro.0106-24.2024. PMID: 38834299, PMCID: PMC11185043, DOI: 10.1523/eneuro.0106-24.2024.Peer-Reviewed Original ResearchOlfactory bulbOlfactory epitheliumPiriform cortexOlfactory tractOlfactory systemSARS-CoV-2Projection neuronsMyelination defectsOlfactory sensory neuronsLateral olfactory tractLoss of olfactionRespiratory epithelial cellsLamina propria macrophagesSARS-CoV-2 infectionInfected SCDays of infectionIntegrity of myelinOlfactory dysfunctionInfected microgliaSensitive to infectionOlfactory deficitsSensory neuronsSustentacular cellsNasal cavityNeuronal conduction
2023
Distinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological featuresSARS-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 genesSubvariantsExpression
2022
Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein
Lapidus S, Liu F, Casanovas-Massana A, Dai Y, Huck J, Lucas C, Klein J, Filler R, Strine M, Sy M, Deme A, Badiane A, Dieye B, Ndiaye I, Diedhiou Y, Mbaye A, Diagne C, Vigan-Womas I, Mbengue A, Sadio B, Diagne M, Moore A, Mangou K, Diallo F, Sene S, Pouye M, Faye R, Diouf B, Nery N, Costa F, Reis M, Muenker M, Hodson D, Mbarga Y, Katz B, Andrews J, Campbell M, Srivathsan A, Kamath K, Baum-Jones E, Faye O, Sall A, Vélez J, Cappello M, Wilson M, Ben-Mamoun C, Tedder R, McClure M, Cherepanov P, Somé F, Dabiré R, Moukoko C, Ouédraogo J, Boum Y, Shon J, Ndiaye D, Wisnewski A, Parikh S, Iwasaki A, Wilen C, Ko A, Ring A, Bei A. Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein. Scientific Reports 2022, 12: 22175. PMID: 36550362, PMCID: PMC9778468, DOI: 10.1038/s41598-022-26709-7.Peer-Reviewed Original ResearchConceptsCross-reactive antibodiesSARS-CoV-2Positive SARS-CoV-2 antibody resultsPositive SARS-CoV-2 antibodiesSARS-CoV-2 reactivitySARS-CoV-2 antibodiesAcute malaria infectionSpike proteinAntibody test resultsPre-pandemic samplesMalaria-endemic countriesPopulation-level immunityMalaria-endemic regionsSpike S1 subunitNon-endemic countriesSARS-CoV-2 spike proteinSARS-CoV-2 proteinsPopulation-level exposureCOVID-19 transmissionMalaria exposureFalse-positive resultsMalaria infectionDisease burdenPlasmodium infectionAntibody resultsSerological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration
Fiedler S, Devenish S, Morgunov A, Ilsley A, Ricci F, Emmenegger M, Kosmoliaptsis V, Theel E, Mills J, Sholukh A, Aguzzi A, Iwasaki A, Lynn A, Knowles T. Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration. Scientific Reports 2022, 12: 19791. PMID: 36396691, PMCID: PMC9672333, DOI: 10.1038/s41598-022-22214-z.Peer-Reviewed Original ResearchConceptsSerum antibody responseAntiviral activityHigh antiviral activityAntibody responseTherapeutic mAbsReduced antiviral activityVirus neutralization assaysSARS-CoV-2 virusSARS-CoV-2Convalescent individualsNeutralization assaysTherapeutic monoclonal antibodiesSame mAbMonoclonal antibodiesNew therapeuticsTherapeutic antibodiesMAbsAntibodiesRBDSotrovimabWild typeActivitySerumMild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, O'Dea MR, Dutton S, Shamardani K, Nwangwu K, Mancusi R, Yalçın B, Taylor KR, Acosta-Alvarez L, Malacon K, Keough MB, Ni L, Woo PJ, Contreras-Esquivel D, Toland AMS, Gehlhausen JR, Klein J, Takahashi T, Silva J, Israelow B, Lucas C, Mao T, Peña-Hernández MA, Tabachnikova A, Homer RJ, Tabacof L, Tosto-Mancuso J, Breyman E, Kontorovich A, McCarthy D, Quezado M, Vogel H, Hefti MM, Perl DP, Liddelow S, Folkerth R, Putrino D, Nath A, Iwasaki A, Monje M. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 2022, 185: 2452-2468.e16. PMID: 35768006, PMCID: PMC9189143, DOI: 10.1016/j.cell.2022.06.008.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMicroglial reactivityCognitive impairmentCSF cytokines/chemokinesCytokines/chemokinesSARS-CoV-2Early time pointsCCL11 levelsMild COVIDRespiratory influenzaHippocampal neurogenesisOligodendrocyte lossHippocampal pathologyMyelin lossNeurological symptomsImpaired neurogenesisCOVID survivorsNeurobiological effectsNeural dysregulationMyelin dysregulationCCL11Neural cellsTime pointsNeurogenesisMiceUnexplained 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 medicinePatientsInflammasome 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 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 infectionTargeting 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-19Patients
2021
Impact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines
Yang Y, Iwasaki A. Impact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines. Current HIV/AIDS Reports 2021, 19: 5-16. PMID: 34843064, PMCID: PMC8628277, DOI: 10.1007/s11904-021-00590-x.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human immune deficiency virus (HIV) infectionSARS-CoV-2 acute infectionImmune systemSevere acute respiratory syndrome coronavirus 2Severe SARS-CoV-2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Chronic HIV infectionSyndrome coronavirus 2Effectiveness of vaccinesHost immune systemCOVID-19 diseaseRecent FindingsPeopleAntiretroviral therapyImmunological changesAcute infectionHIV infectionDisease complicationsPersistent inflammationCoronavirus 2Functional impairmentVirus infectionImmune responseHigh-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 proteomeA stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacyImpact 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 reductionPrevention 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 effectsMucosa