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 featuresEnhanced 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 ResearchMeSH KeywordsAntibodies, NeutralizingAntibodies, ViralBreakthrough InfectionsCOVID-19HumansReinfectionSARS-CoV-2Spike Glycoprotein, CoronavirusConceptsMHC-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 genesSubvariantsExpressionSARS-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 effectsAge-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
Filardi B, Monteiro V, Schwartzmann P, do Prado Martins V, Zucca L, Baiocchi G, Malik A, Silva J, Hahn A, Chen N, Pham K, Pérez-Then E, Miric M, Brache V, Cochon L, Larocca R, Della Rosa Mendez R, Silveira D, Pinto A, Croda J, Yildirim I, Omer S, Ko A, Vermund S, Grubaugh N, Iwasaki A, Lucas C, Initiative Y, Vogels C, 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. Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose. Science Translational Medicine 2023, 15: eade6023. PMID: 36791210, DOI: 10.1126/scitranslmed.ade6023.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, ViralAntibody FormationBNT162 VaccineCOVID-19HumansImmunoglobulin GSARS-CoV-2ConceptsBooster doseAntibody responseNeutralization titersVirus-specific IgG titersOlder adultsAntiviral humoral immunityPlasma antibody responsesHigh-risk populationSARS-CoV-2 spikeYears of ageAge-dependent impairmentHeterologous regimensBooster dosesBooster vaccineCoronaVac vaccineIgG titersProtective immunityHumoral immunityHumoral responseCoronaVacOmicron waveBooster strategyAge groupsEarly controlVaccine
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 ResearchMeSH KeywordsAntibodies, ViralCOVID-19Cross ReactionsEpitopesHumansMalariaN-Acetylneuraminic AcidSARS-CoV-2Spike Glycoprotein, CoronavirusConceptsCross-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 resultsUnadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses
Mao T, Israelow B, Peña-Hernández MA, Suberi A, Zhou L, Luyten S, Reschke M, Dong H, Homer RJ, Saltzman WM, Iwasaki A. Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science 2022, 378: eabo2523. PMID: 36302057, PMCID: PMC9798903, DOI: 10.1126/science.abo2523.Peer-Reviewed Original ResearchConceptsRespiratory mucosaSystemic immunityLethal SARS-CoV-2 infectionAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicSARS-CoV-2 infectionProtective mucosal immunityCross-reactive immunityT cell responsesCoronavirus 2 pandemicPrimary vaccinationParenteral vaccinesMucosal immunityVaccine strategiesRespiratory tractImmunoglobulin AMemory BImmune memoryPartial immunityCell responsesPoor immunityImmunitySpike proteinMucosaVaccineSerological 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 typeActivitySerumNo 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 2High-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-19PatientsNeutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination
Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, Vogels CBF, Malik AA, De la Cruz E, Jorge A, De los Santos M, Leon P, Breban MI, Billig K, Yildirim I, Pearson C, Downing R, Gagnon E, Muyombwe A, Razeq J, Campbell M, Ko AI, Omer SB, Grubaugh ND, Vermund SH, Iwasaki A. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nature Medicine 2022, 28: 481-485. PMID: 35051990, PMCID: PMC8938264, DOI: 10.1038/s41591-022-01705-6.Peer-Reviewed Original ResearchConceptsTwo-dose regimenOmicron variantVaccine boosterMRNA vaccinesNeutralization activityDelta variantTwo-dose mRNA vaccinesVirus-specific antibody levelsSARS-CoV-2 Omicron variantMRNA vaccine boosterNeutralization of OmicronNumerous spike mutationsSARS-CoV-2 DeltaPotent neutralization activityInfection-induced immunityCOVID-19 vaccineBNT162b2 boosterBooster vaccinationPrime vaccinationAntibody levelsAntibody titersHumoral immunityImmune escapeInactivated vaccinesVaccineDevelopment 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 vaccine
2021
High-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 proteomeLongitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient
Klein J, Brito AF, Trubin P, Lu P, Wong P, Alpert T, Peña-Hernández MA, Haynes W, Kamath K, Liu F, Vogels CBF, Fauver JR, Lucas C, Oh J, Mao T, Silva J, Wyllie AL, Muenker MC, Casanovas-Massana A, Moore AJ, Petrone ME, Kalinich CC, Dela Cruz C, Farhadian S, Ring A, Shon J, Ko AI, Grubaugh ND, Israelow B, Iwasaki A, Azar MM, Team F. Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient. The Journal Of Infectious Diseases 2021, 225: 374-384. PMID: 34718647, PMCID: PMC8807168, DOI: 10.1093/infdis/jiab553.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, NeutralizingAntibodies, ViralCOVID-19HumansMaleOrgan TransplantationPhylogenyReinfectionSARS-CoV-2Transplant RecipientsConceptsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfectionLongitudinal immune profilingTransplant recipientsImmune profilingPrimary SARS-CoV-2 infectionCD4 T cell poolMale renal transplant recipientSolid organ transplant recipientsSARS-CoV-2 reinfectionSARS-CoV-2 antibodiesSARS-CoV-2 infectionWhole viral genome sequencingRenal transplant recipientsImmune escape mutationsOrgan transplant recipientsT cell poolTime of reinfectionCoronavirus disease 2019Lower neutralization titersHumoral memory responsesViral genome sequencingInitial diagnosisImmunologic deficiencyHumoral responseImmunologic investigationsImpact 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 reductionCOVID-19 vaccines: Keeping pace with SARS-CoV-2 variants
Cevik M, Grubaugh ND, Iwasaki A, Openshaw P. COVID-19 vaccines: Keeping pace with SARS-CoV-2 variants. Cell 2021, 184: 5077-5081. PMID: 34534444, PMCID: PMC8445744, DOI: 10.1016/j.cell.2021.09.010.Peer-Reviewed Original ResearchPrevention 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 ResearchMeSH KeywordsAntibodies, ViralCOVID-19COVID-19 VaccinesHumansImmunoglobulin AImmunoglobulin GVirus ReplicationConceptsSARS-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 effectsMucosaAssociations 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 dataDelayed 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 onsetB cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection
Gehlhausen JR, Iwasaki A. B cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection. Journal Of Clinical Investigation 2021, 131: e148300. PMID: 33938452, PMCID: PMC8087191, DOI: 10.1172/jci148300.Peer-Reviewed Original ResearchConceptsAntibody-secreting cellsB cellsRecurrent lesionsHerpes simplex virus 2 infectionHSV-2-specific antibodiesRecurrent genital herpes lesionsSimplex virus 2 infectionGenital herpes lesionsHSV-2 lesionsVirus 2 infectionT cell clustersSkin biopsy specimensB cell subsetsB cell populationsNaive B cellsStage of infectionLesion reactivationDisease resolutionImmune infiltratesAntibody levelsHerpes lesionsCell subsetsBiopsy specimensHost responseLesionsThe 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