2025
Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID
Grady C, Bhattacharjee B, Silva J, Jaycox J, Lee L, Silva Monteiro V, Sawano M, Massey D, Caraballo C, Gehlhausen J, Tabachnikova A, Mao T, Lucas C, Peña-Hernandez M, Xu L, Tzeng T, Takahashi T, Herrin J, Güthe D, Akrami A, Assaf G, Davis H, Harris K, McCorkell L, Schulz W, Griffin D, Wei H, Ring A, Guan L, Dela Cruz C, Krumholz H, Iwasaki A. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID. Communications Medicine 2025, 5: 163. PMID: 40346201, PMCID: PMC12064684, DOI: 10.1038/s43856-025-00829-3.Peer-Reviewed Original ResearchSpike protein-specific IgGProtein-specific IgGSelf-antigensImmune response to COVID-19 vaccinationCOVID-19 vaccineAntibody responseResponse to COVID-19 vaccinationT cell expansionSARS-CoV-2-specific antibody responsesAssociated with no improvementLong COVIDAssociated with symptom improvementChest painCirculating cytokinesImmune phenotypeProspective studyImmune featuresTransient improvementPrimary seriesVaccine doseHerpes virusImmune responseSymptom improvementSignificant elevationImpact of COVID-19 vaccinationTherapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice
Sharma L, Singh R, Ngeow C, van der Geest R, Duray A, Tolman N, McVerry B, Dela Cruz C, Alcorn J, Bain W, Robinson K. Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice. Physiological Reports 2025, 13: e70232. PMID: 39921246, PMCID: PMC11805821, DOI: 10.14814/phy2.70232.Peer-Reviewed Original ResearchConceptsMurine model of influenzaIL-6 deletionMRSA pneumoniaModel of influenzaInflammatory cell recruitmentIL-6Interferon-stimulated genesMurine modelCell recruitmentJAK inhibitionElevated levels of IL-6Tissue injuryLevels of IL-6IL-6 deficiencyJAK inhibitor baricitinibSuppression of cytokinesLimit tissue injuryLung tissue injurySecondary bacterial infectionInfluenza infectionJAK/STAT signaling pathwayBaricitinib treatmentInhibitory therapyClinical efficacyBacterial burdenDamage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection
Kim J, Yuan Y, Agaronyan K, Zhao A, Wang V, Gau D, Toosi N, Gupta G, Essayas H, Kaminski A, McGovern J, Yu S, Woo S, Lee C, Gandhi S, Saber T, Saleh T, Hu B, Sun Y, Ishikawa G, Bain W, Evankovich J, Chen L, Yun H, Herzog E, Dela Cruz C, Ryu C, Sharma L. Damage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection. Mucosal Immunology 2025 PMID: 39884393, DOI: 10.1016/j.mucimm.2025.01.008.Peer-Reviewed Original ResearchToll-like receptor 9Anti-influenza immunityToll-like receptor 9 activationImpaired viral clearanceViral clearanceMyeloid cellsTissue injuryInflammatory responseInfluenza infectionPersistent inflammationLung injuryTissue damageToll-like receptor 9 deficiencyReceptor 9Toll-like receptor 9 signalingToll-like receptor 9 ligandInfection of immune cellsInfluenza-infected individualsPersistent lung injuryTLR9-/- miceInfected myeloid cellsInflammatory lung injurySensing tissue damageUnmethylated CpG DNA sequencesMitochondrial DNA
2024
Streptococcus pneumoniae Serotype Distribution Among US Adults Hospitalized With Community-Acquired Pneumonia, 2019–2020
Ramirez J, Hubler R, Ali M, Gray S, Carrico R, McNaughton C, Wunderink R, Dela Cruz C, Chilson E, Cané A, Isturiz R, Pride M, Jodar L, Gessner B, Grant L. Streptococcus pneumoniae Serotype Distribution Among US Adults Hospitalized With Community-Acquired Pneumonia, 2019–2020. Open Forum Infectious Diseases 2024, 12: ofae727. PMID: 39758745, PMCID: PMC11697090, DOI: 10.1093/ofid/ofae727.Peer-Reviewed Original ResearchCommunity-acquired pneumoniaPneumococcal conjugate vaccineStreptococcus pneumoniae</i>Urinary antigen detectionSerotype-specific urinary antigen detectionStreptococcus pneumoniae serotypes distributionUrinary antigen detection assayPneumococcal community-acquired pneumoniaAdult community-acquired pneumoniaRadiographic evidence of community-acquired pneumoniaHigher-valent pneumococcal conjugate vaccinesMedical chart reviewYears of ageCommunity-acquiredSerotype distributionRespiratory samplesChart reviewConjugate vaccineSerotype pneumococciPer-protocolChronic medical conditionsRadiographic evidenceAntigen detectionCoronavirus disease 2019Proportion of adultsEarly antiviral use and supplemental oxygen decrease the risk of secondary bacterial infections: a multi-centre, nested, case–control study
Zhu Y, Hu H, Guo X, Zhang H, Li D, Dela Cruz C, Xie W, Xie L, Sharma L, Chang D. Early antiviral use and supplemental oxygen decrease the risk of secondary bacterial infections: a multi-centre, nested, case–control study. Journal Of Hospital Infection 2024, 156: 87-95. PMID: 39701496, DOI: 10.1016/j.jhin.2024.12.005.Peer-Reviewed Original ResearchConceptsRisk of secondary bacterial infectionIncidence of secondary bacterial infectionSecondary bacterial infectionAge-adjusted Charlson Comorbidity IndexCase-control studyPropensity-score matchingBacterial infectionsCOVID-19 patientsParenteral nutritionSupplemental oxygenTreatment strategiesAssociated with significant protectionAssociated with decreased incidenceAssociated with increased incidenceConditional logistic regression analysisSusceptibility to secondary bacterial infectionsAssociated with protectionCharlson Comorbidity IndexLogistic regression analysisAssociated with significant increasesAntiviral useGastric tubeAntibacterial therapyComorbidity indexIntravenous injectionHost-Directed Adjunctive Therapies in Immunocompromised Patients with Pneumonia
Hensley M, Dela Cruz C. Host-Directed Adjunctive Therapies in Immunocompromised Patients with Pneumonia. Clinics In Chest Medicine 2024, 46: 37-48. PMID: 39890291, DOI: 10.1016/j.ccm.2024.10.003.Peer-Reviewed Original ResearchContext‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchConceptsIII interferon signalingType III interferon signalingLung injuryInterferon signalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recoveryPrior knowledge-guided vision-transformer-based unsupervised domain adaptation for intubation prediction in lung disease at one week
Yang J, Henao J, Dvornek N, He J, Bower D, Depotter A, Bajercius H, de Mortanges A, You C, Gange C, Ledda R, Silva M, Dela Cruz C, Hautz W, Bonel H, Reyes M, Staib L, Poellinger A, Duncan J. Prior knowledge-guided vision-transformer-based unsupervised domain adaptation for intubation prediction in lung disease at one week. Computerized Medical Imaging And Graphics 2024, 118: 102442. PMID: 39515190, DOI: 10.1016/j.compmedimag.2024.102442.Peer-Reviewed Original ResearchUnsupervised domain adaptationSpatial prior informationDomain adaptationLabeled dataData-driven approachUnsupervised domain adaptation modelMedical image analysis tasksImage analysis tasksTransformer-based modelsMedical image analysisPrior informationOutcome prediction tasksAdversarial trainingDistribution alignmentDomain shiftAttention headsClass tokenPoor generalizationAnalysis tasksTarget domainPrediction taskData distributionKnowledge-guidedLocal weightsMedical imagesPostinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report.
Auld S, Sheshadri A, Alexander-Brett J, Aschner Y, Barczak A, Basil M, Cohen K, Dela Cruz C, McGroder C, Restrepo M, Ridge K, Schnapp L, Traber K, Wunderink R, Zhang D, Ziady A, Attia E, Carter J, Chalmers J, Crothers K, Feldman C, Jones B, Kaminski N, Keane J, Lewinsohn D, Metersky M, Mizgerd J, Morris A, Ramirez J, Samarasinghe A, Staitieh B, Stek C, Sun J, Evans S. Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report. Annals Of The American Thoracic Society 2024, 21: 1219-1237. PMID: 39051991, DOI: 10.1513/annalsats.202406-651st.Peer-Reviewed Original ResearchConceptsPulmonary infectionTreatment of pulmonary infectionsLower respiratory tract infectionsLong-term morbidityRespiratory tract infectionsShort-term outcomesAberrant host responseBurden of morbidityReview potential mechanismsPulmonary complicationsTract infectionsPulmonary pathogensSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Causative pathogenRespiratory syndrome coronavirus 2Therapeutic strategiesSyndrome coronavirus 2Host responseInfectionMorbidityPotential mechanismsCoronavirus 2Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantThe protein disulfide isomerase A3 and osteopontin axis promotes influenza‐induced lung remodelling
Kumar A, Mark Z, Carbajal M, DeLima D, Chamberlain N, Walzer J, Ruban M, Chandrasekaran R, Daphtary N, Aliyeva M, Poynter M, Janssen‐Heininger Y, Bates J, Alcorn J, Britto C, Dela Cruz C, Jegga A, Anathy V. The protein disulfide isomerase A3 and osteopontin axis promotes influenza‐induced lung remodelling. British Journal Of Pharmacology 2024, 181: 4610-4627. PMID: 39118388, DOI: 10.1111/bph.16511.Peer-Reviewed Original ResearchProtein disulfide isomerase A3Secreted phosphoprotein 1Lung fibrosisLung remodelingFibrotic remodelingViral infectionAssociated with pulmonary fibrosisInfluenza-infected patientsMacrophage colony-stimulating factorFibrotic lung remodelingSPP1 expressionRespiratory viral infectionsImproved oxygen saturationColony-stimulating factorLung fibrotic remodelingDebilitating clinical sequelaeIAV infectionFibrotic sequelaeClinical sequelaeTherapeutic optionsPulmonary fibrosisRetrospective analysisNeutralizing antibodiesCell culture modelHealthy controlsLongitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure
Kitsios G, Sayed K, Fitch A, Yang H, Britton N, Shah F, Bain W, Evankovich J, Qin S, Wang X, Li K, Patel A, Zhang Y, Radder J, Dela Cruz C, Okin D, Huang C, Van Tyne D, Benos P, Methé B, Lai P, Morris A, McVerry B. Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure. Nature Communications 2024, 15: 4708. PMID: 38830853, PMCID: PMC11148165, DOI: 10.1038/s41467-024-48819-8.Peer-Reviewed Original ResearchConceptsAcute respiratory failureRespiratory failureCohort of COVID-19 patientsLung microbiotaMechanically ventilated patientsChronic obstructive pulmonary diseaseIllumina amplicon sequencingDNA sequencing technologiesHost-microbiota interactionsObstructive pulmonary diseaseCOVID-19 patientsAssociated with specific patternsAntibiotic exposureClinical factorsNanopore metagenomicsPredicting survivalPrecision medicine interventionsPrognostic biomarkerSequencing technologiesAmplicon sequencingPulmonary diseaseGut microbiotaCritical illnessMicrobial diversityHuman microbiomeClinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis
Xiao Z, Lin M, Song N, Wu X, Hou J, Wang L, Tian X, An C, Dela Cruz C, Sharma L, Chang D. Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis. IScience 2024, 27: 110110. PMID: 38974472, PMCID: PMC11225851, DOI: 10.1016/j.isci.2024.110110.Peer-Reviewed Original ResearchViral sepsisCausative agent of sepsisAgent of sepsisCases of sepsisSusceptibility to secondary bacterial infectionsNon-sepsis patientsSecondary bacterial infectionPlatelet activation pathwaysMetabolomic characteristicsPlatelet dysfunctionSepsis phenotypesClinical featuresSystemic disease phenotypeSepsis patientsSepsisCOVID-19 pathologyBacterial infectionsProteomic signatureDisease phenotypeComplement proteinsBacterial pathogensProteomic dataActivation pathwayFunctional consequencesPathway proteinsLung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury
Shah F, Bahudhanapati H, Jiang M, Tabary M, van der Geest R, Tolman N, Kochin M, Xiong Z, Al-Yousif N, Sayed K, Benos P, Raffensperger K, Evankovich J, Neal M, Snyder M, Eickelberg O, Ray P, Dela Cruz C, Bon J, McVerry B, Straub A, Jurczak M, Suber T, Zhang Y, Chen K, Kitsios G, Lee J, Alder J, Bain W. Lung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury. American Journal Of Respiratory Cell And Molecular Biology 2024, 70: 379-391. PMID: 38301257, PMCID: PMC11109583, DOI: 10.1165/rcmb.2023-0429oc.Peer-Reviewed Original ResearchConceptsLung injuryPlasma levelsLung epitheliumGDF15 levelsAssociated with plasma levelsAcute respiratory distress syndromeGrowth differentiation factor 15Acute respiratory failureRespiratory distress syndromeWild-type miceLung cytokine levelsHuman lung epitheliumAcute lung injuryDifferentiation factor 15Levels of GDF15Critically ill humansPrognostic of mortalitySARS-CoV-2 infectionCirculating GDF15 levelsRespiratory tract levelRespiratory failureDistress syndromeCytokine profileStress cytokinesCytokine levelsAnti-inflammatory Roles of Type I Interferon Signaling in the Lung
Feng J, Liu Y, Kim J, Ahangari F, Kaminski N, Bain W, Jie Z, Dela Cruz C, Sharma L. Anti-inflammatory Roles of Type I Interferon Signaling in the Lung. 2024, a6230-a6230. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6230.Peer-Reviewed Original ResearchInitial and Residual Cardiovascular Damage Remaining at Day 30 in Community-acquired Pneumonia
Méndez Ocaña R, González-Jiménez P, Mengot N, España P, Uranga A, Almirall J, Boixeda R, Alonso R, Piqueras M, Martínez-Dolz L, Dela Cruz C, Menéndez R. Initial and Residual Cardiovascular Damage Remaining at Day 30 in Community-acquired Pneumonia. 2024, a6241-a6241. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6241.Peer-Reviewed Original ResearchInhibition of Protein Disulfide Isomerase A3 and Osteopontin Attenuates Influenza-induced Lung Fibrosis
Kumar A, Mark Z, Janssen-Heininger Y, Poynter M, Dela Cruz C, Britto-Leon C, Alcorn J, Jegga A, Anathy V. Inhibition of Protein Disulfide Isomerase A3 and Osteopontin Attenuates Influenza-induced Lung Fibrosis. 2024, a2819-a2819. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2819.Peer-Reviewed Original ResearchChitotriosidase Regulates Host Response to Influenza Lung Infection
Kim J, Amick A, Sharma L, Dela Cruz C. Chitotriosidase Regulates Host Response to Influenza Lung Infection. 2024, a4183-a4183. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4183.Peer-Reviewed Original ResearchRapid Metagenomic Sequencing (RaMSes) for Comprehensive Detection of Respiratory Pathogens in Patients With Hematologic Malignancy
Hensley M, Sayed K, Haidar G, Wang X, Benos P, Ito S, Im A, Geramita E, Dela Cruz C, Morris A, Kitsios G. Rapid Metagenomic Sequencing (RaMSes) for Comprehensive Detection of Respiratory Pathogens in Patients With Hematologic Malignancy. 2024, a2915-a2915. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2915.Peer-Reviewed Original ResearchSARS-CoV-2 Viremia Associates With Thrombosis and Mortality in the ACTIV-4a Trial
Zuchelkowski B, Nouraie M, Naqvi A, Qin S, Zhang Y, Dela Cruz C, Zhang L, Mcverry B, Morris A, Neal M, Seheult J, Kitsios G, Mellors J, Kim P, Jacobs J, Bain W. SARS-CoV-2 Viremia Associates With Thrombosis and Mortality in the ACTIV-4a Trial. 2024, a5011-a5011. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5011.Peer-Reviewed Original Research
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