6533b836fe1ef96bd12a15dc
RESEARCH PRODUCT
Genetic justification of severe COVID-19 using a rigorous algorithm
Ioanna SakellariStyliani I. KokorisTasoula TouloumenidouPanagiotis G. AsterisApostolia PapalexandriChristos VarelasDimitrios ChatzidimitriouMilly BitzaniMohammadreza KoopialipoorIoannis KioumisDanial Jahed ArmaghaniDiamantis ChlorosMaria KoutraRobert A. BrodskyEvaggelia Evdoxia KoravouPenelope Georgia PapayanniAnastasia PapadopoulouDimitrios T. BoumpasSavvas GrigoriadisMaria ChatzidimitriouEvdoxia RaptiDamianos SotiropoulosEleni GavriilakiFani ChatzopoulouStefanos T. ParastatidisAchilles AnagnostopoulosIoannis G. KalantzisAnastasia VeleniEvaggelos KaimakamisLiborio CavaleriArgyris TsantesVassiliki Karalisubject
0301 basic medicineMaleThrombomodulinSeverity of Illness Index0302 clinical medicineRisk FactorsImmunology and AllergyMedicineComplement ActivationRigorous algorithmmedicine.diagnostic_testHigh-Throughput Nucleotide SequencingComplement C3EculizumabEculizumabMiddle AgedHospitalizationSettore ICAR/09 - Tecnica Delle CostruzioniIntensive Care UnitsFactor HComplement Factor HFemaleAlgorithmsmedicine.drugmedicine.medical_specialtyThrombotic microangiopathyCritical CareImmunologyComplementADAMTS13 Protein03 medical and health sciencesInternal medicineFull Length ArticleSeverity of illnessGenetic predispositionGenetic susceptibilityHumansGenetic Predisposition to DiseaseGenetic TestingRisk factorGenetic testingAgedbusiness.industryThrombotic MicroangiopathiesCOVID-19medicine.diseaseComplement system030104 developmental biologySARS-CoV2business030215 immunologydescription
Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (p = 0.022). Analysis of almost infinite variant combinations showed that patients with rs1042580 in thrombomodulin and without rs800292 in complement factor H did not require ICU hospitalization. We also observed gender differences in ADAMTS13 and complement-related variants. In light of encouraging results by complement inhibitors, our study highlights a patient population that might benefit from early initiation of specific treatment.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-04-01 | Clinical Immunology (Orlando, Fla.) |