Dataset Information

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19.

ABSTRACT: Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.

SUBMITTER: Zguro K

PROVIDER: S-EPMC9227269 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Carriers of <i>ADAMTS13</i> Rare Variants Are at High Risk of Life-Threatening COVID-19.

Zguro Kristina K Baldassarri Margherita M Fava Francesca F Beligni Giada G Daga Sergio S Leoncini Roberto R Galasso Lucrezia L Cirianni Michele M Rusconi Stefano S Siano Matteo M Francisci Daniela D Schiaroli Elisabetta E Luchi Sauro S Morelli Giovanna G Martinelli Enrico E Girardis Massimo M Busani Stefano S Parisi Saverio Giuseppe SG Panese Sandro S Piscopo Carmelo C Capasso Mario M Tacconi Danilo D Spertilli Raffaelli Chiara C Giliberti Annarita A Gori Giulia G Katsikis Peter D PD Lorubbio Maria M Calzoni Paola P Ognibene Agostino A Bocchia Monica M Tozzi Monica M Bucalossi Alessandro A Marotta Giuseppe G Furini Simone S Gen-Covid Multicenter Study Renieri Alessandra A Fallerini Chiara C

Viruses 20220529 6

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging t ...[more]

PMID: 35746657

Similar Datasets

Project description:BackgroundWith the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections.MethodsBased on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza.ResultsIn the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33-10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34-6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05-9.75]) and seasonal influenza (6.01 [95% CI 3.53-10.26], p for difference = 0.902) cohorts.ConclusionCOVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.

Dataset Information

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19.

Publications

Carriers of <i>ADAMTS13</i> Rare Variants Are at High Risk of Life-Threatening COVID-19.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets