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Genome-wide PBMCs Profiling Reveals Early Detection of Immunothrombotic Dysregulation in COVID-19 based on Blood Routine Test: A Multi-Center Retrospective Study of 1219 Patients

ABSTRACT: The present study aimed to develop algorithms for early identification of patients who are at risk of being involved in abnormal immunothrombosis, enabling prompt interventions and averted progression of disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE167930 | GEO | 2021/10/06

REPOSITORIES: GEO

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Project description:BackgroundImplausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases.MethodsUsing a data set of 88,294 NIPT performed at University Hospital Leuven (Belgium) between November 2013 and March 2020, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection. In this approach, whole-genome cell-free DNA (cfDNA) data from NIPT were scrutinized for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy, using an unbiased NIPT analysis pipeline coined GIPSeq. For suspected cases, the presence of a maternal cancer was evaluated via subsequent multidisciplinary clinical follow-up examinations. The cancer-specificity of the identified CNAs in cfDNA was assessed through genetic analyses of a tumor biopsy.FindingsFifteen women without a cancer history were identified with a GIPSeq result suggestive of a malignant process. Their cfDNA profiles showed either genome-wide aberrations or a single trisomy 8. Upon clinical examinations, a solid or hematological cancer was identified in 4 and 7 cases, respectively. Three women were identified as having a clonal mosaicism. For one case no underlying condition was found. These numbers add to a PPV of 73%. Based on this experience, we presented a multidisciplinary care path for efficient clinical management of these cases.InterpretationThe presented approach for analysing NIPT results has a high PPV, yet unknown sensitivity, for detecting asymptomatic malignancies upon routine NIPT. Given the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting, such as via the care model that we presented here.FundingThis work was supported by Research Foundation Flanders and KU Leuven funding.

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Genome-wide PBMCs Profiling Reveals Early Detection of Immunothrombotic Dysregulation in COVID-19 based on Blood Routine Test: A Multi-Center Retrospective Study of 1219 Patients

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