Efficacy and safety of convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized clinical trial

Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. The CORIPLASM study was an open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19, including immunocompromised patients. Patients hospitalised with COVID-19 and less than 9 days since symptoms onset were assigned to receive 4 units of plasma over 2 days ({approx} 840 ml)(CCP) or usual care alone (UC). Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) [≥]6 on the 10-point scale on day (d) 4 and survival without ventilation or additional immunomodulatory treatment by d14. A total of 120 patients were recruited and assigned to CCP (n=60) or UC (n=60), including 22 (CCP) and 27 (UC) immunocompromised patients. Thirteen (22%) patients with CCP had a WHO-CPS [≥]6 at d4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95%CI 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0{middle dot}10 -1{middle dot}53]), and 7 (12%) with CCP and 12 (20%) with UC at d28 (aHR 0.51 [95%CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in immunocompromised patients (HR 0.37 [95%CI 0.14-0.97]). CCP treatment did not improve early outcomes in patients with moderate COVID-19 but was associated with reduced mortality in the subgroup of immunocompromised patients.

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts.

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs.

Identification of driver genes for severe forms of COVID-19 in a deeply phenotyped young patient cohort

The etiopathogenesis of severe COVID-19 remains unknown. Indeed given major confounding factors (age and co-morbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major co-morbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 "critical" (in the ICU under mechanical ventilation) and 25 "non-critical" (in a noncritical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from noncritical patients, several driver genes promoted severe COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was replicated in an independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible. One sentence summaryEtiopathogenesis of severe COVID19 in a young patient population devoid of comorbidities.