Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings

There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays-a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)-on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

Applying precision medicine to unmet clinical needs in psoriatic disease

Psoriatic disease is a heterogeneous condition that can affect peripheral and axial joints (arthritis), entheses, skin (psoriasis) and other structures. Over the past decade, considerable advances have been made both in our understanding of the pathogenesis of psoriatic disease (PsD) and in the treatment of its diverse manifestations. However, several major areas of continued unmet need in the care of patients with PsD have been identified. One of these areas is the prediction of poor outcome, notably radiographic outcome in patients with psoriatic arthritis, so that stratified medicine approaches can be taken; another is predicting response to the numerous current and emerging therapies for PsD, so that precision medicine can be applied to rapidly improve clinical outcome and reduce the risk of toxicity. In order to address these needs, novel approaches, including imaging, tissue analysis and the application of proteogenomic technologies, are proposed as methodological solutions that will assist the dissection of the critical immune-metabolic pathways in this complex disease. Learning from advances made in other inflammatory diseases, it is time to address these unmet needs in a multi-centre partnership aimed at improving short-term and long-term outcomes for patients with PsD.Cambridge Arthritis Research Endeavour (CARE) National Institute for Health Researc