Role of prior immunity in binding to spike of "future" Omicron subvariants.

BACKGROUND: Throughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. The binding of these to spike protein of "future" variants in the context of such heterogeneous exposure has not been studied. METHODS: We tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework. RESULTS: Antibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both 'High S' and 'Low S' of Delta and Omicron periods were closely related to "future" subvariants by Antigenic Cartography. Sera from different S groups clustered together with 'Low S' interspersed between 'High S' on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies. CONCLUSIONS: Hybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to "future" variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the 'Low S' antibody demonstrates similar binding.

Common mental disorders in South Asian patients with systemic sclerosis: a CIS-R-based cross-sectional study.

There are not many studies looking at psychological impact of physical morbidities amongst patients with systemic sclerosis. Our aim was to describe the prevalence of common mental disorders (CMD) in systemic sclerosis patients, as against the population prevalence of CMDs. We also wanted to assess the utility of revised clinical interview schedule (CIS-R), a standardised interview technique for screening CMDs in systemic sclerosis (SSc). We prospectively recruited 93 consecutive patients fulfilling the 2013 ACR/EULAR criteria for systemic sclerosis from our single tertiary care centre. They were interviewed using CIS-R interviewing technique. These patients were assessed for the presence of psychiatric symptoms and presence of common mental disorders. Various associations of documented mental health issues and ICD-10-based psychiatric diagnosis were also analysed. A total of 29 (31%) out of 93 individuals with systemic sclerosis had a common mental disorder as per the earlier defined CIS-R cut off score of 12 and above. Fatigue (50.5%) and sleep issues (43%) were the commonest symptoms. Thirty-four patients (33.6%) fulfilled a total of 39 ICD-10 psychiatric diagnoses. Total CIS-R score is significantly associated with duration of Scleroderma in univariate analysis (p = 0.019), but there was no significant association on a multivariate analysis. Depression [18.3% as against 5% in Asian Indian general population], followed by obsessive compulsive disorder (OCD) [15.1% as against 0.7% in general population in India] were the top two ICD-10 psychiatric diagnosis in SSc. The occurrence of both depression and OCD, therefore, are far in excess compared to community prevalence. Additionally, modified CIS-R cut off of 10 instead of 12 can also improve the sensitivity (94%) of this screening interviewing tool for an ICD-10 psychiatric diagnosis. Depression is 3.4 times and OCD is 20 times commoner in our cohort of SSc than general population in India. A modified CIS-R cut-off score of 10 may further help in early recognition of these mental disorders in SSc and their referral to a psychiatrist.

Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.