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New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron's spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of CPA relies on the detection of the IgG Aspergillus antibody, which is not freely available, especially in resource-poor settings. Point-of-care tests like LDBio Aspergillus ICT lateral flow assay, evaluated in only a few studies, have shown promising results for the diagnosis of CPA. However, no study has compared the diagnostic performances of LDBio LFA in setting of tuberculosis endemic countries and have compared it with that of IgG Aspergillus. Objectives: This study aimed to evaluate the diagnostic performances of LDBio LFA in CPA and compare it with existing the diagnostic algorithm utilising ImmunoCAP IgG Aspergillus. Methods: Serial patients presenting with respiratory symptoms (cough, haemoptysis, fever, etc.) for >4 weeks were screened for eligibility. Relevant investigations, including direct microscopy and culture of respiratory secretions, IgG Aspergillus, chest imaging, etc., were done according to existing algorithm. Serums of all patients were tested by LDBio LFA and IgG Aspergillus (ImmunoCAP Asp IgG) and their diagnostic performances were compared. Results: A total of 174 patients were included in the study with ~66.7% patients having past history of tuberculosis. A diagnosis of CPA was made in 74 (42.5%) of patients. The estimated sensitivity and specificity of LDBio LFA was 67.6% (95% CI: 55.7–78%) and 81% (95% CI: 71.9–88.2%), respectively, which increased to 73.3% (95% CI: 60.3–83.9%) and 83.9% (95% CI: 71.7–92.4%), respectively, in patients with a past history of tuberculosis. The sensitivity and specificity of IgG Aspergillus was 82.4% (95% CI: 71.8–90.3%) and 82% (95% CI: 73.1–89%); 86.7% (95% CI: 75.4–94.1%) and 80.4% (95% CI: 67.6–89.8%), in the whole group and those with past history of tuberculosis, respectively. Conclusions: LDBio LFA is a point-of-care test with reasonable sensitivity and specificity. However, further tests may have to be done to rule-in or rule-out the diagnosis of CPA in the appropriate setting. [ABSTRACT FROM AUTHOR]