Role of Potential Biomarkers in Management and Prognosis of Corona Virus Disease.

Corona virus disease is a global pandemic. One of the key issues has been the very high volume of patients presenting to health centres or hospitals during the outbreak. It clearly overwhelms the human and mechanistic capacities available. Therefore, early and effective predictors of clinical outcomes are required for risk stratification. MATERIAL: This is hospital based retrospective study on patients who were admitted in Covid wards/ICU at IGGMC. Patients were divided into 3 groups- mild-moderate; severe; and critical based on their clinical presentation on admission. Several biomarkers like WBC, platelets, N/L, CRP, LDH, S. ferritin, d-dimer, CPK-MB, Serum creatinine, BUL, SGOT, SGPT, Serum albumin were analysed before and after treatment. OBSERVATION: 110 patients were enrolled in this study, 36 were classified into mild-moderate, 56 into severe and 18 into critical. As all of mild-moderate patients were discharged and majority of critical patients expired, biomarkers were compared between severe patients who were discharged vs severe patients who died. Out of these biomarkers, CRP was significantly decreased during course of treatment in severe patients who were discharged (p = 0.004) in comparison to severe patients who died where CRP was significantly increased (p = 0.001) (p value of difference being 0.00001). There was also significant change in ferritin levels (p = 0.006), while other biomarkers like WBC (p = 0.07), platelets (p = 0.066), N/L (p = 0.3), LDH (p = 0.06), d-dimer (p = 0.1), CPK-MB (p = 0.49), serum creatinine (p = 0.05), urea (p = 0.06), S. albumin (p= 0.3), SGOT (p =0.07), SGPT (p=0.25) did not show promising results. In addition, various treatment protocols were analysed by comparing CRP before and after treatment. Severe patients were divided into 2 groups, who took injection Remdesivir along with antibiotics, LMWH, systemic steroids vs who didn't, and CRP level were compared, but the difference was not significant (p = 0.06). Pre and post treatment CRP was also compared for Tocilizumab, Fevipiravir, Hydroxychloroquine, Doxycyline, but none of them were able to decrease CRP significantly (p > 0.05) in the severe or critical group but these drugs were effective in reducing CRP significantly (p<0.05) when given in mild-moderate group or if the treatment was started early. CONCLUSION: Increment in CRP and ferritin could effectively predict clinical outcome and could be used for risk stratification but no available drug is effective in reducing these biomarkers significantly in severe or critical group.

Implementation of Plate Imaging for Demonstration of Monoclonality in Biologics Manufacturing Development.

Monoclonality of mammalian cell lines used for production of biologics is a regulatory expectation and one of the attributes assessed as part of a larger process to ensure consistent quality of the biologic. Historically, monoclonality has been demonstrated through statistics generated from limiting dilution cloning or through verified flow cytometry methods. A variety of new technologies are now on the market with the potential to offer more efficient and robust approaches to generating and documenting a clonal cell line.Here we present an industry perspective on approaches for the application of imaging and integration of that information into a regulatory submission to support a monoclonality claim. These approaches represent the views of a consortium of companies within the BioPhorum Development Group and include case studies utilising imaging technology that apply scientifically sound approaches and efforts in demonstrating monoclonality. By highlighting both the utility of these alternative approaches and the advantages they bring over the traditional methods, as well as their adoption by industry leaders, we hope to encourage acceptance of their use within the biologics cell line development space and provide guidance for regulatory submission using these alternative approaches.LAY ABSTRACT: In the manufacture of biologics produced in mammalian cells, one recommendation by regulatory agencies to help ensure product consistency, safety, and efficacy is to produce the material from a monoclonal cell line derived from a single, progenitor cell. The process by which monoclonality is assured can be supplemented with single-well plate images of the progenitor cell. Here we highlight the utility of that imaging technology, describe approaches to verify the validity of those images, and discuss how to analyze that information to support a biologic filing application. This approach serves as an industry perspective to increased regulatory interest within the scope of monoclonality for mammalian cell culture-derived biologics.