B CELL CHARACTERISTICS at BASELINE PREDICT HUMORAL RESPONSE UPON SARS-COV-2 VACCINATION among PATIENTS TREATED with RITUXIMAB

Background: Vaccination is considered efficient in controlling infections incl. SARS-CoV-2. Prior studies showed that patients receiving rituximab (RTX) with low B cell counts are at increased infectious risk (1) and risk of inadequate vaccination responses (2, 3). Thus, the ability to further defne and predict vaccination responses in these patients may guide their optimal protection. Objectives: To assess predictive biomarkers of vaccination responses upon SARS-CoV-2 vaccination in RTX treated patients. Methods: B cell characteristics before vaccination were evaluated to predict responses in 15 patients with autoimmune infammatory rheumatic diseases receiving RTX. 11 patients with rheumatoid arthritis on other therapies (RA), 11 kidney transplant recipients (KTR) and 15 healthy volunteers (HC) served as controls. A multidimensional analysis of B cell subsets and a correlation matrix were performed to identify predictive biomarkers. Results: Signifcant differences regarding absolute B cell counts and specifc subset distribution pattern between the groups were validated at baseline. Here, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) comprised naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells (Figure 1). Moreover, there was a positive correlation between neutralizing antibodies and absolute B cell numbers with B cells expressing HLA-DR and CXCR5 (involved in antigen presentation and germinal center formation) as well as an inverse correlation with CD95 expression and CD21low expression (marker for activation and exhaustion) on B cells. Conclusion: Substantial repopulation of naïve B cells upon RTX therapy appears to be essential for an adequate vaccination response requiring germinal center formation. In contrast, expression of exhaustion markers (CD21low, CXCR5-, CD95+) indicate negative predictors of vaccination responses. These results may guide optimized vaccination strategies in RTX treated patients clearly requiring antigen-inexperienced B cells for appropriate protection.

Omicron - The new SARS-CoV-2 challenge?

SARS-CoV-2 virus has infected nearly 300 M people worldwide and has been associated with over 6 M deaths by March 2022. Since the virus emergence in December 2019 in Wuhan, several new mutations have been described. The World Health Organization has developed a working name for these emerging variants according to their impact on the worldwide population. In this context a high alert has been paid to variants of concern (VOC) due to their high infectiousness and transmissibility patterns. The most recent VOC, Omicron (B.1.1.529), has become dominant in the shortest time ever and has placed Europe under an overwhelming and unprecedented number of new cases. This variant has numerous mutations in regions that are associated with higher transmissibility, stronger viral binding, affinity and antibody escape. Moreover, the mutations and deletions present in the spike protein suggest that the SARS-CoV-2 specific attachment inhibitors may not be the best option for Omicron therapy. Omicron is the dominant variant circulating worldwide and, at the end of February 2022, it was responsible for nearly all sequences reported to GISAID. Omicron is made up of several sublineages, where the most common are BA.1 and BA.2 (or Nextstrain clade 21K and 21L, respectively). At a global level, it is possible to say that the proportion of BA.2 has been increasing relative to BA.1 and in some countries it has been replacing it at high rates. In order to better assess the Omicron effectiveness on antibody escape, spread and infectious ability it is of the highest relevance to maintain a worldwide tight surveillance. Even though this variant has been associated with a lower death rate, it is important to highlight that the number of people becoming infected is concerning and that further unpredictable mutations may emerge as the number of infected people rises.

SOCIAL IMPACT FOR THE COVID-19 IN ECUADOR

The COVID-19 it is an originated illness for the SAKS virus CoV-2, that has floated countries and continent, has occasioned an unusual level of human suffering social agitation and damage economic, but, although the expansion of the current crisis not has not preceding someone, the new crown virus are the new succeeding thing of a lineage of illnesses that have emerged in recent decades. In the Ecuadoran economy the impact of the COVID-19, is significant, due to the abutment of the peoples in your homes, the parayzation of activities, the reduction of personnel in the undertakings;the diminution of the formal commerce and unreliable, which has caused a serious economic crisis for the population, whom fights day to day to supply your basic needs., adapt and it, fulfills one's obligations to the new ready measures for the national Ecuadoran government. In agreement with it related the objective of the present work is to decide the social impact that the COVID-19, has occasioned in equator, for such end employed a descriptive and exploratory investigation, centered in an analysis on the reality of the social institutes;in the equator in front of the COVID-19. Given the complexity of the problem of the pandemic at worldwide level and of country it is verified as main indicators of social impacts. the increase of the indexes of poverty and of extreme poverty the persistence of the inequalities and the generalized displeasure of the population with the actions of the central government in front of the COVID-19.