The Role of Convalescent Plasma and Tocilizumab in the Management of COVID-19 Infection: A Cohort of 110 Patients from a Tertiary Care Hospital in Oman.

AIM: As Coronavirus Disease-2019 (COVID-19) pandemic continues to evolve, the search for safe and effective therapeutic interventions remain essential. METHODS: We conducted a retrospective cohort study on patients hospitalized with laboratory confirmed severe acute respiratory syndrome coronavirus-2 infection, comparing standard of care along with Convalescent Plasma with or without Tocilizumab (CP vs. CPT). RESULTS: A total of 110 patients were enrolled with an overall mean age of 50 ± 16 years. Patients on CPT were more likely to have had acute respiratory distress syndrome (77% vs. 42%; p < 0.001), sepsis (9.7% vs. 0; p = 0.036), chest X-ray abnormalities (71% vs. 44%; p = 0.004), intensive care unit admission (84% vs. 56%; p = 0.001) as well as being on mechanical ventilation (79% vs. 48%; p = 0.001). After CPT treatment, all measured inflammatory markers, except interleukine-6, showed an overall steady decline over time (all p-values <0.05) and the ventilatory parameters showed significant improvement of PaO2/FiO2 ratio from 127 to 188 within 7 days (p < 0.001). Additionally, 52% (32/62) of the patients had favorable outcome, either as improvement of ventilatory parameters or extubation within 14 days of hospitalization. However, mortality rate in those on CPT was higher than those who received CP alone (24% vs. 8.3%; p = 0.041). CONCLUSION: In patients with severe COVID-19 infection, using tocilizumab with convalescent plasma is associated with improvement in inflammatory and ventilatory parameters but no effect on mortality. These findings require validation from randomized clinical trials.

Early-phase GVHD gene expression profile in target versus non-target tissues: kidney, a possible target?

GVHD is a major complication after allo-SCT. In GVHD, some tissues like liver, intestine and skin are infiltrated by donor T cells while others like muscle are not. The mechanism underlying targeted tropism of donor T cells is not fully understood. In the present study, we aim to explore differences in gene expression profile among target versus non-target tissues in a mouse model of GVHD based on chemotherapy conditioning. Expression levels of JAK-signal transducers and activators of transcription (STAT), CXCL1, ICAM1 and STAT3 were increased in the liver and remained unchanged (or decreased) in the muscle and kidney after conditioning. At the start of GVHD the expression levels of CXCL9, ITGb2, SAA3, MARCO, TLR and VCAM1 were significantly higher in the liver or kidney compared with the muscle of GVHD animals. Moreover, biological processes of inflammatory reactions, leukocyte migration, response to bacterium and chemotaxis followed the same pattern. Our data show that both chemotherapy and allogenicity exclusively induce expression of inflammatory genes in target tissues. Moreover, gene expression profile and histopathological findings in the kidney are similar to those observed in the liver of GVHD mice.

Omega-3 from fish oil augments GVHD through the enhancement of chemotherapy conditioning regimen and selective FoxP3 depletion.

Omega-3 is known to enhance the effects of several chemotherapeutic agents and to exert several immunoregulatory actions In the present study, we evaluated the effects of a 21-day feeding regimen with omega-3-rich fish oil (FO) and its corresponding control, omega-6 rich corn oil (CO), on the BU-CY conditioning and the development of GVHD after BMT in mice. Before conditioning, FO, but not CO, feeding caused a significant attenuation in the number and functionality of splenic FoxP3+ T regulatory cells (Treg). FO feeding also enhanced the effects of the conditioning through severe depletion of Treg cells in the spleen and CD11b+ myeloid cells in both the BM and spleen. Consequently, FO-fed animals conditioned with BU-CY showed exacerbated GVHD following transplantation with allogeneic BM and splenic cells. In contrast, identical transplantation in CO-fed mice resulted in poor engraftment and body weight loss. Moreover, in standard-fed recipients, BMT with cells from FO-fed donors resulted in moderate GVHD and improved the survival time, whereas BMT with cells from CO-fed donors shortened the survival time and caused anemia. We conclude that food supplements should be considered in patients undergoing BMT and/or chemotherapy treatment.

Histocompatibility antigens in Omanis: Comparison with other Gulf populations and implications for disease association.

BACKGROUND: This is the first comprehensive report of HLA antigens in Omanis, and the first application of HLA sequence-specific primer (SSP) DNA typing in a Gulf population. The objective was to compare the findings with other Gulf populations and assess their implications for disease association. PATIENTS AND METHODS: HLA typing was carried out on 321 healthy Omanis. One hundred and twenty-six of these were typed for Class II antigens by low-resolution SSP DNA typing. The results were compared with other HLA antigen frequencies recorded from Kuwait and Saudi Arabia. RESULTS: The Omani population was characterized by a very high incidence of HLA-DR2 (66%), with associated HLA-DQ1 (76%) and a reduced incidence of DR4, DR7 and DR53. The incidence of DR2 is the highest recorded worldwide. HLA-A11, A32, B17, B35 and B40 were significantly higher than in Kuwait and Saudi Arabia, and A9, B21(B50) significantly lower (Pc<0.05). HLA-B27 is very low in the Omani population (0.3%). The high incidence of HLA-DR2 in Oman and disparities in the frequency of other antigens would indicate that there has not been any significant migration from northern Arabia. Class II DNA typing revealed that DR16 was the predominant split of DR2 (63%), with DR15 being 18% and both DR15 and 16 being found in 6%, giving a total of 87% for A centAADR2A centAA-associated antigens (serology of the same individuals gave a DR2 incidence of 74%). The major disparity between serology and DNA typing was in the definition of DR4 (serology 8%, DNA 14%) and DR51 (53% vs. 70%). CONCLUSION: The frequency of many HLA antigens in Omanis differs significantly from frequencies found in the populations of Kuwait and Saudi Arabia, possibly reflecting different migration patterns. The high incidence of HLA-DR2 in Oman may have important implications for disease association.

HLA antigens in Omanis with blinding trachoma: markers for disease susceptibility and resistance.

AIM: To determine the presence of HLA antigens in people with blinding trachoma. METHODS: Fifty Omanis with blinding trachoma were serologically typed for HLA A, B, C, DR, and DQ antigens and DNA typed for class II DR beta and DQ beta alleles and compared with a population of 100 healthy controls. RESULTS: chi 2 analysis of serological reactions did not reveal any significant differences in HLA antigen frequencies after correction of probability, although DR4, DR7, and DR53 were completely absent in the patients and all of the patients were HLA DQ1 positive. In the case of DQ1 the relative risk was 22.6 (95% confidence interval of 20.7-24.7). Class II DNA low resolution DR beta typing showed a significant increase in HLA DR16 (pc = 0.036, relative risk = 3.8) and a significant decrease in HLA DR53 (pc = 0.018, relative risk = 0.05). CONCLUSION: The finding that HLA DR16 (a DR2 subtype) is associated with susceptibility to blinding trachoma, a disease that is caused by an intracellular micro-organism, is consistent with reports of an HLA DR2 association with leprosy and tuberculosis, diseases also caused by an intracellular micro-organism. Similarly, resistance to leprosy is associated with HLA DR53 as is the case with blinding trachoma described here. It is postulated that HLA DR2 or subtypes in association with HLA DQ 1 may enable an intracellular micro-organism to enter the cell or are involved in presentation of peptides derived from intracellular micro-organisms to T lymphocytes initiating a delayed hypersensitivity or autoimmune reaction. These findings are the first report that genetic factors are of major importance in the development and protection against blinding trachoma.