The aim of this study was to evaluate the efficacy of anakinra in patients who were admitted to hospital for severe COVID-19 pneumonia requiring oxygen therapy. A prospective, open-label, interventional study in adults hospitalized with severe COVID-19 pneumonia was conducted. Patients in the interventional arm received subcutaneous anakinra (100 mg twice daily for 3 days, followed by 100 mg daily for 7 days) in addition to standard treatment. Main outcomes were the need for mechanical ventilation and in-hospital death. Secondary outcomes included successful weaning from supplemental oxygen and change in inflammatory biomarkers. Outcomes were compared with those of historical controls who had received standard treatment and supportive care. A total of 69 patients were included: 45 treated with anakinra and 24 historical controls. A need for mechanical ventilation occurred in 14 (31%) of the anakinra-treated group and 18 (75%) of the historical cohort (p < 0.001). In-hospital death occurred in 13 (29%) of the anakinra-treated group and 11 (46%) of the historical cohort (p = 0.082). Successful weaning from supplemental oxygen to ambient air was attained in 25 (63%) of the anakinra-treated group compared with 6 (27%) of the historical cohort (p = 0.008). Patients who received anakinra showed a significant reduction in inflammatory biomarkers. In patients with severe COVID-19 pneumonia and high oxygen requirement, anakinra could represent an effective treatment option and may confer clinical benefit. ISRCTN74727214.

: Identifying immune cells involved in COVID-19 disease progression and predictors of poor outcomes is important to manage patients adequately. : A prospective observational cohort study enrolled 53 mild non-hospitalized and 48 hospitalized confirmed COVID-19 patients to a tertiary hospital in Oman. : Hospitalized patients were older (58 years vs 36 years, p <0.001) and had more comorbid conditions like diabetes (65 % Vs 21% p<0.001). Hospitalized patients had significantly higher inflammatory markers (p<0.001); C-reactive protein (CRP) (114 vs 4 mg/L), Interleukin-6 (IL-6) (33 vs 3.71pg/ml), lactate dehydrogenase (LDH) (417 vs 214 U/L), ferritin (760 vs 196 ng/mL), fibrinogen (6 vs 3 g/L), D-dimer (1.0 vs 0.3 mcg/mL), disseminated intravascular coagulopathy (DIC) score (2 vs 0) and neutrophil/lymphocyte ratio (4 vs 1.1), (p<0.001). In multivariate regression analysis, statistically significant independent early predictors of ICU admission or death were higher levels of IL-6 (OR 1.03, p=0.03), frequency of large inflammatory monocytes (CD14+CD16+) (OR 1.117, p=0.010) and frequency of circulating naïve CD4+ T cells (CD27+CD28+CD45RA+CCR7+) (OR 0.476, p=0.03). : IL-6, frequency of large inflammatory monocytes, and circulating naïve CD4 T cells can be used as independent immunological predictors of poor outcomes in COVID-19 patients to prioritize critical care and resources.

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.

There are limited data on short- versus long-term changes in adaptive immune response across different COVID-19 disease severity groups. A multicenter prospective study of 140 adult patients with COVID-19 (a total of 325 samples) were analyzed for inflammatory markers and lymphocyte subsets at presentation, week 2, and week 24. Inflammatory markers at presentation were higher in the critical/severe than in moderate and mild groups. A predominance of memory B cell response in the mild and moderate group was noted by week 2. In contrast, the immune system in the severe/critical group was dysfunctional, with expansion of exhausted CD8+ T cells and atypical memory B cells. By 24 weeks, there was a possible trend of normalization. There was substantial difference in the degree of inflammation and distribution of different B and T cell subsets in the different disease severity groups. Despite the initial dysfunctional immune response in the severe/critical group, a comparable memory B and CD8+ T cell responses to the mild group was achieved at 24 weeks.