Objective: To determine the clinical outcomes of older COVID-19 patients who received DMB compared to those who did not. We hypothesized that fewer patients administered DMB would require oxygen therapy and/or intensive care support than those who did not. Methodology: Cohort observational study of all consecutive hospitalized COVID-19 patients aged 50 and above in a tertiary academic hospital who received DMB compared to a recent cohort who did not. Patients were administered oral vitamin D3 1000 IU OD, magnesium 150mg OD and vitamin B12 500mcg OD (DMB) upon admission if they did not require oxygen therapy. Primary outcome was deterioration post-DMB administration leading to any form of oxygen therapy and/or intensive care support. Results: Between 15 January and 15 April 2020, 43 consecutive COVID-19 patients aged ≥50 were identified. 17 patients received DMB and 26 patients did not. Baseline demographic characteristics between the two groups was significantly different in age. In univariate analysis, age and hypertension showed significant influence on outcome while DMB retained protective significance after adjusting for age or hypertension separately in multivariate analysis. Fewer DMB patients than controls required initiation of oxygen therapy during their hospitalization (17.6% vs 61.5%, P=0.006). DMB exposure was associated with odds ratios of 0.13 (95% CI: 0.03 – 0.59) and 0.20 (95% CI: 0.04 – 0.93) for oxygen therapy and/or intensive care support on univariate and multivariate analyses respectively. Conclusions: DMB combination in older COVID-19 patients was associated with a significant reduction in proportion of patients with clinical deterioration requiring oxygen support and/or intensive care support. This study supports further larger randomized control trials to ascertain the full benefit of DMB in ameliorating COVID-19 severity.

Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA⁺, CD127⁺, CCR7⁺, CD62L⁺, CXCR3⁺) first developed into effector T cells (CD45RA^+/−, CD127^+/−, CCR7^+/−, CD62L⁺, CXCR3⁺), followed by three intermediate stages: intermediate T cells 1 (CD45RO⁺, CD127^+/−, CCR7⁺, CD62L⁺, CXCR3⁺), intermediate T cells 2 (CD45RO⁺, CD127⁻, CCR7⁻, CD62L⁺, CXCR3⁺), and intermediate T cells 3 (CD45RO^+/−, CD127⁺, CCR7⁺, CD62L⁻, CXCR3⁺) before reverting to stable CD45RA⁺ central memory T cells (CD45RA⁺, CD127⁺, CCR7⁺, CD62L⁺, CXCR3⁺). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO⁺, CD127⁻, CCR7⁻, CD62L⁻, CXCR3⁺). Furthermore, intermediate T cells 2 or effector memory T cells, when cultured in persistent inflammatory cytokines devoid of anti-CD3, were converted to central memory T cells (CD45RO⁺, CCR7⁺, CD62L⁺). Overall, these results support ex vivo memory-like T lymphocyte production and favor a developmental pathway including both divergent and linear relationships.

Aim: The new radioimmunotherapeutic regime GAP15R aims to stimulate glucocorticoid-induced TNF-related protein (G) to overcome Treg suppression; add IFN- (A) to promote inflammatory milieu; block PD1 (P) to disinhibit T effector cytotoxicity; add IL-15 (15) to enhance danger signals & T-cell expansion; and apply radiation (R) at critical time point to sustain localized inflammation. Patients & methods/materials & methods: This was tested in a murine 4T1 metastatic breast carcinoma model given GAP15R with regular monitoring of tumor volume and complications. Results: We had demonstrated long-term complete remission up to 50% of treated mice, which is not associated with major treatment-related complication, in cases with specific tumor burden. Conclusion: GAP15R is efficacious with potential to be applicable to other tumors.

COVID-19 and metabolic syndrome, though seemingly different disorders, appear to share certain common pathogenic components, especially in the development of COVID-19-associated diabetes mellitus. The similarities include impairment in immunoendothelial, gastrointestinal, pancreatic, adipose and mitochondrial functions, with several critical micronutrients undergirding the intricate interactions among these dysfunctions. This discussion aims to highlight the parallels between COVID-19 and metabolic syndrome and to propose the possibility of SARS-CoV-2 being a prototype of an acquired etiological agent which can eventually lead to the development of classical metabolic syndrome. Based on the proposed model, the discussion will include the implication for early management of COVID-19 and metabolic syndrome.

We report a successful case of immune tolerance to factor VIII (FVIII) inhibitor after a major operation. An attempt was made to induce immune tolerance with inhibitor in a haemophilia A patient, who was required to undergo an above-knee amputation. We opted to give high-dose FVIII infusion with no immunosuppression. The highest preoperative FVIII inhibitor level was 5 BU and the peak postoperative FVIII inhibitor level was 1.5 BU demonstrated on Day 9 post operation. High-dose FVIII support was provided during the perioperative period and continued with a low maintenance dose to achieve a FVIII level of 30% to 40%. The requirement of high-dose FVIII lasted from day 6 to 23 post operation and this was tailed down to a maintenance dose over the next 37 days. There were only 2 episodes of mild oozing from the wound at around Day 9, which coincided with the peak postoperative FVIII inhibitor level. Both bleeding episodes were arrested adequately by administering a single dose of FEIBA during each episode. Immune tolerance was demonstrated after around 3 months and a follow-up period of 233 days showed no recurrence of FVIII inhibitor with the normalisation of FVIII half-life study. After immune tolerance, the patient suffered fewer episodes of joint haemorrhage and required a lower amount of FVIII infusion as well. The cost may be high initially but the longterm cost-effectiveness has to be carefully evaluated.