Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Adult T-cell lymphoma/leukaemia with haematemesis as a prodromal manifestation.

We report a case of adult T-cell leukaemia/lymphoma (ATLL) with haematemesis as a prodromal manifestation. The patient was a 34-year-old woman from Yazd. She also gave a history of a fluctuating skin lesions consisting of non-pruritic papules and ulcers on her feet. Upper gastrointestinal endoscopy disclosed obvious nodularities without ulceration in the antrum of the stomach. Histological and immunohistochemical studies of the gastric biopsy specimen showed lymphomatous infiltration of diffuse pleomorphic type with a T-cell phenotype. Laboratory investigations revealed leucocytosis (consisting of highly atypical lymphocytes, many with clover-leaf-shaped nuclei) and hypercalcaemia. She was found to be seropositive for human T-lymphotropic virus type 1. A diagnosis of overt ATLL was made. The findings in this case indicate that an awareness of the existence of this disease in a non-endemic area such as Yazd is necessary to avoid potential misdiagnosis and be helpful in appropriate therapeutic decision.

The efficacy of magnesium sulfate loading on microalbuminuria following SIRS: One step forward in dosing.

BACKGROUNDS: Magnesium has been known for its antioxidative and antiinflammatory properties in many studies. In this study two dosing regimens of magnesium were compared with a placebo control group in order to investigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma patients. Inflammatory and oxidative factors were measured in this trial. METHODS: 45 trauma patients with systemic inflammatory response syndromes (SIRS) were randomly assigned into 2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g of MgSO4 over 4 hour infusion, and placebo group received saline alone. The initial and post magnesium sulfate injections levels of tumor necrosis factor alpha (TNF-α), total antioxidant power and lipid peroxidation were measured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level of microalbuminuria were also determined. RESULTS: Repeated measurements illustrated that there was no significant difference in TNF-α, total antioxidant power and lipid peroxidation levels among groups during the period of analysis. The microalbuminuria at 36 hour post infusion of high dose group was lower than that of control group (p = 0.024). Patient's mortality (28 day) was similar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing any complications. CONCLUSION: No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive patients was found. Magnesium in high doses may be recommended for traumatic patients with SIRS status to prevent microalbuminuria.