Background Information on the clinical characteristics and outcomes of hospitalized Covid-19 patients with or without diabetes mellitus (DM) is limited in the Arab region. This study aims to fill this gap. Methods In this single-center retrospective study, medical records of hospitalized adults with confirmed Covid-19 [RT-PCR positive for SARS-CoV2] at King Saud University Medical City (KSUMC)-King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia from May to July 2020 were analyzed. Clinical, radiological and serological information, as well as outcomes were recorded and analyzed. Results A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency (74.7%), DM (68.3%), hypertension (42.6%) and obesity (42.2%). During hospitalization, 77 out of the 439 patients (17.5%) died. DM patients have a significantly higher death rate (20.5% versus 12.3%; p = 0.04) and lower survival time (p = 0.016) than non-DM. Multivariate cox proportional hazards regression model revealed that age [Hazards ratio, HR 3.0 (95% confidence interval, CI 1.7–5.3); p < 0.001], congestive heart failure [adjusted HR 3.5 (CI 1.4–8.3); p = 0.006], smoking [adjusted HR 5.8 (CI 2.0–17.2); p < 0.001], β-blocker use [adjusted HR 1.7 (CI 1.0–2.9); p = 0.04], bilateral lung infiltrates [adjusted HR 1.9 (CI 1.1–3.3); p = 0.02], creatinine > 90 µmol/l [adjusted HR 2.1 (CI 1.3–3.5); p = 0.004] and 25(OH)D < 12.5 nmol/l [adjusted HR 7.0 (CI 1.7–28.2); p = 0.007] were significant predictors of mortality among hospitalized Covid-19 patients. Random blood glucose ≥ 11.1 mmol/l was significantly associated with intensive care admission [adjusted HR 1.5 (CI 1.0–2.2); p = 0.04], as well as smoking, β-blocker use, neutrophil > 7.5, creatinine > 90 µmol/l and alanine aminotransferase > 65U/l. Conclusion The prevalence of DM is high among hospitalized Covid-19 patients in Riyadh, Saudi Arabia. While DM patients have a higher mortality rate than their non-DM counterparts, other factors such as old age, congestive heart failure, smoking, β-blocker use, presence of bilateral lung infiltrates, elevated creatinine and severe vitamin D deficiency, appear to be more significant predictors of fatal outcome. Patients with acute metabolic dysfunctions, including hyperglycemia on admission are more likely to receive intensive care.

Aims/hypothesis Impaired fibrin clot lysis is a key abnormality in diabetes and complement C3 is one protein identified in blood clots. This work investigates the mechanistic pathways linking C3 and hypofibrinolysis in diabetes using ex vivo/in vitro studies. Methods Fibrinolysis and C3 plasma levels were determined in type 1 diabetic patients and healthy controls, and the effects of glycaemia investigated. C3 incorporation into fibrin clots and modulation of fibrinolysis were analysed by ELISA, immunoblotting, turbidimetric assays and electron and confocal microscopy. Results Clot lysis time was longer in diabetic children than in controls (599±18 and 516±12 s respectively; p<0.01), C3 levels were higher in diabetic children (0.55±0.02 and 0.43± 0.02 g/l respectively; p<0.01) and both were affected by improving glycaemia. An interaction between C3 and fibrin was confirmed by the presence of lower protein levels in sera compared with corresponding plasma and C3 detection in plasma clots by immunoblot. In a purified system, C3 was associated with thinner fibrin fibres and more prolongation of lysis time of clots made from fibrinogen from diabetic participants compared with controls (244±64 and 92±23 s respectively; p<0.05). Confocal microscopy showed higher C3 incorporation into diabetic clots compared with controls, and fully formed clot lysis was prolonged by 764±76 and 428±105 s respectively (p<0.05). Differences in lysis, comparing diabetes and controls, were not related to altered plasmin generation or C3-fibrinogen binding assessed by plasmon resonance. Conclusions/interpretation C3 incorporation into clots from diabetic fibrinogen is enhanced and adversely affects fibrinolysis. This may be one novel mechanism for compromised clot lysis in diabetes, potentially offering a new therapeutic target.

Women with type 2 diabetes have compact clots with compromised fibrinolysis compared with men. There are gender-specific associations between clotting parameters and cardiometabolic risk factors in this population, whereas vascular abnormalities, impaired renal function, and smoking are associated with prothrombotic clot structure profile regardless of gender.

Purpose As the world continues to cautiously navigate its way through the coronavirus disease 2019 (COVID-19) pandemic, several breakthroughs in therapies and vaccines are currently being developed and scrutinized. Consequently, alternative therapies for severe acute respiratory coronavirus 2 (SARS-CoV-2) prevention, such as vitamin D supplementation, while hypothetically promising, require substantial evidence from countries affected by COVID-19. The present retrospective casecontrol study aims to identify differences in vitamin D status and clinical characteristics of hospitalized patients screened for SARS-CoV-2, and determine associations of vitamin D levels with increased COVID-19 risk and mortality. Methods A total of 222 [SARS-CoV-2 (+) N = 150 (97 males; 53 females); SARS-CoV-2 (−) N = 72 (38 males, 34 females)] out of 550 hospitalized adult patients screened for SARS-CoV-2 and admitted at King Saud University Medical City-King Khalid University Hospital (KSUMC-KKUH) in Riyadh, Saudi Arabia from May-July 2020 were included. Clinical, radiologic and serologic data, including 25(OH)D levels were analyzed. Results Vitamin D deficiency (25(OH)D < 50 nmol/l) was present in 75% of all patients. Serum 25(OH)D levels were significantly lower among SARS-CoV-2 (+) than SARS-CoV-2 (−) patients after adjusting for age, sex and body mass index (BMI) (35.8 ± 1.5 nmol/l vs. 42.5 ± 3.0 nmol/l; p = 0.037). Multivariate regression analysis revealed that significant predictors for SARS-CoV-2 include age > 60 years and pre-existing conditions (p < 0.05). Statistically significant predictors for mortality adjusted for covariates include male sex [Odds ratio, OR 3.3 (95% confidence interval, CI 1.2-9.2); p = 0.02], chronic kidney disease [OR 3.5 (95% CI 1.4-8.7); p = 0.008] and severe 25(OH)D deficiency (< 12.5 nmol/l), but at borderline significance ; p = 0.06]. Conclusion In hospital settings, 25(OH)D deficiency is not associated with SARS-CoV-2 infection, but may increase risk for mortality in severely deficient cases. Clinical trials are warranted to determine whether vitamin D status correction provides protective effects against worse COVID-19 outcomes. KeywordsVitamin D • COVID-19 • Case-control • Saudi Arabia • Severe vitamin D deficiency AbdullahM. Alguwaihes and Shaun Sabico contributed equally.