ABO Blood Group in Relation to COVID-19 Susceptibility and Clinical Outcomes: A Retrospective Observational Study in the United Arab Emirates.

(1) Background: The association between ABO blood groups and COVID-19 outcomes was investigated in several studies. The results were controversial. This study aimed to explore the association between ABO blood groups and COVID-19 outcomes. (2) Methods: This retrospective study included 303 COVID-19 patients treated at the NMC Royal Hospital in the United Arab Emirates between 8 April 2020 and 30 June 2020. (3) Results: The mean age of patients included in the study was 39.3 ± 10.7 years, and 72.9% of patients were males. The prevalence of blood groups O, A, B, and AB was 40.3%, 27.7%, 25.1%, and 6.9%, respectively. The correlation between ABO blood groups and COVID-19 outcomes was insignificant except in the AB group, with significantly higher odds of disease severity. Increased age, higher body mass index (BMI), and being of male gender increased the risk for pneumonia among all blood groups. Both increased age and higher BMI increased the risk of mortality, and increased age increased the risk of disease severity. Troponin and platelet counts were significantly different in the A group compared to the non-A groups. Time to viral clearance was not different among blood groups. However, adjustment for Rh groups resulted in a significantly shorter time in the B group. (4) Conclusions: There was no significant association between ABO blood groups and COVID-19 outcomes, with the exception of group AB.

The significance of antiglobulin (Coombs) test reactivity in patients with COVID-19.

Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or "Coombs" test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.

Vitamin D Status in Relation to the Clinical Outcome of Hospitalized COVID-19 Patients.

Coronavirus Disease (COVID-19) is a newly emerged infectious disease that first appeared in China. Vitamin D is a steroid hormone with an anti-inflammatory protective role during viral infections, including SARS-CoV-2 infection, via regulating the innate and adaptive immune responses. The study aimed to investigate the correlation between serum 25-hydroxyvitamin D (25[OH]D) levels and clinical outcomes of COVID-19. This was a retrospective study of 126 COVID-19 patients treated in NMC Royal Hospital, UAE. The mean age of patients was 43 ± 12 years. Eighty three percentage of patients were males, 51% patients were with sufficient (> 20 ng/mL), 41% with insufficient (12-20 ng/mL), and 8% with deficient (<12 ng/mL) serum 25(OH)D levels. There was a statistically significant correlation between vitamin D deficiency and mortality (p = 0.04). There was a statistically significant correlation between 25(OH)D levels and ICU admission (p = 0.03), but not with the need for mechanical ventilation (p = 0.07). The results showed increased severity and mortality by 9 and 13%, respectively, for each one-year increase in age. This effect was maintained after adjustment for age and gender (Model-1) and age, gender, race, and co-morbidities (Models-2,3). 25(OH)D levels (<12 ng/mL) showed a significant increase in mortality by eight folds before adjustments (p = 0.01), by 12 folds in Model-1 (p = 0.04), and by 62 folds in the Model-2. 25(OH)D levels (< 20 ng/mL) showed no association with mortality before adjustment and in Model-1. However, it showed a significant increase in mortality by 29 folds in Model-3. Neither 25(OH)D levels (<12 ng/mL) nor (< 20 ng/mL) were risk factors for severity. Radiological findings were not significantly different among patients with different 25(OH)D levels. Despite observed shorter time till viral clearance and time from cytokine release storm to recovery among patients with sufficient 25(OH)D levels, the findings were statistically insignificant. In conclusion, we demonstrated a significant correlation between vitamin D deficiency and poor COVID-19 outcomes.

Reduced ADAMTS13 Activity in Correlation with Pathophysiology, Severity, and Outcome of COVID-19: A Retrospective Observational Study.

BACKGROUND: Low ADAMTS13 activity has been suggested to be an interplaying factor in the pathogenesis of COVID-19, considering that it is a thromboinflammatory disease with high risk of microthrombosis. OBJECTIVES: The study aimed to explore the correlation between ADAMTS13 activity and the pathophysiological pathway of COVID-19. METHODS: We carried out a retrospective observational study of 87 patients with COVID-19 in NMC Royal Hospital, Abu Dhabi, UAE. ADAMTS13 activity was measured and compared with patients' characteristics and clinical outcomes. RESULTS: Low ADAMTS13 activity was associated with pneumonia (p = 0.007), severity of COVID-19 (p <0.001), and mechanical ventilation rates (p = 0.018). Death was more frequently observed among patients (5 patients) with low ADAMTS13 activity compared with normal activity (1 patient), as well as inflammatory markers. Decreased ADAMTS13 activity increased with the risk of pneumonia, severity of COVID-19, need for mechanical ventilation, and use of anticoagulants ([OR = 4.75, 95% CI 1.54-18.02, p = 0.011], [OR = 6.50, 95% CI 2.57-17.74; p <0.001], [OR = 4.10, 95% CI 1.29-15.82; p = 0.024], [OR = 8.00, 95% CI 3.13-22.16; p <0.001], respectively). The low ADAMTS13 activity group had a slightly longer time to viral clearance than the normal ADAMTS13 activity group, but it was not statistically significant (20 days, 95% CI 16-27 days vs 17 days, 95% CI 13-22 days; p = 0.08; Log rank = 3.1). CONCLUSIONS: Low ADAMTS13 activity has been linked to pneumonia, COVID-19 severity, use of anticoagulants, and need for mechanical ventilation but not to mortality. We propose rADAMTS13 as a novel treatment for severe COVID-19.

Treatment Outcomes of Tocilizumab in Critically-Ill COVID-19 Patients, Single-Centre Retrospective Study.

(1) Background: Severe COVID-19 outcomes are associated with cytokine release syndrome, characterized by the release of several immune modulators, including Interleukin-6 (IL-6). Tocilizumab (TCZ) is an IL-6 receptor antagonist used to treat rheumatic arthritis. The study aimed to evaluate the efficacy and safety of TCZ against COVID-19. (2) Methods: This was a retrospective study including 49 severe COVID-19 patients who received TCZ therapy in NMC Royal Hospital, UAE. (3) Results: Before Tocilizumab administration, the median temperature was 37.0 (IQR 36.0-39.6), and after day seven, the median reduced to 36.5 (IQR 35.8-37.9), p > 0.001. Thirty (61.2%) patients were admitted to the ICU, of which, eight (16.3%) were on WHO scale 4, sixteen (32.6%) on scale 5, and six (20.0%) on scale 6. TCZ reduced inflammatory markers over time, including CRP, D-Dimer, Ferritin, and Fibrinogen. By the end of week seven, 14 patients died (28.6%) while 35 (71.4%) improved and were discharged. (4) Conclusions: The study showed limited improvements in COVID-19 outcomes with TCZ therapy and highlighted the importance of D-Dimer monitoring for possible risk of thrombosis. Additionally, it could be recommended to upgrade the anti-coagulation dose to therapeutic levels once TCZ therapy is decided upon.

Pharmaceutical evaluation and dynamic vapor sorption studies of fast dissolving intraoral films of Loratadine.

The aim of the study was to develop intraoral films (IOFs) of loratadine and to assess the storage conditions by dynamic vapour sorption studies. The excipient selection was guided by drug excipient compatibility studies and the incompatibility of loratadine with dibutylphathalate and Tween20 was confirmed by Electro-spray Ionization Mass Spectrometry. Thus intaroral films were developed using HPMC E-15 LV and polyvinyl alcohol (PVA) as lone and mixed film formers to get eighteen formulations (F1- F18) that varied in the type and amount of plasticizer used. Four formulations selected on the basis of pharmacotechnical characteristics were improvised by inclusion of Poloxamer407 that lowered the dissolving time to the tune of 36-55%. Dynamic vapour sorption studies of the improvised films (PF1-PF4) demonstrated an increase of 2% by weight at 50% relative humidity (RH) and 25°C suggesting storage of the films below the stated conditions. In vitro drug release studies in phosphate buffer pH 6.8 demonstrated more than 94% cumulative drug release from the formulations. Analysis of model independent parameters identified PF2 as the best formulation that was nine times superior in its dissolution efficiency to Lorafast tablets(®).