Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia.

Purpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group "ivermectin group" included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients "placebo group" who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No: NCT04951362.

Diabetic ketoacidosis in patients with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA). OBJECTIVES: To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA. DESIGN: A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. METHODS: Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis. We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient's final treatment outcome (survival or death). RESULTS: Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from < 1 years to 66 years across studies. Most of the patients (n = 309, 48.3%) had pre-existing type 2 diabetes mellitus. The majority of the patients were male (n = 373, 58.4%) and belonged to Hispanic (n = 156, 24.4%) and black (n = 98, 15.3%) ethnicity. The median random blood glucose level, HbA1c, pH, bicarbonate, and anion gap in all included patients at presentation were 507 mg/dl [IQR 399-638 mg/dl], 11.4% [IQR 9.9-13.5%], 7.16 [IQR 7.00-7.22], 10 mmol/l [IQR 6.9-13 mmol/l], and 24.5 mEq/l [18-29.2 mEq/l]; respectively. Mortality rate was [63/243, 25.9%], with a majority of death in patients of Hispanic ethnicity (n = 17, 27%; p = 0.001). The odd ratios of death were significantly high in patients with pre-existing diabetes mellitus type 2 [OR 5.24, 95% CI 2.07-15.19; p = 0.001], old age (≥ 60 years) [OR 3.29, 95% CI 1.38-7.91; p = 0.007], and male gender [OR 2.61, 95% CI 1.37-5.17; p = 0.004] compared to those who survived. CONCLUSION: DKA is not uncommon in SARS-CoV-2 patients with diabetes mellitus and results in a mortality rate of 25.9%. Mortality key determinants in DKA patients with SARS-CoV-2 infection are individuals with pre-existing diabetes mellitus type 2, older age [≥ 60 years old], male gender, BMI ≥ 30, blood glucose level > 1000 mg/dl, and anion gap ≥ 30 mEq/l.

Therapeutic efficacy of macrolides in management of patients with mild COVID-19.

Evidence on the efficacy of adding macrolides (azithromycin or clarithromycin) to the treatment regimen for COVID-19 is limited. We testify whether adding azithromycin or clarithromycin to a standard of care regimen was superior to standard of supportive care alone in patients with mild COVID-19.This randomized trial included three groups of patients with COVID-19. The azithromycin group included, 107 patients who received azithromycin 500 mg/24 h for 7 days, the clarithromycin group included 99 patients who received clarithromycin 500 /12 h for 7 days, and the control group included 99 patients who received standard care only. All three groups received only symptomatic treatment for control of fever and cough .Clinical and biochemical evaluations of the study participants including assessment of the symptoms duration, real-time reverse transcription-polymerase chain reaction (rRT-PCR), C-reactive protein (CRP), serum ferritin, D-dimer, complete blood count (CBC), in addition to non-contrast chest computed tomography (CT), were performed. The overall results revealed significant early improvement of symptoms (fever, dyspnea and cough) in patients treated with either azithromycin or clarithromycin compared to control group, also there was significant early conversion of SARS-CoV-2 PCR to negative in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).There was no significant difference in time to improvement of fever, cough, dyspnea, anosmia, gastrointestinal tract "GIT" symptoms and time to PCR negative conversion between patients treated with azithromycin compared to patients treated with clarithromycin (p > 0.05 for all). Follow up chest CT done after 2 weeks of start of treatment showed significant improvement in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).Adding Clarithromycin or azithromycin to the therapeutic protocols for COVID-19 could be beneficial for early control of fever and early PCR negative conversion in Mild COVID-19.Trial registration: (NCT04622891) www.ClinicalTrials.gov retrospectively registered (November 10, 2020).

Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19.

BACKGROUND: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. OBJECTIVE: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. METHODS: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. RESULTS: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. CLINICALTRIALSGOV IDENTIFIER: NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

Olfactory Disturbances as Presenting Manifestation Among Egyptian Patients with COVID-19: Possible Role of Zinc.

COVID-19 is a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). Deficiency of zinc has been supposed to contribute to loss of smell and taste in COVID-19 patients. Our study aimed to assess the serum zinc levels among patients with COVID-19 of various severities, with and without olfaction dysfunction, and to evaluate the effect of zinc therapy in recovery of smell dysfunction among such patients. This study included 134 patients; real-time reverse transcription-polymerase chain reaction (rRT-PCR) proved SARS-CoV-2. Serum zinc levels were measured for all infected patients. One hundred and five patients were detected to have anosmia and/or hyposmia and were categorized randomly into 2 groups; the first group included 49 patients who received zinc therapy and the second group included 56 patients who did not received zinc. All patients were followed up for the recovery duration of olfactory and gustatory symptoms and duration of complete recovery of COVID-19. Olfactory dysfunction was reported in 105 patients (78.4%). Serum zinc levels were not significantly different between the patient subgroups regarding disease severity or the presence or absence of olfactory and/or gustatory dysfunction (p ˃ 0.05). The median duration of recovery of gustatory and/or olfactory function was significantly shorter among patients who received zinc therapy than those who did not received zinc (p < 0.001), while the median duration of complete recovery from COVID-19 was not significantly different among the two groups (p ˃ 0.05). Although the zinc status of COVID-19 patients did not exhibit a significant role in development of anosmia and/or hyposmia or disease severity, zinc therapy may have a significant role in shortening the duration of smell recovery in those patients without affecting the total recovery duration from COVID-19.

Characteristics, Outcomes and Indicators of Severity for COVID-19 Among Sample of ESNA Quarantine Hospital's Patients, Egypt: A Retrospective Study.

BACKGROUND: The risk factors, disease characteristics, severity, and mortality of COVID-19 are unclear, particularly in Egypt. OBJECTIVE: The objective was to analyze the patients' characteristics, hematological, biochemical, and chest imaging findings among the cohort of patients with COVID-19 in Egypt and also to shed light on the predictors of COVID-19 severity. PATIENTS AND METHODS: A retrospective study was conducted on 66 patients with COVID-19 in Egypt. Medical history, imaging data (CT chest findings), and measured hematological and biochemical parameters at diagnosis were recorded in the form of complete blood counts and differential counts; CRP, ESR, serum ferritin, creatinine, and liver function tests . Results of real-time reverse transcription-polymerase chain reaction (rRT-PCR) for detection of SARS-CoV-2 RNA at diagnosis and during follow up of these patients were also recorded. RESULTS: The study included 36 patients with mild to moderate COVID-19 and 30 patients with severe/critical infection. There was a significant older age among severe (62.6 years old ±10.1SD) than mild to moderate infection (55.5 ± 10.1) (p˂0.05). Fever, dry cough, dyspnea, and sore throat malaise were highly frequent among COVID-19 patients, while headache and diarrhea were the least frequently occurring manifestations. All included cases (30 patients, 100%) with severe COVID-19 showed crazy-paving appearance (in the form of reticular and/or interlobular septal thickening) with or without GGO. There were significantly lower mean values of WBCs, lymphocytic count, total protein, and albumin among the severely infected than those who had mild to moderate COVID-19 infection, p˂0.05 for all. Additionally, there were significantly higher mean values of CRP, ESR, ferritin, ALT, and AST among patients with severe/critical COVID-19 when compared with those having mild to moderate COVID-19, p˂0.05 for all. CONCLUSION: Among the studied demographic, clinical, hematological, biochemical, and imaging data, dyspnea, diabetes mellitus, lymphopenia, raised CRP, ESR, ferritin, ALT, AST, low albumin, and presence of CT chest findings could be considered as predictors for COVID-19 severity using binary logistic regression analysis.

Indicators of Critical Illness and Predictors of Mortality in COVID-19 Patients.

COVID-19 is an emerging disease all over the world and spreading at an unpredicted rate, resulting in significant influences on global economies and public health. Clinical, laboratory, and imaging characteristics have been partially described in some observational studies. Not enough systematic reviews on predictors of critical illness and mortality in COVID 19 have been published to date. In this review, we had illustrated the prognostic predictors of COVID-19 by gathering published information on the risk factors related to the outcomes of SARS-CoV-2 infections.