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.

Differential alterations in peripheral lymphocyte subsets in COVID-19 patients: upregulation of double-positive and double-negative T cells.

BACKGROUND: Viral infections cause alteration in the total number of lymphocytes and their subset distribution. We aimed to study peripheral blood lymphocyte subsets in COVID-19 patients and to correlate these subsets with clinical and laboratory data, which may help in clarifying the pathogenesis to develop novel diagnostic and prognostic biomarkers for COVID-19. METHODS: Twenty-six reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 patients were subjected to medical history-taking and a thorough clinical examination. Laboratory tests included complete blood count, D dimer, ferritin, and C-reactive protein (CRP). Chest CT was used to diagnose COVID-19 pneumonia. Lymphocyte subsets were compared with those in 20 healthy controls using flow cytometry. RESULTS: Leucopenia, relative neutrophilia, lymphopenia, eosinopenia together with marked elevation in neutrophil/lymphocyte ratio were observed in our COVID-19 patients. A marked reduction was observed in T cells, including both CD4 and CD8 cells, natural killer (NK), and natural killer T cells (NKT). Double-positive T (DPT) cells, double-negative T (DNT) cells, and B cells were elevated in the patients relative to the other lymphocyte subsets. CONCLUSION: Immune-inflammatory parameters are of utmost importance in understanding the pathogenesis and in the provisional diagnosis of COVID-19. Yet, adequate care must be taken during their interpretation because of the vast discrepancies observed between studies even in the same locality. Further studies are needed to clarify the role of B cells, DPT, and DNT cells in the pathogenesis and control of COVID-19.

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.