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Purpose: In the present study, biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) containing insulin were loaded in sodium alginate/jeffamine (ALG/jeff) hydrogel for prolonged delivery of insulin. The main aim of this work was to fabricate an efficient insulin delivery system to improve patient adherence by decreasing the repetition of injections., Methods: Swelling and morphological properties and crosslinking efficiency of ALG/jeff hydrogel were assessed. The composite hydrogel was prepared by adding PHBV NPs to ALG/jeff hydrogel concurrently with crosslinking process. The morphology and loading capacity of composite hydrogel were analyzed., Results: Circular dichroism measurement demonstrated that insulin remains stable following fabrication process. The release profile exhibited 54.6 % insulin release from composite hydrogel within 31 days with minor initial burst release equated to nanoparticles and hydrogels. MTT cell viability analysis was performed by applying L-929 cell line and no cytotoxic effect was observed., Conclusions: Favorable results clearly introduced fabricated composite hydrogel as an excellent candidate for drug delivery systems and also paves the route for prolonged delivery systems of other proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: This retrospective cross-sectional study aimed to assess the outcomes of Covid-19 patients who received remdesivir therapy at the outpatient department of Ziaian Hospital., Method: A total of 514 eligible patients were included between May and September 2021. Covid-19 diagnosis was confirmed through positive SARS-COV-2 PCR tests or chest CT scans. Due to limited hospital beds, patients received remdesivir on an outpatient basis., Results: Patients received six daily doses of remdesivir for 5 days. Those referred to a physician within 7 days of symptom onset had similar hospitalization rates compared to later referrals. Lower blood saturation levels were associated with a higher likelihood of hospital admission, indicating that earlier administration of remdesivir may be more effective. Patients with over 50% lung involvement had higher rates of disease progression despite treatment. Corticosteroids did not significantly improve outcomes in patients with saturation above 90%. Discontinuation of remdesivir due to side effects was rare, with only 1% experiencing increased liver enzymes, 1.2% facial redness and tremors, and 1.5% allergies. After 1 week of treatment, patients commonly reported symptoms such as hair loss, fatigue, body pain, lethargy, and anorexia, particularly among hospitalized patients., Discussion: Patients generally preferred outpatient treatment over hospitalization. Body mass index (BMI) did not significantly impact hospitalization rates, although average weight tended to be higher among inpatients. The study confirmed the effectiveness of remdesivir therapy with a low occurrence of side effects., Conclusion: This retrospective study evaluated the outcomes of Covid-19 patients receiving remdesivir at an outpatient department. Early administration of remdesivir showed better outcomes, while corticosteroids had limited benefits. Outpatient treatment was favored, and BMI did not significantly influence hospitalization rates. Remdesivir demonstrated efficacy with a low incidence of side effects., Competing Interests: The authors declare that they have no conflicts of interest. The authors are responsible for the content and accuracy of the manuscript. The manuscript was reviewed and approved by all authors before submission. The authors agree to the terms and conditions of the journal's publication policy., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Non-pharmacological strategies that have been proposed by complementary medical systems, can be effective in management of COVID-19., Methods: This study was designed as a three-arm, assessor-blinded, randomized controlled trial. A total of 139 hospitalized COVID-19 patients were randomly assigned into three groups: (1) acupuncture (ACUG), (2) cupping (CUPG), and (3) control (CTRG). All participants received conventional treatment. The primary study endpoint included changes in respiratory signs including oxygen saturation (SpO 2 ) and respiratory rate (RR). The secondary endpoints were COVID-19-related hospitalization duration and serious adverse events such as intensive care unit (ICU) admission, intubation or death, all up to day 30. Also, improvements in cough, dyspnea, chest tightness, oxygen demand, anorexia, headache, weakness, sore throat, and myalgia were evaluated., Results: Forty-two patients in ACUG, 44 patients in CUPG, and 42 patients in CTRG completed the trial. After 3 days, SpO 2 and RR improved significantly in CUPG and ACUG compared with CTRG (effect size: 8.49 (6.4 to 10.57) and 8.51 (6.67 to 10.34), respectively: p<0.001). Compared with CTRG, patients in CUPG and ACUG recovered faster (mean difference: 6.58 (4.8 to 8.35) and 9.16 (7.16 to 11.15), respectively) and except for two patients in ACUG who were admitted to ICU, none of patients in ACUG or CUPG needed ICU or intubation (p<0.001 in comparison to CTRG). Amelioration of clinical COVID-19 related symptoms reached a high level of statistical significance in CUPG and ACUG in comparison with CTRG (p<0.01)., Conclusion: Cupping and acupuncture are promising safe and effective therapies in management of COVID-19. Trial registration: This study was registered at Iranian Registry of Clinical Trials: IRCT20201127049504N1 (https://en.irct.ir/trial/52621)., (© 2022 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

The COVID-19 gold standard assessment tool remained the RT-PCR of upper respiratory tract specimen extracted by the nasopharyngeal swab. A positive result would decrease through a three-week course and eventually be undetectable. The maximum duration of viral shedding is 83 days. Besides, COVID-19 RT-PCR remained positive for 74 days in a patient suffering from lymphoma. In this study, we have presented a 56-year-old male patient, a known case of lymphoma since 2015, who experienced many episodes of chemotherapy with a five-month positive RT-PCR COVID-19 laboratory test and finally was intubated and then died of opportunistic pulmonary infections. COVID-19 patients with concurrent lymphoma failed to remove the virus thoroughly, despite providing appropriate treatment regimens., Competing Interests: The authors declare that they have no conflicting interests., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome., Methods: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models., Results: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region., Interpretation: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission., Competing Interests: TS is part of the Data Safety Monitoring Committee of a study to evaluate the safety and immunogenicity of a candidate Ebola Vaccine in children - the GSK3390107A (ChAd3 EBO-Z) vaccine; he is a panel member of Covid-19 Vaccine Benefit Risk Expert Working Group for the Medicines and Healthcare Regulatory Agency (UK); he is a member of COVID-19 Therapeutics Advisory Panel for the UK Department of Health & Social Care; he is the Chair/Co-Chair of the COVID-19 Rapid Response and Rolling Funding Initiatives, which supported the development of the Oxford-AstraZeneca Covid-19 vaccine. In addition, Dr. Solomon has a diagnostic test for bacterial meningitis, based on a blood test, filed for patent pending.

It has been more than a year since the outbreak of COVID-19, and it is still the most critical issue of the healthcare system. Discovering effective strategies to treat infected patients is necessary to decrease the mortality rate. This study aimed to determine the effects of nanocurcumin on the severity of symptoms and length of hospital stay (LOS) in COVID-19 patients. Forty-eight COVID-19 patients were randomly assigned into nanocurcumin (n = 24) and placebo (n = 24) groups receiving 160 mg/day nanocurcumin or placebo capsules for 6 days. Mean differences of O 2 saturation were significantly higher in patients who received nanocurcumin supplements (p = 0.02). Also, nanocurcumin treatment significantly reduced the scores of domains 3 and 4 and the total score of Wisconsin Upper Respiratory System Survey (WURSS-24), indicating milder symptoms in the treatment group (p = 0.01, 0.03, and 0.01 respectively). Besides, the LOS in curcumin groups was lower than in the placebo group, although the difference was not statistically significant (6.31 ± 5.26 vs. 8.87 ± 8.12 days; p = 0.416). CBC/differentiate, hs-CRP level and the pulmonary involvement in CT scan were not different between the two groups. As nanocurcumin can be effective in increasing O 2 saturation and reducing the severity of symptoms in COVID-19 patients, it could probably be used as a complementary agent to accelerate the recovery of patients., (© 2022 John Wiley & Sons Ltd.)

Objective: The goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D 3 (25(OH)D 3 ) in improving vitamin D status in vitamin D-deficient/vitamin D-insufficient patients infected with the SARS-CoV-2 (COVID-19) virus., Methods: This is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review]., Results: A total 106 hospitalized patients who had a circulating 25(OH)D 3 concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D 3 had a sufficient circulating 25(OH)D 3 concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D 3 concentration during the 2-month follow-up. We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D 3 group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D 3 was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality., Conclusion: Our analysis indicated that oral 25(OH)D 3 was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D 3 may be needed to confirm the potential effect of 25(OH)D 3 on reducing clinical outcomes in patients with COVID-19., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Persian medicine has recommended clinical experiences and proper herbal remedies for prevention and treatment of microbial infections and respiratory diseases. An open-label, randomized, controlled, multicenter trial was conducted at five hospitals in Tehran and Isfahan provinces of Iran on 358 hospitalized adult patients. A total of 174 patients received standard care and 184 received herbal remedies (polyherbal decoction every 8 hr and two herbal capsules every 12 hr) plus standard care for 7 days. The primary clinical endpoint was the duration of hospital stay, and secondary outcomes were clinical improvement of symptoms based on self-assessment questionnaire. Results demonstrated that these natural decoction and capsules treatment plus routine care significantly decreased duration of hospital dyspnea (3.291 day vs. 6.468 days), accelerated clinical improvement, and decreased symptoms such as dry cough, dyspnea, muscle pain, headache, fatigue, anorexia, chills, runny nose, sputum cough, and vertigo in the treatment group compared with standard-care group. Significant effects of these polyherbal formulations on improving the symptoms of COVID-19 could be incredibly promising for managing this pandemic with acceptable tolerability., (© 2021 John Wiley & Sons Ltd.)

Background: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease., Methods: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen., Results: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO 2 ) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO 2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups., Conclusions: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

Introduction: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients., Methods: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day -1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population., Results: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study., Conclusions: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase., Competing Interests: Conflict of interest: M. Edalatifard has nothing to disclose. Conflict of interest: M. Akhtari has nothing to disclose. Conflict of interest: M. Salehi has nothing to disclose. Conflict of interest: Z. Naderi has nothing to disclose. Conflict of interest: A. Jamshidi has nothing to disclose. Conflict of interest: S. Mostafaei has nothing to disclose. Conflict of interest: S.R. Najafizadeh has nothing to disclose. Conflict of interest: E. Farhadi has nothing to disclose. Conflict of interest: N. Jalili has nothing to disclose. Conflict of interest: M. Esfahani has nothing to disclose. Conflict of interest: B. Rahimi has nothing to disclose. Conflict of interest: H. Kazemzadeh has nothing to disclose. Conflict of interest: M. Mahmoodi Aliabadi has nothing to disclose. Conflict of interest: T. Ghazanfari has nothing to disclose. Conflict of interest: M. Sattarian has nothing to disclose. Conflict of interest: H. Ebrahimi Louyeh has nothing to disclose. Conflict of interest: S.R. Raeeskarami has nothing to disclose. Conflict of interest: S. Jamalimoghadamsiahkali has nothing to disclose. Conflict of interest: N. Khajavirad has nothing to disclose. Conflict of interest: M. Mahmoudi has nothing to disclose. Conflict of interest: A. Rostamian has nothing to disclose., (Copyright ©ERS 2020.)

As no specific pharmacological treatment has been validated for use in coronavirus disease 2019 (COVID-19), we aimed to assess the effectiveness of azithromycin (AZM) in these patients at a referral centre in Iran. An open-label, randomised controlled trial was conducted on patients with laboratory-confirmed COVID-19. A total of 55 patients in the control group receiving hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) were compared with 56 patients in the case group who in addition to the same regimen also received AZM. Patients with prior cardiac disease were excluded from the study. Furthermore, patients from the case group were assessed for cardiac arrythmia risk based on the American College of Cardiology (ACC) risk assessment for use of AZM and HCQ. The main outcome measures were vital signs, SpO 2 levels, duration of hospitalisation, need for and length of intensive care unit admission, mortality rate and results of 30-day follow-up after discharge. Initially, there was no significant difference between the general conditions and vital signs of the two groups. The SpO 2 levels at discharge were significantly higher, the respiratory rate was lower and the duration of admission was shorter in the case group. There was no significant difference in the mortality rate between the two groups. Patients who received AZM in addition to HCQ and LPV/r had a better general condition. HCQ+AZM combination may be beneficial for individuals who are known to have a very low underlying risk for cardiac arrhythmia based on the ACC criteria., (Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated., Objectives: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients., Patients and Methods: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method., Results: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs., Conclusion: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients., (© 2020 Blackwell Verlag GmbH.)