Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Correlation between herpes zoster and stroke-A case-control study.

Cerebrovascular accident is the second most common cause of death in the world. Herpes zoster (HZ) is reported to be a major trigger of the stroke syndrome. Considering the high prevalence of stroke in Iran, we carried out a study to assess the correlation between stroke and HZ. This is one of the very few studies carried out on this correlation in Asian nations. One hundred and five cases and 105 controls were included in this study. The cases had been diagnosed with stroke by a neurologist and confirmed by brain imaging. The controls had never had any type of stroke. Both groups were between 30 and 90 years of age. We looked for the HZ infection in both groups. Logistic regression analysis was used to evaluate the association between stroke and HZ. The mean age of the cases was 63.95 ± 12.24 years and the man age of the controls was 66.99 ± 14.58 years. There was a significant difference in the HZ infection between the cases and the controls (P < .0001). Head zoster (including ophthalmic zoster) was significantly higher in the case group than the control group (P < .0001). The risk of stroke was the highest 2-4 weeks after the onset of HZ and the incidences of ischemic stroke were higher than those of hemorrhagic stroke (P < .0001). In an analysis adjusted for the age, sex, and hypertension, HZ was found to be associated with an increased risk of stroke (odds ratio, 5.84; 95% confidence interval, 1.98-8.23). Close monitoring is suggested for cerebrovascular diseases in patients who have had the head zoster, especially in the first month after the infection.

Effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19: a randomized controlled trial.

Objective: Spirulina (arthrospira platensis) is a cyanobacterium proven to have anti-inflammatory, antiviral, and antioxidant effects. However, the effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19 is currently unclear. This study aimed to evaluate the efficacy and safety of high-dose Spirulina platensis for SARS-CoV-2 infection. Study Design: We conducted a randomized, controlled, open-label trial involving 189 patients with COVID-19 who were randomly assigned in a 1:1 ratio to an experimental group that received 15.2g of Spirulina supplement plus standard treatment (44 non-intensive care unit (non-ICU) and 47 ICU), or to a control group that received standard treatment alone (46 non-ICU and 52 ICU). The study was conducted over six days. Immune mediators were monitored on days 1, 3, 5, and 7. The primary outcome of this study was mortality or hospital discharge within seven days, while the overall discharge or mortality was considered the secondary outcome. Results: Within seven days, there were no deaths in the Spirulina group, while 15 deaths (15.3%) occurred in the control group. Moreover, within seven days, there was a greater number of patients discharged in the Spirulina group (97.7%) in non-ICU compared to the control group (39.1%) (HR, 6.52; 95% CI, 3.50 to 12.17). Overall mortality was higher in the control group (8.7% non-ICU, 28.8% ICU) compared to the Spirulina group (non-ICU HR, 0.13; 95% CI, 0.02 to 0.97; ICU, HR, 0.16; 95% CI, 0.05 to 0.48). In non-ICU, patients who received Spirulina showed a significant reduction in the levels of IL-6, TNF-α, IL-10, and IP-10 as intervention time increased. Furthermore, in ICU, patients who received Spirulina showed a significant decrease in the levels of MIP-1α and IL-6. IFN-γ levels were significantly higher in the intervention group in both ICU and non-ICU subgroups as intervention time increased. No side effects related to Spirulina supplements were observed during the trial. Conclusion: High-dose Spirulina supplements coupled with the standard treatment of COVID-19 may improve recovery and remarkably reduce mortality in hospitalized patients with COVID-19. Clinical Trial Registration: https://irct.ir/trial/54375, Iranian Registry of Clinical Trials number (IRCT20210216050373N1).

Is single point HbA1c a reliable predictor for death in severe COVID-19?

Introduction: The severity of COVID-19 infection is affected by several risk factors such as Diabetes Mellitus (DM). The current study aimed to determine the effect of single-point HbA1c on the severity and mortality of hospitalized COVID-19 patients. Methods: This cross-sectional study was conducted among hospitalized moderate and severe COVID-19 patients in Baharloo Hospital in Iran between December 23rd and February 23rd, 2021. The patients have been diagnosed by Polymerase Chain Reaction (PCR) and Chest Computed Tomography (CT) imaging as COVID-19. Demographic data, clinical presentation, laboratory results, and treatments along with the HbA1c data were included. Results: 165 COVID-19 cases were included in this study; 126 (76.4%) of which were severe cases. 89 (53.9%) patients were male, with a mean age of 59.89 ± 16.59 years. Severe COVID-19 patients were more prone to a longer hospital stay, and a higher level of inflammatory mediators, compared to the moderate COVID-19 patients (p < 0.05). No significant association was found between single point HbA1c, FBS, and severity and mortality of COVID-19 cases (p > 0.05). Conclusions: Single point HbA1c was not a reliable mediator for the prediction of severity or death in hospitalized COVID-19 patients.

Sputnik V vaccine-related complications and its impression on inflammatory biomarkers in healthcare providers.

PURPOSE: The current pandemic made scientists create new platforms of vaccines to fight against SARS-CoV-2. Without a doubt, the new forms of present vaccines could develop a diversity of unknown complications. Sputnik V vaccine with two different adenovirus vectors (Ad26 priming and Ad5 boost) was first announced safe and effective by Russia. However, there are controversies surrounding this vaccine such as the possible decline of its immunogenicity and diminished neutralizing capacity against some Covid-19 variants. In addition, its impression on serum biomarkers is not clearly surveyed. The present study aimed to evaluate the frequency of Sputnik V vaccine-related complications and its impression on inflammatory and hematologic biomarkers. MATERIALS &METHODS: An observational cohort study was performed to evaluate the side effects and serum biomarkers changes in healthcare workers receiving Sputnik V vaccine. The vaccine adverse events were recorded daily within 60 days. The blood samples were obtained before vaccination, and on the10th day after each dose of vaccination. The prevalence of all complications and inflammatory biomarkers levels were compared between two doses. All analyses were performed using SPSS software version 22.0. RESULTS: Totally, 126 participants completed the study. The mean age was 37.19 â€‹± â€‹7.73 years. The prevalence of all complications was higher following the first dose than the second dose. The most common side effects were pain at the injection site, body pain, fever, headache, weakness, vertigo, sore throat and sleep disorder. The hematocrit, mean corpuscular volume of red blood cells and neutrophils count declined following vaccination significantly (P-value; 0.04, 0.039, 0.000 respectively). CONCLUSION: It seems the side effects of Sputnik-V vaccine are mild and decrease significantly after the second dose. The decreasing level of hematocrit, MCV and neutrophil count was found significant following vaccination.

Global COVID-19 vaccine acceptance rate: a systematic review and meta-analysis.

Aim: Achieving high COVID-19 vaccination coverage rates is essential as soon as a vaccine is available to deal with and end this pandemic. Due to the different amounts of COVID-19 vaccine acceptance rates in different regions, the pooled estimation of this rate is essential. Therefore, we conducted a systematic review and meta-analysis to investigate worldwide COVID-19 vaccine acceptance rates. Subject and methods: International databases (including, Web of sciences, PubMed, and Scopus) were searched to identify related studies. The heterogeneity among studies was assessed using the I2 index, the Cochran Q test, and T2. A random-effects model was used to pool estimate vaccine acceptance rates. Results: The overall pooled estimate of COVID-19 vaccine acceptance rate was 65.1 (95% CI 60.1-70.1; P < 0.001, I2 = 99.8). The vaccine acceptance rate in the general population was 68.5 (95% CI 62.5-74.5; P < 0.001, I2 = 99.8) and among healthcare workers (HCWs) was 55.9 (95% CI 47.8-64.1; P < 0.001, I2 = 99.6). The lowest COVID-19 vaccine acceptance rate was in the Middle East (46.1% (35.1-57.0)), and the highest coverage rate was (85% (71-99.1)) in South America. Conclusion: COVID-19 vaccine acceptance rate among HCWs is lower than the general population. More studies are recommended to identify related factors to the COVID-19 vaccine acceptance rate.

Renin-Angiotensin-Aldosterone Axis Inhibition Improves Outcome of Diabetic Patients with Chronic Hypertension and COVID-19: An Iranian Perspective.

Background: Safe use of drugs such as angiotensin-converting enzyme 2 (ACE2) inhibitors and angiotensin receptor blockers (ARBs) in COVID diabetic patients needs comprehensive studies. This study addressed this issue from the Iranian perspective. Materials and Methods: Admitted COVID-19 patients were divided into four groups in this historical cohort study. Group 1 included 740 non-diabetic, non-hypertensive patients. Group 2 included 132 non-hypertensive diabetic patients. Group 3 included 154 non-diabetic hypertensive patients. Group 4 included 183 diabetic patients who were under ACE inhibitors or ARBs. Death, intensive care unit (ICU) admission, and length of hospitalization were compared between the groups. Results: After considering associated factors such as age, gender, dyslipidemia, cardiovascular diseases, rheumatoid arthritis (RA), chronic kidney disease (CKD), history of surgery, and corticosteroid use, diabetic patients (group 2) were associated with increased mortality (CI 95%, OR 1.93 [1.11-3.33]). Presence of diabetes (group 2) and hypertension were associated with an increased need for ICU admission (CI 95%, OR 1.69 [1.04-2.76]; CI 95%, OR 1.71 [1.08-2.71], respectively). Group 4 patients although having a similar rate of ICU admission with group 2 and 3 patients, had significantly better ICU survival. Conclusions: The current study suggests that ACE inhibitors and ARBs are associated with decreased mortality, ICU admission, and better ICU survival in the diabetic subgroup of hypertensive patients.

High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial.

Objective: In the COVID-19 pandemic, the SARS-CoV-2 virus has infected millions of people worldwide. Mortality primarily results from the inflammation state and its complications. High-dose melatonin has been established as an anti-inflammatory agent. This study evaluated high-dose melatonin as an adjuvant therapy in critically ill patients with SARS-CoV-2 infection. Methods: We conducted a double-blinded, randomized clinical trial of 21 mg of melatonin per day compared with a placebo in 67 patients with COVID-19. We enrolled patients older than 18 years of age with documented SARS-CoV-2 infection, who were admitted to the intensive care unit and underwent invasive mechanical ventilation. Administration of melatonin and placebo through a nasogastric tube continued for 5 days. The main outcomes were mortality rate, duration of mechanical ventilation, changes in oxygenation indices, and C-reactive protein (CRP) levels. Results: No significant differences were observed in mortality and duration of mechanical ventilation between the control and intervention groups. After 5 days of the intervention, the mean (±standard deviation) CRP and platelet count were 47.28 (±38.86) mg/L and 195.73 (±87.13) × 1000/µL, respectively, in the intervention group and 75.52 (±48.02) mg/L and 149.62 (±68.03) × 1000/µL, respectively, in the control group (P < 0.05). Conclusion: High-dose melatonin in intubated patients with COVID-19 was associated with a decrease in CRP levels. However, this treatment did not apparently affect patient outcomes.

A historical cohort study to investigation of statins safety in COVID-19 hospitalized patients.

BACKGROUND AND OBJECTIVES: A notable proportion of COVID-19 patients need statins for their co-existing conditions. Statins possess several anti-inflammatory properties. We have attempted to describe potential association of exposure to statins and severity of COVID symtpoms in a historical study in hospitalized COVID-19 patients. METHODS: This single-center, historical cohort study was performed in Baharloo hospital as a referral hospital for COVID-19 patients in Tehran. Patients were divided into two groups; 163 statins users and 547 non-users. Mortality rate, intensive care unit (ICU) admission and length of hospitalization were compared between studied groups. In addition, during the investigation, pre-existing conditions were evaluated for groups. If a significant difference was observed between groups, the feature was considered in the adjustment of the odds ratio. RESULTS: At the beginning, statistical analysis study showed that statins users had significantly (p<0.0001) higher mortality rate, ICU admission and length of hospitalization. But after implementation of variables such as age, sex, diabetes, hypertension status, stroke, dyslipidemia, cardiovascular diseases, chronic kidney disease (CKD), corticosteroids, renin-angiotensin-aldosterone axis inhibitors and proton pump inhibitors (PPIs) for adjustment of the odds ratio, a considerable alteration appeared in the studied values. Following adjustment of odds ratio it was shown that statins did not change mortality (95% CI, OR 0.71 (0.41-1.22), p=0.22), ICU admission (95% CI, OR 1.05 (0.66-1.66), p=0.835) and length of hospitalization (95% CI, OR 1.30 (0.78-2.17), p=0.311). In addition, we found that statins could not decrease inflammatory markers in COVID-19 infected patients. CONCLUSION: The use of statins did not seem to change outcomes in COVID19.

Antibiotic resistance: a comparison between inpatient and outpatient uropathogens.

BACKGROUND: Urinary tract infection is one of the most common infections and its treatment is complicated by the emergence of antibiotic resistance. Resistance patterns of organisms differ between community-acquired and hospital-associated urinary tract infections. AIMS: The aim of this study was to determine the most effective antibiotics against uropathogens and if antibiotic resistance differed by setting (inpatient versus outpatient). METHODS: This 2016-2017 cross-sectional study examined 300 midstream clean-catch urine samples with positive culture (150 outpatient and 150 inpatient samples) for the uropathogens isolated and the resistance of these pathogens to different antibiotics. Samples were obtained from the laboratory of Baharloo hospital, Tehran. The differences in antibiotic resistance between inpatient and outpatient uropathogens were analysed using the chi-squared test. RESULTS: Escherichia coli (72.0% of the 300 samples) and Klebsiella spp (13.0%) were the most common uropathogens isolated. A greater proportion of inpatient samples showed resistance to ceftriaxone, cefixime, sulfamethoxazole-trimethoprim, ciprofloxacin and nalidixic acid than the outpatient samples (P < 0.05). The most effective antibiotics for Gram-negative uropathogens were imipenem (only 6.0% of these uropathogens overall were antibiotic-resistant), amikacin (6.3%) and nitrofurantoin (10.3%). CONCLUSIONS: Uropathogen resistant rates in inpatients were higher than outpatient rates. The use of imipenem and amikacin instead of traditional first-line empirical therapy (fluoroquinolone and sulfamethoxazole-trimethoprim) is advised for hospitalized patients with urinary tract infections.

Characteristics and outcomes of COVID-19 pneumonia in pregnancy compared with infected nonpregnant women.

OBJECTIVE: To compare the clinical and paraclinical features and outcomes of pregnant and nonpregnant women with COVID-19. METHODS: A multicenter retrospective cohort study of pregnant and nonpregnant women of reproductive age hospitalized between March and October 2020 in Tehran, Iran. Medical records were reviewed and women who tested positive for SARS-CoV-2 on RT-PCR were included. Extracted data were compared and logistic regression performed. RESULTS: A total of 110 pregnant and 234 nonpregnant COVID-19-positive women were included. Frequency of severe disease was higher in nonpregnant women than pregnant women (29% vs 11.8%; P < 0.001). Symptoms including cough, dyspnea, chill, fatigue, and headache were more frequent in nonpregnant women (P < 0.05). Pregnant women had higher oxygen saturation levels and lower lymphocyte count (P = 0.001). Six (5.5%) pregnant and 12 (5.1%) nonpregnant women died (P = 0.80). No significant differences between the groups were found for ICU admission and end organ failure. Significantly more nonpregnant women had acute respiratory distress syndrome (ARDS, 9.4% vs 0%; P = 0.001). Univariate regression indicated association between hypertension and death; oxygen saturation and ARDS; and body mass index and ICU admission. No association was found between pregnancy and death, ICU admission, or ARDS. CONCLUSION: Pregnant women with COVID-19 are not at higher risk of adverse outcomes compared with nonpregnant women.

Can laboratory tests at the time of admission guide us to the prognosis of patients with COVID-19?

INTRODUCTION: To enhance the COVID-19 patients' care and to optimize utilizing medical resources during the pandemic, relevant biomarkers are needed for prediction of the disease's progression. The current study was aimed to determine the factors that affect the mortality of COVID-19 patients admitted in Baharloo hospital in Iran. METHODS: in the current retrospective study, 56 survived patients and 56 patients who were died (a total of 112 cases) because of COVID-19 infection were randomly selected from those who were admitted to Baharloo hospital. Each patient who was diagnosed with COVID-19 and had recovered from it matched with each non-survived patient in the term of age. Laboratory tests of all these patients at the time of admission were recorded and compared. All analyses performed using spss version 22 by considering α = 0.05 as a significant level. RESULTS: There was no statistical difference in the age and gender distribution between the two groups (p > 0.05). The prevalence of diabetes among survived patients was 37.5% and among non-survived patients was 26.8% and there was no statistical difference between two groups regarding this comorbidity (p = 0.22). Also, there was no statistical difference in the prevalence of hypertension and coronary heart diseases between two groups (p > 0.05). Lymphocyte percentage, blood oxygen level, and platelet (PLT) count was significantly higher in patients who had recovered (P < 0.05). CONCLUSIONS: LDH level, Lymphocyte percentage, PLT count, and blood Oxygen saturation have associations with severe forms of COVID-19 infection and can be used as predictors to assess the patients who are suspected of infection with COVID-19 at the time of admission.

Determine the most common clinical symptoms in COVID-19 patients: a systematic review and meta-analysis.

INTRODUCTION: COVID-19 is an emerging infectious disease. The study about features of this infection could be very helpful in better knowledge about this infectious disease. The current systematic review and meta-analysis were aimed to estimate the prevalence of clinical symptoms of COVID-19 in a systematic review and meta-analysis. METHODS: A systematic review using Medline/PubMed, Scopus, and Google scholar has been conducted. In the current systematic review and meta-analysis, the articles published in the period January 1, 2020, to April 2, 2020, written in English and reporting clinical symptoms of COVID-19 was reviewed. To assess, the presence of heterogeneity, the Cochran's Q statistic, the I2 index, and the tau-squared test were used. Because of significant heterogeneity between the studies the random-effects model with 95% CI was used to calculate the pooled estimation of each symptom prevalence. RESULTS: The most common symptoms in COVID-19 patients include: Fever 81.2% (95% CI: 77.9-84.4); Cough: 58.5% (95% CI: 54.2-62.8); Fatigue 38.5% (95% CI: 30.6-45.3); Dyspnea: 26.1% (95% CI: 20.4-31.8); and the Sputum: 25.8% (95% CI: 21.1-30.4). Based on the meta-regression results, the sample size used in different studies did not have a significant effect on the final estimate value (P > 0.05). CONCLUSIONS: Considering the main symptoms of COVID-19 such as Fever, Cough, Fatigue, and Dyspnea can have a key role in early detection of this disease and prevent the transmission of the disease to other people.

Factors Associated with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The current study aimed to identify effective factors on the death among COVID-19 patients. METHODS: All articles published in the period Jan 1, 2020, to Mar 23, 2020, written in English and reporting factors associated with COVID-19 mortality were reviewed. The random-effects model with 95% CI was used to calculate the pooled Odds Ratio (OR) and Hazard Ratio (HR). Data were analyzed using Stata ver.11.0. RESULTS: The older age OR: 1.21(1.10-1.33) and male gender OR: 1.41(1.04-1.89) were most prone to death due to COVID-19. The Comorbidity with some chronic diseases such as Diabetes type2 OR: 2.42(1.06-5.52), Hypertension OR: 2.54(1.21-5.32), Kidney disorder OR: 2.61(1.22-5.60), Respiratory disorder 3.09 (1.39-6.88) and Heart diseases OR: 4.37 (1.13-16.90) can increase the risk of COVID19 mortality. CONCLUSION: Infection with COVID-19 is associated with substantial mortality mainly in older patients with comorbidities. We found the significant effect of age, gender and comorbidities such as Diabetes Mellitus, Hypertension, Kidney disorders and Heart diseases on the risk of death in patients with COVID-19. The factors associated with mortality found in this research can help to recognize patients with COVID-19 who are at higher risk of a poor prognosis. Monitoring these factors can serve to give early warning for the appropriate interventions.

Spontaneous pneumothorax followed by reversed halo sign in immunocompromised patient with pulmonary mucormycosis.

Mucormycosis, an invasive fungus with a variety of clinical presentation, is a devastating infection in immunocompromised host. Here an unusual case of pulmonary mucormycosis is introduced in an immunodeficient patient in which pneumothorax was followed by reversed halo sign (RHS). The clinicians, who visit immunocompromised persons with pneumothorax, should be considerate to take immediate imaging and pathologic measures to confirm or reject mucormycosis.