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.

Epidemiological, imaging, laboratory, and clinical characteristics and factors related to mortality in patients with COVID-19: a single-center study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a novel pandemic. Considerable differences in disease severity and the mortality rate have been observed in different parts of the world. The present study investigated the characteristics and outcomes of patients hospitalized with COVID-19 in Iran. METHODS: We established a retrospective cohort to study hospitalized COVID-19 patients in Iran. Epidemiological, imaging, laboratory, and clinical characteristics and outcomes were recorded from medical documents. The chi-square test, t-test, and logistic regression models were used to analyze the data. A p<0.05 was considered to indicate statistical significance. RESULTS: In total, 364 cases (207 males and 157 females) were analyzed. The most common symptoms were cough, fever, and dyspnea. Multifocal bilateral ground-glass opacities with peripheral distribution were the predominant imaging finding. The mean age of patients was 54.28±18.81 years. The mean age of patients who died was 71.50±14.60 years. The mortality rate was 17.6%. The total proportion of patients with a comorbidity was 47.5%, and 84.4% of patients who died had a comorbidity. Sex, history of diabetes mellitus, and dyslipidemia were not significantly associated with mortality (p>0.05). However, mortality showed significant relationships with body mass index; age; history of hypertension, chronic kidney disease (CKD), ischemic heart disease, cerebrovascular accident (CVA), pulmonary disease, and cancer; and abnormal high-resolution computed tomography (HRCT) findings (p<0.05 for all). Cancer had the highest odds ratio. CONCLUSION: Comorbidities (especially cancer, CKD, and CVA), severe obesity, old age, and abnormal HRCT findings affected the health outcomes of patients hospitalized with COVID-19.

Prevalence and Associated Risk Factors of HTLV-1 and Co-infections of Blood-Borne Viruses in Birjand, Iran's Eastern Border.

BACKGROUND: Blood-borne viruses (BBVs) are one of the most important public health concerns. South Khorasan has a long border with Afghanistan and concern has risen there about blood-borne oncogenic viral infections. The aim of the present study was to evaluate the prevalence and associated risk factors of human T-lymphotropic virus 1 (HTLV-1) and co-infections of BBVs in Birjand, Iran's eastern border. METHODS: In this cross-sectional study, 3441 subjects were tested for sero-prevalence of HTLV-1 by ELISA. The data on demographic features, HTLV-1-related risk factors and other characteristics of the population were analyzed by Pearson chi-square and logistic regression tests. Finally, the co-infection of BBVs was evaluated in the study. RESULTS: The prevalence of HTLV-1 was 0.3% (95% CI: 0.12-0.48). Notably, the sero-prevalence of HIV, hepatitis B virus (HBV), hepatitis D virus (HDV), and hepatitis C virus (HCV) in our previous studies was reported at 0%, 0.2%, 1.2% and 1.6%, respectively. The results indicated that the occurrence of HTLV-1 infection was associated only with the history of hospitalization (odds ratio [OR]: 0.27, 95% CI: 0.07-0.97, with P = 0.04). The co-infection of HBV with HCV was the most common (2.35%), while a co-infection rate of 1.17% was found for both HBV/HTLV-1 and HBV/HDV. CONCLUSION: Although a higher prevalence of the viruses was expected, it was close to the overall Iranian population. With respect to close relationship with an HTLV-1 endemic area (Mashhad and Neyshabour), the prevalence is very low; however, more attention is needed. Our findings reinforce the importance of increasing knowledge about BBV-related health risk behaviors to prevent the emergence of new cases, especially in low-risk populations.

Epidemiology, risk factors, and molecular characterization of occult hepatitis B infection among anti-hepatitis B core antigen alone subjects.

OBJECTIVES: Features of occult hepatitis B virus (HBV) infection among the anti-hepatitis B core antigen (anti-HBc) positives have yet to be described in more details. This study aimed to determine the molecular prevalence of occult HBV infection (OBI), and association to risk factors among seropositives for anti-HBc. METHODS: This was part of a community-based screening project that included 5234 cases. All participants completed a questionnaire on demographic and socio-epidemiological information. Then, the blood samples were collected and tested for anti-HBc and HBsAg using ELISA method. To identify OBI, nested-polymerase chain reaction (PCR) assays were performed for HBV-S and X genes, and viral load was determined using an in-house real-time PCR. Sequencing and phylogenetic analysis have been implemented for genotyping. RESULTS: Overall, 596 cases, positive only for anti-HBc were included in the study. OBI was detected among 61 cases (10.2%). The genotype and subgenotype of HBV among all of them was D1, except one that was D4. Most of them had low viral loads ranged from 1.2 × 102 to 1.34 × 10 3 copies/mL; 19.6% had undetectable viral loads. Important mutations in surface protein and reverse transcriptase were sI92T, sQ129H, rtL80I, rtS85F, rtL91I. The prevalence of OBI was related to some risk factors, such as tattooing (P = 0.02), sexual activities (P = 0.009), and diabetes (P = 0.031). CONCLUSION: Our study suggests that OBI should be considered among anti-HBc seropositive subjects. This form of HBV infection was accompanied with some mutations, risk factors, and diseases. However, further investigations are needed to determine virological importance of documented mutations.

Persistence of immunity to hepatitis B vaccine as infants, 17 years earlier.

BACKGROUND: In Iran since 1992, hepatitis B vaccination was a part of the national vaccination program. Hepatitis B vaccination is effective in the epidemiology of hepatitis B. The aim of this study was to evaluate the long - term persistence of immunity. METHODS: This cross-sectional analytical study was conducted on children and adolescents aged between 6-18 years in Birjand, who received a three - dose hepatitis B vaccination in accordance with the national immunization program. No students were infected with hepatitis B. Antibody titer higher than10 IU/L was considered positive. RESULTS: A total of 530 patients (307 boys and 223 girls) were recruited for the study of which 44% had positive antibody titer (≥10 IU / L). The geometric concentration mean (GMCs) of antibody in subjects was 64.9±34.2, HBS antibody titer was positive in 40.4% of the boys and 59.6% of the girls. A significant difference in antibody titers was observed in terms of gender and according to the time elapsed since the last vaccination. Antibody titer in children older than 13 years had passed since their last vaccination and was significantly less than those children younger than thirteen years old had passed since their vaccination logistic regression analysis showed that the only predictive factor of anti-HBS low titer (<10 IU/L) is elapsed time of vaccination. CONCLUSIONS: Based on results of this study, hepatitis B vaccine has created a good level of protection in 44% of the adolescents after 17 years.

Seroprevalence and Risk Factors for Hepatitis B in an Adult Population: The First Report from Birjand, South Khorasan, Iran.

BACKGROUND: Infection with the hepatitis B virus (HBV) is an important global health problem. Knowledge of the geographic distribution pattern of HBV infection can help to control the spread of the disease. OBJECTIVES: To determine the prevalence of HBV infections and risk factors for the disease for the first time in Birjand, Southeastern Iran. METHODS: This was an analytical cross-sectional study conducted in 2013 - 2014 of 5235 HBV cases in Birjand, South Khorasan Iran. Subjects aged 15 - 70 y were selected using the cluster sampling method. Blood samples were taken and tested at a reference laboratory for the hepatitis B core antibody (anti-HBc). Seropositive specimens were tested for the hepatitis B surface antigen (HBsAg). RESULTS: The mean age (± SD) was 39.07 (± 14.04) y, and 786 (15%) subjects were anti-HBc positive. The prevalence of HBsAg was 1.6% (n = 85). The prevalence of anti-HBc seropositivity was significantly higher in subjects with a lower level of education (P = 0.09), older subjects (P = 0.001), intravenous (IV) drug users (P<0.05), subjects with piercings (P < 0.001), and subjects with a positive history of familial HBV or HCV infection (P < 0.05). It was also significantly higher in those who drank alcohol (P = 0.09) or had a history of blood transfusions (P = 0.001), cupping (P = 0.004), hospital admission (P = 0.03), or endoscopy (P = 0.002). The rate of HBsAg positivity was significantly higher in subjects with a history of cupping (P=0.03), a positive history of familial HBV or HCV infection (P < 0.05), and older subjects (P = 0.015). CONCLUSIONS: Although the frequency of HBsAg seropositivity in the present study was close to that observed in the overall Iranian population, the seroprevalence of anti-HBc was higher, possibly due to the exposure of the elderly to more risk factors. The risk factors were similar. These included a history of blood transfusions, cupping, hospital admission, endoscopy, or familial HBV/HCV infection, in addition to piercings and drug abuse.

A case report of inhalation anthrax acquired naturally.

BACKGROUND: Anthrax is a zoonotic occupational disease caused by Bacillus anthracis, a rod-shaped immobile aerobic gram-positive bacteria with spore. Anthrax occurs in humans randomly and with low frequency. Most cases of anthrax are acquired through contact with infected animals or contaminated animal products. This old disease became particularly important since 2001 that the biological spores were exploited in America. Depending on the transmission method of the disease, clinical manifestations occur in three classes: Cutaneous, respiratory, and gastrointestinal anthrax. The respiratory form is considered as the most fatal and a rare form of anthrax intending to show complicated and unusual manifestations. CASE PRESENTATION: In this case report a rare case of inhalation anthrax acquired naturally in southeast of Iran is presented. A blind 65-year-old man, living in a rural area, was admitted with respiratory infection, fever, dyspnea, loss of appetite, and myalgia. The patient was treated with outpatient antibiotics a week ago. After admission, the patient was again treated for pneumonia, but there was no improvement despite treatment and the patient was suffering from septicemia symptoms. Radiographic images showed wide mediastinum. Bacillus anthracis was isolated from blood and sputum culture and the results were confirmed by colony morphology, biochemical reactions and PCR. The treatment was changed to ciprofloxacin, clindamycin, and penicillin. On the second day of anthrax treatment, the patient was complicated with jaundice, elevation of liver enzymes, and a significant drop in hemoglobin, hematocrit, and platelet despite lack of obvious bleeding and was complicated with respiratory distress and sepsis and died a week after treatment. CONCLUSIONS: We could discover no specific exposure associated with anthrax infection for this patient. However, due to being located in an endemic and enzootic area, it is proposed that the exposure occurred through contact with infected airborne dust or an unknown contaminated item. Despite many advances in preventing anthrax, still some rare cases of respiratory and complicated anthrax are emerging. With regard to the threat of bioterrorism, medical staff's sensitivity to the clinical syndrome, methods of prophylaxis and treatment of anthrax must be raised. Fast diagnosis and successful treatment the lethal cases of this infection are of utmost important.

Time to Sputum Smear Conversion in Smear-Positive Pulmonary Tuberculosis Patients and Factors for Delayed Conversion.

Pulmonary tuberculosis is a common infection worldwide. In the eastern part of Iran, fluctuations in tuberculosis prevalence are seen due to the migration of people from Afghanistan. The aim of this study was to evaluate the time of bacteriologic sputum conversion after treatment and affecting factors in those whose smear does not become negative. This study was carried out on 85 smear-positive pulmonary tuberculosis patients with the mean age of 65.6±16.7 years. There were 38 male patients (44.7%), 47 urban residents (55.3%), and only 6 patients (7.1%) from Afghanistan. The mean time of sputum conversion after starting treatment was 1.99±1.06 months. The mean time of sputum conversion was significantly higher in males (P=0.046), increased bacilli density in the primary sputum sample (P<0.0001, R=0.507), and pre-existing medical illness (P=0.001). In this study, it was revealed that pre-existing illness, bacilli density in initial smear, and severe involvement of the lung on radiography, could be associated with delay in sputum smear conversion.

Tuberculosis of the breast: a case report.

Primary tuberculosis of the breast is a rare disease. It usually occurs in female of reproductive age. Any form of tuberculosis mastitis may present with feature of malignancy. Diagnosis is mainly based on identification of tubercle bacilli. We report a 42-year-old woman with primary tuberculosis abscess of the breast, who underwent surgical resection. Fine needle biopsy failed to achieve specific diagnosis before surgical operation. She responded to anti-TB therapy postoperatively. In endemic area, tuberculosis should be considered in the differential diagnosis of breast tumors.

Chlamydia pneumoniae infection and cardiac risk factors in patients with myocardial infection.

BACKGROUND: Evidences support the possible involvement of microorganisms such as Chlamydia pneumonia in the pathogenesis of ischemic heart diseases through a chronic inflammatory process. The aim of this study was to determine the relation between Chlamydia pneumoniae seropositivity with acute myocardial infarction and its related risk factors. METHODS: In this case-control study, 88 patients admitted in CCU with a diagnosis of acute coronary syndrome, without a history of chronic diseases including cancers were selected as cases and 49 surgical patients without an evidence of cardiovascular disease according to clinical examinations and ECG were selected as controls. Demographic characteristics and background risk factors were obtained using a questionnaire by expert nurses. Venous blood sample was obtained from participants for measuring the anti Chlamydia IgG and IgM antibodies using ELISA method. The prevalence of antibodies was compared in both groups and its relation with coronary syndrome was evaluated. RESULTS: 88 and 49 patients were enrolled in case and control groups, respectively. Mean age of patients and the controls was 14±59.7 and 13±56.9 years, respectively (P=0.26). Anti Chlamydia IgG seropositivity rate was 63(71.9%) and 23(46.9%) in case and controlcontrol groups, respectively (P<0.01; OR: 2.85; CI 95%: 1.38-5.9). Anti Chlamydia IgM was positive in 1 patient and 1 control. Anti Chlamydia IgG seropositivity rate was higher in patients older than 50 years old than those younger than 50 years old (OR: 2.83; CI 95%: 1.31 -1.14). There was a significant relation between BMI, smoking and Anti Chlamydia IgG seropositivity. CONCLUSION: Considering the relation between anti Chlamydia antibody IgG seropositivity with BMI and myocardial infarction, it seems that appropriate diagnosis and treatment of these prone patients can be benefical.

The relationship between helicobacter pylori infection and myocardial infarction.

BACKGROUND: Coronary Artery Disease is known as the main cause of death in industrialized countries. Relation between this disease and some infections such as Helicobacter pylori (H.pylori) has been shown in several studies. The purpose of this study was to dermine the relationship between Hypylori and mycardical infarctions. METHODS: Seventy-three myocardial infarction patients and 78 individuals with no history of this disease were compared. Patients and control matched for age and sex person to person by the match method. Levels of serum IgA and IgG antibodies against H. pylori were measured by Elisa method. Also, cholesterol, triglyceride, LDL, HDL measured in both groups and data were compared between two groups in terms of relation with cardiac risk factors. RESULTS: From 151 participants, 73 were patients and 78 were control subjects. The percentage of IgG positive cases against H. pylori was 57.5% in the case group and 32.1% in the control group (p=0.002, OR: 2.87 CI: 95%; 1.5-5.6). Meanwhile, there was no significant difference in IgA positive cases between the two groups (42.5% and 48.7% in the case and control groups, respectively) (p=0.44; OR: 0.78 95% CI; 0.41-1.48). The study showed 74.2% of cases in the case group and 45.2% in the control group were positive for both IgG and IgA (p=0.01; OR: 3.5 95% CI; 1.3-9.5). No significant differences were found between two groups in terms of relation between H. pylori related antibodies level and heart disease classic risk factors (smoking, hypertension,…), sex, and age, but between dyslipidemia and H. pylori related antibodies was significant differences in case group (p=0.05). CONCLUSION: According to the results, it seems there is a relation between H. pylori infection and myocardial infarction. Also, between dislipidemia and H. Pylori antibodies in case group were significant difference. Therefore, H. pylori can be a new risk factor for atherosclerosis or can be exacerbate effect of other risk factors. Proper diagnosis and treatment of these infections can be useful in prone patients. More studies with larger sample groups are needed to review the possible role of this pathogen as a heart disease risk factor.

Evaluation of the Prevalence of Hepatitis B, Hepatitis C, and HIV in Inmates with Drug-Related Convictions in Birjand, Iran in 2008.

BACKGROUND AND AIMS: Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are common infections among prisoners. Addicted prisoners are at a higher risk than the normal population for contracting these diseases. Many studies have reported higher prevalence rates of HBV, HCV, and HIV in prisoners. Because of this problem, this study was conducted to evaluate the serologic prevalence of these three diseases in prisoners convicted of drug-related crimes. METHODS: A descriptive cross-sectional study was conducted on a random sample of prisoners with drug charges who were inmates in a prison in Birjand, Iran. Information was collected via questionnaire after obtaining prisoners' informed consent and blood samples were tested for hepatitis B surface antigen (HBsAg), antibodies to HCV (anti-HCV), and antibodies to HIV (anti-HIV). The results were analyzed by chi-square tests. RESULTS: In this study, 358 prisoners were selected. 80.2% of prisoners were male, and 19.8% were female. The average age was 34.7±12 years. 39.1% were addicted to drugs, 54.2% were smokers, and 19.3% had tattoos. 8.4% had had extramarital intercourse, and 16.8% had had a sexually transmitted disease (STD) in past. HBsAg, anti-HCV, and anti- HIV prevalence in these samples were 6.1%, 8.1%, and 0%, respectively.The prevalence rate of HBV in the addicted prisoners was 4.3%, and the rate in non-addicted prisoners was 7.3% (P = 0.24).The prevalence of HCV in addicted prisoners was 15.7%, and the prevalence in non-addicted prisoners was 3.2%; this difference was significant (P < 0.001).Furthermore, a significant difference between the prevalence of HBV and extramarital intercourse was noted (P < 0.005).A significant difference between HCV and transfusion, history of STDs, addiction, and tattooing was noted. CONCLUSIONS: The survey showed that HCV, HBV, and HIV prevalence rates in prisoners were 8.1%, 6.1%, 0%, respectively. The prevalence rates of HCV and HBV in addicted prisoners were 15.7% and 4.3 %, respectively. Studies performed in Iran and other countries have shown that the prevalence rates of HBV, HCV, and HIV in addicted prisoners were higher than the rates in non-addicted prisoners. These results indicate that HBV, HCV, and HIV are significant problems in prisons, and efforts to reduce the risk of these infections, such as education and vaccination, should be considered.