Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study.

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O2Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O2Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

Occupational burnout in Iranian health care workers during the COVID-19 pandemic.

BACKGROUND AND AIM: Health care workers (HCWs), mostly frontliners, are encountering numerous physical and psychosocial stressors, and even managing some conflicts over the course of the novel coronavirus disease 2019 (COVID-19). In this respect, the present study was to investigate the prevalence rate of occupational burnout (OB) in such workers during this pandemic. MATERIALS AND METHODS: This cross-sectional study was conducted between April 6 and May 30, 2020, via an online survey in 31 provinces of Iran, on HCWs selected based on convenience sampling method. For data collection, a socio-demographic information form and the Maslach Burnout Inventory (MBI) was utilized. Descriptive statistics, Chi-square test, and multivariate regression analysis were also applied to test the research hypotheses. RESULTS: In total, 7626 HCWs participated in the present study. Accordingly, 73.2 and 26.8% of the workers were female and male, respectively. As well, 57.8% of the respondents were nurses and 14.4% of the cases were clinicians. Moreover, 44.8% of the participants had thus far worked in isolation wards and 40.3% of these individuals reported working for 4-8 hours with COVID-19 patients. The prevalence rate of OB was 18.3%. Besides, 34.2, 48.7, and 56.1% of the respondents had severe levels of emotional exhaustion (EE), higher depersonalization (DP), and decreased sense of personal accomplishment (PA), respectively. Besides, the HCWs at the age range of 20 to 30, having female gender, no children, and a bachelor's degree, and working in isolation wards showed the higher levels of OB with reference to the Chi-square test results (p < 0.001). Accordingly, the statistical test outcomes demonstrated that a history of physical illnesses (p = 0.001) and psychiatric disorders (p = 0.044) could be the best predictor of OB throughout the first peak of the COVID-19 pandemic. CONCLUSION: Regarding the high prevalence rate of OB among the HCWs and the remaining COVID-19 journey in Iran, health care managers are recommended to orient the required management and coping strategies toward improving mental health in these individuals.

Apoptosis and immunophenotyping of peripheral blood lymphocytes in Iranian COVID-19 patients: Clinical and laboratory characteristics.

A novel member of human coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been recently recognized in China and rapidly spread worldwide. Studies showed the decreasing of peripheral blood lymphocytes in a majority of patients. In this study, we have reported the clinical features, laboratory characteristics, the frequency of peripheral blood lymphocyte subpopulations, and their apoptosis pattern in Iranian coronavirus infectious disease (COVID-19) patients. Demographic and clinical data of 61 hospitalized confirmed cases with COVID-19 at Imam Khomeini Hospital were collected and analyzed. Peripheral blood mononuclear cells were isolated from all samples and the apoptosis pattern was evaluated using Annexin V/propidium iodide method. The frequency of lymphocyte subsets, including T-CD4+ , T-CD8+ , NK, B cells, and monocytes, was measured in all patients and 31 controls by flow cytometry. Our findings demonstrated that the percentage of lymphocytes, CD4+ , and CD8+ T cells were decreased in COVID-19 patients compared with the control group. Regarding the clinical severity, the number of lymphocytes, CD4+ , CD8+ T cells, and NK cells were also decreased in severe cases when compared with mild cases. Finally, our data have also indicated the increase in apoptosis of mononuclear cells from COVID-19 patients which was more remarkable in severe clinical cases. The frequency of immune cells is a useful indicator for prediction of severity and prognosis of COVID-19 patients. These results could help to explain the immunopathogenesis of SARS-CoV-2 and introducing novel biomarkers, therapeutic strategies, and vaccine candidates.

The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximise the use of everything that exists about the role of vitamin D in the COVID-19. METHODS: A systematic search was performed in PubMed, Scopus, Embase and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. RESULTS: Twenty-three studies containing 11 901 participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 are 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4). CONCLUSION: This study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin-D-deficient individuals and about five times higher probability of developing the severe disease in vitamin-D-deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

Immunologic markers, vasculitis-associated autoantibodies, and complement levels in patients with COVID-19.

BACKGROUND: The cause of coronavirus disease 2019 (COVID-19) is a virus which can lead to severe acute respiratory syndrome-CoV-2 (SARS-COV-2). There are evidences of involvement of immune system in pathogenesis of this disease. We investigated the presence of various vasculitis-associated autoantibodies and complement levels in patients with COVID-19. MATERIALS AND METHODS: Patients with severe or critical type of COVID-19 were evaluated for symptoms, signs, and laboratory tests of vasculitis syndromes including rheumatoid factor (RF), antinuclear antibody (ANA), anti-double-stranded DNA, c and p anti-neutrophilic cytoplasmic antibody (c ANCA and P ANCA), and complement levels. RESULTS: The study was performed in forty patients with severe or critical illness. The mean age of the participants was 48.5 ± 9.8 years. All patients had pulmonary involvement in lung computed tomography scans. Vasculitis laboratory test results included RF in two patients, ANA in three patients, and ANCA in one patient. Seventeen (42.5%) patients had hypocomplementemia in one or more complement tests. Four patients expired, of whom three had a decrease in complement level. CONCLUSION: Decrease in complement levels may predict a critical state of COVID-19 disease. Therefore, measuring its levels may be of great benefit in making earlier decisions to initiate disease-suppressing treatments including corticosteroids.

Multicenter Cryptococcal Antigen Screening of HIV-Infected Patients in Iran.

Early diagnosis and targeted preemptive antifungal treatment are crucial in reducing cryptococcal meningitis (CM)-related mortality in individuals living with human immunodeficiency virus (HIV). The present study was performed to determine cryptococcal antigenemia and outcomes among HIV-infected patients in Iran. This multicenter prospective study was conducted between October 2016 and December 2018. For the purpose of the study, blood samples were randomly collected from 177 profoundly immunosuppressed (CD4+ counts < 200 cells/µL) HIV-positive individuals in six major cities of Iran. The patients were antiretroviral therapy-naive or had received inadequate medication. The stored sera were screened for cryptococcal antigen (CrAg), using point-of-care lateral flow assay (IMMY® diagnostics, Norman, OK, US). Overall, out of the 174 asymptomatic patients, 3 (1.72%) cases were CrAg-positive using the LFA in serum. Accordingly, the prevalence of cryptococcal antigenemia was 7.14%, 0%, and 1.2% in the patients with the CD4+ counts of < 50, 50-100, and 100-200 cells/µL, respectively. The median age of the patients with antigenemia was 36 years (age range 8-55 years). The median CD4+ count of the cohort was 98 cells/µL (range 14-200 cells/µL). Routine screening of Iranian HIV-infected patients with CD4+ count of < 50 cells/µL before initiating antiretroviral therapy is justified. It is suggested to conduct more inclusive research throughout the whole country on more patients to recommend screening cryptococcal antigen strongly.

High-resolution computed tomography finding in 552 patients with symptomatic COVID-19: first report from north of Iran.

PURPOSE: Due to the emergence of the new coronavirus 2019 and the lack of sufficient information about infected patients, this study was conducted to investigate the chest high-resolution computed tomography (HRCT) findings of patients infected with the new coronavirus 2019. METHODS: This cross-sectional study was performed on COVID-19 patients referred to Medical Imaging Centers of Sari, Mazandaran, Iran, on March 2020 for computed tomography (CT) scan. Symptomatic patients were referred to the Medical Imaging Center for diagnosis confirmation through CT scan. In addition to age and sex, HRCT findings were collected from the picture archiving and communication system (PACS) for further evaluations. RESULTS: Out of 552 patients with mean age of 51.2 ± 14.8 years, the male/female ratio was 1.38 to 1. The most common expressive findings in patients were ground-glass opacity (GGO) (87.3%), peripheral distribution (82.4%), and posterior distribution (81.5%). The most conflicting findings in patients were pleural effusion (7.6%), peribronchovascular distribution (7.6%), and lymphadenopathy (5.1%). The peripheral distribution (p = 0.034), round opacities (p = 0.02), single lobe (p = 0.003), and pleural effusion (p = 0.037) were significant in people under and over 50 years of age. CONCLUSION: In summary, the present study indicated that in addition to GGO, peripheral distribution findings could be a vital diagnostic choice in COVID-19 patients.

Clinical and laboratory manifestation and outcome of icterohemorrhagic leptospirosis patients in Northern Iran.

BACKGROUND: Icterohemorrhagic form of leptospirosis has a high mortality rate. In this study, the clinical manifestations, epidemiologic and laboratory findings and outcome of Weil's disease were investigated. METHODS: A descriptive cross- sectional study was conducted on 66 consecutive patients with icterohemorrhagic leptospirosis who were admitted to Razi Hospital (The Therapeutic Center of Infectious Diseases in the North of Iran) in 2013. The inclusion criteria were as follows: All patients who had clinical and epidemiological data suggestive of leptospirosis and displayed icterohemorrhagic form at the time of admission or during hospitalization. All patients were visited on admission, one, two and six weeks later. Demographic data, clinical, laboratory features and complications were evaluated, and statistical analysis was performed using SPSS version 13.0. RESULTS: Among 66 patients, 89.4% (n = 59) were male, 60% (n = 40) were farmers and 9.1% (n= 6) had a history of swimming in rivers. The most common complaints were fever and jaundice, respectively. The most common clinical symptoms were fever (90.9%), myalgia (75.8%), chills (70.8%) and headache (65.1%). Hyponatremia and hypernatremia were seen in 7.6% and 72.8% of the participants, respectively. Also, hypokalemia was observed in two patients (3%). Approximately, half of the cases had leukocytosis and 90% had thrombocytopenia. Rise of AST, ALT, ALP and bilirubin were seen in 95.2%, 93.6%, 76.2% and 100% of the patients, respectively. Of the patients, 42.4% experienced complications of icterohemorrhagic leptospirosis including acute renal failure (30.3%) pneumonia (25.8%), pancreatitis (4.5%), subarachnoid hemorrhage (1.5%) and gastrointestinal bleeding (1.5%). Three cases (4.5%) died, 42 cases (63.7%) were discharged with residual effects and 52 patients (78.8%) had positive serology. CONCLUSION: The most significant biochemical abnormalities were thrombocytopenia, hyperbilirubinemia, hyponatremia and hypernatremia and azotemia and the latter remained stable in 2% of the patients at least until the end of the 6-week period.

Evaluation of IFNAR2 and TYK2 transcripts' prognostic role in COVID-19 patients: a retrospective study.

Background and objectives: This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions. Methods: We conducted a retrospective study including COVID-19 adult patients. All blood samples were collected before any interventions. The expressions of IFNAR2 and TYK2 were assessed using real-time PCR in venous blood samples of 54 cases and 56 controls. The transcript quantities of IFNAR2 and TYK2 genes were assessed using a Delta-Ct method. Results: Our findings show no significant differences in gene expression levels for IFNAR2 and TYK2 between patients who required oxygen (O2) therapy and those who did not (p-value = 0.732 and p-value = 0.629, respectively). Likewise, there were no significant differences in IFNAR2 and TYK2 expressions between patients hospitalized for less than 7 days and those hospitalized for 7 days or more (p-value = 0.455 and p-value = 0.626, respectively). We also observed a weak correlation between IFNAR2 expression and CRP (p-value = 0.045, r = 0.192). There was a negative correlation between the expression levels of IFNAR2 and TYK2 transcripts in COVID-19 patients (p-value = 0.044; partial correlation coefficient = -0.283). Additionally, IFNAR2 and TYK2 were significantly downregulated in the COVID-19 group compared to healthy subjects (p-value = 0.002 and p-value = 0.028, respectively). However, neither IFNAR2 nor TYK2 expression was significantly different between the case subgroups based on COVID-19 severity. The IFNAR2 ΔΔCt (B = -0.184, 95% CI: -0.524-0.157, p-value = 0.275) and the TYK2 ΔΔCt (B = 0.114, 95% CI: -0.268-0.496, p-value = 0.543) were not found to be significant predictors of hospitalization duration. The area under the curve (AUC) for IFNAR2 expression is 0.655 (p-value = 0.005, 95% CI: 0.554-0.757), suggesting its poor discriminative value. Conclusion: We were unable to comment definitively on the prognostic power of IFNAR2 and TYK2 expressions in COVID-19 patients, and larger-scale studies are needed. The principal limitations of this study included the lack of longitudinal analysis and limited sample size.

Frequency of delirium and its associated factors among COVID-19 inpatients in Iran.

BACKGROUND AND AIM: Delirium has been presented as the leading cause of sudden change in the mental state of patients with coronavirus disease 2019 (COVID-19). Given that the delayed diagnosis of such a dysfunction is often associated with excess mortality, it seems essential to devote vastly more attention to this significant clinical characteristic. MATERIALS AND METHODS: This cross-sectional study was performed on 309 patients [viz. 259 cases hospitalized in general wards and 50 individuals admitted to the intensive care unit (ICU)]. For this purpose, a Demographic-Clinical Information Questionnaire, the Confusion Assessment Method (CAM), the Confusion Assessment Method for the ICU (CAM-ICU), the Richmond Agitation-Sedation Scale (RASS) and face-to-face interviews were completed by a trained senior psychiatry resident. The data analysis was further done with the SPSS Statistics V22.0 software package. RESULTS: Out of 259 patients admitted to the general wards and 50 cases in the ICU due to COVID-19, 41 (15.8%) and 11 (22%) individuals were diagnosed with delirium, respectively. As well, a significant relationship was observed between the incidence rate of delirium and age (p < 0.001), level of education (p < 0.001), hypertension (HTN) (p = 0.029), a history of stroke (p = 0.025), a history of ischemic heart disease (IHD) (p = 0.007), a history of psychiatric disorders, a history of cognitive impairment (p < 0.001), use of hypnotic and antipsychotic medications (p < 0.001) and a history of substance abuse (p = 0.023). Among 52 patients with delirium, only 20 cases had received psychiatric consultation by consultation-liaison psychiatry service for the possibility of delirium. CONCLUSION: In view of the high frequency of delirium among COVID-19 inpatients, their screening for this important mental state should be a priority in clinical settings.

Renal aspergillosis after COVID-19-associated pulmonary aspergillosis: A case report.

Key Clinical Message: Renal aspergillosis is a rare condition and this case the first case of Renal aspergillosis reported after COVID-19-associated pulmonary aspergillosis. Renal symptoms should arise clinical suspicion to renal involvement that happened as a result of hematogenous spreading of pulmonary aspergillosis. Abstract: Secondary fungal infections are among the most significant complications that can arise after COVID-19 and have the potential to lead to a high rate of morbidity and mortality. As COVID-19 primarily involves the airway, the majority of fungal infections reported have been related to the respiratory system. However, renal aspergillosis that we have reported is a rare condition that also can occur. A 67-year-old man was referred to our hospital and admitted as a COVID-19 patient. After the initial recovery, he experienced a recurrence of fever accompanied by a productive cough. The histopathological studies were conducted on the sputum and bronchoalveolar lavage samples, which revealed the presence of Aspergillus flavus. We treated the patient with voriconazole and the patient was discharged after a period of time. However, after approximately 6 months, he returned to the hospital with a fever and abdominal pain. We started a fever workup. Two new hypoechoic abscess-like masses were spotted in the right kidney in the ultrasonography (U/S) and the direct molecular studies of the biopsy sample obtained under U/S guidance identified Aspergillus flavus. Although renal aspergillosis is a rare condition, it should not be overlooked, especially in patients with severe COVID-19 and pulmonary aspergillosis, as these conditions can lead to renal aspergillosis, which may present with symptoms such as abdominal pain with fever. Therefore, it is necessary to perform radiological and histopathological studies when renal aspergillosis is suspected.

Efficacy and safety of adding fluoxetine to the treatment regimen of hospitalized patients with non-critical COVID-19 pneumonia: A double-blind randomized, placebo-controlled clinical trial.

INTRODUCTION: Selective serotonin reuptake inhibitors are considered the drugs, whose effectiveness in viral pandemics has been studied. The aim of this study was to evaluate of adding fluoxetine to the treatment regimen of patients with COVID-19 pneumonia. METHODS: This study was a double-blind randomized placebo controlled clinical trial .36 patients in the fluoxetine and 36 patients in the placebo group were enrolled. Patients in the intervention group were first treated with fluoxetine 10 mg for 4 days and then the dose of 20 mg was continued for 4 weeks. Data analysis was conducted using SPSS V. 22.0. RESULTS: There was no statistically significant difference between the two groups in terms of clinical symptoms at the beginning of the study and also the score of anxiety and depression, oxygen saturation at the time of hospitalization, mid-hospitalization and discharge periods. The need for mechanical ventilator support (p = 1.00), the need for admission in the intensive care unit (ICU) (p = 1.00), rate for mortality (p = 1.00), and discharge with relative recovery (p = 1.00) were not significantly different between the two groups. The distribution of CRP within the study groups showed a significant decrease during different time periods (p = 0.001), and although there was no statistically significant difference between the two groups on the first day (p = 1.00) and at discharge (p = 0.585), mid-hospital CRP showed a significant decrease in the fluoxetine group (p = 0.032). CONCLUSION: Fluoxetine resulted in a faster reduction of patients' inflammation without association with depression and anxiety.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Senility and COVID-19 as two possible risk factors for loss of consciousness: A rare case report.

Introduction: and Importance: More than two years after the start of the COVID-19 pandemic, the world is still grappling with this dilemma. COVID-19 covers a wide range of symptoms. Loss of consciousness (LOC) is a very rare symptom that can threaten a patient's life and blur the prognosis of recovery. Case presentation: An 89-year-old woman was presented to the emergency department with LOC (Glasgow Coma Scale (GCS) score = 3) without any history of the underlying disease and was immediately admitted to the intensive care unit. In brain imaging, severe small vessel disease was diagnosed by observing partial dilatation of the ventricles, sulcus, and hypodense areas in the periventricular area. Lung imaging propounded COVID-19 by detecting the ground glass pattern with 50%-75% involvement. After detecting severe acute respiratory syndrome coronavirus 2 nucleic acid by reverse transcription-polymerase chain reaction, COVID-19 treatment was performed according to the national protocol. Finally, she was discharged after 26 days of hospitalization with partial recovery. Clinical discussion: COVID-19-induced cytokine storm along with old age appears to increase LOC risk. It can be claimed that COVID-19-induced LOC can be considered as one of the symptoms of COVID-19 in the elderly population. Therefore, more attention should be paid to this population, which is more at risk. Conclusion: Few reports illustrate the LOC as a COVID-19 presentation. This report highlights the fact that older people are more at risk for COVID-19-induced LOC than other age groups and should be given more care.

Atazanavir versus lopinavir on Covid-19 infection: A retrospective protease inhibitors comparative study 2020.

Background: Evaluation of protease inhibitors (PIs) is important in terms of prescribing an effective regimen for reducing mortality and hospitalization in Covid-19. Therefore, follow-up of patients better determines the characteristics of existing regimens. Methods: We retrospectively evaluated the demographic, co-morbidities, gastrointestinal (GI) and liver complications of patients at two teaching hospitals from the first of March to the end of July 2020. All patients received one of two recommended regimens including hydroxychloroquine (HCQ) (400 mg BD on the first day and then 200 mg BD) plus atazanavir/ritonavir (ATV) (300/100 mg daily) or HCQ with the same dose plus lopinavir/ritonavir (Kaletra) (400/100 mg BD) for 5-7 days. Results: We chose 170 cases that received 2 different regimens. In group one, 85(57.6% males) patients received Kaletra and HCQ and group two, 85 (55.3% males) patients received ATV and HCQ. The study of hospitalization in both groups showed no difference in more or less than 5 days hospitalization. (P=0.757) Comparison of mortality rates has not shown a significant difference including 19 (22.4%) deaths in group 1 and 15(17.6%) deaths in group 2 (P=0.443). Nausea followed by diarrhea was the most common side effects in group 1. But no side effects were reported in group 2 (P=0.000). Abnormal liver function tests (LFTs) were seen in both groups. Conclusion: Comparison of hospitalization and mortality were not statistically significant. It seems that a respect to similar effect on mortality and hospitalization. ATV regimen is superior to Kaletra especially for better GI tolerance and less daily pills.

Helicobacter pylori Infection and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Since numerous studies have stated that there may be a relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease, and because of the high prevalence of both conditions worldwide, this study investigated the risk of non-alcoholic fatty liver disease in patients infected with H. pylori. Following a systematic review of PubMed, Scopus, Web of Science and Embase, and a search in Google Scholar using MeSH terms such as H. pylori and non-alcoholic fatty liver disease, the relevant papers up to November 2020 were reviewed. All cohort, case-control, and cross-sectional studies that examined the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori entered this study. A meta-analysis was conducted in STATA 11. This systematic review examined 22 papers with 117 117 participants (33 711 patients infected with H. pylori and 83 406 participants as control) and 20 studies were subjected to meta-analysis The results indicated a 22% to 27% increase in the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori (crude odds ratio: 1.27, 95% CI: 1.17-1.33; and adjusted odds ratio: 1.22, 95% CI: 1.09-1.35). According to the subgroup analysis, the study region, sample size, and the method of diagnosing H. pylori were the factors contributing to the high heterogeneity. The meta-analysis revealed the increased risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori. This indicates that H. pylori is a serious risk factor in patients susceptible to NAFLD.

Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials.

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p-value = 0.16). Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

Heerfordt-Waldenström Syndrome, A Rare Presentation of Sarcoidosis in a Patient with Old Ocular Toxoplasmosis.

BACKGROUND: There are similarities between the ophthalmic presentation of toxoplasmosis and sarcoidosis, and there are some concerns of immunosuppressive treatments for sarcoidosis, which may lead to T. gondii reactivation. We report a rare case with acute sarcoidosis (Heerfordt- Waldenström syndrome) with a history of ocular toxoplasmosis from the North of Iran. CASE PRESENTATION: The patient was a 36-year-old woman with left painful eye and swollen parotid, right facial paresis, maculopapular rash in left eyebrow and erythema nodosa on both legs. Anti-Toxoplasma IgG antibody was positive, and IgM was not detectable. Radiographic findings on the chest revealed bilateral hilar lymphadenopathy. The initial treatment was sulfamethoxazole- trimethoprim to prevent the recurrence of retinal toxoplasmosis and corticosteroid and mycophenolate mofetil for sarcoidosis. The patient showed clinical and vision improvement without recurrences during three months follow-up. DISCUSSION: Ophthalmological examinations and laboratory tests to rule out toxoplasmosis could be considered in known cases of sarcoidosis, particularly in ocular sarcoidosis status. To the best of our knowledge, this is the first report of comorbidity of ocular toxoplasmosis/sarcoidosis from Iran and possibly the world.

Assessing mental health status among Iranian healthcare workers in times of the COVID-19 pandemic: A web-based cross-sectional study.

OBJECTIVES: The present study was conducted to assess 3(HCWs) during the COVID-19 pandemic. METHODS: A total number of 7626 HCWs were included in this web-based cross-sectional study, via the convenience sampling technique. To collect the required data, the sociodemographic characteristics information form, the Depression Anxiety Stress Scale-21 (DASS-21), and the Corona Disease Anxiety Scale (CDAS) were also employed. In addition, data analysis was performed using the SPSS Statistics software (ver. 24), as well as descriptive statistics, Chi-square test (χ2 ), and univariate/multivariate logistic regression models. RESULTS: The CDAS results revealed that 47.9% and 70.5% of the HCWs had experienced moderate levels of physical and psychological anxiety, respectively. Based on the DASS results, 44.8%, 43%, and 34.8% of the HCWs had been subjected to depression, anxiety, and stress symptoms during the COVID-19 pandemic, respectively. The logistic regression models correspondingly showed that depression among the HCWs was significantly correlated with risk factors, such as the age groups of 20-30 years (p = .001), 31-40 years (p = .006), female HCWs (p> .001), history of physical illnesses (p = .004), and history of psychiatric disorders (p> .001). Moreover, factors including the age groups of 20-30 years (p < .001), 31-40 years (p < .001), 41-50 years (p < .001), female HCWs (p> .001), history of physical illnesses (p < .001), and history of psychiatric disorders (p>.001) were assumed as significant predictors of anxiety in these individuals. Besides, factors such as the age groups of 20-30 years (p = .002), 31-40 years (p = .004), female HCWs (p>.001), occupation (p = .016), history of physical illnesses (p < .001), and history of psychiatric disorders (p> .001) could significantly predict the prevalence rate of stress in the HCWs in times of this crisis. CONCLUSION: Given the importance of mental health status among HCWs during the COVID-19 pandemic, health administrators and policymakers of the Ministry of Health and Medical Education in Iran are suggested to provide psychological screening and supportive care programs for HCWs with the aim of enhancing their mental health and successful coping with critical circumstances.