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COVID-19 first emerged in Wuhan, China, in December 2019. Since that time, the frequency of bacterial and fungal coinfections has been continuously increasing. Although invasive pulmonary aspergillosis is being increasingly recognized in association with COVID-19, there is limited information regarding COVID-19-associated mucormycosis. We describe a 50-year-old woman with uncontrolled diabetes who received systemic corticosteroids and remdesevir during her admission for COVID-19. A few days after discharge, the patient was readmitted because of facial swelling and numbness, and a diagnosis of COVID-19-associated rhinosinusitis mucormycosis caused by Rhizopus arrhizus (formerly called Rhizopus oryzae) was confirmed with sequencing of the internal transcribed spacer region of the ribosomal DNA. This report aimed to address the importance of short-term follow-up for COVID-19 patients who have received systemic corticosteroids, particularly those with predisposing conditions, because early detection and prompt, aggressive treatment are essential for the management of invasive fungal infections.

BackgroundAlthough the many aspects of COVID-19 have not been yet recognized, it seems that the dysregulation of the immune system has a very important role in the progression of the disease. In this study the lymphocyte subsets were evaluated in COVID-19 patients with different severity.MethodsIn this prospective study, the levels of peripheral lymphocyte subsets (CD3+, CD4+, CD8+T cells; CD19+and CD20+B cells; CD16+/CD56+NK cells, and CD4+/CD25+/FOXP3+regulatory T cells) were measured in 67 confirmed patients with COVID-19 on the first day of admission.ResultsThe mean age of cases was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases and 11 (16.4%) patients were categorized as critical. The frequency of blood lymphocytes, CD3+cells, CD25+FOXP3+T cells; and absolute count of CD3+T cells, CD25+FOXP3+T cells, CD4+T cells, CD8+T cells, CD16+56+lymphocytes were lower in more severe cases in comparison to milder cases. Percentages of lymphocytes, T cells, and NK cells were significantly lower inthe patients who died (p= 0.002 and P= 0.042, p=0.006, respectively).ConclusionFindings of this cohort study suggests that the frequency of CD4+, CD8+, CD25+FOXP3+T cells, and NK cells were difference in the severe COVID-19 patients. Moreover, lower frequency of, T cells, and NK cells are predictors of mortality of these patients.

Coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China in December 2019, and since then the frequency of bacterial and fungal coinfections has been continuously rising. While invasive pulmonary aspergillosis is increasingly being recognized in association with COVID-19, there is limited information with regards to COVID-19 associated mucormycosis. Here, we describe a 50-year-old woman with uncontrolled diabetes who received systemic corticosteroids and remdesevir during her admission for COVID-19. Few days after discharge, the patient was readmitted due to facial swelling and numbness, and a diagnosis of COVID-19 associated rhinosinusitis mucormycosis due to Rhizopus oryzae was confirmed with PCR and DNA sequencing. This report aims to address the importance of short-term follow-up in COVID-19 patients who have received systemic corticosteroids, particularly those with predisposing conditions, as early detection and prompt, aggressive treatment is essential for the management of invasive fungal infections.

Highlights: • To date, there is not any specific agent to treat COVID-19. • Interferon-β1 can be used as a treatment of COVID-19. • Interferon-β1-a can reduce mortality rate in admitted patients with COVID-19. • Interferon-β1-a can improve oxygen support in hospitalized patients with COVID-19., Interferon Beta-1a (IFN-β1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-β1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-β1-a and Lopinavir 400mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-β1-a on outcome and all-cause mortality. 152 cases in IFN-β1-a group and 304 cases as control group were included. IFN-β1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p=0.001) and (34% vs. 24%, p=0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-β1-a (HR 5.12, 95% CI: 2.77- 9.45), comorbidity (HR 2.28, 95% CI: 1.13- 4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56- 4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-β1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-β1-a in COVID-19 treatment.

Highlights • The pathophysiology of severe SARS-CoV-2 infection may be attributed to cytokine release syndrome. • In this syndrome, inflammatory cytokines (especially interleukin 6) are released after the activation of the inflammatory cascade. • The mortality rate among patients receiving tocilizumab with severe or critical SARS-CoV-2 infection was reported 16% in the current study comparing to 49 % based on the recent studies. • Tocilizumab, as an interleukin 6 antagonist, may be a promising agent to decrease the mortality rate in severe or critical SARS-CoV-2 infection., Background The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. Methods In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. Results Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. Conclusions Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.

Background and Purpose: Candidemia is a life-threatening fungal infection with significant mortality and morbidity in neutropenic individuals, immunosuppressive chemotherapy recipients, and broad-spectrum antibiotics consumers. The epidemiology and antifungal susceptibility testing of non-albicans Candida species have been poorly studied. These species are characterized by low susceptibility to azoles and echinocandins. Herein, we report the first pediatric case of candidemia due to C. guilliermondii in Iran and review the literature on fungemia caused by C. guilliermondii.Case report: We presented the first candidemia case due to C. guilliermondii in a 4-month-old male infant with neuroblastoma in Iran. This study also involves a comprehensive literature review on fungemia caused by C. guilliermondii during a period of 18 years (i.e., 2000-2018) to discuss the epidemiology, clinical features, and treatment of this disease. The literature review resulted in the identification of 501 cases of candidemia caused by C. guilliermondii. Most of the patients were adults and had multiple risk factors. However, the main risk factors were significantly related to cancer chemotherapy, followed by central venous catheter use and Intensive Care Unit admission. Mortality rate due to this disease had a range of 3.4-66.6%, in this regard, the patients with cancer had the highest mortality rate.Conclusion: Given the high mortality of candidemia, the early diagnosis of this infection and timely initiation of antifungal therapy significantly improve the patients’ survival rate and result in better outcomes. Consequently, it is highly recommended to monitor the local epidemiology of this life-threatening infection and raise awareness in this regard.

Background Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. Methods This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. Results The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. Conclusion It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P

Highlights • Intravenous immunoglobulin (IVIg) administration was not effective in the management of severe COVID-19 cases. • Intravenous immunoglobulin (IVIg) administration did not improve the radiographing changes in severe COVID-19 cases. • The length of hospital stay may be reduced upon early IVIg initiation., Background The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. Methods In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. Results The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value

Cystic fibrosis (CF) is associated with increased rates of morbidity and mortality due to fungal and bacterial colonisation of the airways or respiratory infections. The prevalence of fungi in Iranian CF population has been underestimated. Therefore, the current study was conducted to define the frequency of fungi in respiratory specimens obtained from Iranian CF patients based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed on the obtained isolates according to the guidelines from the Clinical and Laboratory Standards Institute. A cohort of 42 CF patients, including 29 males and 13 females, were categorised according to the referenced diagnostic criteria. Candida albicans (n = 24, 80%), C. dubliniensis (n = 2, 6.6%), C. parapsilosis (n = 2, 6.6%), C. tropicalis (n = 1, 3.3%), C. glabrata (n = 1, 3.3%) and Meyerozyma caribbica (n = 1, 3.3%) were isolated from 73.8% of the CF patients. Aspergillus terreus (n = 3, 42.8%) was identified as the most common Aspergillus species, followed by A. fumigatus (n = 2, 28.5%), A. oryzae (n = 1, 14.2%) and A. flavus (n = 1, 14.2%). Bacterial and fungal co-colonisation was detected in 7 (16.6%) and 22 (52.3%) samples that were positive for Aspergillus and Candida species, respectively. However, Scedosporium species and Exophiala dermatitidis never were detected. In terms of geometric mean (GM) minimum inhibitory concentrations (MICs), posaconazole (0.018 μg/mL) and caspofungin (0.083 μg/mL) exhibited the highest antifungal activities against all Candida species. In addition, posaconazole exhibited the lowest MIC range (0.008-0.063 μg/mL) against all Aspergillus species, followed by caspofungin (0.016-0.125 μg/mL) and voriconazole (0.125-0.25 μg/mL). To conclude, it is essential to adopt a consistent method for the implementation of primary diagnosis and determination of treatment regimen for the CF patients. However, further studies are still needed to better define the epidemiology of fungal organisms in CF patients from the Middle East and the clinical significance of their isolation.

Gastrointestinal basidiobolomycosis (GIB), a rare fungal infection associated with high mortality, has been reported worldwide mainly from tropical and subtropical regions of Asia, USA, and Latin America. The clinical manifestations are highly diverse and non-specific depending on the underlying disease, but fever, abdominal pain, weight loss, diarrhea, constipation and chills have been observed. There are no prominent risk factors for GIB but climatic conditions and life style are related to this infection in arid and semi-arid regions. Therefore timely diagnosis and early treatment is a challenge. Herein, we present an unusual case of gastrointestinal basidiobolomycosis in a 54-year-old male, initially misdiagnosed as colon cancer. After follow-up, no evidence of relapse and the patient was successfully cured by liposomal amphotericin B. In addition, the differential diagnosis and histopathological findings are discussed with a review of the literature.

Introduction: The caspase recruitment domain containing protein 9 (CARD9) deficiency is a primary immunodeficiency disorder that affects the innate immune system, resulting in increased susceptibility to fungal infections. We describe progressive disseminated phaeohyphomycosis due to a melanized fungus in a 26-year-old healthy female with inherited CARD9 deficiency to highlight the clinical presentation of this disorder. Case Presentation: The diagnosis of disseminated phaeohyphomycosis due to melanized fungi was made on the basis of clinical and histopathological findings. CARD9 gene was sequenced and a homozygous c.883C>T mutation in exon 6 at codon 295 was found, resulting in a mutation at position 295, Q295X. Conclusions: There are more cases of fungal infection associated with CARD9 deficiency in Iran compared to other Asian countries. Although consanguineous marriage is common in the Middle East, severe fungal infections related to CARD9 deficiency were only reported from Iran and Turkey. The higher incidence in comparison to other Middle Eastern countries may be associated with rapid population growth, large family size, and the availability of diagnostic facilities. Although Iranian patients with Q295X mutation are susceptible to candidiasis and dermatophytosis, our patient is the first report of phaeohyphomycosis related to Q295 mutation.

Objective: Due to devastating consequences of coronary artery disease (CAD) in young population, this study was designed to evaluate the prevalence of preventable risk factors and severity of atherosclerosis for Iranian young adults (≤45 years) diagnosed with premature CAD. Method: A cross sectional, descriptive study comprised 1093 consecutive patients (≤45 years), with a diagnosis of CAD, who underwent percutaneous intervention (PCI) or coronary bypass graft (CABG) from 2010 to 2012. Data on demographic features, cardiovascular risk factors, and angiographic findings were studied. Result: There were 1093 young patients (234 females, 859 males) with proven CAD; the mean age of 39 ± 3 years and the mean BMI were 28 ± 4.7 kg/m2. According to the treatment plan, patients were classified into two groups: PCI and CABG groups (n = 898,195 respectively). Obesity was the most prevalent risk factor (73.6%). In the risk factor assessment, it was noticed: 27% with diabetes mellitus, 37% with hypertension, 38% with family history, 39% with hyperlipidimia, and 54% smokers. Angiographic study revealed that 10 (1%) had left main coronary disease, 747 (68%) patients had single vessel disease, 181 (17%) had two-vessel disease and that 155 (14%) had three-vessel disease. The most common anatomical involvement was the anterior wall territory. Conclusion: Young CAD patients from Iran have different risk profile. Although atherosclerosis of the coronary arteries is less prominent in young patients, more often it is accompanied by decreased left ventricular function. There is a need for prevention plan to control obesity by targeting young adults in the population.

Context: It has been estimated that one-third of the world’s population are suffering from latent tuberculosis infection (LTBI). In order to control tuberculosis in high-risk groups proper diagnosis and treatment is essential. Evidence Acquisition: Useless and expensive tests such as unfocused population-based tests can lead to futile and unnecessary treatments. Targeted screening approaches and individualization of LTBI treatment protocols must be a priority. Results: Diagnostic methods with immune based tests such as the tuberculin skin test (TST) or interferon gamma release assays (IGRA) can accurately detect LTBI. However, interferon-gamma release assays have higher specificity than TST in Bacille Camette-Gurin (BCG)-vaccinated populations; both tests are precise to identify latent tuberculosis. However, it is of great concern that both tests have insignificant roles in predicting risk of progression to active tuberculosis. Conclusions: Here we review the clinical applications, advantages, and limitations of the tuberculin skin test and interferon-gamma release assays and provide an overview of the most recent systematic reviews conducted for the comparison of these tests.