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Introduction: Patients with primary or secondary immunodeficiency are at higher risk of severe disease and death following SARS-CoV-2 infection compared with the general population. We describe here the effect of rituximab therapy in 5 patients with humoral and cellular immune deficiencies (1 patient with thymoma or Good`syndrome, 1 HIV/AIDS positive patient, 2 patients with Multiple Sclerosis (MS) and 1 patient with chronic lymphocytic leukemia (CLL). T cell responses were evaluated using the QuantiFERON SARS-CoV-2 assay following incubation with the SARS-CoV-2 Ag1, Ag2 and Ag3 viral antigens. Immunephenotyping of T cells (TCD4+, TCD8+) and B cells (CD19+ and CD20+) was determined by flow cytometry. Results: All studied immunocompromised patients showed reduced cellular immune responses (release of interferon (IFN)-g) to SARS-CoV-2 antigens than healthy controls [patients; Ag1, Ag2 and Ag3 and Nil (Median 5-95% percentile) (12 (1-95), 12 (1.5-78), 13.5 (12-95) and 3 (1-98) U/ml)], ]controls; Ag1,Ag2 and Ag3 and Nil (Median 5-95% percentile) 24.5 (7-89), 65 (31-173), 53.5 (13-71.5) and 3 (1-14) U/ml)]. The frequency of peripheral blood B cells was also reduced in these patients compared to healthy control subjects (p=0.0282). Conclusion: T-cell dependent antibody responses require the activation of B cells by helper T cells. Reduced B cell numbers in immunocompromised patients infected with SARS-CoV-2 indicates the need for these patients to take additional precautions to prevent COVID-19 infection

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.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (

Co-infection between SARS-CoV-2 and other pathogens have become a serious threat. There are reports of fungal, bacterial and viral co-infections with SARS-COV-2. Herein, we report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia and also klebsiella pneumoniae empyema as the complication of COVID-19 infection.

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.

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized 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 arrhizus (formerly Rhizopus oryzae) was confirmed with sequencing of the internal transcribed spacer (ITS) region of the ribosomal DNA. 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.

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

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.