Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies.

The rapid emergence of multiple strains of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has sparked profound concerns regarding the ongoing evolution of the virus and its potential impact on global health. Classified by the World Health Organization (WHO) as variants of concern (VOC), these strains exhibit heightened transmissibility and pathogenicity, posing significant challenges to existing vaccine strategies. Despite widespread vaccination efforts, the continual evolution of SARS-CoV-2 variants presents a formidable obstacle to achieving herd immunity. Of particular concern is the coronavirus spike (S) protein, a pivotal viral surface protein crucial for host cell entry and infectivity. Mutations within the S protein have been shown to enhance transmissibility and confer resistance to antibody-mediated neutralization, undermining the efficacy of traditional vaccine platforms. Moreover, the S protein undergoes rapid molecular evolution under selective immune pressure, leading to the emergence of diverse variants with distinct mutation profiles. This review underscores the urgent need for vigilance and adaptation in vaccine development efforts to combat the evolving landscape of SARS-CoV-2 mutations and ensure the long-term effectiveness of global immunization campaigns.

Genomic Testing Identifies Monogenic Causes in Patients with Very Early-Onset Inflammatory Bowel Disease: A Multi-center Survey in an Iranian Cohort.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multi-center study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in one patient, respectively. In 3 patients (18.7%) no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

The association between various viral infections and multiple sclerosis: An umbrella review on systematic review and meta-analysis.

Multiple Sclerosis (MS) is one of the immune-mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the pathogenesis of MS. Also, it can be said that infections are a key component of the host's response to MS development. Finally, we evaluated the relationship between different pathogens and MS disease in this umbrella research. We systematically collected and analysed multiple meta-analyses focused on one particular topic. We utilised the Scopus, PubMed, and Web of Science databases starting with inception until 30 May 2023. The methodological quality of the analysed meta-analysis has been determined based on Assessing the Methodological Quality of Systematic Reviews 2 and Grade, and graph construction and statistical analysis were conducted using Comprehensive Meta-Analysis. The Confidence Interval of effect size was 95% in meta-analyses, and p < 0.05 indicated a statistically meaningful relationship. The included studies evaluated the association between MS and 12 viruses containing SARS-CoV-2, Epstein-Barr virus (EBV), Hepatitis B virus, varicella-zoster virus (VZV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, HSV-1, HSV-2, Cytomegalovirus, Human Papillomavirus, and influenza. SARS-CoV-2, with a 3.74 odds ratio, has a significantly more potent negative effect on MS among viral infections. After that, EBV, HHV-6, HSV-2, and VZV, respectively, with 3.33, 2.81, 1.76, and 1.72 odds ratios, had a significantly negative relationship with MS (p < 0.05). Although the theoretical evidence mostly indicates that EBV has the greatest effect on MS, recent epidemiological studies have challenged this conclusion and put forward possibilities that SARS-CoV-2 is the culprit. Hence, it was necessary to investigate the effects of SARS-CoV-2 and EBV on MS.

Unusual herpetic reactivation in a young female following botox injection: a case report study.

BACKGROUND: Botox injections are commonly used for cosmetic and therapeutic purposes because they temporarily paralyze muscles, reduce wrinkles, and alleviate certain medical conditions. Although generally considered safe and effective, Botox injections may cause potential complications. While herpes reactivation is more commonly associated with immunosuppressive therapies, such as chemotherapy or corticosteroid use, its association with Botox injection is poorly documented. CASE PRESENTATION: A 33-year-old woman presented with progressive painful rashes and vesicles on her forehead, scalp, and right upper eyelid, accompanied by fever and malaise following a Botox injection to treat wrinkles. A positive Tzanck smear test result confirmed the diagnosis of herpes infection. The patient was treated with antiviral medication, and her symptoms gradually regressed over several days. CONCLUSIONS: Although herpes reactivation is more commonly associated with immunosuppressive therapies, few cases of herpes zoster and herpes simplex following Botox injection have been reported. The pathogenesis of herpes reactivation following Botox injection is unclear; however, it has been hypothesized that the Botox protein is a potent antigen that may activate the cellular immune system, making it easier for the virus to reactivate. Healthcare providers should be aware of this potential complication and consider it when evaluating patients who present with painful rashes following Botox injections. In addition, individuals who want to receive Botox injections should be informed of this complication. The diagnosis of herpetic infection should be made promptly, and antiviral therapy should be initiated to minimize the risk of complications. Further research is needed to better understand the pathogenesis and risk factors for herpes following Botox injection and to develop strategies for preventing and managing this complication.

The Radiological Manifestations of Phagocytic Primary Immunodeficiencies in Children.

Primary immunodeficiencies are a diverse group of rare genetic disorders, among which phagocytic dysfunction impairs neutrophil function in a wide range of inherited disorders. Due to the heterogeneity of the disorders a multidisciplinary approach is often required for early diagnosis and initiation of appropriate treatments. The aim of this study was to evaluate the imaging findings in children admitted with phagocytic primary immunodeficiencies. Thirty-five children who fulfilled the inclusion criteria for phagocytic dysfunction were enrolled in this study. The patients were under close observation and monitoring from January 2011 until data locking in December 2017. The diagnosis of phagocytic immunodeficiency was confirmed by the patient's clinical course, presentation features, and laboratory data.  Among the 35 patients studied, the most frequent condition was chronic granulomatous disease (CGD) (23 patients), followed by different types of neutropenia (8 patients) and Job's syndrome (4 patients). Mediastinal and hilar lymphadenopathies and consolidation were the most frequent presentations. There was a significant relationship between mediastinal/hilar lymphadenopathies and fungal infections. A meaningful relationship was also found between pulmonary nodules without halo signs in patients with concomitant tuberculosis and fungal infections. A significant correlation was found between CGD, pulmonary fibrotic changes, and mediastinal lymphadenopathies. The most frequent radiological manifestations in children included mediastinal and hilar consolidations. Physicians' awareness of the radiological and clinical manifestations of these inherited diseases may be helpful in the early diagnosis and timely initiation of specific prophylaxis measures to prevent infections and also to initiate hematopoietic stem cell transplantation as the curative management modality.

Investigation of the Relationship between Aspirin-Sensitivity and Poor Response to Medical Management in NSAIDs-exacerbated Respiratory Disease Patients with Sinonasal Polyposis.

Background: NSAID-exacerbated respiratory disease (N-ERD) is a highly heterogeneous disorder with various clinical symptoms. The aspirin challenge test is a gold standard method for its diagnosis, and there are still no reliable in vitro diagnostic biomarkers yet. Oral challenge tests are time-consuming and may be associated with a risk of severe systemic reactions. This study aimed to evaluate whether patients with poor responses to medical management are more susceptible to being aspirin-sensitive. Methods: In this cohort study, after CT scanning of all patients and subject selection, conventional medical treatment was started as follows and continued for three consecutive months: at first, saline nose wash twice per day, intranasal beclomethasone spray one puff in each nostril twice per day, montelukast 10 mg tablet once daily, a ten-day course of oral prednisolone starting with the dose of 25 mg per day and taper and discontinued thereafter. Sinonasal outcome test 22 (SNOT22) was used for the evaluation of symptom severity. Statistical analyses were performed with SPSS version 23, and data were analyzed using an independent samples T-test, paired T-test, and Receiver operating curve analysis. Results: 25 males and 53 females were enrolled in this study, with an average age of 41.56 ± 11.74 years old (18-36). Aspirin challenge test results were positive in 29 (37.2%) patients. The average SNOT22 scores before the treatment were 52.97 ± 17.73 and 47.04 ± 18.30 in aspirin-sensitive and aspirin-tolerant patients, respectively, and decreased to 27.41 ± 16.61 and 24.88 ± 16.72 in aspirin-sensitive and aspirin-tolerant patients after the treatment, respectively. There was no significant difference in SNOT22 scores between the groups. Conclusion: The severity of symptoms before treatment and clinical improvement after treatment are not good predictors of N-ERD.

Evaluation of the frequency of attention deficit hyperactivity disorder in patients with asthma.

BACKGROUND: Asthma is the most prevalent respiratory disease caused by chronic airway inflammation. Attention Deficit Hyperactivity Disorder (ADHD) is children's most common psychological and neurodevelopmental disorder. Increased risk for ADHD in patients with inflammatory and autoimmune diseases supports the role of inflammatory mechanisms in the occurrence of ADHD. However, the association between asthma and ADHD remains unclear. OBJECTIVE: This study was designed to evaluate the prevalence of ADHD in patients with asthma who were referred to the clinic of allergy and clinical immunology. METHODS: This cross-sectional study was conducted on children aged 6 to 18 with asthma at Imam Ali hospital, Karaj, Iran. The patient's demographic data, history of childbirth delivery type, premature birth, hospital admission, family income, birth rate, and family history information related to the patient's asthma and medicines were recorded. ADHD diagnosis was made using the Persian version of Conners Parent Behavioral Problems Rating Scale (CPRS-26). RESULTS: In this study, 677 asthmatic patients were enrolled; 46 patients (6.8%) had ADHD. The probability of ADHD in asthmatic patients inhabited in a rural area, males, and patients with a history of food allergy, allergic rhinitis, urticaria, and eczema was significantly higher (p < 0.05). In addition, our result demonstrated that the likelihood of ADHD in patients with asthma and a history of PICU admission was significantly higher (p < 0.05). CONCLUSIONS: The present study showed that severe asthma, was the risk factor for ADHD in patients with asthma. Physicians should be aware of this co-morbidity to refer asthmatic patients who have the symptoms of ADHD to a psychologist.

Autoimmune versus Non-autoimmune Cutaneous Features in Monogenic Patients with Inborn Errors of Immunity.

Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient's demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5-5.2) years; a total of 66 (40.7%) of these patients initially presented with these manifestations. Patients with cutaneous involvement were generally older at the time of diagnosis [5.0 (1.6-8.0) vs. 3.0 (1.0-7.0) years; p = 0.022]. Consanguinity was more common among patients who developed skin disorders (81.4% vs. 65.2%, p < 0.001). The overall skin infection rate and the type of dominant pathogens were significantly different among the IEI patients in different phenotypical classifications (p < 0.001). Atopic presentation, including urticaria, was highly prevalent among patients with congenital defects of phagocytes (p = 0.020). The frequency of eczema was also significantly higher among cases with both syndromic and non-syndromic combined immunodeficiency (p = 0.009). In contrast, autoimmune cutaneous manifestations, including alopecia and psoriasis, were most common in patients with immune dysregulation (p = 0.001) and defects in intrinsic or innate immunity (p = 0.031), respectively. The presence of autoimmune cutaneous complications significantly improved the survival rate of IEI patients (p = 0.21). In conclusion, cutaneous manifestations were observed in nearly 44% of Iranian patients with monogenic IEI. A considerable number of patients with cutaneous involvements developed these disorders as their first manifestation of the disease, which was particularly noticeable in patients with non-syndromic combined immunodeficiency and phagocytic defects. The neglected skin disorders in IEI patients might delay diagnosis, which is generally established within a 3-year interval from the development of skin-related problems. Cutaneous disorders, especially autoimmune features, might indicate a mild prognosis in IEI patients.

Evaluating the Effect of Eicosapentaenoic Acid in Children With Atopic Dermatitis: A Randomized Triple-Blind Clinical Trial.

OBJECTIVE: To evaluate the effects of dietary eicosapentaenoic acid (EPA) in children with atopic dermatitis. METHODS: Forty-eight children with atopic dermatitis were randomly allocated to receive either 250 mg twice daily EPA (n = 24) or placebo (n = 24) for 4 weeks. The absolute improvement in the SCORing Atopic Dermatitis (SCORAD) index and the necessity to use topical corticosteroids was evaluated. RESULTS: Based on an intention-to-treat analysis, after 2 weeks the scores decreased to 30.50 ± 8.91 and 38.34 ± 10.52 in the EPA and placebo groups, respectively (p = 0.015). Per-protocol analysis showed a decrease in scores to 18.01 ± 10.63 in the EPA group and to 30.11 ± 9.58 in the placebo group (p = 0.001). After 2 weeks, corticosteroid was needed in 11 (50.0%) patients in the EPA group and 14 (58.3%) patients in the placebo group (p = 0.571), and after 4 weeks, it was needed in 7 (33.3%) patients in the EPA group and 14 (63.6%) patients in the placebo group, respectively (p = 0.047). CONCLUSIONS: Our results show significant favorable effects of EPA on the SCORAD scale and with regard to the necessity for corticosteroid readministration. Few adverse effects were reported in the 2 groups. We conclude that EPA supplementation is a well-tolerated and effective add-on strategy for reducing the severity of atopic dermatitis in children.

Characterization of occult hepatitis B infection among Iranian liver transplant recipients.

BACKGROUND: The prevalence of occult hepatitis B infection (OBI) among Iranian liver transplant recipient patients has not been explored yet. The present study aimed to determine the OBI prevalence among Iranian liver transplant recipients. METHODS: This study encompassed 97 patients having undergone liver transplantation due to several clinical backgrounds in the Liver Transplantation Center, Tehran, Iran. After serological evaluation, two different types of PCR methods were applied for amplification of HBV DNA, followed by the direct sequencing of whole hepatitis B virus (HBV) surface genes. RESULTS: At the time of admission, none of the patients were positive for HBsAg. However, 24 (25%), 12 (12.3%), and 5 (5.1%) cases were positive for anti-HBc, hepatitis C virus (HCV), and hepatitis delta virus (HDV) antibodies, respectively. Moreover, two males were positive for OBI (2.1%). Both were positive for anti-HBc and negative for anti-HBs, anti-HCV, and anti-HDV. HBV-related cirrhosis was the underlying reason for their liver transplantation. HBsAg sequences revealed no amino acid substitution. CONCLUSIONS: The prevalence of OBI in the Iranian liver transplantation patients was relatively low. Future longitudinal studies with a larger sample size are suggested to explore the significance of this clinical finding, including the reactivation of cryptic HBV DNA, in liver transplant subjects.

Occult Hepatitis B Infection among Hemodialysis in Tabriz, Northwest of Iran: Prevalence and Mutations within the S Region.

Regardless of the extensive screening for the detection of hepatitis B surface antigen (HBsAg), hemodialysis (HD) patients are still severely at the risk of occult hepatitis B virus infection (OBI), especially in developing countries. OBI is defined as the presence of HBV DNA with undetectable HBsAg in the liver and/or Serum. This study aims to determine the prevalence of OBI in HD patients in Tabriz Province, northwest of Iran, and inquire about the mutations in the detected HBsAg. In this cross-sectional descriptive study, ELISA method assessed serum and plasma samples of 118 HBsAg-negative patients undergoing HD treatment for HBV serological markers (HBsAg and Anti-HBc). Specific primers by nested polymerase chain reaction have been utilized to examine HBV DNA; also, direct sequencing of surface genes was carried out to characterize the viral genotypes and S gene mutations. Finally, followed by real-time PCR, the quantity of viral load in OBI-positive patients was determined. A total of 118 HD patients were included (63.6% were male and 36.4% female), with an overall mean age of 60.8 ± 12.8 years old. The prevalence of antihepatitis B core antibody (Anti-HBc) in the study population was 26.3% (31/118). Five patients (4.2%) were positive for HBV DNA and labeled OBI-positive; their plasma HBV-DNA load was less than 100 IU/ml. Following the phylogenetic analysis, the samples with OBI roughly belonged to genotype D, subtype ayw2 and only two had mutations within the S 'gene's major hydrophilic region (MHR), including T123I, C124F, and P127T. This study reports the prevalence of OBI in the HBsAg-negative HD patients being at a rate of 4.2%, which can be a clinically vital consideration in this region. HBV serologic screening approaches need to be renewed to cover nucleic acid testing in the setting of hemodialysis and all the other high-risk groups associated with it (i.e., blood and organ donors).

The role of antigen-presenting cells in the pathogenesis of COVID-19.

Coronavirus Disease 2019 (COVID-19) is one of the three lethal coronavirus outbreaks in the recent two decades and a serious threat to global health all over the world. The principal feature of the COVID-19 infection is the so-called "cytokine storm" exaggerated molecular response to virus distribution, which plays massive tissue and organ injury roles. Immunological treatments, including monoclonal antibodies and vaccines, have been suggested as the main approaches in treating and preventing this disease. Therefore, a proper investigation of the roles of antigen-presenting cells (APCs) in the aforementioned immunological responses appears essential. The present review will provide detailed information about APCs' role in the infection and pathogenesis of SARS-CoV-2 and the effect of monoclonal antibodies in diagnosis and treatment.

SARS-CoV-2: Receptor and Co-receptor Tropism Probability.

The recent pandemic which arose from China, is caused by a pathogenic virus named "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)". Its rapid global expansion has inflicted an extreme public health concern. The attachment of receptor-binding domains (RBD) of the spike proteins (S) to the host cell's membrane, with or without the help of other cellular components such as proteases and especially co-receptors, is required for the first stage of its pathogenesis. In addition to humans, angiotensin-converting enzyme 2 (ACE2) is found on a wide range of vertebrate host's cellular surface. SARS-CoV-2 has a broad spectrum of tropism; thus, it can infect a vast range of tissues, organs, and hosts; even though the surface amino acids of the spike protein conflict in the receptor-binding region. Due to the heterogeneous ACE2 distribution and the presence of different domains on the SARS-CoV-2 spike protein for binding, the virus entry into diverse host cell types may depend on the host cells' receptor presentation with or without co-receptors. This review investigates multiple current types of receptor and co-receptor tropisms, with other molecular factors alongside their respective mechanisms, which facilitate the binding and entry of SARS-CoV-2 into the cells, extending the severity of the coronavirus disease 2019 (COVID-19). Understanding the pathogenesis of COVID-19 from this perspective can effectively help prevent this disease and provide more potent treatment strategies, particularly in vulnerable people with various cellular-level susceptibilities.

The First Iranian Cohort of Pediatric Patients with Activated Phosphoinositide 3-Kinase-δ (PI3Kδ) Syndrome (APDS).

BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently defined combined primary immunodeficiency disease (PID) characterized by recurrent respiratory tract infections, lymphoproliferation, autoimmunity and lymphoma. Gain-of-function mutations in PIK3CD and loss-of-function of PIK3R1 genes lead to APDS1 and APDS2, respectively. METHODS: Demographic, clinical, immunological and genetic data were collected from medical records of 15 pediatric patients, who were genetically identified using the whole-exome sequencing method. RESULTS: Fifteen patients (6 APDS1 and 9 APDS2) were enrolled in this study. Recurrent respiratory tract infections followed by lymphoproliferation and autoimmunity were the most common manifestations (86.7%, 53.3% and 26.7%, respectively). Five patients (33.3%) had a Hyper-IgM-syndrome-like immunoglobulin profile. In the APDS1 group, splice site and missense mutations were found in half of the patients and the C-lobe domain of PIK3CD was the most affected region (50%). In the APDS2 group, splice site mutation was the most frequent mutation (77.8%) and the inter-SH2 domain was the most affected region of PIK3R1 (66.7%). Mortality rate was significantly higher in APDS2 group (P = .02) mainly due to chronic lung infections. CONCLUSION: Respiratory tract infections and humoral immunodeficiency are commonly the most important complication in pediatric APDS patients, and they can be fatal by ultimately causing catastrophic damage to the structure of lungs. Hence, physicians should be aware of its significance and further work-up of patients with recurrent respiratory tract infections especially in patients with lymphoproliferation. Moreover, delineation of genotype-phenotype associations with disease severity could be helpful in the timely application of appropriate management and patients' survival.

Pulmonary Radiological Manifestations of Humoral and Combined Immunodeficiencies in a Tertiary Pediatric Center.

Respiratory diseases are considered as significant causes of morbidity and mortality in primary immunodeficiencies. This study aimed to reveal the radiologic patterns of thoracic involvement in these disorders. A total of 58 patients, including 38 cases with combined cellular-humoral and 20 cases with humoral immunodeficiencies, were enrolled in this study. The "combined" group consisted of 12 cases with severe combined immunodeficiency (SCID) and 26 cases with combined immunodeficiency. The "humoral" group included seven patients with Hyper IgM syndrome (HIGMs), seven cases with common variable immunodeficiency (CVID), three patients with X-linked agammaglobulinemia, and three patients with other types of humoral primary immunodeficiencies (PIDs). The mean age of patients at the time of evaluation was 3.3±3.8 and 5.3±3.9 years in combined and humoral groups, respectively. The findings of chest X-rays and CT scans were interpreted and compared. There was a significant difference for alveolar opacification between combined and humoral immunodeficiencies (58% vs. 30%). The bronchopneumonia-like pattern was detected as a significant finding in patients with SCID (42%) and HIGMs (43%). Atrophy of the thymus was detected significantly often in cases of SCID (67%). Two patients with CVID and lipopolysaccharide-responsive and beige-like anchor protein deficiency showed parenchymal changes of granulomatous lymphocytic interstitial lung disease. No significant difference was detected for bronchiectasis, bronchitis/bronchiolitis patterns, pleural effusion, and thoracic lymphadenopathy. Distinct subtypes of primary immunodeficiency may provoke differing and comparable radiological patterns of thoracic involvement; which can clue the clinician and radiologist to the diagnosis of the disease.

Adverse reactions in a large cohort of patients with inborn errors of immunity receiving intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. METHODS: Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. RESULTS: 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. CONCLUSION: The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.

The Effect of Aspirin on Moderate to Severe Asthmatic Patients with Aspirin Hypersensitivity, Chronic Rhinosinusitis, and Nasal Polyposis.

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.

The Prevalence of Atopic Manifestations in 313 Iranian Patients with Inborn Errors of Immunity.

INTRODUCTION: Inborn errors of immunity (IEIs) are rare inherited disorders with a broad spectrum of manifestations. Here, we aimed to delineate the atopy burden in a cohort of patients with IEIs. METHODS: 313 patients with IEIs were enrolled in the study within a 9-years period, and data were collected via a questionnaire. All statistical analyses were performed using SPSS software (v. 25.0, Chicago, IL, USA). The statistical significance level was set at p < 0.05. RESULTS: Overall, 51 out of 313 (16.3%) patients were identified to have atopic manifestations. Food allergy was detected in 34 (10.2%), atopic dermatitis in 21 (6.7%), as well as allergic asthma and allergic rhinitis each in 4 (1.3%) patients. The allergic disorders were reported as initial manifestations among 14 out of 35 (40.0%) atopic patients. Most of these 51 patients fell within the category of combined immunodeficiency (CID) (n = 38, 74.5%), followed by, severe CID (SCID) (n = 5, 9.8%), common variable immunodeficiency (n = 3, 5.9%), chronic granulomatous disease (n = 3, 5.9%), selective IgA deficiency (n = 1, 2.0%), and leukocyte adhesion defect (n = 1, 2.0%). No patient with Mendelian susceptibility to mycobacteria was found to have atopic manifestation. Atopic dermatitis (p = 0.001) and food allergy (p < 0.001) were both significantly higher in patients with CID than in other IEI groups. Among atopic patients with CID and SCID, food allergy and atopic dermatitis were the most prevalent comorbidities. DISCUSSION/CONCLUSION: Atopic diseases may contribute to the clinical picture of IEIs, particularly in patients with CID. Atopy in association with other warning signs of IEIs increases the possibility of an underlying IEI.

Viral coinfections in COVID-19.

The most consequential challenge raised by coinfection is perhaps the inappropriate generation of recombinant viruses through the exchange of genetic material among different strains. These genetically similar viruses can interfere with the replication process of each other and even compete for the metabolites required for the maintenance of the replication cycle. Due to the similarity in clinical symptoms of most viral respiratory tract infections, and their coincidence with COVID-19, caused by SARS-CoV-2, it is recommended to develop a comprehensive diagnostic panel for detection of respiratory and nonrespiratory viruses through the evaluation of patient samples. Given the resulting changes in blood markers, such as coagulation factors and white blood cell count following virus infection, these markers can be of diagnostic value in the detection of mixed infection in individuals already diagnosed with a certain viral illness. In this review, we seek to investigate the coinfection of SARS-CoV-2 with other respiratory and nonrespiratory viruses to provide novel insights into the development of highly sensitive diagnostics and effective treatment modalities.

SARS-CoV-2 infection: The role of PD-1/PD-L1 and CTLA-4 axis.

The outbreak of SARS-CoV-2 in Wuhan of China in December 2019 and its worldwide spread has turned into the COVID-19 pandemic. Respiratory disorders, lymphopenia, cytokine cascades, and the immune responses provoked by this virus play a major and fundamental role in the severity of the symptoms and the immunogenicity which it causes. Owing to the decrease in the inflammatory responses' regulation in the immune system and the sudden increase in the secretion of cytokines, it seems that an investigation of inhibitory immune checkpoints can influence theories regarding this disease's treatment methods. Acquired cell-mediated immune defense's T-cells have a key major contribution in clearing viral infections thus reducing the severity of COVID-19's symptoms. The most important diagnostic feature in individuals with COVID-19 is lymphocyte depletion, most importantly, T-cells. Due to the induction of interferon-γ (INF-γ) production by neutrophils and monocytes, which are abundantly present in the peripheral blood of the individuals with COVID-19, the expression of inhibitory immune checkpoints including, PD-1 (programmed death), PD-L1 and CTLA4 on the T-cells' surface is enhanced. The purpose of this review is to discuss the functions of these checkpoints and their effects on the dysfunction and exhaustion of T-cells, making them almost ineffective in individuals with COVID-19, especially in the cases with extreme symptoms.