Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Approach to the child with recurrent infections

Children with a history of recurrent, severe, or unusual infections present a diagnostic challenge. It is important to maintain a high index of suspicion for the diagnosis of immunodeficiency, for early diagnosis and treatment can improve outcome. Differentiation between infections caused by common risk factors, or immune dysfunction should be based on a detailed history and physical examination and, if indicated, followed by appropriate laboratory studies. This paper aims at providing guidelines for the evaluation of children with recurrent infections. It provides an overview of the diagnostic approach including important details required from the history, physical examination, and an appropriate choice of screening test to be ordered

Perception of Saudi Undergraduate Students Towards Professionalism in Medicine

Objectives: Professionalism has garnered immense attention in medical education due to increased societal accountability and focus on excellence in healthcare. However, less attention has been given to identifying attitudes about professionalism in medical students who are the future advocates of the healthcare system. This study aimed to assess perceptions of Saudi undergraduate medical students towards professionalism. Methods: A crosssectional survey was carried out among second and sixth year students of the College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, in September 2018. A self-administered professionalism questionnaire was anonymously completed. Students were asked to provide their level of agreement with 18 survey items using a 5-point Likert scale. Results: Overall, 288 students participated in the study (males: 49.3% and females: 50.7%), with a response rate of 90%. The median professionalism score was high (71.0; range: 64–76) regardless of age, gender or level of education. Similar high scores were noted in the following subscales: Excellence, 20.0 (range: 18–21); Respect for Others, 17.0 (14–18); Altruism, 12.0 (10–13); Duty, 8.0 (7–9); Accountability, 7.0 (6–8) and Honour and Integrity, 8.0 (7–10). No gender differences were observed in the majority of subscales. However, males demonstrated higher scores in the Duty subscale (males: 9.0 versus females: 8.0; P = 0.026). Conclusion: Medical students demonstrated high professionalism scores. Future studies are needed to assess the impact of the course curriculum on their level of professionalism over time. Keywords: Attitudes; Curriculum; Medical Students; Professionalism; Survey; Saudi Arabia

Sensitization to common aeroallergens in asthmatic children in the Eastern region of Saudi Arabia

Background: Allergic disorders, particularly bronchial asthma, are one of the most common chronic childhood diseases. Bronchial asthma is more prevalent among children of the Eastern Province of Saudi Arabia compared with the other provinces. Environmental factors play major roles in the disease pathogenesis in genetically predisposed hosts. In this study, we characterize the pattern of allergenicity in asthmatic children in the Eastern Province of Saudi Arabia. Materials and Methods: This study is a retrospective, cross-sectional analysis of skin sensitization profiles of 100 Saudi asthmatic children living in Al-Khobar, Saudi Arabia. The group compromised 32 females and 68 males, aged 5–14 years with a mean age of 8.98 ± 2.93 years. Skin prick tests were performed in a regional tertiary center, in the period between January 2011 and December 2012, using a variety of indoor and outdoor allergens. Results: The most common indoor sensitizing allergens found were the house dust mite (54%), cat fur (53%) and the German cockroach (26%). Among outdoor allergens, Salsola kali was the most common (48%), followed by Timothy grass (23%) and Chenopodium album (23%). Among trees, Prosopis glandulosa was found to be the most prevalent sensitizer (19%). Among the molds, Alternaria and Aspergillus species were the most prevalent (21% each). Conclusion: A high rate of sensitization to aeroallergens was found in asthmatic children living in Al-Khobar city. The pattern of sensitization found in our study reflects the newly altered nature of an ancient humid desert that has been influenced by the recent artificial modernization of the region

Atypical pityriasis rosea: a case report and a review of literature

Aim: Pityriasis rosea (PR) is a common acute inflammatory skin disease characterized by pruritic erythematous papulosquamous eruption that is self-limited which can rarely pose a diagnostic challenge. In this report, we present a rare presentation of PR.Method: the case was completely evaluated including laboratory works and a final diagnosis of erythema multiforme-like PR was reached. Besides, we reviewed all atypical presentations of PR that are reported in the medical literature.Results: our patient has a morphological variant of PR which is erythema multiforme-like. The presence of a herald patch and  the rapid resolution of the symptoms supports our diagnosis. This variant is considered rare and to our knowledge, this is the seventh case of erythema multiforme-like PR reported in the medical literature.In conclusion: we report a case of erythema multiforme-like PR. It is important that physicians recognize the wide spectrum of PR variants so that appropriate management can be arranged. </p

Атиповий рожевий лишай: опис симптомів та огляд літератури

Aim: Pityriasis rosea (PR) is a common acute inflammatory skin disease characterized by pruritic erythematous papulosquamous eruption that is self-limited which can rarely pose a diagnostic challenge. In this report, we present a rare presentation of PR.Method: the case was completely evaluated including laboratory works and a final diagnosis of erythema multiforme-like PR was reached. Besides, we reviewed all atypical presentations of PR that are reported in the medical literature.Results: our patient has a morphological variant of PR which is erythema multiforme-like. The presence of a herald patch and  the rapid resolution of the symptoms supports our diagnosis. This variant is considered rare and to our knowledge, this is the seventh case of erythema multiforme-like PR reported in the medical literature.In conclusion: we report a case of erythema multiforme-like PR. It is important that physicians recognize the wide spectrum of PR variants so that appropriate management can be arranged. Рожевий лишай (РЛ) – це гостре запальне захворювання шкіри, що характеризується еритематозним папулосквамозним висипанням, яке є самообмеженим, і, як правило, зникає протягом 8-10 тижнів. Незважаючи на класичні уявлення, РЛ може представляти діагностичну проблему. У цій статті ми представляємо випадок однорічної дівчинки, який являв собою поліморфну еритему, як висипання, та в кінцевому підсумку був поставлений діагноз РЛ. Обговорюються проблеми та література з атипового Р

Prevalence and pattern of dermatological disorders in the pediatric emergency service

Background: Dermatological disorders are common in children. This study sought to describe the prevalence and pattern of dermatological emergencies encountered in the pediatric emergency room (ER). Methods: This was a retrospective study of patients with dermatological complaints visiting the pediatric ER at a teaching hospital in Saudi Arabia during the year 2014. Results: A total of 44,162 ER visits were recorded among children aged ⩽13 years, of which 2070 (4.7%) involved dermatological complaints. Over 80 dermatological conditions were encountered, the most common of which was atopic dermatitis (10.8%), followed by urticaria (9.7%). Categorization of diseases according to etiology revealed that the largest proportion of patients had infectious diseases (25.2%). Rare genetic disorders and life-threatening dermatological conditions were also encountered. A total of 10.5% of patients did not receive a diagnosis. Conclusions: Our study revealed a high frequency and wide spectrum of dermatological disorders in the pediatric ER. Considering the high rate of undiagnosed cases, this study highlights the need to objectively measure physicians’ abilities to diagnose dermatological disorders. Identification of common and potentially dangerous disorders can aid in the development of educational resources for trainees and in the allocation of future resources for the treatment of common conditions

Adverse Drug Reactions (ADRs) of Montelukast in Children

Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies have reported several adverse events, such as neuropsychiatric disorders and sleep disturbances, among children. Objective: To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders. Method and results: We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4–9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%). Conclusion: These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans