Spontaneous Pneumothorax in a Child with COVID-19

Introduction: SARS-CoV2 (COVID-19) is a serious and global infection that has spread to numerous countries, including Iran. Pneumothorax may occur in cases of COVID-19 as a consequence of lung parenchymal damage, which can disrupt the healing process and increase mortality. Case Presentation: This manuscript describes the case of a 2-year-old boy with hyper IgM syndrome and COVID-19 infection. The patient developed spontaneous pneumothorax and recovered without chest tube by supportive care and was discharged in good general condition after the completion of the antibiotic course and cessation of fever. Conclusions: The severity, prognosis, and best treatment for spontaneous pneumothorax in COVID-19 infection, especially in children, remain nebulous. It is recommended that conservative treatment be performed if the patient has stable vital signs and no severe respiratory failure. However, this requires more detailed clinical evaluations.

Cryptococcal Meningitis and Post-Infectious Inflammatory Response Syndrome in a Patient With X-Linked Hyper IgM Syndrome: A Case Report and Review of the Literature

The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse.

Identification of genetic sequence variations associated with the pathogenesis of X-linked hyper-IgM syndrome

Background: X-Linked Hyper-IgM Syndrome (X-HIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand gene (CD40LG). It is characterized by normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE levels. Patients with this syndrome are often prone to infections. Environmental and genetic (especially genetic mutation) factors may play an important role in etiology, development, and pathogenesis of X-HIGM. Methods: DNA from a male child diagnosed as having X-HIGM and DNA from his healthy mother were used for whole-exome (next-generation) sequencing and targeted gene sequencing. The results were analyzed using Exome Aggregation Consortium data and the Genome Aggregation Database and were further validated using Sanger sequencing. Results: Next-generation sequencing results indicated that the CD40LG gene in the child had a p.R203I variant. In addition, his mother was a carrier, suggesting that the child’s p.R203I homozygous mutation was inherited from his mother. The functional prediction scores from SIFT, MetaSVM, and FATHMM software indicated that this genetic variant may be harmful. Conclusions: Single variations in many exons of the CD40LG gene can lead to X-HIGM. Although the pathogenicity of the variant identified in the present study has not been previously reported, prediction software found that it would be harmful. Thus, CD40LG may be related to this genetic disease. Despite these limitations, our findings provided insight into X-HIGM pathogenesis and suggested a potential target for therapeutic drug development.

Insights into the Structures and Multimeric Status of APOBEC Proteins Involved in Viral Restriction and Other Cellular Functions

Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of deaminase proteins that can catalyze the deamination of cytosine to uracil on single-stranded DNA or/and RNA. APOBEC proteins are involved in diverse biological functions, including adaptive and innate immunity, which are critical for restricting viral infection and endogenous retroelements. Dysregulation of their functions can cause undesired genomic mutations and RNA modification, leading to various associated diseases, such as hyper-IgM syndrome and cancer. This review focuses on the structural and biochemical data on the multimerization status of individual APOBECs and the associated functional implications. Many APOBECs form various multimeric complexes, and multimerization is an important way to regulate functions for some of these proteins at several levels, such as deaminase activity, protein stability, subcellular localization, protein storage and activation, virion packaging, and antiviral activity. The multimerization of some APOBECs is more complicated than others, due to the associated complex RNA binding modes.