Implications of Complement Imbalance in COVID-19: A Molecular Mechanistic Discussion on the Importance of Complement Balance

Two central questions in COVID-19 treatment which should be considered are: “How does the imbalance of the complement system affect the therapeutic approaches?” and “Do we consider complement inhibitors in therapeutic protocols?”. The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms “COVID-19”, “Complement”, “Complement inhibitor”, “SARS-CoV-2”, and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in “KEGG pathway database”. Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors

X-linked hyper-IgM syndrome associated with pulmonary manifestations: A very rare case of functional mutation in CD40L gene in Iran

Hyper IgM (HIGM) syndromes are a complex of primary immunodeficiency disorders. A 4-years-old boy with recurrent fever and chills, dyspnea, sort throat for a month was admitted to emergency department. In the current case, whole exome sequencing followed by Sanger sequencing were employed in order to screen probable functional mutations. Molecular analysis revealed a functional mutation across the CD40L gene (NM_000074: exon5: c.T464C) resulted in amino acid change p.L155P attributed to X-linked hyper IgM syndrome. The findings of the current study signify the critical role of microbial infection as well as XHIGM screening, particularly in those children cases with respiratory symptoms.status: publishe

Colonization and antifungals susceptibility patterns of Candida species isolated from hospitalized patients in ICUs and NICUs

Background: Several studies have shown that there are an increasing in invasive candidiasis during 2-3 last decades. Although, Candida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents. Resistance to fluconazole among non-albicans species is an important problem for clinicians during therapy and prophylaxis. Objectives: The aim of current study was to detect the Candida species from hospitalized neonatal and children in intensive care units (ICUs) and neonatal intensive care units (NICUs). In addition, the susceptibility of isolated agents were also evaluated against three antifungals. Materials and Methods: In the present study 298 samples including 98 blood samples, 100 urines and 100 swabs from oral cavity were inoculated on CHROMagar Candida. Initial detection was done according to the coloration colonies on CHROMagar Candida. Morphology on cornmeal agar, germ tube formation and growth at 45°C were confirmed isolates. Amphotericin B, fluconazole and terbinafine (Lamisil) were used for the susceptibility tests using microdilution method. Results: In the present study 21% and 34% of urines and swabs from oral cavity were positive for Candida species, respectively. The most common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C. glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most tested species of Candida, 70.3% were sensitive to fluconazole at the concentration of ≤8 μg/mL. Whereas 9 (14.1%) of isolates were resistant to amphotericine B at ≥8 μg/mL. Conclusions: This study demonstrates the importance of species identification and antifungals susceptibility testing for hospitalized patients in ICUs and NICUs wards

The barriers and challenges of applying new strategies in the clinical evaluation of nursing students from the viewpoints of clinical teachers

Background: Numerous studies have emphasized the use of new approaches in clinical evaluation. However, there are some challenges and barriers to applying these new approaches. The aim of the present study was to investigate the barriers and challenges of applying new strategies in the clinical evaluation of nursing students from the viewpoints of clinical teachers. Materials and Methods: This cross-sectional study was conducted among 151 clinical teachers. A researcher-made questionnaire was used to collect data. The questionnaire was validated using library references and a variety of texts, as well as thorough consulting with 15 clinical teachers. The questionnaire's reliability was approved with a Cronbach's alpha of 78%. Data analysis was conducted using Pearson's correlation coefficient, one-way analysis of variance (ANOVA), and descriptive statistics in SPSS software. Results: The highest score was related to the “students and clinical environment” domain [24.05 (8.10)], and the lowest to the “facilities” domain [13.31 (1.50)]. One-way ANOVA results showed a significant relationship between the mean scores of academic degree and the two domains of “tests” (F = 9.66, p < 0.001) and “facilities” (F = 8.26, p < 0.001). Conclusions: The implementation of a new approach for evaluating clinical training requires infrastructure and overcoming executive obstacles. Educating students and clinical teachers on new evaluation methods requires their familiarity with the implementation process as well as encouragement and support by their educational institution and administrators

A Review of SARS-CoV-2 Genetic and Structure: Hot Cellular Targets for Virus Entry: Genetic and structure of COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses several molecules such as angiotensin-converting enzyme 2 (ACE2), cluster of differentiation 26 (CD26), Ezrin, and Neuropilin-1 (NRP-1) for viral entry. In this review, the entire structural and genomic combination and the mechanism of virus entry, are discussed. This study might be useful for further drug design studies. SARS-CoV-2 neutralization allows the immune system to fight the virus before its entry. COVID-19 enters the host bloodstream by infecting endothelial cells via a cluster of differentiation 147 (CD147). SARS-CoV-2 not only uses ACE2 for its entry but also affects ACE-2 and its enzymatic activity on Ang II and bradykinin, it also imbalances the RAAS and bradykinin system and elevates the inflammation. High levels of bradykinin, cause nonproductive cough as the result of fluid extravasation and leukocyte recruitment to the lung. Accordingly, we suggest replicase transcriptase complex (RTC) and specific non-structural proteins (Nsps) such as Nsp7,8, Nsp10, Nsp12, and Nsp16 are perfect targets of study because RTC and Nsps are the golden elements in the maintenance of COVID-19 appearance and masking. Base on this evidence COVID-19 uses various receptors for its entry and it might block these receptors' activity to evade the immune system and spread to other cells. *Corresponding Authors: Elham Rajaei, Email: [email protected];&nbsp;ORCID: https://orcid.org/0000-0002-8231-0138 Please cite this article as: Torabizadeh M, Ghobadi Dana V, Aghapour SA, Zibara K, Deris Zayeri Z, Rajaei E. A Review of SARS-CoV-2 Genetic and Structure: Hot Cellular Targets for Virus Entry. Arch Med Lab Sci. 2021;7:1-9 (e15). https://doi.org/10.22037/amls.v7.3421