SARS-CoV2 infection induce miR-155 expression and skewed Th17/Treg balance by changing SOCS1 level: A clinical study.

BACKGROUND: One of the regulators in severe acute respiratory syndrome coronavirus2 (SARS-CoV2) infection is miRNAs. In COVID-19 patients, immunological responses to SARS-CoV2 infection may be impacted by miR-155, a miRNA associated to inflammation. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 50 confirmed COVID-19 patients /Healthy Controls (HCs) was isolated by Ficoll. The frequency of T helper 17 and regulatory T cells was analyzed by flowcytometry. The RNA was extracted from each sample and after synthesis of c-DNA, the relative expression of miR-155, suppressor of cytokine signaling (SOCS-1), Signal transducer and activator of transcription 3(STAT3), and Fork Head Box Protein 3 (FoxP3) was evaluated by real-time PCR. The protein level of STAT3, FoxP3 and RORγT in the isolated PBMCs measured by western blotting. The serum level of IL-10, TGF-ß, IL-17 and IL21 was assessed by ELISA method. RESULTS: The population of Th17 cells showed a significant rise, whereas Treg cells reduced in COVID-19 cases. The master transcription factor of Treg (FoxP3) and Th17 (RORγT) relative expression showed the same pattern as flowcytometry. STAT3 level of expression at RNA and protein level increased in COVID-19 cases. FOXP3 and SOCS-1 proteins were down-regulated. The relative expression of miR-155, up-regulated in PBMC of COVID-19 patients and revealed a negative correlation with SOCS-1. The serum cytokine profile showed a reduction in TGF-ß, on the other hand an increase was seen in IL-17, IL-21 and IL-10 in COVID-19 cases toward control group. CONCLUSION: Based on the studies conducted in this field, it can be suggested that Th17/Treg in covid-19 patients can be affected by miR-155 and it can be considered a valuable diagnostic and prognostic factor in this disease.

Association between leukocyte telomere length and COVID-19 severity.

Background: Inter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases. Result: In this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity. Conclusions: These findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1186/s43042-023-00415-z.

Vitamin D in respiratory viral infections: a key immune modulator?

Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.

Efficient dispersive solid-phase extraction of methylprednisolone from exhaled breath of COVID-19 patients.

In the current study, bismuth ferrite nano-sorbent was synthesized and utilized as a sorbent for the dispersive solid-phase extraction of methylprednisolone from exhaled breath samples. The size and morphology of the nano-sorbent were characterized by X-ray diffraction analysis and scanning electron microscopy. Following its desorption with acetonitrile, methylprednisolone was quantified by a high-performance liquid chromatography-ultraviolet detector. Factors affecting the extraction of methylprednisolone were optimized. Under optimized experimental conditions, a linear relationship between the analytical signals and methylprednisolone concentration was obtained in the range of 0.001-0.2 µg mL-1 for exhaled breath condensate samples and 0.002-0.4 µg per filter for filter samples. A pre-concentration factor of 6.4-fold, corresponding to an extraction recovery of 96.0%, was achieved. The validated method was applied for the determination of methylprednisolone in real samples taken from the exhaled breath of COVID-19 patients under mechanical ventilation.

Immune system-related soluble mediators and COVID-19: basic mechanisms and clinical perspectives.

During SARS-CoV-2 infection, an effective immune response provides the first line of defense; however, excessive inflammatory innate immunity and impaired adaptive immunity may harm tissues. Soluble immune mediators are involved in the dynamic interaction of ligands with membrane-bound receptors to maintain and restore health after pathological events. In some cases, the dysregulation of their expression can lead to disease pathology. In this literature review, we described current knowledge of the basic features of soluble immune mediators and their dysregulation during SARS-CoV-2 infections and highlighted their contribution to disease severity and mortality. Video Abstract.

SARS-CoV-2 vaccines: A double-edged sword throughout rapid evolution of COVID-19.

After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody-dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed.

Bell's Palsy and COVID-19 Vaccination: A Systematic Review.

Background: Bell's palsy is a rare adverse event reported in COVID-19 vaccines. Given the importance of neurological manifestations, the necessity to highlight and scrutinize the incidence of them following COVID-19 vaccination is needed. This study aimed to systematically review the reported cases of Bell's palsy following vaccination against COVID-19. Methods: This systematic review is conducted based on the Cochrane Collaboration Handbook and PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyzes) and using the Joanna Briggs Institute (JBI) methodology for systematic reviews. The inclusion criteria for the included published studies were patient age ≥18 years, history of Bell's palsy after COVID-19 vaccination and established diagnosis in the patients with COVID-19 vaccination. The exclusion criteria were repeated cases and missing clinical information. The search strategy aimed to find both published and unpublished studies in August 2021 and updated by hand searching in May 2022 using the identified keywords and index terms in Cochrane Library, MEDLINE (PubMed), Web of Science, Scopus, ProQuest, and Google scholar. Finally, the reference lists of all identified reports and articles were searched for additional studies. The JBI critical appraisal tools for case reports or case series were used to assess the risk of bias in the included studies. Results: During the electronic search, hand search, and reference check, we identified 1281 citations, and in hand searching, we detected additional 15 studies. After omitting duplicated citations and assessing the title, abstract, and full text 15 case-report and two case-series studies were included for the critical appraisal process and were included in this study. Pfizer and Moderna vaccines were the most common vaccines among articles that reported the cases of Bell's palsy. Left-sided paralysis was more common than right-sided paralysis. The interval between receiving the vaccine and the onset of facial weakness was between 1 and 48 days. Conclusion: Further studies with larger sample sizes are necessary to assess the association between Bell's palsy and the dose-response of the COVID-19 vaccine.

A comprehensive evaluation of the immune system response and type-I Interferon signaling pathway in hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic has become the world's main life-threatening challenge in the third decade of the twenty-first century. Numerous studies have been conducted on SARS-CoV2 virus structure and pathogenesis to find reliable treatments and vaccines. The present study aimed to evaluate the immune-phenotype and IFN-I signaling pathways of COVID-19 patients with mild and severe conditions. MATERIAL AND METHODS: A total of 100 COVID-19 patients (50 with mild and 50 with severe conditions) were enrolled in this study. The frequency of CD4 + T, CD8 + T, Th17, Treg, and B lymphocytes beside NK cells was evaluated using flow cytometry. IFN-I downstream signaling molecules, including JAK-1, TYK-2, STAT-1, and STAT-2, and Interferon regulatory factors (IRF) 3 and 7 expressions at RNA and protein status were investigated using real-time PCR and western blotting techniques, respectively. Immune levels of cytokines (e.g., IL-1ß, IL-6, IL-17, TNF-α, IL-2R, IL-10, IFN-α, and IFN-ß) and the existence of anti-IFN-α autoantibodies were evaluated via enzyme-linked immunosorbent assay (ELISA). RESULTS: Immune-phenotyping results showed a significant decrease in the absolute count of NK cells, CD4 + T, CD8 + T, and B lymphocytes in COVID-19 patients. The frequency of Th17 and Treg cells showed a remarkable increase and decrease, respectively. All signaling molecules of the IFN-I downstream pathway and IRFs (i.e., JAK-1, TYK-2, STAT-1, STAT-2, IRF-3, and IRF-7) showed very reduced expression levels in COVID-19 patients with the severe condition compared to healthy individuals at both RNA and protein levels. Of 50 patients with severe conditions, 14 had anti-IFN-α autoantibodies in sera. Meanwhile, this result was 2 and 0 for patients with mild symptoms and healthy controls, respectively. CONCLUSION: Our results indicate a positive association of the existence of anti-IFN-α autoantibodies and immune cells dysregulation with the severity of illness in COVID-19 patients. However, comprehensive studies are necessary to find out more about this context. Video abstract.

Roles of mitochondrial DNA in dynamics of the immune response to COVID-19.

Mitochondria dynamics have a pivotal role in many aspects of immune function. Viral infections affect mitochondrial dynamics and trigger the release of mitochondrial DNA (mtDNA) in host cells. Released mtDNA guides the immune response towards an inflammatory response against pathogens. In addition, circulating cell-free mtDNA (ccf-mtDNA) is considered an invaluable indicator for the prognosis and severity of infectious diseases. This study provides an overview of the role of mtDNA in the dynamics of the immune response to COVID-19. We focused on the possible roles of mtDNA in inducing the signaling pathways, and the inflammasome activation and regulation in SARS-CoV-2. Targeting mtDNA-related pathways can provide critical insights into therapeutic strategies for COVID-19.

Spontaneous pneumomediastinum, pneumothorax and subcutaneous emphysema in critically ill COVID-19 patients: A systematic review.

Objectives: COVID-19 patients develop Life-threatening complications like pneumomediastinum/pneumothorax and emphysema which might experience prolonged hospital stays and additional costs might be imposed on the patient and the health system. The clinical features and outcomes of mechanically ventilated patients with COVID-19 infection who develop a pneumothorax, pneumomediastinum and subcutaneous emphysema has not been rigorously described or compared to those who do not develop these complications. So a systematic review of studies conducted on this subject was carried out to better manage these complications by investigating the underlying factors in COVID-19 patients. Methods: The search was conducted between early January and late December 2020 in databases including PubMed, Scopus, ProQuest, Embase, Cochrane Library, and Web of Science, using the following keywords and their combinations: COVID-19 Complication, Pneumothorax, Pneumomediastinum, Pneumopericardium, and Subcutaneous Emphysema. The extracted studies were screened separately by two researchers based on the PRISMA statement. After eliminating the duplicate studies, the title, abstract, and full text of the remaining studies were reviewed. Disagreements in the screening and selection of the studies were resolved by consensus or through a third-party opinion. Results: A total of 793 articles were retrieved through the literature search, and 99 studies conducted on a total of 139 patients were finally included The patient mortality was found to have a significant relationship with positive pressure ventilation (P=0.0001). There was no significant relationship between the patients' death and chest tube insertion (P=0.2) or between the interval of time from the onset of symptoms to the diagnosis of pneumothorax (P=0.7). The mean age was higher in the deceased cases, and the mean difference observed was statistically significant (P=0.001). Conclusion: With the expansion of our clinical understanding of COVID-19, recognition of the uncommon complications of COVID-19 especially pneumothorax is crucial. Although in our review we couldn't find a causal relationship between COVID-19 and pneumothorax or association between pneumothorax and death, as it is limited by many variables such as included studies' design, or incomplete outcome data especially more information about the associated risk factors, we recommend performing more well-designed studies to describe the pneumothoraxes' incidence, risk factors, and outcomes in COVID-19 patients.

Serum levels of vitamin D and immune system function in patients with COVID-19 admitted to intensive care unit.

OBJECTIVE: Vitamin D is believed to affect the functionality of the immune system for the prevention of coronavirus disease. To investigate the role of this vitamin against the Coronavirus, this study analyzed the serum levels of vitamin D, the transcription pattern of inflammatory cytokines, and the frequency of total lymphocytes, TCD4+, TCD8+, and NK cells in 50 COVID-19-affected subjects in comparison to 50 healthy participants. MATERIALS AND METHODS: This study diagnosed and evaluated 100 patients. Frequency of lymphocytes was determined using flow cytometry. Cytokine expression levels were measured using Real-Time PCR. Serum levels of vitamin D and cytokines levels in cultured cell supernatant were measured by ELISA. RESULTS: Patients with COVID-19 exhibited decreased serum levels of vitamin D versus the healthy participants (p = 0.0024). The total number of lymphocytes, TCD4+, TCD8+, and NK cells was significantly reduced in patients with COVID-19 (p < 0.0001). Considerable upregulation of IL-12, IFN-γ, and TNF-α was seen in COVID-19 patients compared to the control group, whereas IFN-α was downregulated in COVID-19 patients. ELISA results also had increased levels of IL-12, TNF-α, and IFN-γ (p = 0.0014, 0.0012, and p < 0.0001, respectively), and decreased level of IFN-α (p = 0.0021) in patients with COVID-19 compared to the control group. CONCLUSION: These findings suggest a probable association among vitamin D concentrations, immune system function, and risk of COVID-19 infection. As a result, it is recommended that vitamin D be considered as a candidate for handling and controlling COVID-19 because of its ability to target the cytokine storm and its antiviral effects.

Clinical Applications of Aspirin as a Multi-potent Drug Beyond Cardiovascular Implications: A Proof of Concept for Anesthesiologists- A Narrative Review.

To the best of our knowledge, aspirin (ASA) is known as a commonly used medication worldwide. Although the cardiovascular aspects of ASA are well-established, recently, it has been identified that ASA can yield multiple extra-cardiovascular therapeutic potencies in facing neurodegenerative disorders, various cancers, inflammatory responses, and the COVID-19 pandemic. In this review, we aimed to highlight the proven role of ASA administration in the variety of non-cardiovascular diseases, particularly in the field of anesthesiology.

Clinical Efficacy of Hydroxychloroquine or Chloroquine in Patients with COVID-19: An Umbrella Review

[...]8 studies were included. Glucocorticoids, Azithromycin, Remdesivir, Ropinavir/ritonavir combination therapy, Chloroquine (CQ), Hydroxychloroquine (HCQ), Interferon beta, IL-6 inhibitor (Tocilizumab), and Favipiravir are some of the drugs being recently used for patients with COVID-19. Results To evaluate the clinical efficacy of CQ and HCQ on the treatment of COVID-19-induced pneumonia and their effect on mortality and disease progression in this group of patients, eight studies (including five systematic reviews and three systematic reviews with meta-analysis) were included. [...]its clinical use must either adhere to the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) framework or be ethically approved by the World Health Organization as a validated test. 2- Patil et at.2 announced the results of 100 studies, including 590368 cases, as follows: HCQ and CQ are effective in several studies (in vitro and clinical studies) in the treatment of mild to severe pneumonia

Gut microbial signature and gut-lung axis: A possible role in the therapy of COVID-19.

The impact of gut as the origin of different disorders has led to the "gut-origin concept" of diseases. The gut microbiome regulates host defenses against viral infections, thus dysbiosis can play a major role in triggering the cascade of inflammation and causing immune imbalances in COVID-19 patients. It appears that gut microbial signature in COVID-19 patients can be used as a potential diagnostic, therapeutic, and even a prognostic marker. Personalized nutrition therapy can be used by profiling the gut microbiota of individual patients and specialized probiotics/synbiotics to modify gut dysbiosis. Hence, improving overall immune responses can be recommended in these patients.

Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity.

Within the past several decades, the emergence and spread of infectious diseases with pandemic potential have endangered human lives. Coronavirus disease 2019 (COVID-19) outbreak represents an unprecedented threat for all health systems worldwide. The clinical spectrum of COVID-19 is highly heterogeneous, ranging from asymptomatic and mild upper respiratory tract illness to severe interstitial pneumonia with respiratory failure and even death. Highly age-dependent patterns of immune response potentially explain the higher rates of the severe forms of COVID-19 in elderly patients. However, genetic and epigenetic architecture can influence multiple biological processes during the lifespan, therefore as far as our knowledge shows, vulnerability to viral infection concerning telomere length and epigenetic signature is not a new idea. This review aims is to summarize the current understanding of the role of telomere length and epigenetic mechanisms on the severity of COVID-19. The current knowledge highlights the significant association between the shorter telomere length and the higher risk of developing severe COVID-19. Differential DNA methylation patterns and miRNA expression profiles imply that these hallmarks can play a pivotal role in COVID- 19 pathogenesis. Understanding the causes of inter-individual variations in COVID-19 outcomes could provide clues to the development of the personalized therapeutic intervention.

Immune response variables and viral mutations impact on COVID-19 reinfection and relapse.

The possibility of human reinfection with SARS-CoV-2, the coronavirus responsible for COVID-19, has not previously been thoroughly investigated. Although it is generally believed that virus-specific antibodies protect against COVID-19 pathogenesis, their duration of function and temporal activity remain unknown. Contrary to media reports that people retain protective antibody responses for a few months, science does not exclude reinfection and disease relapse shortly after initiating all immune responses during the primary onset of COVID-19. Despite production of antiviral antibodies, activated CD4+/CD8+ lymphocytes, and long-lived memory B cells, susceptibility to reinfection in humans for extended periods cannot be precluded due to repeated exposures to coronavirus or potential reactivation of the virus due to incomplete virus clearance. However, the mechanism of reinfection remains unknown. The biological characteristics of SARS-CoV-2, such as emergence of multiple mutations in the virus RNA molecules, transmissibility, rates of infection, reactivation and reinfection, can all affect the trajectory of the virus spread. Innate and adaptive immune response variables, differences in underlying diseases, and comorbidities, particularly in high risk individuals, can influence the dynamics of the virus infection. In this article, immune parameters and viral mutations pertaining to reinfection and disease relapse are reviewed and scientific gaps are discussed.

Reduction and exhausted features of T lymphocytes under serological changes, and prognostic factors in COVID-19 progression.

AIMS: Coronavirus disease 2019 (COVID-19) is a novel viral infection threatening worldwide health as currently there exists no effective treatment strategy and vaccination programs are not publicly available yet. T lymphocytes play an important role in antiviral defenses. However, T cell frequency and functionality may be affected during the disease. MATERIAL AND METHODS: Total blood samples were collected from patients with mild and severe COVID-19, and the total lymphocyte number, as well as CD4+ and CD8 + T cells were assessed using flowcytometry. Besides, the expression of exhausted T cell markers was evaluated. The levels of proinflammatory cytokines were also investigated in the serum of all patients using enzyme-linked immunesorbent assay (ELISA). Finally, the obtained results were analyzed along with laboratory serological reports. RESULTS: COVID-19 patients showed lymphopenia and reduced CD4+ and CD8 + T cells, as well as high percentage of PD-1 expression by T cells, especially in severe cases. Serum secretion of TNF-α, IL-1ß, and IL-2 receptor (IL-2R) were remarkably increased in patients with severe symptoms, as compared with healthy controls. Moreover, high levels of triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), were correlated with the severity of the disease. CONCLUSION: Reduced number and function of T cells were observed in COVID-19 patients, especially in severe patients. Meanwhile, the secretion of proinflammatory cytokines was increased as the disease developed. High level of serum IL-2R was also considered as a sign of lymphopenia. Additionally, hypercholesterolemia and hyperlipidemia could be important prognostic factors in determining the severity of the infection.