scholarly journals Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 830
Author(s):  
Sara H. A. Agwa ◽  
Marwa Mostafa Kamel ◽  
Hesham Elghazaly ◽  
Aya M. Abd Elsamee ◽  
Hala Hafez ◽  
...  

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. Aim: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like–1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. Methods: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. Results: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. Conclusion: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

2020 ◽  
Vol 15 (6) ◽  
pp. 27-34
Author(s):  
L.T. Yeraliyeva ◽  
◽  
Zh.N. Suleymenova ◽  
M.A. Smagul ◽  
M.K. Smagulova ◽  
...  

Objective. To evaluate preventive efficacy and reactogenicity of Grippol® plus vaccine in children aged 8 to 14 years residing in Almaty (Republic of Kazakhstan). Patients and methods. This open-label prospective study was conducted between October 2019 and April 2020 and included 600 children aged 8 to 14 years (mean age 10.6 ± 4.9 years) studying in two schools of Almaty. Study participants were divided into two groups (300 children in each): experimental group, in which children were vaccinated with Grippol® plus (Petrovax Pharm, Russia) in accordance with all rules and control group. Patients in both groups were matched for gender; children of the Mongoloid race prevailed in the experimental group. Parents (or official representatives) of all participants signed an informed consent before the enrollment. The efficacy of vaccination was evaluated by active monitoring (telephone contacts with parents) and assessment of the incidence of influenza and acute respiratory viral infections (ARVIs) during the next 6 months. We calculated the efficacy index and efficacy coefficient. Data analysis was performed using the Statistica 6.0 software; differences were considered significant at p < 0.05. Results. Follow-up of study participants during 6 months after vaccination demonstrated significant differences in the incidence of ARVIs and influenza between the two groups: 7 cases among vaccinated children (2,3%) vs 21 cases among controls (7%) (p < 0.05). One child from the control group had two episodes of ARVI. Mean duration of influenza and ARVIs in the experimental group was 1.8 times lower than that in the control group. The efficacy index and efficacy coefficient, calculated with the consideration of influenza diagnosis confirmation by polymerase chain reaction, were 3% and 66.7%, respectively. Local and systemic reactions to vaccination were observed in 3 children, were transient, and disappeared after 2–3 days. Conclusion. The trivalent inactivated polymer-subunit vaccine Grippol® plus was safe and effective in children aged between 8 and 14 years. Key words: vaccine, influenza, children, incidence, acute respiratory viral infections, efficacy


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-16
Author(s):  
Hassaan Imtiaz ◽  
Muhammad Saad Farooqi ◽  
Unaiza Faizan ◽  
Saad Ur Rehman ◽  
Muhammed Hamza Arshad ◽  
...  

Introduction Allogenic hematopoietic stem cell transplantation (Allo-HSCT) used for the treatment of multiple hematological malignancies requires immunosuppression, that can lead to the reactivation of viruses like EBV, CMV, adenovirus (AdV). These viruses pose a life-threatening risk to an individual like Graft vs Host Disease (GVHD) and other virus-specific complications. Adoptive T cell therapy (ATC) is an approach to treat refractory post-Allo-HSCT transplant viral infections. The aim of this study is to assess the efficacy of various ATCs being developed against various viruses. Methods A systematic search on PubMed, Embase, Clinicaltrials.gov, and Web of Science was performed for adoptive immunotherapy in viral infections after stem cell transplantation from inception to May 28, 2020. Out of 604 studies, 13 phase I and II clinical trials were selected for the systematic review. Results A total of 13 studies were included of which two studies included data on the pediatric population (n=13). A total of 335 patients (pts) were enrolled in 13 studies of which 264 were evaluable. CMV Perruccio et al. (2005) in a randomized controlled trial (RCT) assessed the efficacy of ATC against both Aspergillus and CMV after alloSCT. Median follow up (f/u) was six months. For Aspergillus (n=23), 90% and 54% achieved clearance, while for CMV (n=68) 92% and 9% didn't develop CMV reactivation in treatment and control group respectively. Overall Survival (OS) and progression-free survival (PFS) rate at two years were 92% and 80% respectively. Smith et al. (2018) (n=21) in a phase I trial studied the transfusion of virus-specific T cells (VST) (n=13) against CMV infection after undergoing alloSCT. After a median f/u of 28 weeks, overall response rate (ORR) was 85%. Bao et al. (2012) (n=10) conducted a study with VST transfusion against CMV infection (n=7). ORR was 85% of which 3 pts who were on immunosuppressive had shown reactivation. Miej et al. (2012) in phase I/II study (n=6) assessed the response of VST against refractory CMV with CR of 100% Neuenhahn et al. (2017) studied a phase I/II prospective trial (n=17) (CMV Seropositive graft donor (D+) 9/17 and CMV Seronegative graft donor (D-) 8/17) with CR of 62% in D+ group. In D- group only 37% developed T cells after Third-Party Donor transfer and only these achieved CR, while pts with no T cell detection in D- group (63%), only one achieved CR. Micklethwaite et al. (2008) did a phase I clinical trial (n=12) of CMV specific T cells given prophylactically. Only four pts showed CMV reactivation. Adenovirus Feucht et al. (2019) performed a phase I/II clinical trial (n=30) of VST against refractory AdV infection. 47% showed CR, 13% with negative blood AdV cleared virus from other sites, 10% showed PR. OS at six months was 71%. Winnie et al. (2018) (n=8) conducted phase I/II RCT among pediatric pts. Median f/u was six months. All patients have shown a decrease in AdV viral load. Qasim et al. (2013) conducted a prospective trial (n=5) among pediatric pts with CR of 60% until six weeks f/u. 20% died due to AdV viremia. Multi-virus CTLs Gerdemann et al. (2013) (n=36) did a clinical trial by infusing multi-virus cytotoxic T lymphocytes (CTLs) (n=10), reactive against CMV, EBV, and AdV. CR in 80% of the pts. Muranski et al. (2017) performed a phase I trial (n=9) and infused multi-virus CTLs prophylactically. No AdV, BK, or EBV related disease was observed in any pts while 11% pts had asymptomatic AdV viremia. Only those pts who received steroid therapy had CMV reactivation (44%). Ma et al. (2015) performed a phase I/II RCT with an intervention group (n=19, evaluable=10) and control group (n=33) with an infusion of multi-virus CTLs against CMV, EBV, AdV, and VZV after alloSCT, prophylactically. Pts in the intervention group had no reactivation of EBV, AdV, or VZV. 6 (60%) pts with CMV had reactivation; four before T cell therapy and two in the context of steroid therapy. OS at one year was 89% and 81% in the intervention and control group respectively. Third-Party Donor T-cells Tzannou et al. (2017) (n=37) in a phase II study demonstrated ORR of 92% (95% CI, 78.1% to 98.3%) in various viruses with ORR for BK virus 100%, CMV 94%, Adv 71%, EBV 100% and HHV-6 67%. Conclusion Adoptive T cell therapy for viral infections has shown efficacy in Post- allo-SCT pts who achieved complete clearance of infection in many cases, showed only minimal adverse events, and no major risk for GVHD related to this therapy was noted. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.


2021 ◽  
Author(s):  
xiaochen Yang ◽  
Xingjiang Xiong ◽  
Yun Zhang ◽  
Yongmei Liu ◽  
Hongzheng Li ◽  
...  

Abstract IntroductionHypertension is one of the most important risk factors for cardiovascular disease, and its treatment and control rates are still low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) may suppress ventricular hypertrophy and inflammatory responses, lower blood pressure and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension.Methods and analysisThis trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experiment group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is blood pressure, which is reduced to a threshold set out in Guiding Principles for Clinical Research of New Chinese Medicines. The secondary outcomes include the change in 24-h average systolic and diastolic blood pressure, heart rate variability, pharmacogenomic Evaluation, improvement in TCM Syndrome, serum pro-inflammatory/anti-inflammatory cytokines, etc. between the two groups. Safety in medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0.Ethics and dissemination This study has been approved by Research Ethics Committee of Guang’anmen Hospital,China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences. DiscussionWe hypothesize that patients with low-to-medium risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians.


2004 ◽  
Vol 12 (4) ◽  
pp. 301-306 ◽  
Author(s):  
Claudio Maranhão Pereira ◽  
Fábio Ramôa Pires ◽  
Maria Elvira Pizzigatti Corrêa ◽  
Osvaldo di Hipólito Júnior ◽  
Oslei Paes de Almeida

Hemophilia is a common hereditary hemorrhagic disorder, however little is known about the oral microflora of hemophilic patients. The aim of this study was to quantify the Candida and identify its species in non-stimulated saliva of hemophilic patients, and consider its relationship with clinical factors influencing Candida carriage. This study comprised evaluation of 86 hemophilic patients of the Hematology Center/UNICAMP and 43 healthy subjects as controls. All patients were submitted to anamnesis, intraoral examination and unstimulated saliva collection. Candida counts and species identification were performed in salivary samples. Candida was present in 64% of the hemophilic patients and in 44% of the healthy controls. C. albicans represented 65% and 68% of the isolated species, in hemophiliacs and control group respectively, and C. tropicalis was the second most common species in both groups. These results indicate that hemophilic patients carry Candida more frequently and in higher counts than healthy controls, independently of oral clinical parameter considered, as viral infections, complete dentures, transfusions of hemoderivatives, and salivary flow.


2021 ◽  
Vol 20 (4) ◽  
pp. 6-12
Author(s):  
O. I. Afanasyeva ◽  
E. G. Golovacheva ◽  
L. V. Osidak ◽  
V. S. Timonina ◽  
V. V. Gonchar ◽  
...  

Objective: to study the dynamics of local and systemic cytokine production in children with different clinical forms of acute respiratory viral infections (ARVI), including COVID-19, and to assess the effectiveness of local interferon-based therapy.Patients and methods: The study included 180 patients aged from 1 month to 17 years with сonfirmed acute respiratory viral infections (ARVI), including COVID-19. Patients were divided into 2 groups (main and control) of 90 people each. In the main group patients received the intranasal interferon-based medicine Grippferon® in addition to the basic therapy, the control group patients received only basic therapy. The cytokine status was assessed by the content of IFN-α and -γ, IL-1β, IL-8, IL-4, IL-10, IL-17 in blood serum and in nasopharyngeal secretions by enzyme immunoassay kits ("Cytokine", St. Petersburg).Results: Statistically significant differences were revealed in the systemic and local content of individual cytokines in ARVI of different etiologies, depending on the level of damage to the respiratory tract. The use of the interferon-based medicine Grippferon® for intranasal use in children in the early stages of ARVI, including COVID-19, helps to decrease the high content of cytokines IL-1β and IL-8 in the nasopharynx by reducing the viral load. As a result, the duration of catarrhal disease symptoms and intoxication was also significantly reduced as well as the pathogen elimination time.


2020 ◽  
Author(s):  
Ali Ghazavi ◽  
Ghasem Mosayebi ◽  
Nafiesh Keshavarzian ◽  
Somayeh Rabiemajd ◽  
Ali Ganji

Abstract Background: The complement system, consisting of more than 20 soluble proteins, has a key role in innate immunity and inflammation that eliminates pathogens and viral infections. Therefore, we investigated the titer of C3, C4, and total IgG in the serum of the non-severe and severe COVID-19 patients. Methods: For this purpose, peripheral blood samples were collected from 30 non-sever, 30 severe COVID-19 patients, and 30 healthy individuals with similar age and sex as the control group. The amount of total IgG, C3, and C4 were analyzed in the serum samples. Also, white blood cells, platelets (PLTs), and lymphocytes were counted by the auto-analyzer. Results: White blood cells had no difference between patients and control groups. The results showed a significant decrease in lymphocyte and PLTs in COVID-19 patients compare to control. Complement proteins including C3 and C4 were increased in non-severe COVID-19 patients than the other groups. Total IgG showed a notable decrease in severe patients. In conclusion, the level of C3 and C4 complement proteins were increased in non-severe-COVID-19 patients; however, in the severe COVID-19 patients their concentrations were decreased. Conclusion: However, inflammatory C3 and C4 complement factors increase in non-severe COVID-19, it decreased in the severe patients that may be because of more consumption by the formation of the immune complex. These results can shed light on the inflammatory role of C3 and C4 proteins in various phases of the disease and could provide a basis for further exploration of the pathophysiological significance and can suggest them for specific interventions.


2021 ◽  
Vol 14 (10) ◽  
Author(s):  
Mahin Ahangar Oskouee ◽  
Jamal Sarvari ◽  
Afagh Moattari ◽  
Ahmad Habibi ◽  
Amir Taher Eftehkar Sadat

Background: Given the fact that viral infections play an important role, either directly or indirectly, in around 20 percent of human cancers, this study aimed at investigating the potential association of Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections in esophageal cancer that is the sixth most common cause of cancer-related deaths. Methods: In this case-control study, a total of 200 paraffin-embedded biopsies of cancerous and benign esophageal tissues were gathered from the biopsy bank of Imam Reza Hospital, Tabriz, Iran in 2017. All samples were first deparaffinized, and then subjected to commercial DNA extraction. The quality of extracted DNA was evaluated by amplification of the beta globulin gene. Identification of EBV and CMV DNA was performed using primers designed for the EBER region of EBV and the immediate early (IE) region of the CMV genome, respectively. Results: The mean age of the subjects in the test and control groups was 52.2 (17.1) and 59.9 (18.9), respectively. The distribution of gender (male/female) in patient and control groups was 54/46 and 53/47, respectively. Our results showed that the frequency of EBV (P < 0.001) and CMV (P < 0.001) in cancerous samples was statistically higher than control group. Moreover, in the cancerous group the rate of EBV was significantly higher in the esophageal adenocarcinomas (EAC) sample (12 out of 70) than esophageal squamous cell carcinomas (ESCC) (0 out of 30) (P = 0.016) but, in the ESCC group, 17 out of 30 subjects were positive for CMV which was significantly higher in comparison with EAC patients (1 out of 70) (P < 0.001). Conclusions: Findings indicated that EBV and CMV might be contributed to the pathogenesis of EAC and ESCC types of esophageal carcinoma, respectively, although further studies are warranted.


2020 ◽  
Author(s):  
Antonio Cristiano ◽  
Valentina Fortunati ◽  
Fabio Cherubini ◽  
Sergio Bernardini ◽  
Marzia Nuccetelli

Abstract Introduction: Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as “COVID-19 Associated Coagulopathy” (CAC), corresponding to a worsening in patients’ conditions, whose causes are still to be elucidated. A link between anti-phospholipids antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for Anti-phospholipid Syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cells damage and thrombotic complications.Method: We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-β2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time) and a negative control group. IgG CICs analysis followed to evaluate inflammatory status, through a possible complement system activation.Results: Our results showed low positive cases percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-β2-glycoprotein-1 assays (4.54%, 6.25%, 4.55%; in early infection group, late infection group and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; no IgG CICs positivity in any patient.Conclusions: In conclusion, our data show a low aPLs prevalence, likely excluding an involvement in the pathogenesis of CAC.Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a “COVID-19-induced-APS-like-syndrome” in predisposed patients.Finally, even though aPLs are transient, they may still have a thrombotic potential in genetically predisposed COVID-19 patients.


2014 ◽  
Vol 3 (1) ◽  
pp. 29
Author(s):  
Hala Mohamed Majeed Hassan ◽  
Abdulghani Mohamed Alsamarai ◽  
Zainab Khalil Aljumaili ◽  
Amina Hamed Alobaidi ◽  
Ferah Ghali Alsalihi

<p>The human cytomegalovirus (CMV) is one of the common viral infections worldwide that represent a major causes of congenital infections. To determine the seroprevalence of CMV in women with bad obstetric history and sociodemographic characteristics that may influence the seropositivity, a case<strong> </strong>control descriptive prospective study  was conducted in Kirkuk, Iraq. A 838 women with age range from 14 to 48 were included in the study. Of the total, 547 women were with bad obstetric history(BOH) and 291 women with normal previous pregnancy as control group. All the serum samples collected from the study and control groups were tested for CMV IgM and IgG antibodies by ELISA kits. CMV IgM seroprevalence was higher in women with BOH.<strong> </strong>CMV IgG seroprevalence was with no significant  difference between BOH and control. CMV IgG seroprevalence significantly influenced by age, education, smoking, and family size. However, CMV IgM seroprevalence significantly associated with pregnancy, residence, and animal exposure. Odd ratio confirmed the association between CMV IgG and age, crowding index, residence, smoking, and number of abortion in women with BOH.  In addition, current CMV infection significantly associated with residence in women with BOH.</p>


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Gordana Taleska Stupica ◽  
Maja Sostaric ◽  
Marija Bozhinovska ◽  
Lea Rupert ◽  
Zoran Bosnic ◽  
...  

Extracorporeal hemadsorption may reduce inflammatory reaction in cardiopulmonary bypass (CPB) surgery. Glucocorticoids have been used during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in final analysis. Allocation was into three groups: Methylprednisolone (n = 20), Cytosorb (n = 20), and Control group (usual care, n = 20). Proinflammatory (TNF-α, IL-1β, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines which complement C5a, CD64, and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Methylprednisolone group, compared to Cytosorb and Control had significantly lower levels of TNF-α (until the end of surgery, p<0.001), IL-6 (until 48 h after surgery, p<0.001), and IL-8 (until 24 h after surgery, p<0.016). CD64 expression on monocytes was the highest in the Cytosorb group and lasted until the 5th postoperative day (p<0.016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (until 48 h after surgery) were the highest in the Methylprednisolone group (p<0.016, for all measurements between three groups). No differences between groups in the cardiac index or clinical outcome parameters were found. Methylprednisolone more effectively ameliorates inflammatory responses after CPB surgery compared to hemadsorption and usual care. Hemadsorption compared with usual care causes higher prolonged expression of CD64 on monocytes but short lasting expression of CD163 on granulocytes. Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).


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