ABSTRACT
The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.
ABSTRACT
In our study, we aimed to evaluate the significance of specific cytokines in blood plasma as predictive markers of COVID-associated mortality. Materials and methods. In plasma samples of 29 patients with PCR-confirmed COVID-19 we measured the concentrations of 47 molecules. These molecules included: interleukins and selected pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNalpha2, IFNgamma, TNFalpha, TNFbeta/Lymphotoxin-alpha(LTA));chemokines (CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROalpha, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine);anti-inflammatory cytokines (IL-1Ra, IL-10);growth factors (EGF, FGF-2/FGF-basic, Flt-3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGFAB/BB, TGFalpha, VEGF-A);and sCD40L. We used multiplex analysis based on xMAP technology (Luminex, USA) using Luminex MagPix. As controls, we used plasma samples of 20 healthy individuals. Based on the results, we applied Receiver Operating Characteristic (ROC) analysis and Area Under Curve (AUC) values to compare two different predictive tests and to choose the optimal division point for disease outcome (survivors/non-survivors). To find optimal biomarker combinations, we as used cytokines concentrations as dependent variables to grow a regression tree using JMP 16 Software.Results. Out of 47 studied cytokines/chemokines/growth factors, we picked four pro-inflammatory cytokines as having high significance in evaluation of COVID-19 outcome: IL-6, IL-8, IL-15, and IL-18. Based on the results received, we assume that the highest significance in terms of predicting the outcome of acute COVID-19 belongs to IL-6 and IL-18. Conclusion. Analyzing concentrations of IL-6 and IL-18 before administering treatment may prove valuable in terms of outcome prognosis. Copyright © Arsentieva N.A. et al., 2022.
ABSTRACT
The recently identified 2019 novel coronaviruses (2019-nCoV) has caused extra-human infections. 2019-nCoV identified a global threat that is causing an outbreak of unusual viral pneumonia in patients with severe acute respiratory syndrome (SARS)-coronaviruses 2 (SARS-CoV-2). Considering the relatively high identity of the receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS-CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. The zinc metallopeptidase angiotensin-converting enzyme 2 (ACE2) is the only known human homolog of the key regulator of blood pressure ACE. ACE2 also serves as the cellular entry point for the SARS virus, therefore, a prime target for pharmacological intervention. SARS-CoV-2 uses the SARS-CoV receptor for entry and the serine protease transmembrane protease serine 2 for spike (S) protein priming. That it is still necessary to develop novel mAbs that could bind specifically to 2019-nCoV RBD. Cell entry of coronaviruses depends on the binding of the viral S proteins to cellular receptors and S protein priming by host cell proteases. A transmembrane protease serine 2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats. We provide a brief introduction to the pathogenesis of SARS-CoV and Middle East respiratory syndrome-CoV and interaction between the RBD of coronavirus spike protein and ACE2.
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Introduction: The induction of regulatory T cells (Tregs) is indicated as a potential therapeutic strategy in inflammatory lung diseases including, asthma, viral-induced pneumonia, viral-induced acute lung injury (ALI), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and SARSCoV- 2-induced ALI. We previously identified that components of the bacteria Streptococcus pneumoniae (T + P) are able to increase Tregs to suppress experimental allergic airways disease, however, this mechanism of suppression and therapy has not been examined in ALI. Methods: We established a murine model of ALI using aerosolized LPS (100 μg/ml) in BALB/c mice. ALI was measured by the presence of neutrophils in the airways up to 96 hours post-exposure, and Tregs and dendritic cells were assessed by flow cytometry. To assess the therapeutic of T + P in ALI and the mechanisms involved, the combination was administered prior to LPS exposure in the absence or presence of anti-CD25. Results: Treatment with T + P significantly reduced total airway inflammation and suppressed the neutrophil chemokine C-X-C motif chemokine ligand 1 (Cxcl1) compared to Saline+LPS alone in experimental ALI. The numbers of Tregs were reduced in experimental ALI model and were restored by T + P treatment. Depletion of Tregs with anti- CD25 confirmed that the suppressive effects of T + P on ALI was through the induction of Tregs. Conclusion: Treatment with S. pneumoniae components T + P suppresses neutrophilic inflammation in ALI through immunoregulatory mechanisms that involve Tregs and may be a novel treatment for ALI including in COVID-19.
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Introduction. ARDS (acute respiratory distress syndrome) is a direct cause of death due to lung lesions of various origins including SARS-CoV-2 infection. Most lung and respiratory diseases are characterized by inflammation, which in turn causes occlusions, mucous hypersecretion, shortness of breath, cough and other symptoms of airway inflammation. Understanding the pathological processes involved in the regulation of the immune response may lead to the discovery of new mechanisms that support or suppress inflammatory processes in the lungs and respiratory tract. Methods. In order to develop the experimental model of ARDS we used precision pulmonary hyperventilation and intratracheal administration of poly I:C, which reproduces the body's response to viral infection (mimic viral infection). The severity of ARDS was estimated by the following parameters: the ratio of wet lung weight to dry lung (wet/dry lung weight), extensibility, impedance, lung stiffness, protein level and the number of neutrophils in the bronchial lavage, the level of proinflammatory cytokines in lung tissue. Moreover, we provide a method of simultaneous registration of the lungs vagal nerve activation parameters due to ARDS induction. It is known that the lungs have a massive innervation of the peripheral nervous system and such innervation has a powerful effect on the cells of the immune system. Results. The biologically active substances of neurons affect the activity of immune cells, and the activity of the immune system affects the functioning of the nervous system. That is why the investigation of neuro-immune interaction has a great potential in studying ARDS. Evaluation of dynamic changes in respiratory function due to simulated ARDS showed a significant increase in such parameters as Newtonian resistance, tissue stiffness, static elongation, and a decrease in elasticity and tissue dumping, which is fully consistent with the pathogenesis of ARDS in patients. Analysis of the dry/wet lung ratio showed a two-fold increase in pulmonary edema, a severe, life-threatening condition that develops as a result of ARDS. Significant increase of the protein content and concentration of neutrophils in bronchopulmonary lavage indicates an increase in the permeability of the pulmonary capillaries due to ARDS. The real time PCR identified significant increase of proinflammatory chemokine Cxl2 concentration. Also we observed an increase of neutrophil-activating protein 3 cytokine Gro1, which stimulates the migration of neutrophils. Electrophysiological registration of the activity of the vagal nerve innervating the lungs showed a significant increase in the activity of nociceptive and mechanosensitive fibers, especially in the last stage of acute respiratory distress syndrome, which confirms the role of the nervous system in this pathology. Conclusion. As a result we obtained a model that reproduces ARDS most relevant to human pathological condition.
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Introduction Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) can induce a strong host immune response. Several groups have investigated the course of antibody responses in patients recovering from SARS-CoV-2 infections but little is known about the recovery of cellular immunity. This study investigated the cellular immune response in people who had recovered from SARS-CoV2 infection. Methods 162 coronavirus disease 2019 (COVID-19) convalescent plasma donors (CCD) and 40 healthy donor (HD) controls were enrolled prospectively in an IRB-approved protocol (Clinical Trials Number: NCT04360278) and provided written informed consent to participate in the study. Using the nCounter platform and host response panel with 785 genes across more than 50 pathways, we compared transcriptomic profiles on RNA samples obtained from the peripheral blood leukocytes of these 162 CCD and 40 HD. Additionally, in 69 of the 162 CCD samples, we evaluated transcriptomic trends at more than one-time point during the convalescent period. Results Age, sex, ethnicity, and body mass index distributions were similar among the CCD and HD. With respect to baseline complete blood counts, hemoglobin, platelets, and absolute basophil and eosinophil counts, all were similar among CCD and HD (Table 1). However, despite sample collections occurring several days after convalescence, mean counts for absolute neutrophil counts, absolute monocyte counts, and absolute lymphocyte counts were significantly higher among CCD compared to HD. 30-90 days after diagnosis, 19 of 773 genes differed (FDR < 0.05) between the average CCD and HD samples. Up-regulated genes included MAFB, CTLA4, PTGS2, and the chemokine signaling genes CXCR4, CXCL5, CXCL2 and CCR4. Down-regulated genes included PTGER2, CASP8, and the interleukins IL36A, IL31, IL20 and IL21 (Figure 1 a,b). Differential gene expression persisted for months. At 90-120 days, 13 genes were differentially regulated, including again MAFB CXCR4, PTGS2, CXCL2 and PTGER2, plus SMAD4. At 120-150 days post-diagnosis, 58 genes were differentially expressed (FDR < 0.05) compared to HD. Pathways with up-regulated genes included Treg differentiation, type III interferon signaling and chemokine signaling. 150-360 days post-diagnosis, 4 genes remained up-regulated on average (FDR < 0.05): PTGS2, PIK3CR, CXCL1 and SMAD4 (Figure 1 c,d). Individual patients varied considerably from the mean trend. Scoring samples by their similarity to the gene expression profile of the mean HD sample, 21 CCD samples from 20 unique patients (12%) were identified as highly perturbed from HD. 84% of these highly perturbed samples were collected > 90 days post-diagnosis. Of these 21 samples, 6 were distinguished by > 2-fold up-regulation of a cluster of interleukin and type-1 interferon genes (Figure 2). Conclusions Overall, our study identified important gene expression trends in CCD compared to HD in the post-acute period. The changes varied with time and among donors. As the expression of T-cell inhibitory molecule CTLA4 fell, the number of differentially expressed increased with the most marked changes occurring 120 to 150 days post-diagnosis in genes in chemokine signaling, type III interferon signaling and Treg pathways. Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed in individuals following recovery from COVID-19 infection. Our data may serve as the basis for risk modification strategies in the period of active infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. [Formula presented] Disclosures: Danaher: NanoString Technologies: Current Employment, Current holder of individual stocks in a privately-held company.