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This paper presents raw plant materials and their characteristic compounds which may affect the immune system. Plant-derived agents in specific doses affect the body's non-specific, antigen-independent defense system. They have immunostimulatory effects on the entire immune regulatory system. They can enhance the immune response through various factors such as macrophages, leukocytes, and granulocytes, as well as through mediators released by the cellular immune system. This paper was inspired by the threats caused by the COVID-19 pandemic. The proper functioning of the immune system is important in limiting the effects of viral infection and restoring the normal functioning of the body. This paper also emphasizes the importance of the skillful use of plant immunostimulants by potential patients, but also by those who prescribe drugs. It is important not only to choose the right plant drug but above all to choose the correct dose and duration of treatment.
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SARS-CoV-2 infection in pregnancy is associated with increased risk for severe COVID-19 disease including ICU admission, need for invasive ventilation, extracorporeal membrane oxygenation, and death. In addition, COVID-19 in pregnancy is associated with adverse pregnancy and neonatal outcomes. This presentation will review: (1) what is known about increased maternal and obstetric risk in the setting of SARS-CoV-2 infection;(2) how underlying comorbidities and viral strain may impact disease severity;(3) impact of COVID-19 in pregnancy on the placenta and how this may be altered by fetal sex and viral strain;(4) fetal risk and protection including vertical transmission, antibody-mediated protection, and later-life neurodevelopmental or metabolic risk in the setting of maternal immune activation.
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Background & Aim: Amniotic fluid (AF)-derived EVs are currently under investigation for use as anti-inflammatory therapeutics in COVID-19 and COVID-19 long haulers. The dysregulation of the immune response induced by SARS-COV-2 is a key driver of both acute COVID-19 induced lung injury and long term COVID-19 sequela. There is a clear need to identify therapeutics that suppress excessive inflammation and reduce immune cell exhaustion to improve patient short term and long-term outcomes. Amniotic fluid (AF)- derived extracellular vesicles (EVs) have previously been shown to deliver anti-inflammatory and immune-modulatory signals to diverse cellular targets. We aimed to test if AF-EVs carry immune-suppressive molecules and can suppress T-cell immune activation and exhaustion in vitro. Methods, Results & Conclusion(s): The AF-EV biologic tested was derived from AF collected from consenting donors during planned, fullterm cesarean sections. AF was centrifuged and filtered to remove cellular debris and create a product containing AF-EVs and soluble extracellular components. Fluorescent EXODOT analysis was performed to demonstrate the presence of EV markers CD9, CD81, ALIX, and immune suppressive molecule PD-L1. T-cell activation/exhaustion was induced in vitro by treating human peripheral blood mononuclear cells with activation agent PHA for 3 days with the addition of AF-EVs or saline control. Immune activation/exhaustion was measured by flow cytometry to determine the expression of PD-1 on CD3+ T-cells. The AF-EV biologic was characterized to contain EVs with positive expression of CD9, CD81, ALIX, and PL-L1. T-cell activation/exhaustion was upregulated in response to PHA and was significantly reduced by 8% in AF-EV treated T-cells compared to saline control (77.7% vs 85.7%, respectively P<0.05). These findings demonstrate that AF-EVs do express PD-L1, a surface marker that has previously been demonstrated to contribute to exosome-mediated immunosuppression. Furthermore, we confirmed in vitro that AF-EVs suppress T-cell activation/ exhaustion in the presence of a T-cell activation agent. COVID-19 long haulers have been described to have upregulated and pro-longed immune activation and T-cell exhaustion, marked by an increase in PD1+ T-cells. Therefore, this finding serves as a starting point for the development of a potential mechanism of action that may describe AF-EV's therapeutic effect in COVID-19 long hauler patients.Copyright © 2023 International Society for Cell & Gene Therapy
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In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
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It is now widely accepted that SARS-CoV-2 infection can affect long-term health and quality of life. Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC) characterized by persistent unexplained symptoms, has a major impact on the health of many COVID-19 survivors. Although many individuals (up to 30%) experience some limited symptoms in the weeks and months following COVID-19, the prevalence of severe disabling Long COVID is less common (perhaps <5%). Long COVID syndromes are variable and include general (e.g., fatigue) and organ-system specific symptoms (e.g., shortness of breath, palpitations, neurocognitive symptoms), as well as symptoms resembling other medically unexplained syndromes (e.g., myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia, post-exertional malaise). For reasons not yet understood, female sex is a strong predictor of Long COVID, as is the presence of certain comorbidities, particularly obesity. Mechanisms that might plausibly contribute to Long COVID include irreversible tissue damage associated with acute infection, persistence of SARS-CoV-2 antigen or possibly a viral reservoir, residual or ongoing immune activation and inflammation, reactivation of other latent human viruses, microvascular dysregulation and thrombotic events, microbial translocation, dysbiosis, and autoimmune phenomena. These mechanisms may act in isolation or in combination to drive Long COVID syndromes. Notably, many if not all of these pathways have been implicated as possible mechanisms for the excess rate of cardiovascular disease and other comorbidities in people living with HIV. Industry engagement in Long COVID research is growing, and NIH funding for clinical trials is emerging through programs such as the RECOVER Initiative. As a result, we are entering an era of experimental medicine, in which potential interventions will be used as tools to probe the biology of the disease. This presentation will provide an overview of the proposed biological mechanisms contributing to Long COVID, with a focus on the current state of evidence, human and animal models, and the emerging therapeutic agenda.
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Background: SARS-CoV-2 infection typically causes self-limited disease, but a subset of individuals experience more severe disease associated with respiratory manifestations, hospitalization and mortality. People living with HIV (PLWH) have been shown to have chronic immune activation and inflammation despite effective antiretroviral therapy. During the COVID pandemic, PLWH were found to have an increased risk of hospitalization and mortality with acute COVID-19. The immune response driving these worsened outcomes in PLWH is not defined. We analyzed immune activation and exhaustion markers, as well as antigen specific T cell responses during acute COVID-19 in PLWH versus HIV-seronegative controls to determine the impact of chronic HIV infection and inflammation on acute COVID-19. Method(s): We performed flow cytometric analyses on peripheral blood mononuclear cells from: 1) PLWH with acute COVID-19 (HIV+COVID), 2) HIVseronegative individuals with acute COVID-19 (COVID) and 3) pre-COVID-19 pandemic PLWH (HIV). COVID(+) samples were collected at an average of 4.7 (range 0-16) and 5.5 (range 0-20) days post-symptom onset for the COVID and HIV+COVID cohorts, respectively. Cells were stained for surface markers of activation/exhaustion and intracellular cytokines (with and without SARS-CoV- 2-specific antigen stimulation). Observed immune responses were correlated with disease severity. Result(s): PLWH with acute COVID-19 had increased classical (CD14+) monocytes compared to HIV-seronegative individuals with acute COVID-19. The HIV+COVID cohort also had higher expression of activation (OX40, CD137) and exhaustion (PD1, TIGIT) markers on CD4+ and CD8+ T cells compared to HIV-seronegative individuals. SARS-CoV-2 antigen stimulation resulted in similar response frequencies between the HIV+COVID and COVID cohorts. Conclusion(s): PLWH had increased activation and exhaustion and increased classical monocytes compared to HIV-seronegative presentations of COVID-19, highlighting the persistent immune dysregulation associated with chronic HIV infection. Our findings aid in further characterization of how chronic immune dysregulation impacts the immune response to acute SARS-CoV-2 infection. Future studies include characterizing the impact of acute SARS-CoV-2 infection duration, as well as how chronic immune dysregulation impacts the development of long COVID. (Table Presented).
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In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
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Background: Better understanding of host inflammatory changes that precede development of severe COVID-19 could improve delivery of available antiviral and immunomodulatory therapies, and provide insights for the development of new therapies. Method(s): In plasma from individuals with COVID-19, sampled <=10 days from symptom onset from the All-Ireland Infectious Diseases Cohort study, we measured 61 biomarkers, including markers of innate immune and T cell activation, coagulation, tissue repair, lung injury, and immune regulation. We used principal component analysis (PCA) and k-means clustering to derive biomarker clusters, and univariate and multivariate ordinal logistic regression to explore association between cluster membership and maximal disease severity, adjusting for risk factors for severe COVID-19, including age, sex, ethnicity, BMI, hypertension and diabetes. Result(s): From March 2020-April 2021, we included 312 individuals, (median (IQR) age 62 (48-77) years, 7 (4-9) days from symptom onset, 54% male) in the analysis. PCA and clustering derived 4 clusters. Compared to cluster 1, clusters 2-4 were significantly older and of higher BMI but there were no significant differences in sex or ethnicity. Cluster 1 had low levels of inflammation, cluster 2 had higher levels of markers of tissue repair and endothelial activation (EGF, VEGF, PDGF, TGFalpha, serpin E1 and p-selectin). Cluster 3 and 4 were both characterised by higher overall inflammation, but compared to cluster 4, cluster 3 had downregulation of growth factors, markers of endothelial activation, and immune regulation (IL10, PDL1), but higher alveolar epithelial injury markers (RAGE, ST2). In univariate analysis, compared to cluster 1, cluster 3 had the highest odds of severe disease (OR (95% CI) 9.02 (4.62-18.31), followed by cluster 4: 5.59 (2.75-11.72) then cluster 2: 4.5 (2.38-8.81), all p < 0.05). Cluster 3 remained most strongly associated with severe disease in fully adjusted analyses;cluster 3: OR(95% CI) 5.99 (2.69-13.35), cluster 2: 3.14 (1.54-6.42), cluster 4: 3.13 (1.36-7.19), all p< 0.05). Conclusion(s): Distinct early inflammatory profiles predicted maximal disease severity independent of known risk factors for severe COVID-19. A cluster characterised by downregulation of growth factor and endothelial markers and early evidence of alveolar injury was associated with highest risk of developing severe COVID19. Whether this reflects a dysregulated inflammatory response that could improve targeted treatment requires further study. Heatmap of biomarker derived clusters and forest plot of association between clusters and disease severity. A: Heatmap demonstrating differences in biomarkers between clusters B: Forest plot demonstrating odds ratio of specific clusters for progressing to moderate or severe disease (reference Cluster 1), calculated using ordinal logistic regression. Odds ratio (95% CI) presented as unadjusted and fully adjusted (for age, sex, ethnicity, BMI, hypertension, diabetes, immunosuppression, smoking and baseline anticoagulant use). Maximal disease severity graded per the WHO severity scale.
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Background: Neurocognitive symptoms are common in acute as well as convalescent (post-acute sequelae of COVID-19 [PASC]) COVID-19, but mechanisms of CNS pathogenesis are unclear. The aim of this study was to investigate cerebrospinal fluid (CSF) biomarker evidence of CNS infection, immune activation and neuronal injury in convalescent compared with acute infection. Method(s): We included 68 (35% female) patients >=18 years with CSF sampled during acute (46), 3-6 months after (22) SARS-CoV-2 infection or both (17), and 20 (70% female) healthy controls from longitudinal studies. The 22 patients sampled only at 3-6 months were recruited in a PASC protocol. CSF N-Ag was analyzed using an ultrasensitive antigen capture immunoassay platform (S-PLEX SARS-CoV-2 N Kit, Meso Scale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF beta2-microglobulin (beta2M)], IFN-gamma, IL-6, TNF-alpha neurofilament light (NfL), and total and phosphorylated tau. Log-transformed CSF biomarkers were compared using ANOVA (Tukey post-hoc test). Result(s): Patients sampled during acute infection had moderate (27) or severe (19) COVID-19. In patients sampled at 3-6 months, corresponding initial severity was 10 (mild), 14 (moderate), and 15 (severe). At 3-6 months, 31/39 patients reported neurocognitive symptoms;8/17 patients also sampled during acute infection reported full recovery after 3-6 months. CSF biomarker results are shown in Figure 1. SARS-CoV-2 RNA was universally undetectable. N-Ag was detectable only during acute infection (32/35) but was undetectable in all follow up and control samples. Significantly higher CSF concentrations of beta2M (p< 0.0001), IFN-gamma (p=0.02), IL-6 (p< 0.0001) and NfL (p=0.04) were seen in acute compared to post-infection. Compared to controls, beta2M (p< .0001), IL-6 (p< 0.0001) and NfL (p=0.005) were significantly higher in acute infection. No biomarker differences were seen post-infection compared with controls. No differences were seen in CSF GFAp, t-tau or p-tau. Conclusion(s): We found no evidence of residual infection (RNA, N-Ag), inflammation (beta2M, IL-6, IFN-gamma, TNF-alpha), astrocyte activity (GFAp) or neuronal injury (NfL, tau) 3-6 months after initial COVID-19, while significantly higher concentrations of several markers were found during acute infection, suggesting that PASC may be a consequence of earlier injury rather than active CNS damage. CSF beta2M, IL-6, IFN-gamma and NfL were significantly lower after 3-6 months than during acute COVID-19 and not different from healthy controls. (Figure Presented).
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Background: While immune checkpoint inhibitors (ICI) -induced myocarditis and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis are considered to be rare;they are both significant side effects, suggested being caused by activation of the immune system against the myocardium. We aimed to assess whether both phenomena share similar presenting characteristics. Method(s): We included patients diagnosed with either ICI or COVID-19 vaccine-induced myocarditis at our medical center. We performed a retrospective assessment of clinical presentation, blood tests, and advanced echocardiography, including speckle strain. Result(s):We included 18 patients diagnosed with ICI (ICI group) or COVID- 19 vaccine (COVID-19 group)-induced myocarditis, and 20 patients with viral myocarditis (Viral group) as a control group. The median age was significantly older in the ICI group (74 years) compared to the COVID-19 and Viral groups (20 and 24 years), p<0.001. The clinical presentation in the COVID-19 group was more similar to the Viral group, presenting mainly with chest pain and fever, while the ICI group presented mainly with dyspnea. ST-elevation was frequent in the COVID-19 and Viral groups and absent in the ICI group, p=0.004. Median peak high sensitivity troponin I values were markedly lower in the ICI group compared to the COVID-19 and Viral groups (619 ng/L vs. 15527 ng/L vs. 7388 ng/L, p=0.004). While the median left ventricular ejection fraction was 60% among all groups, patients in the ICI group presented with mean lower LV global longitudinal strain (-13%) and left atrial conduit strain (17%), compared to the COVID-19 (-17% and 30%) and Viral groups (-18% and 37%), p=0.016 and p=0.001. Conclusion(s): While the suspected mechanism is an activation of the immune system in both ICI and the COVID-19 vaccine-induced myocarditis, we found that the clinical presentation, cardiac biomarkers, and advanced echocardiography of the COVID-19 vaccine, are more similar to viral myocarditis than to ICI-induced myocarditis.
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Background: Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2- negative breast cancer (BC) remains an unmet medical need. However, no therapies to date have tested their activity directly in chemo-resistant RD. Here, we hypothesized that combining an oncolytic virus such as T-VEC with atezolizumab may offer clinical benefit in patients (pts) with RD after standard NAC. To our knowledge, PROMETEO is the first trial that examines the activity of immunotherapy in pts with RD prior to surgery. Method(s): PROMETEO (NCT03802604) is a singlearm, open-label, multicenter phase II trial. Women with triple-negative BC (TNBC) or hormone receptor-positive/HER2-negative (HR+/HER2-) BC with baseline (i.e., before NAC) ki67 >= 20% were eligible. RD was confirmed with a magnetic resonance imaging (MRI) showing a tumor diameter >= 10 mm and a core-biopsy detecting the presence of invasive cells. Before surgery, T-VEC was administered intratumorally on week 1 (106 pfu/mL), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) was administered intravenously every 2 weeks for 4 infusions, starting at week 4. Surgery was performed in < 3 weeks after completing the treatment. The primary objective was to evaluate the efficacy of the combination, measured by the rate of residual cancer burden (RCB) class 0/1 at surgery. Tumor samples collected at 5 timepoints (before NAC, during screening period, after first dose of T-VEC, after first dose of T-VEC and atezolizumab and at surgery) were mandatory to assess gene expression, tumor-infiltrating lymphocytes (TILs), immune cells PD-L1 IHC (SP142), tumor mutational burden (TMB) by FoundationOne and other translational endpoints. Result(s): Between Dec 2018 to Feb 2022, 28 pts were enrolled: 20 pts with HR+/HER2- disease and 8 pts with TNBC. Median age was 47 (range 31-71) and 71% of pts were premenopausal. At diagnosis before NAC, clinical stage II disease represented 60.7%, cN+ 60.7%, median Ki-67 was 37.5% (range 20%-95%), high TILs (>=10%) 37%, median TMB was 3 (0-19) and only 1 of 27 pts (3.7%) had a PD-L1-positive tumor. After NAC, mean tumor size by MRI was 28.3 mm (10-93). Two pts discontinued from the trial (1 withdrawal of consent and 1 COVID infection). The completion of 5 cycles of treatment was achieved by 73% of pts. The overall RCB-0/1 rate was 25% (7 of 28, 95% IC 10.7 - 44.9%), all with RCB 0 (pathologic complete response [pCR]). The pCR rate was 30% in HR+/HER2- disease and 12.5 % in TNBC. Radiological response by MRI was achieved by 3 of 28 pts (10.7%). Interestingly, none of the 7 pts with a pCR had radiological response (stable disease n=5, progressive disease [PD] n=2). Six pts (21.4%) had radiological PD and had RCB 2/3. Overall, 27 (96%) patients had at least one treatment-emergent adverse event (TEAE) of any grade. Most common grade 1 or 2 AEs were fever (11 pts, 39.3%), ALT increased (9 pts, 32.1%), AST increased (8 pts, 28.6%), arthralgia (6 pts, 21.4%) and anemia (6 pts, 21.4%). Grade 3 reversible neutropenia occurred in 1 patient. Across all pts, significant increases (p< 0.001) in TILs, immune genes and immune PDL1+ cells were observed after 1 dose of TVEC, 1 dose of the combination and at surgery. Intrinsic subtype changes at surgery occurred in 73.1% of cases, mostly (46.1%) Luminal A/B converting to Normal-like. At surgery, 19 of 26 (73.1%) of tumors were PDL1+. Conclusion(s): Two months of T-VEC in combination with atezolizumab induced a pCR in a subgroup of pts with chemoresistant HER2- breast cancer. This effect is probably related to the immune activation provoked by the combined treatment. Interestingly, a high discrepancy was observed between the presurgical radiological imaging and the actual surgical pathological report. Pre-operative window-ofopportunity trials in this context might provide important clues regarding the activity of novel treatment strategies.
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Introduction: There have been some reports on flare-ups of kidney diseases following COVID-19 vaccines such as IgA nephropathy and minimal change disease. However, there have been few reports on those of IgA vasculitis following the vaccines yet. We report a case of IgA vasculitis with a flare-up of gross hematuria and lower-limb purpura following Moderna COVID-19 vaccines. Method(s): The patient is a 16-year-old female with no previous history of abnormal results of urinalyses before April in 2021. She had developed microscopic hematuria, proteinuria and purpura on both of her lower limbs that emerged and then disappeared repeatedly since then. She received Moderna COVID-19 vaccines in August and September in 2021, both of which were followed by gross hematuria lasting for around 10 days. The lower-limb purpura reemerged at the same time as the hematuria. Microscopic hematuria of around 30-49 RBC/HPF, glomerular hematuria of moderate degree and urine protein-to-creatinine ratio (UPCR) of around 0.8 g/gCr had continuously been detected. Skin and kidney biopsies were performed in December in 2021 and in February in 2022 respectively. Result(s): The skin tissue showed formation of leukocytoclastic vasculitis, and the kidney tissue showed that of cellular and fibrocellular crescents and endocapillary hypercellularity. Immunofluorescence staining of both tissues showed deposition of galactose-deficient IgA1(Gd-IgA1) and C3, and she was diagnosed as IgA vasculitis. She received steroid pulse therapy followed by tonsillectomy. The lower-limb purpura has disappeared after she received three courses of the steroid pulse therapy, but microscopic hematuria and UPCR of around 0.8 g/gCr have still continued. Conclusion(s): IgA vasculitis is leukocytoclastic vasculitis characterized by deposition of Gd-IgA1 on microvessel walls in skin and on glomerular capillaries in kidneys. The detailed mechanism of IgA vasculitis has not been fully elucidated yet. Gross hematuria following an upper respiratory infection is considered as a characteristic clinical symptom of IgA vasculitis as well as IgA nephropathy. Post-vaccination gross hematuria of patients with IgA nephropathy has been reported, and it is believed that innate immunity is related to its mechanism. Moderna COVID-19 vaccines, which the patient received, are mRNA vaccines. We estimate that exposure to the mRNA vaccine triggered excess glomerular deposition of Gd-IgA1-containing immune complexes and subsequent gross hematuria by overactivation of innate immunity such as Toll-like receptors that detect RNA. This case suggests that such immune activation by a mRNA vaccine might be related not only to the mechanism of IgA nephropathy but also to that of IgA vasculitis. No conflict of interestCopyright © 2023
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Patients suffering severe COVID-19 show an aggressive and excessive immune response against the SARS-CoV-2 coronavirus, known as a cytokine storm. If left untreated these patients face the risk of tissue damage, multi-organ failure and death. A high relative abundance of Prevotella copri has been reported in patients with newly diagnosed rheumatoid arthritis (RA). On the other hand, it has been observed that Prevotella histicola can modulate the inflammatory manifestations of autoimmune diseases like multiple sclerosis, and it is now being evaluated as a monoclonal microbial treatment in COVID-19. We observed that pre-treatment with P. histicola decreased NF-kB activation, while pre-treatment with P. histicola and P. copri decreased IRF activation in monocytes upon SARS-CoV-2 glycoprotein. Our findings suggest that exposure of blood immune cells, such as monocytes, to commensal species of Prevotella may reduce the inflammatory response to SARS-CoV-2 glycoprotein. Besides treatments targeting the viral infection, other treatments such as immunomodulation by bacteria aiming to reduce or regulate the inflammatory process in COVID-19 to avoid the development of related complications may be considered.
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Mentions the pandemic as starting in China, with a subsequent worldwide spread. The viral infection can seriously affect multiple organs, mainly lungs, kidneys, heart, liver, and brain, and may lead to respiratory, renal, cardiac, or hepatic failure. Vascular thrombosis of unexplained mechanism may lead to widespread blood clots in multiple organs and cytokine storms that are a result of over-stimulation of the immune system subsequent to lung damage, may lead to sudden decompensation due to hypotension and cause more damage to liver, kidney, brain or lungs. Until now, no drug has proved to be efficient in getting rid of the problem and controlling the pandemic mainly depends on preventive measures. Many measures can be considered to prevent the worldwide spread of the viral transmission. Polyunsaturated long chain fatty acids (PUFAs), medium chain saturated fatty acids (MCSFAs), and their corresponding monoglycerides have high antiviral activities against the enveloped viruses, which reached more than 10,000-fold reduction in the viral titers in vitro and in vivo after testing for gastric aspirate, and can contribute to the systemic immunity against the enveloped viruses.Copyright © 2021 Bentham Science Publishers.
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Background: Infections are considered the most common known trigger of acute urticaria. Vaccinations can mimic infections and are also able to trigger urticaria. Method(s): This paper describes four exemplary patients with urticaria after SARSCoV-2 vaccination and discusses the occurrence of this adverse event with recent findings from the literature. Result(s): After SARS-CoV-2 vaccination, both acute (case 1) and chronic spontaneous urticaria (CSU) may occur for the first time (case 2) but a stable well-adjusted CSU may also worsen (case 3) or a pre-existing CSU may recur (case 4). The underlying pathomechanisms are not fully elucidated but activation of the immune system by vaccination seems plausible, similar to infection-triggered urticaria. Subsequent vaccinations are recommended even in the presence of a positive history of urticaria after SARS-CoV-2 vaccination and is often well tolerated;prophylactic administration of antihistamines should be considered. Allergy to vaccine components such as polyethylene glycol (PEG), which can lead to anaphylaxis, is comparatively rare. In cases of urticaria after SARS-CoV-2 vaccination, an accurate history allows risk assessment and provides the indication for further allergy diagnostic workup. Conclusion(s): Various forms of urticaria are a relatively common cutaneous side effect of SARS-CoV-2 vaccination in cases of pre-existing predisposition. They are not a contraindication to further vaccination. There is no need for further allergy diagnosis in the majority of cases.Copyright ©2023 Dustri-Verlag Dr. K. Feistle.
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To date, there is no consensus explaining the relationship between varying concentrations of IFNgamma and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNgamma in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNgamma which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNgamma activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNgamma exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNgamma concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNgamma and COVID-19 severity. In a number of studies, the significantly high levels of IFNgamma in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNgamma concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNgamma concentrations in convalescent patients, the mechanism of antagonism between IFNgamma and IL-4 is considered, where the decreases serum concentrations of IFNgamma along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNgamma are at reduced risk for severe course of COVID-19. Copyright © 2022, SPb RAACI.
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Background: Systemic lupus erythematosus (SLE), a multisystem autoimmune disease more common in females, is associated with autoantibodies against different autoantigens forming immune complexes. Inadequate removal of these complexes from the host triggers inflammatory response which causes tissue damage. Some antiviral vaccines have been associated with the onset of SLE. Few cases of SLE occurring after SARS-CoV- 2 vaccines have been reported. Herein, we describe a case of new-onset SLE associated with COVID-19 vaccine. Case Summary: A previously well 36-year- old male with unremarkable family history of autoimmune disease started to develop muscle and joint pains, hair thinning, and ecchymoses 2 months after receiving second dose of inactivated SARS-CoV- 2 vaccine. He was subsequently admitted after consultation due to thrombocytopenia (platelet count of 58). He was given high dose steroid with tapering dose during the entire 14 days admission with significant increase of platelet count after 72 hours of repeat complete blood count. He went consult at rheumatology clinic a month after due to persistent joint and muscle pains, and progression of hair fall with associated facial rash, oral ulcers, easy fatigability and weight loss. Physical exam disclosed an ambulatory well-built male with normal vital signs, alopecia, malar rash, oral ulcers, joint tenderness and no objective muscle weakness. Complete blood counts and Anti-smith were within normal. Urinalysis, Antinuclear antibody (ANA), Anti-SSA, Anti-SSB, complement factor 3 (C3), and Anti-dsDNA were positive. He was managed with tapering prednisone and hydroxychloroquine with significant improvement at time of this report. Conclusion(s): Development of autoimmune reaction following COVID-19 vaccine has been described extensively;however, evidence of autoimmunity following vaccination seems to be lacking at present. Pathomechanisms include defective elimination and/or control of self-reactive lymphocytes resulting in over-stimulation of the immune system leading to clinical manifestations strikingly similar to the infection itself. Management approach to these autoimmune reactions address the immune hyper-stimulation with immunosuppressive or immuno-modulating agents including steroids and hydroxychloroquine.
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Background. Many individuals infected with SARS-CoV-2 are left with persistent symptoms of COVID-19. Post-acute sequelae of COVID-19 (PASC) can affect quality of life and functionality. The mechanism underlying PASC is unknown but elevated inflammatory markers several months post infection have been found in those with PASC. Methods. Individuals diagnosed with COVID-19 were evaluated longitudinally for PASC and persistent symptoms. CD4+ and CD8+ cellular markers and intracellular cytokines were assessed at each follow-up time point and analyzed by individual PASC symptoms reported. Results. Participants who reported persistent dyspnea, forgetfulness, confusion, and chest pain had significantly higher levels of CD8+Ki67+ cells. Those with dyspnea also had significantly higher levels of CD8+CD38+, CD8+Granzyme B+, and CD8+IL10+ cells. Those who suffered from forgetfulness, chest pain, and joint pain had significantly higher levels of CD4+CD25+ cells. Conclusion. These findings suggest continued CD8+ T cell and CD4+CD25+ T cell activation and response following SARS-CoV-2 infection in patients with PASC. An increase in T regulatory cells suggests an ongoing attempt to control host inflammation in a subset of these patients. These results shed further light on continued immune system activation and chronic inflammation as a link to symptoms in COVID-19 survivors suffering from PASC. (Figure Presented).
ABSTRACT
Introduction: COVID-19 raises serious concerns regarding its unknown consequences for health, including psychiatric long term outcomes. Historically, influenza virus has been responsible for pandemics associated with schizophrenia. Epidemiological studies showed increased risk for schizophrenia in children of mothers exposed to the 1957 influenza A2 pandemic. Controversy remains concerning the mechanisms of pathogenesis underlying this risk. Objective(s): We aim to review the evidence for the association between influenza infection and schizophrenia risk, the possible pathogenic mechanisms underlying and correlate these findings with the schizophrenia hypothesis of neurodevelopment. Method(s): We reviewed literature regarding evidence from epidemiological, translational animal models and serological studies using medline database. Result(s): The biological mechanisms likely to be relevant account to the effects of infection-induced maternal immune activation, microglial activation, infection-induced neuronal autoimmunity, molecular mimicry of the influenza virus, neuronal surface autoantibodies and psychosis with potential infectious antecedents. Influenza infection may fit into the theory of the neurodevelopment of schizophrenia as a factor that alters the normal maturation processes of the brain (possible second or third hit). Conclusion(s): Influenza infection has multiple pathogenic pathways in both pre and post natal processes that might increase the risk of schizophrenia or psychosis. The existing evidence regarding the relationship between influenza virus and psychosis might help us draw similar long-term concerns of COVID-19.
ABSTRACT
Introduction: De novo and relapsed glomerulonephritis (GN), including membranous nephropathy (MN), have been reported after COVID-19 mRNA-vaccination. We report a case of MN that relapsed following COVID-19 vaccination after 26 years of remission. Case Description: A 78-year-old man presented with nephrotic syndrome (UPC 8.0). His history was notable for primary MN diagnosed by kidney biopsy in 1994. He was treated with prednisone and ACE inhibitor with full resolution of proteinuria. He received COVID-19 vaccine (mRNA-1273, Moderna) March 3 and April 1, 2021. Between the two doses, he had onset of leg swelling. This was attributed to amlodipine, which was discontinued by his PCP. After the second dose of vaccine, edema progressed to anasarca. Urine protein was 5.73g/day. Two months later, the UPC was 8.0, serum creatinine 0.86 mg/dL, and serum albumin 2.7mg/dL. Anti-PLA2R was positive (24RU/mL, ref. >19RU/mL). Renal biopsy showed recurrent MN, EM stage 3-4, PLA2R1 positive. Due to regional surge of COVID-19 Omicron variant, immunosuppression was held to administer EvuSheld for COVID-19 prophylaxis. Proteinuria improved initially without intervention (UPC 2.7) but increased again (UPC 4.7) a month later. Rituximab was initiated three months after biopsy resulting in undetectable anti-PLA2R 1 week after treatment, with reduction in UPC to 3.7 and improvement of anasarca 2 weeks after treatment. Discussion(s): Onset or relapse of GN after vaccination historically has rarely been reported. There are numerous reports of de novo or relapsed GN after COVID-19 infection, and increasing reports of GN after COVID-19 vaccination with mRNA and traditional vaccine platforms. The pathogenesis of GN in this setting has not been established. Nonspecific immune activation and specific COVID-19-related immune reaction have been postulated. MN related to COVID-19 vaccination, although rarely reported, has been treated with standard immunosuppression with favorable results. Management of MN and other forms of GN will evolve with greater understanding of disease course in the setting of COVID-19 infection and vaccination. Patients with a history of GN, including MN, should be counseled about the possibility of relapse with COVID-19 infection or vaccination, even if their original disease was remote.