THE KINETICS OF HUMORAL AND CELLULAR RESPONSES AFTER THE BOOSTER DOSE OF COVID-19 VACCINE IN INFLAMMATORY ARTHRITIS PATIENTS

BackgroundImpaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to unstudied kinetics of the immune response after booster vaccinations.ObjectivesThis study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster.MethodsIn 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2.ResultsIA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2).ConclusionOur study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Boosting the Immune System with Vitamin D: Special Focus on Prevention of COVID-19 and Complications

In addition to the classical functions of the musculoskeletal system and calcium homeostasis, the function of vitamin D as an immune modulator is well established. The vitamin D receptors and enzymes that metabolize vitamin D are ubiquitously expressed in most cells in the body, including T and B lymphocytes, antigen-presenting cells, monocytes, macrophages and natural killer cells that trigger immune and antimicrobial responses. Many in vitro and in vivo studies revealed that vitamin D promotes tolerogenic immunological action and immune modulation. Vitamin D adequacy positively influences the expression and release of antimicrobial peptides, such as cathelicidin, defensin, and anti-inflammatory cytokines, and reduces the expression of proinflammatory cytokines. Evidence suggestss that vitamin D's protective immunogenic actions reduce the risk, complications, and death from COVID-19. On the contrary, vitamin D deficiency worsened the clinical outcomes of viral respiratory diseases and the COVID-19-related cytokine storm, acute respiratory distress syndrome, and death. The study revealed the need for more preclinical studies and focused on well-designed clinical trials with adequate sizes to understand the role of vitamin D on the pathophysiology of immune disorders and mechanisms of subduing microbial infections, including COVID-19.Copyright © 2023 Bentham Science Publishers.

Should Young Covid-19 Patients be Suplemented with Vitamin D?

It is well known that vitamin D's general immunomodulatory actions are helpful in viral infections and that a shortage is linked to a more serious prognosis for Covid-19. In this sistematic review, we examined the existing literature on evidence as to whether there is also link between vitamin D range levels in pediatric population and the outcome of the Covid-19 infection. We looked for studies that measured vitamin D blood concentrations and examined the effects of vitamin D supplementation in young infected patients. Vitamin D may decrease the risk of respiratory infections in a number of ways through its interactions with numerous cells, including by decreasing viral survival and replication, reducing the cytokine storm, raising angiotensin-converting enzyme 2 concentrations (ACE2) while not damaging the endothelial integrity. The incidence or severity of Covid-19 is linked with blood 25-hydroxyvitamin D concentrations, according to many observational studies. However experimental verification is still needed. Given their safety and broad therapeutic window, vitamin D supplements seem to be an effective way for individuals and doctors to prevent or treat Covid-19. Nonetheless, the outcomes of significant vitamin D randomized controlled trials are further needed.Copyright © 2022 Maria Nicolae et al., published by Sciendo.

COVID-19 and immunity

Coronavirus disease-19 (COVID-19), caused by a β-coronavirus and its genomic variants, is associated with substantial morbidities and mortalities globally. The COVID-19 virus enters host cells upon binding to the angiotensin converting enzyme two receptors. Patients afflicted with COVID-19 may be asymptomatic or present with critical symptoms possibly due to diverse lifestyles, immune responses, aging, and underlying medical conditions. Geriatric populations, especially men in comparison to women, with immunocompromized conditions, are the most vulnerable to severe COVID-19-associated infections, complications, and mortalities. Notably, whereas immunomodulation, involving nutritional consumption, is essential to protecting an individual from COVID-19, immunosuppression is detrimental to the host with this hostile disease. As such, immune health is inversely correlated to COVID-19 severity and resulting consequences. Advances in genomic and proteomic technologies have helped us to understand the molecular events underlying symptomatology, transmission, and pathogenesis of COVID-19 and its genomic variants. Accordingly, there has been development of a variety of therapeutic interventions, ranging from mask wearing to vaccination to medication. Regardless of various measures, a strengthened immune system can be considered as a high priority of preventive medicine for combating this highly contagious disease. This chapter provides an overview of pathogenesis, effects of comorbidities on COVID-19 and their correlation to immunity, and prospective therapeutic strategies for the prevention and treatment of COVID-19. © 2023 Elsevier Inc. All rights reserved.

Scientific rationale of Indian AYUSH Ministry advisory for COVID-19 prevention, prophylaxis, and immunomodulation

The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.

Trace Elements Zinc and Selenium: Their Significance in the Conditions of the Covid-19 Pandemic

Within the conditions of the ongoing COVID-19 pandemic, when many questions regarding prevention and treatment strategies remain unsolved and the search for the best antiviral agents is underway, attention should be paid to the role of trace elements zinc and selenium in increasing the body's resistance to viral infections and their direct antiviral activity against SARS-CoV-2. Experimental data show that trace elements zinc and selenium not only actthrough regulating the immune response at all levels of humoral and cellular immunity, but also can play a significant role in adjuvant therapy for viral diseases. This is especially relevant in the case of COVID-19. Studies of the direct antiviral effect of these micro-elements testify to its 3 main ways to SARS-Cov-2: I - counteraction to virus replication and its transcription through: (i) their covalent binding to the SH-group of the cysteine of the main protease M(Pro) of the virus;(ii) inhibition of its RNA polymerase activity by zinc;II - preventing the penetration of the virus into cells due to blocking SH-groups of protein disulfide isomerase (RDI) of the protein of its spikes (peplomers);III - decreasing the adsorption capacity of the virus due to the blocking of the electrostatic interaction of SARS-CoV-2 peplomers and angiotensin-converting enzyme (ACE-2) in ultra-low, uncharacteristic oxidation states (Zn+1and Se-2). The intensity of the antiviral action of these trace elements may depend on their chemical form. It was found that zinc citrate (a five-membered complex of zinc with citric acid) and monoselenium citric acid obtained with the help of nanotechnology have a greater intensity of action and higher chemical purity. Taking into account the immunostimulating and direct antiviral effect of zinc and selenium, their use in the form of pharmaceuticals and dietary supplements should be considered as adjunctive therapy for SARS-CoV-2 in patients, or as a preventive strategy for uninfected people from risk groups during the spread of COVID-19.Copyright © Publisher PH <<Akademperiodyka>> of the NAS of Ukraine, 2023.

Antiviral Effects of Fructans

Infectious diseases of viral origin have never received so much interest globally since the emergence of the COVID-19 pandemic disease. In contrast to bacterial infections, antibiotic treatments do not have any effect on viral infections, requiring alternative solutions to reduce the impact of viral spread on animal populations. More important than curing, preventing viral replication before disease development is probably the best strategy to minimalize the negative effects of viruses on a global scale. Fructans, known to stimulate the immune system (by either interacting directly or indirectly with the immune system), may be interesting candidates as part of this broader prevention strategy. This chapter discusses the potential antiviral properties of fructans in relation to their well-described immunomodulating, antioxidant and prebiotic attributes, as well as a possible role as protein binders which may disturb the proper function of viral proteins, and thus reduce the infection ability of certain viral strains. © 2023 Elsevier Inc. All rights reserved.

Technological Mapping of Plant-Derived Immunomodulator Drugs: A Patent-Guided Overview about Species and its Main Compounds

Research on natural products has investigated and employed many (bio)technologies to find out plant active fractions and optimize extraction and isolation of molecules looking for innovative clinical therapies for several clinical conditions, as well as immune-related diseases. Indeed, the world incidence and prevalence of autoimmune diseases have increased over the last years, while immune therapy has arisen as a new promising tool for cancer treatment. Also, in the emergence of COVID-19 pandemic, immunomodulation has been proved effective to reduce the "cytokine storm” and avoid worsening the clinical condition of patients in the acute stage of respiratory syndrome. These health issues have also driven the search for new immunomodulatory compounds. In this context, prospective analysis is an important tool to identify the most relevant opportunities and demands in research and development (R&D) of pharmaceutical medicines, including substances able to modulate immune and inflammatory responses. In addition, prospection allows understanding the landscape of immunomodulatory plant-derived drugs and the associated technologies described in patents. This chapter employed the descriptors "Immunomodulator*” and "drug” and "plant” in search strategy to map the technological potential of immunomodulatory herbal drugs, using the software VantagePoint, Cortellis Competitive Intelligence, and Orbit Intelligence, respectively. The results provided quantitative data and technological indicators to drive future strategies for the development of these drugs. In conclusion, the most cited plant species in patents expressing molecules with immunomodulatory properties were Curcuma longa, Moringa oleifera, Remirea maritima, Maytenus ssp., Angelica sp., Fagopyrum esculentum, as well as plants from the families Leguminosae, Rosaceae, Iridaceae, Moraceae, and Amaranthaceae, among others. The main chemical classes implicated in immunomodulation were xanthones, coumarins, flavonoids, and (tri)terpenes. The technological mapping also showed that in the year 2002, there was an increased deposit of patents, reaching the highest peak in 2009 with 56 patents. Nowadays, the United States is the country with the biggest number of patents, followed by Canada, Australia, and Korea. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

DO PATIENTS ON SUPPRESSIVE THERAPY HAVE A DECREASED HUMORAL RESPONSE TO SARS-CoV2 VACCINATION?

BackgroundSARS-Cov2 vaccination has been shown to be effective against severe forms of SARS-Cov2 infection. Several studies investigated the humoral and cellular response to SARS-Cov2 vaccines in patients followed for autoimmune and inflammatory diseases under immunosuppressive or immunomodulatory treatments. It has been shown that patients on immunosuppressive or immunomodulatory therapies have a poor humoral response to the vaccine[1]ObjectivesThe aim of our study was to investigate the humoral response in patients under conventional immunosuppressive and biotherapies compared to healthy controls.MethodsPatients followed for immuno-inflammatory diseases under immunosuppressive or immunomodulatory drugs who received at least one dose of anti- SARS-Cov2 vaccines were included. Quantitative Anti- SARS-Cov2 antibodies (IgM and IgG assay) VIDAS ® were assessed for all patients. Patients were then compared with healthy controls.ResultsWe enrolled 93 blood samples (63 patients with autoimmune and inflammatory disease and 30 healthy controls), the median age was 52 years [Q1 43, Q3 56]. The immuno-inflammatory diseases were: Crohn's disease (n=28), Rheumatoid arthritis (n=9), Hemorrhagic rectocolitis (n=5), Behçet's disease (n=5), Systemic lupus erythematosus (n=4), Sjogren's syndrome (n=3), Sarcoidosis (n=2), Takayasu disease (n=1). All patients continued their treatment during and after vaccination. Nineteen patients were on biotherapies: Infliximab (n=12), Adalimumab (n=3), etanercept (n=2), Ustekinumab (n=1), tocilizimab (n=1). Forty-three patients were on conventional immunosuppressive: azathioprine (n=18), methotrexate (n=16), corticosteroids > 10 mg/d (n=12). All patients had received at least one dose of vaccine: the median number of doses in both groups was 2[1-4] with no statistically significant difference between the 2 groups (p=0.2). The vaccines received in the group of patients were mRNA vaccine (n=35) and other type of vaccine (n=28). In the healthy control group, type of vaccine were mRNA (n=13) other type vaccine (n=17). The patient had a lower mean level of Ig G against SARS-Cov2 antibodies (24.64 IU +/- 16.65) comparing to healthy controls (33.05+/- 10) with statically significant difference (p= 0.014). No difference between the 2 groups was noted in Ig G levels according to the history of SARS-Cov2 infection. No difference was found between conventional immunosuppressive drugs and biotherapies regarding to the level of antibodies.ConclusionOur study highlights that patients with autoimmune disease and under immunosuppressive therapy displayed a decrease of humoral response comparing to healthy controls. This finding was reported in several studies, Geisen et al[2] reported that patients with chronic inflammatory condition and receiving TNF alfa blockers had a decreased protection and a low level Ig A against spike. Based on these data, patients with autoimmune and inflammatory diseases have decreased humoral immunity to SARS-Cov2 and should be encouraged to receive a booster dose of SARS-COv2 vaccine.References[1]Prendecki M, Clarke C, Edwards H, et al. Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression. Ann Rheum Dis 2021;80:1322–9. doi:10.1136/annrheumdis-2021-220626[2]Geisen UM, Sümbül M, Tran F, et al. Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies. RMD Open 2021;7:e002008. doi:10.1136/rmdopen-2021-002008AcknowledgementsMrs Hajer Mediouni.Disclosure of InterestsNone Declared.

Melatonin and Cytokines Modulate Daily Instrumental Activities of Elderly People with SARS-CoV-2 Infection.

The Comprehensive Geriatric Assessment analyzes the health and quality of life of the elderly. Basic and instrumental daily activities may be compromised due to neuroimmunoendocrine changes, and studies suggest that possible immunological changes occur during infections in the elderly. Thus, this study aimed to analyze cytokine and melatonin levels in serum and correlate the Comprehensive Geriatric Assessment in elderly patients with SARS-CoV-2 infection. The sample consisted of 73 elderly individuals, 43 of whom were without infection and 30 of whom had positive diagnoses of COVID-19. Blood samples were collected to quantify cytokines by flow cytometry and melatonin by ELISA. In addition, structured and validated questionnaires were applied to assess basic (Katz) and instrumental (Lawton and Brody) activities. There was an increase in IL-6, IL-17, and melatonin in the group of elderly individuals with infection. In addition, a positive correlation was observed between melatonin and IL-6 and IL-17 in elderly patients with SARS-CoV-2 infection. Furthermore, there was a reduction in the score of the Lawton and Brody Scale in the infected elderly. These data suggest that the melatonin hormone and inflammatory cytokines are altered in the serum of the elderly with SARS-CoV-2 infection. In addition, there is a degree of dependence, mainly regarding the performance of daily instrumental activities, in the elderly. The considerable impact on the elderly person's ability to perform everyday tasks necessary for independent living is an extremely important result, and changes in cytokines and melatonin probably are associated with alterations in these daily activities of the elderly.

Pooled evidence from preclinical and clinical studies for stem cell-based therapy in ARDS and COVID-19.

COVID-19 has severely devastated many lives across the globe. It has been speculated that stem cell-based therapy for COVID-19 treatment could be able to subsidize the effects. In preclinical and clinical studies, stem cell-based therapy has successfully eliminated inflammatory cytokines in ALI, ARDS, and COVID-19. Clinical trials have produced a variety of promising results for validating stem cell therapy in COVID-19 patients. For instance, exosome-based therapy (ExoFlow) showed an 87% survival status, and MSC-based therapy (Mesoblast) achieved an 83% survival rate in moderate to severe COVID-19 patients. This review debates the advantages of cell-free therapy, i.e., stem cell-derived exosome-based therapies, over stem cell-based therapy. This review aims to question whether the immunomodulatory effect of stem cells differs based on their origin and also tries to find possible answers for the best stem cells for treating SARS-CoV-2 infection. The role of stem cells and their extracellular vesicles in the upregulation of regulatory immune cells, growth factors (EGF, FGF, VEGF), and anti-inflammatory cytokines (IL-6, INF-α, galectin-1, notch-1, PDL-1) that promote the tissue regeneration at the injured site. The right side of the image depicts the downregulation of inflammation-inducing immune cells, pro-inflammatory cytokines, and chemokines that could also enhance COVID-19 therapy.

Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay.

Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D3 (25(OH)D3)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D3 followed by treatment as usual (TAU) of daily vitamin D3 daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D3-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups, p = 0.920). We adjusted the length of stay for COVID-19 risk factors (ß = 0.44; 95% CI: -2.17-2.22), and center (ß = 0.74; 95% CI: -1.25-2.73). The subgroup analysis in patients with severe 25(OH)D3-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days, p = 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62-1.48, p = 0.850). Serum 25(OH)D3 level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: -2.73, p < 0.001). The intervention with 140,000 IU vitamin D3 + TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D3 levels.

Cryptococcal meningitis post-covid-19 infection: Immunomodulation, a double-edged sword.

Cryptococcal meningitis is an opportunistic infection associated with altered immunity. Immunomodulatory agent use in severe coronavirus disease 2019 (COVID-19) may predispose such infections. Here, we present a 75-year-old male patient who presented with fever and altered general status after severe COVID-19 infection and developed cryptococcal meningitis. Opportunistic infection may arise from the use of immunomodulation in severe COVID-19, especially in the elderly population. This article describes the case and extensively reviews cryptococcal disease post-COVID-19 literature, highlighting the risk from immunosuppressive treatment.

Host-Based Treatments for Severe COVID-19.

COVID-19 has been a global health problem since 2020. There are different spectrums of manifestation of this disease, ranging from asymptomatic to extremely severe forms requiring admission to intensive care units and life-support therapies, mainly due to severe pneumonia. The progressive understanding of this disease has allowed researchers and clinicians to implement different therapeutic alternatives, depending on both the severity of clinical involvement and the causative molecular mechanism that has been progressively explored. In this review, we analysed the main therapeutic options available to date based on modulating the host inflammatory response to SARS-CoV-2 infection in patients with severe and critical illness. Although current guidelines are moving toward a personalised treatment approach titrated on the timing of presentation, disease severity, and laboratory parameters, future research is needed to identify additional biomarkers that can anticipate the disease course and guide targeted interventions on an individual basis.

Utilization of prophylactic drugs for covid-19 infection among health care workers at government medical college Srinagar-a retrospective observational study

Introduction: Corona virus disease (COVID-19) was declared as a Pandemic by WHO on March 11, 2020. Since health care workers play an important role in providing care to infected patients, they are exposed to unprecedented levels of risk. At the initial phase of this pandemic, no definitive treatment was available, the only way to combat this disease was prevention. A number of prophylactic drugs were being studied during that time for use by health care workers. On 23rd March 2020, Government of India issued recommendation through National Task Force for Covid-19, for using Hydroxychloroquine as prophylaxis for SARS COV-2. Preclinical studies of Azithromycin have shown immunomodulation and in vitro activity against SARS-COV-2, that has led to its widespread usage during COVID-19. Ivermectin, an antiparasitic drug was reported to have an in vitro activity against SARS-COV-2. This orally administered drug was included in India's revised National COVID-19 treatment protocol for people with mild infection. Vitamin C, a water soluble vitamin has been considered for potential beneficial effects in COVID-19 disease. Many animal studies have indicated that a daily intake of vitamin C may prevent infections. Aim(s): To evaluate the pattern of drugs (HCQ, AZITHROMYCIN, IVERMECTIN,and VITAMIN C) used for COVID-19 prophylaxis among health care workers at GMC, Srinagar. MATERIALS AND METHODS: This study is being conducted by using a survey questionnaire. A survey questionnaire in English has been developed after literature review. The responses will be analyzed using descriptive statistics of frequency and percentage.

Clinical features and acute management in children

Children account for a minority of cases of SARS-CoV-2 infection. The majority with acute infection are asymptomatic or have mild disease. Severe disease and mortality are reported in children with associated comorbidities such as complex neurodisability. Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS;also referred to as multisystem inflammatory syndrome in children (MIS-C)) is observed ~3-6 weeks after acute infection in an estimated 0.05% of cases. This is characterised by multiorgan involvement, and >50% of cases have myocardial dysfunction and require critical care admission for supportive care. Neurological, cardiac, gastrointestinal, renal and dermatological symptoms are all reported in acute and post-acute SARS-CoV-2 infection. To date, there is no evidence of a benefit from remdesivir, steroids or other investigative treatment in children during acute infection, and their use is recommended only on a case-by-case compassionate basis. Management of PIMS-TS is based on evidence from Kawasaki disease with immunomodulation and cardiac protection, and urgent RCT data are required. The collateral effects of the pandemic are likely to have long-term effects on children's physical and mental health.Copyright © ERS 2021.

Glioblastoma Susceptibility to SARS-CoV-2: Analysis of Cancer Stem Cells and Immune Tumor Microenvironment on Human Brain, Patient-Derived Tumors, and Organoid Models

INTRODUCTION: Glioblastoma (GBM) is the most common and deadliest primary brain tumor, characterized by chemoradiation resistance and an immunosuppressive tumor microenvironment (TME). SARS-CoV-2, the COVID-19 virus, produces a significant proinflammatory response and a spectrum of clinical presentations after central nervous system infection. METHOD(S): Patient-derived GBM tissue, primary cell lines, and organoids were analyzed with immunohistochemistry and pixel-line intensity quantification. Data from tumor-bulk and single-cell transcriptomics served to describe the cell-specific expression of SARS-CoV-2 receptors in GBM and its association with the immune TME phenotype. Normal brain and iPSC-derived organoids served as controls. RESULT(S): We demonstrate that patient-derivedGBMtissue and cell cultures express SARS-CoV2 entry factors such as ACE2, TMPRSS2, and NRP1. NRP1 expression was higher in GBM than in normal brains (p<0.05), where it plays a crucial role in SARS-CoV-2 infection. NRP1 was expressed in a cell-type and phenotype-specific manner and correlated with TME infiltration of immunosuppressive cells: M2 macrophages (r = 0.229), regulatory T cells (r = 0.459), NK cells (r = -0.346), and endothelial cells (r = 0.288) (p < 0.05). Furthermore, gene ontology enrichment analysis showed that leukocyte migration and chemotaxis are among the top 5 biological functions mediated by NRP1 (p < 0.05). We found our GBM organoids recapitulate tumoral expression of SARSCoV- 2 entry factors, which varies based on distance from surface as surrogate of TME oxygenation (p < 0.05). CONCLUSION(S): GBM cancer cells and immune TME cells express SARS-CoV-2 entry factors. Glioblastoma organoids recapitulate this expression and allow for currently undergoing studies analyzing the effect of SARS-CoV-2 infection in GBM. Our findings suggest that SARSCoV- 2 could potentially target GBM, opening the door to future studies evaluating SARS-CoV-2-driven immune modulation.

Thyroid Adverse Events after SARS-CoV-2 Vaccination

Introduction: Subacute thyroiditis and autoimmune thyroiditis are known complications of COVID-19 infection. With the development of SARS-CoV-2 vaccine, new cases of thyroiditis following vaccination have been reported. In accordance, we report on a series of patients who present with hyperthyroidism, elevated TSH receptor activating antibodies, concerning for activation of Graves disease after receiving SARS-Cov-2 messenger RNA (mRNA) vaccine. This association underpins the possible immune modulation affecting the presentation of autoimmune thyroiditis post vaccination. Case Description: We describe four patients who present with symptoms of hyperthyroidism after receiving SARS-CoV-2 mRNA vaccine. All were females, median age 49 (range 44-59). Two patients presented with de novo hyperthyroidism 25-29 days following SARS-CoV-2 mRNA vaccine. Two patients have previously had diagnosed Graves disease in remission for longer than 3 years and presented after 40-60 days after receiving SARS-CoV-2 mRNA vaccine. All four patients had TSH receptor antibodies positive (range 6.21-11.87IU/L) Discussion: Although vaccines are one of the most successful medical advances clarifying associated conditions and risks is of interest to practicing physicians. It is not known if these 4 cases of Graves disease were diagnosed coincidentally following SARS-CoV-2 vaccine and association between this vaccine and autoimmune manifestations remains to be further investigated. This report adds information to current knowledge and understanding of autoimmune manifestations following SARS-CoV-2 vaccine.Copyright © 2023