Progress in understanding the health promoting effect of egg yolk immunoglobulin

As an important immuneoactive component in eggs, yolk immunoglobulin (IgY) shows great competitiveness in research and production due to its good stability, high safety, low cost, easy availability, strong immune activity, and no drug resistance. This article highlights the significant advantages of IgY as a good antibiotic substitute in the prevention and treatment of viral and bacterial diseases. Also, IgY has great potential in the regulation of nutrient metabolism balance, intestinal microflora and immune homeostasis by affecting key rate-limiting enzymes, and relevant receptors and inflammatory factors specifically. Proper diet and targeted delivery of foodborne IgY may be a new perspective on inflammation regulation, disease control, nutritional balance or homeostasis, and oral microencapsulated IgY is expected to be a new approach against increasing public health emergencies (such as COVID-19 pandemic).

GENE ANALYSIS REVEALED THE USEFULNESS OF TRIPLE THERAPY WITH BARICITINIB, RITUXIMAB AND TACROLIMS FOR ANTI-MDA5 ANTIBODY POSITIVE DERMATOMYOSITIS (MDA5-DM)

BackgroundAnti-MDA5 antibody positive dermatomyositis (MDA5-DM) is characterized by high mortality due to rapid progressive ILD. MDA5 is a cytosolic protein and a family of RIG-I like receptor, which functions as a virus RNA sensor and induces the production of such as type-1 IFN. Although little is known about the pathogenesis of MDA5-DM, it is notable that the similarities were reported between COVID-19 infection and MDA5-DM. It may suggest that there is a common underlying autoinflammatory mechanism. We reported that in MDA5-DM, (1) RIG-I-like receptor signaling is enhanced and (2) antiviral responses such as type 1 IFN signaling are also enhanced as compare with anti-ARS-antibody positive DM, and (3) the key for survival is suppression of RIG-I-like and IFN signaling (EULAR2022, POS0390). We also found that a significant role for uncontrolled macrophage in the pathogenesis of ILD by our autopsy case. Recently, it has been reported that tacrolimus (TAC) and cyclophosphamide (CY) combination therapy (TC-Tx) has improved the prognosis of cases with early onset of the disease, but there are cases that cannot be saved. Therefore, we devised BRT therapy (BRT-Tx). The Tx combines baricitinib (BAR), which inhibits GM-CSF and IFN-mediated signaling and effectively suppresses uncontrolled macrophages, with rituximab (RTX) and TAC, which rapidly inhibits B and T cell interaction and ultimately prevents anti-MDA5 antibody production.ObjectivesTo determine the differences in gene expression between BRT and TC-Tx for MDA5-DM in peripheral blood.MethodsTotal of 6 MDA5-DM (TC: 3, BRT: 3) were included and all of them had multiple poor prognostic factors. Peripheral whole blood was collected at just before and 2-3 months after the treatment. RNA was extracted, and quantified using a next-generation sequencer. Differentially Expressed Genes (DEGs) were identified by pre vs. post treatment. Gene Ontology (GO), clustering and Gene Set Variation Analysis (GSVA) were performed to DEGs. As one BRT case was added since our last year's report, we also reanalyzed the surviving vs. fatal cases. The IFN signature was scored separately for Types 1, 2, and 3, and the changes between pre- and post-treatment were investigated.ResultsTwo of three cases with TC died during treatment, while all three cases on BRT recovered. The cluster analysis of the DEGs separated deaths from survivors, not by type of treatment. Comparing surviving and dead cases, GO analysis revealed that the immune system via immunoglobulins and B cells was significantly suppressed in surviving cases. GO analysis of DEGs in each therapeutic group showed that expression of B cell-related genes such as lymphocyte proliferation and B cell receptor signaling pathway were significantly suppressed in BRT-Tx. On the other hand, TC-Tx significantly suppressed such pathways as cell proliferation and cell surface receptor signaling, and was less specific for the target cells than BRT-Tx. The changes in IFN signature score after treatment showed an increase in type 2 and 3 IFN scores in all fatal cases and an increase in type 1 IFN score in one fatal case.ConclusionBRT-Tx significantly suppressed gene expression associated with B cells, while TC-Tx was characterized by low specificity of therapeutic targets and suppression of total cell proliferation. Comparison of surviving and dead cases revealed that the combination of RTX contributed to the success of treatment, as suppression of the immune system mediated by immunoglobulins and B cells is the key for survival. Analysis of the IFN signature revealed an increase in IFN score after treatment in fatal cases, indicating that the combination of BAR is beneficial. The superiority of BRT-Tx seems clear from the fact that all patients survived with BRT-Tx while only one/three patients survived with TC-Tx.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMoe Sakamoto: None declared, Yu Nakai: None declared, Yoshiharu Sato: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.

DERMATO-NEURO SYNDROME PRECIPITATED BY COVID-19 INFECTION IN THE SETTING OF SCLEROMYXEDEMA

BackgroundA black female in her 40s presented with a nonpruritic rash for 10 months consisting of bumps on the face, hands, forearms, and thighs. She had no prior treatment. Past medical history was significant for pulmonary embolism (PE) 6 years prior. She had no personal or family history of autoimmune disease. Physical exam revealed numerous smooth 2-3 mm skin-colored papules over the bilateral forearm dorsa, hands, anterior thighs, and face. Serum protein electrophoresis revealed monoclonal IgG lambda gammopathy. Skin biopsy of her left elbow showed dermal fibroplasia with mucin deposition. IgG was less than 1.5 grams/deciliter;bloodwork was otherwise stable. The diagnosis of scleromyxedema was rendered.ObjectivesThe objective of this clinical case was to evaluate a neurologic sequela of COVID-19 infection in a patient with scleromyxedema.MethodsOne month following diagnosis of scleromyxedema, our patient was diagnosed with COVID-19 five days before admission to the emergency department with altered mental status and aphasia. Rheumatology was consulted due to malignant hypertension and acute kidney injury with question of scleroderma-like renal crisis in the setting of recently diagnosed COVID-19 infection, although she had no other features of systemic sclerosis. The infectious disease team was consulted due to COVID-19-induced inflammatory reaction.ResultsThe patient's creatinine kinase and brain natriuretic peptide were elevated. Creatinine and potassium trended upwards. She developed seizures and became hemodynamically unstable with rapidly declining clinical status. She was transferred to the intensive care unit, where she developed respiratory arrest, shock, hyperkalemia, and acidemia. She received escalating doses of pressors but experienced frequent arrhythmic disturbances and developed asystole. Resuscitation efforts were unsuccessful;she expired within 24 hours of consultation.ConclusionDermato-neuro syndrome (DNS) is a potential complication of scleromyxedema associated with confusion, dysarthria, seizures, and coma. The patient's clinical presentation is consistent with DNS in the setting of scleromyxedema likely precipitated by COVID-19. Intravenous immunoglobulins are first-line treatment for scleromyxedema;however, it is associated with risk of venous thromboembolism. The patient was considered for treatment as an outpatient but deferred due to history of PE. She was reevaluated for treatment upon presentation to the hospital, but given the severity and rapidity of her condition, it was already too late. This is the second reported case of COVID-19 induced DNS in a patient with scleromyxedema. Given the severity, we recommend early initiation of treatment in patients with scleromyxedema and aggressive treatment for those contracting COVID-19.References[1] Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.[2] Flannery MT, Humphrey D. Deep Venous Thrombosis with Pulmonary Embolism Related to IVIg Treatment: A Case Report and Literature Review. Case Rep Med. 2015;971321.[3] Lee YH, Sahu J, O'Brien MS, D'Agati VD, Jimenez SA. Scleroderma Renal Crisis-Like Acute Renal Failure Associated With Mucopolysaccharide Accumulation in Renal Vessels in a Patient With Scleromyxedema. J Clin Rheumatol. 2011;17:318-322.[4] Hoffman-Vold AM, Distler O, Bruni C, et al. Systemic sclerosis in the time of COVID-19. Lancet Rheumatol. 2022;4:e566-575.[5] Fritz M, Tinker D, Wessel AW, et al. SARS-CoV-2: A potential trigger of dermato-neuro syndrome in a patient with scleromyxedema. JAAD Case Rep. 2021;18:99-102.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Komposisi Nutrien Susu Ibu, Imunologi dan COVID-19

Breast milk is the best food that a mother can give to a newborn baby up to the first six months of age. The purpose of this writing is to provide information on the nutrient content found in breast milk, the antibodies involved in helping reduce the infection of COVID-19 and how to breastfeed. The composition of breast milk will change according to the nutrient needs of the baby at every moment. The enzyme content in breast milk will help digestion and the nutrient content can prevent the baby from getting infections that cannot be replaced by formula milk. Antibodies or immunoglobulins are proteins produced by cells in the body's immune system to fight allergens, bacteria, and viruses that cause disease. The body has different types of antibodies such as IgA, IgG, IgM, and IgE. Newborns have immunoglobulins from the placenta. This immunoglobulin will quickly decrease immediately after the baby is born, while the newborn baby's body is not yet able to form the immunoglobulin. This condition will decrease when the baby gets breast milk. This is because breast milk contains a high level of secretory immunoglobulin A antibodies (sIgA) that will protect babies from various bacterial, viral, parasitic and fungal infections. Antibodies help the body's immune system recognize and destroy pathogens such as COVID-19. All mothers who recover from COVID-19 have antibodies to COVID-19 in their milk. These antibodies are very good at fighting diseases that attack the lining of the lungs such as COVID-19. Women with COVID-19 can breastfeed and the virus cannot be detected in breast milk. Safe breastfeeding involves following good respiratory hygiene, skin-to-skin contact for newborns, sharing a room with their baby, washing hands before and after touching the baby, and keeping all surfaces clean. Susu ibu merupakan makanan terbaik yang dapat diberikan ibu kepada bayi yang baru lahir sehingga usia enam bulan pertama. Tujuan penulisan ini memberikan informasi mengenai kandungan nutrien yang terdapat dalam susu ibu, antibodi yang terlibat membantu menurunkan jangkitan COVID-19 dan cara penyusuannya. Komposisi susu ibu akan berubah sesuai dengan keperluan nutrien bayi pada setiap saat. Kandungan enzim dalam susu ibu akan membantu pencernaan dan kandungan nutrien pula mampu mencegah bayi mendapat infeksi yang sememangnya tidak boleh diganti oleh susu formula. Antibodi atau immunoglobulin adalah protein yang dihasilkan oleh sel dalam sistem imuniti tubuh untuk melawan alergen, bakteria, serta virus penyebab penyakit. Tubuh memiliki pelbagai jenis antibodi seperti IgA, IgG, IgM, dan IgE. Bayi yang baru dilahirkan mempunyai immunoglobulin daripada plasenta. Immunoglobulin ini akan cepat menurun segera setelah bayi dilahirkan, sedangkan tubuh bayi yang baru lahir belum mampu membentuk immunoglobulin tersebut. Keadaan ini akan berkurangan apabila bayi mendapatkan susu ibu. Hal ini kerana susu ibu mengandungi kadar antibodi immunoglobulin A rembesan (sIgA) yang tinggi yang akan melindungi bayi daripada pelbagai penyakit infeksi bakteria, virus, parasit dan kulat. Antibodi membantu sistem imuniti tubuh mengenali dan menghancurkan patogen seperti COVID-19. Semua ibu yang pulih daripada COVID-19 memiliki antibodi untuk COVID-19 dalam susu mereka. Antibodi ini sangat baik dalam melawan penyakit yang menyerang lapisan paru-paru seperti COVID-19. Wanita yang menghidap COVID-19 boleh menyusukan bayi dan virus ini tidak dapat dikesan pada susu ibu. Penyusuan yang selamat harus mengikuti kebersihan pernafasan dengan baik, melakukan kontak kulit ke kulit untuk bayi yang baru lahir, berkongsi bilik dengan bayi mereka, mencuci tangan sebelum dan selepas menyentuh bayi, dan menjaga semua permukaan agar bersih.

Pharmacological Properties and Safe Use of 12 Medicinal Plant Species and Their Bioactive Compounds Affecting the Immune System

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.

MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN ACROSS 16 LATIN AMERICAN COUNTRIES: A MULTICENTER STUDY FROM THE REKAMLATINA NETWORK

BackgroundMultisystem Inflammatory Syndrome in Children (MIS-C) is one of the most feared complications following SARS-CoV2 infection in children and adolescents. Few multinational multicenter studies from Latin America have been published.ObjectivesTo describe the clinical presentation, management, and outcomes of MIS-C in Latin America.MethodsObservational, prospective and retrospective, multicenter study to gather information from 84 participating centers across 16 Latin American countries, between August January 1, 2020 and June 30, 2022.ResultsOf the 1,239 reported cases of MIS-C, 84.2% were previously healthy. The most frequent clinical manifestation in our studied population was abdominal pain (N=804, 64.9%), followed by conjunctival injection (N=784, 63.3%). The median days of fever at the time of hospital admission was 5 and a significant number of subjects required admission to an intensive care unit (N=589, 47.8%). A total of 538 (47.2%) patients had an abnormal initial echocardiogram. Most of the subjects (N= 1,096, 88.7%) were treated with intravenous immunoglobulin (IVIG), while 76.7% (N= 947) were treated with steroids, of which 10.6% (N= 100) did not receive IVIG. The death rate attributed to MIS-C was 4.88%, with a rate of 3.39% for those initially diagnosed with MIS-C and 8.85% for those whose admission diagnosis was not MIS-C (P= 0.00001).ConclusionOne of the most significant findings from our study was the death rate, especially in those not initially diagnosed with MIS-C, in whom it was higher. This highlights the importance of increasing awareness and making an earlier diagnosis of MIS-C in Latin America.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

SAFETY AND PHARMACOKINETICS OF IGPRO20 (SUBCUTANEOUS IMMUNOGLOBULIN) AND IGPRO10 (INTRAVENOUS IMMUNOGLOBULIN) IN ADULTS WITH SYSTEMIC SCLEROSIS (SSC) – RESULTS FROM A PHASE 2 TRIAL

BackgroundSystemic sclerosis (SSc) is a severe, progressive multisystem rheumatic disease with high mortality, but without approved disease-modifying treatment to stop or reverse course of disease. Intravenous immunoglobulin G (IgG) may have a positive impact on SSc based upon available literature reports. However, to date, there have been no clinical trials evaluating subcutaneous IgG (SCIG) in SSc. In particular, the impact of pathologically altered skin in SSc on local safety and pharmacokinetics (PK) of SCIG has not been explored yet.ObjectivesThe primary and secondary objectives of this trial (NCT04137224) included safety, including local infusion safety, and bioavailability of subcutaneous IgG (IgPro20) in adults with diffuse cutaneous SSc (dcSSc).MethodsThis was a randomized, open-label, crossover study. Adult subjects with dcSSc diagnosis within 5 years from first non-Raynaud's phenomenon and modified Rodnan Skin Score of 15-45 at screening were randomized 1:1 to sequence A (IgPro20, 20% normal human subcutaneous immunoglobulin followed by IgPro10, 10% normal human intravenous immunoglobulin) or sequence B (IgPro10 followed by IgPro20). Each subject was to complete two treatment periods (16 weeks each), with up to 40 weeks (including screening) study duration for an individual subject. Doses received were 0.5g/kg/week split over two sessions for IgPro20, and 2g/kg/4 weeks split over 2-5 days for IgPro10. The primary endpoint was safety of IgPro20, described as treatment-emergent adverse events (TEAEs) and changes in clinical observations.Results27 subjects were randomized, with 13 subjects to sequence A and 14 subjects to sequence B. In total, 25 subjects completed the study. Of 27 treated subjects, 107 TEAEs occurred in 22 subjects (81.5%) over the 36-week study period, the majority of which were mild or moderate. The most common TEAEs (>10% of subjects) by preferred term (PT) were headache (12 events occurring in 6 subjects [22.2%]), COVID-19 (3 events occurring in 3 subjects [11.1%]), diarrhoea (3 events occurring in 3 subjects [11.1%]), and vomiting (3 events occurring in 3 subjects [11.1%]).A total of 10 serious AEs (SAEs) were reported in 6 subjects (Viral infection, Chronic gastritis, Vomiting, Dehydration, Upper gastrointestinal haemorrhage, Chest pain, Myocardial infarction, Myocardial ischemia, Breast cancer, Interstitial lung disease). Among these, one subject experienced 2 SAEs (myocardial ischemia & myocardial infarction) and was discontinued from study treatment. None of the SAEs were considered related to study treatment by the investigator, and no deaths were reported.For IgPro20, 14 infusion site reactions (ISRs) occurred in 5 subjects (19.2%), all were mild or moderate in severity. The most common ISRs were infusion site pain and infusion site swelling (3 events in 2 subjects each, 7.7%). In total, 686 IgPro20 infusions were performed, resulting in an overall ISR rate per infusion of 0.02, ie 2 ISRs per 100 infusions. No ISRs were reported for IgPro10.No clinically relevant trends in vital signs, body weight, clinical laboratory tests, electrocardiograms, or pulmonary function tests were observed.PK profiles and bioavailability in dcSSc subjects were similar to those observed in other approved indications such as Primary Immunodeficiency. Population relative bioavailability of IgPro20, based on dose-normalized, baseline-corrected AUC0-tau was 0.761 (90% CI: 0.7033, 0.8232), ie 76.1% compared to IgPro10 (intravenous IgG).ConclusionThe overall safety profiles of IgPro20 and IgPro10 in subjects with dcSSc were consistent with that in approved indications such as CIDP, including a relatively low ISR rate for IgPro20. PK profiles and bioavailability were also similar to other indications. This study indicates that subcutaneous administration of IgPro20 has acceptable safety, bioavailability and PK profiles in patients with dcSSc. AcknowledgementsEditorial assistance was provided by Meridian HealthComms Ltd., funded by CSL Behring.Disclosure of InterestsChristopher P Denton Speakers bureau: Ja ssen, Boehringer Ingelheim, Consultant of: GSK, CSL Behring, Boehringer Ingelheim, Merck, Roche, Sanofi, Grant/research support from: GSK, CSL Behring, Inventiva, Horizon, Otylia Kowal-Bielecka Speakers bureau: Abbvie, Janssen-Cilag, Boehringer Ingelheim, Medac, MSD, Novartis, Pfizer, Sandoz, Consultant of: Boehringer Ingelheim and Novartis, Grant/research support from: Received congress support from Abbvie, Boehringer Ingelheim, and Medac, Susanna Proudman Speakers bureau: Boehringer Ingelheim, Grant/research support from: Janssen, Marzena Olesińska Consultant of: AstraZeneca, Margitta Worm Consultant of: Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc, Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH &Co.KG, ALK-Abelló Arzneimittel GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH, Lilly Deutschland GmbH and GlaxoSmithKline GmbH & Co. KG., Nicoletta Del Papa Speakers bureau: Janssen Cilag, Boehringer Ingelheim., Marco Matucci-Cerinic Speakers bureau: Biogen, Sandoz, Boehringer Ingelheim, Consultant of: CSL Behring, Boehringer Ingelheim, Grant/research support from: MSD, Chemomab, Jana Radewonuk Shareholder of: CSL Behring, Employee of: CSL Behring, Jeanine Jochems Shareholder of: CSL Behring, Employee of: CSL Behring, Amgad Shebl Shareholder of: CSL Behring, Employee of: CSL Behring, Anna Krupa Shareholder of: CSL Behring, Employee of: CSL Behring, Jutta Hofmann Shareholder of: CSL Behring, Employee of: CSL Behring, Maria Gasior Shareholder of: CSL Behring, Employee of: CSL Behring.

Seroprevalence of anti-SARS-CoV-2 antibodies in high-risk occupational and low-risk groups in southwestern Iran

Background: Monitoring the spread of SARS-CoV-2 has been considered by the World Health Organization (WHO). We examined the prevalence of anti-SARS-CoV-2 immunoglobulin antibodies in southwestern Iran in spring 2020. The circulation of SARS-CoV-2 is high in the general population, especially among health care workers (HCWs) who are in close contact with patients. Objectives: The aim of this study was to determine the prevalence of anti-SARS-CoV-2 antigen in high-risk occupational and low-risk groups to investigate risk factors for serum positivity in Shiraz, southwestern Iran. Methods: A cross-sectional survey was performed on 366 participants (204 from high-risk and 162 from low-risk subjects). IgG and IgM antibodies were detected using Pishtaz Teb COVID-19 ELISA Kits to evaluate SARS-CoV-2-antigen in serum samples. After enzyme-linked immunosorbent assay (ELISA), serum prevalence, as well as IgG/IgM positive factors, was determined using logistic regression. Results: From July to September 2020 (a few months after reporting the first case of COVID-19 cases in Iran), out of 366 survived people, 72 (40.9%) were IgG positive, and 50 (27.5%) were IgM positive. The frequency of positive serology for IgG and IgM antibodies in individuals aged < 30 years was higher in the low-risk group than in the high-risk group. Multivariate logistic regression showed that headache (OR 0.312 [95% CI: 0.136 - 0.717]) and cough (OR 0.427 [95% CI: 0.182 - 1.004]) factors were associated with IgG or IgM positive serology. Conclusions: Between July and September 2020, the prevalence of anti-SARS-CoV-2 antigen was high in Shiraz. The prevalence of SARS-CoV-2 IgG/IgM antibodies in the high-risk group and their family as low risk was shown to increase viral infection due to close contact with COVID 19 patients than in the general population. Several factors were found to be related to the prevalence of anti-SARS-CoV-2 antigen that needs to be considered by policymakers to determine what to do about the SARS-CoV-2 pandemic.

Myocardial infarction at night . . . and other stories

Body weight and fat content are known to influence the timing of puberty but the association remained after adjustment for pre-pubertal body mass index. [...]a large retrospective study from the US finds that patients who underwent plasma exchange spent a week longer in hospital and were two to three times more likely to die than those who received immunoglobulin (Muscle Nerve doi:10.1002/mus.26831). A case study in NEJM Catalyst identifies early testing (particularly of people arriving from places where the disease was prevalent), rapid mobilisation of microbiological laboratories, and a coherent and consistent national strategy as crucial interventions.

A Randomized Controlled Study Assessing Convalescent Immunoglobulins versus Convalescent Plasma for Hospitalized COVID-19 Patients.

BACKGROUND: It is unknown whether convalescent immunoglobulins (cIgG) are better than convalescent plasma (CP) for COVID-19 patients. METHODS: In this randomized trial we assigned high risk COVID-19 with ≤10 days of symptoms, to receive cIgG or CP. The primary endpoint was improvement on day 14 according to the WHO scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28 and treatment response in unvaccinated and vaccinated patients. RESULTS: 319 patients were included; 166 received cIgG, and 153 CP. Median age was 64-66 years. 112 patients (67.5%) in the cIgG and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95%CI -10.1-10.4, p=0.026), failing to reach non-inferiority. More patients receiving cIgG improved by day 28 [136 patients (81.9%) and 108 patients (70.6%), respectively, 95% CI 1.9-20.7, p<0.001, for superiority p=0.018)]. 17 patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (p=0.136). 16 (9.6%) and 23 (15%) patients respectively died (p=0.172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs. 66.1%, p<0.024) and survival was better in the cIgG group (89.9% vs. 77.4% p=0.066). CONCLUSIONS: cIgG failed to reach the primary non-inferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgG were better. In the face of new variants, cIgG is a viable option for treating COVID-19. TRIAL REGISTRATION NUMBER: My Trials MOH_2021-01-14_009667.

Modeling of ACE2 and antibodies bound to SARS-CoV-2 provides insights into infectivity and immune evasion.

Given the COVID-19 pandemic, there is interest in understanding ligand-receptor features and targeted antibody-binding attributes against emerging SARS-CoV-2 variants. Here, we developed a large-scale structure-based pipeline for analysis of protein-protein interactions regulating SARS-CoV-2 immune evasion. First, we generated computed structural models of the Spike protein of 3 SARS-CoV-2 variants (B.1.1.529, BA.2.12.1, and BA.5) bound either to a native receptor (ACE2) or to a large panel of targeted ligands (n = 282), which included neutralizing or therapeutic monoclonal antibodies. Moreover, by using the Barnes classification, we noted an overall loss of interfacial interactions (with gain of new interactions in certain cases) at the receptor-binding domain (RBD) mediated by substituted residues for neutralizing complexes in classes 1 and 2, whereas less destabilization was observed for classes 3 and 4. Finally, an experimental validation of predicted weakened therapeutic antibody binding was performed in a cell-based assay. Compared with the original Omicron variant (B.1.1.529), derivative variants featured progressive destabilization of antibody-RBD interfaces mediated by a larger set of substituted residues, thereby providing a molecular basis for immune evasion. This approach and findings provide a framework for rapidly and efficiently generating structural models for SARS-CoV-2 variants bound to ligands of mechanistic and therapeutic value.

[Dermato-neuro syndrome-an acute and life-threatening complication of scleromyxedema Arndt-Gottron]. / Dermato-neurologisches Syndrom ­ eine akute und lebensbedrohliche Komplikation des Skleromyxödems Arndt-Gottron.

Scleromyxedema Arndt-Gottron is the systemic variant of lichen myxedematosus in which mucin accumulation occurs in the dermis. The disease is usually chronically progressive and extracutaneous manifestations or complications are possible. The pathogenesis is unknown and the disease is usually associated with monoclonal gammopathy. High-dose intravenous immunoglobulins (IVIg) are considered to be an effective therapy. We report the case of a patient who developed dermato-neuro syndrome following an interruption of IVIg treatment and a SARS-CoV­2 infection. A similar episode occurred 2 years earlier in association with an influenza A infection. Dermato-neuro syndrome is a potentially lethal neurological complication which is characterized by fever, delirium, convulsions, and coma.

A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection.

While the development of different vaccines slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections has continued to fuel the COVID-19 pandemic. To secure at least partial protection in the majority of the population through 1 dose of a COVID-19 vaccine, delayed administration of boosters has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may induce breakthrough infections due to intermittent lapses in protection. Optimizing vaccine dosing schedules to ensure prolonged continuity in protection could thus help control the pandemic. We developed a mechanistic model of immune response to vaccines as an in silico tool for dosing schedule optimization. The model was calibrated with clinical data sets of acquired immunity to COVID-19 mRNA vaccines in healthy and immunocompromised participants and showed robust validation by accurately predicting neutralizing antibody kinetics in response to multiple doses of COVID-19 mRNA vaccines. Importantly, by estimating population vulnerability to breakthrough infections, we predicted tailored vaccination dosing schedules to minimize breakthrough infections, especially for immunocompromised individuals. We identified that the optimal vaccination schedules vary from CDC-recommended dosing, suggesting that the model is a valuable tool to optimize vaccine efficacy outcomes during future outbreaks.

Qualitative monitoring of SARS-CoV-2 mRNA vaccination in humans using droplet microfluidics.

SARS-CoV-2 mRNA vaccination generates protective B cell responses targeting the SARS-CoV-2 spike glycoprotein. Whereas anti-spike memory B cell responses are long lasting, the anti-spike humoral antibody response progressively wanes, making booster vaccinations necessary for maintaining protective immunity. Here, we qualitatively investigated the plasmablast responses by measuring from single cells within hours of sampling the affinity of their secreted antibody for the SARS-CoV-2 spike receptor binding domain (RBD) in cohorts of BNT162b2-vaccinated naive and COVID-19-recovered individuals. Using a droplet microfluidic and imaging approach, we analyzed more than 4,000 single IgG-secreting cells, revealing high interindividual variability in affinity for RBD, with variations over 4 logs. High-affinity plasmablasts were induced by BNT162b2 vaccination against Hu-1 and Omicron RBD but disappeared quickly thereafter, whereas low-affinity plasmablasts represented more than 65% of the plasmablast response at all time points. Our droplet-based method thus proves efficient at fast and qualitative immune monitoring and should be helpful for optimization of vaccination protocols.

Guest editorial: the relationship between nutrition and COVID-19

[...]the journal Nutrition and Food Science has published this special issue exploring the intersection of nutrition and COVID-19 [1], [2], [3], [4], [5], [6], [7], [8]. [...]a study explored the factors related to sedentary lifestyle in a Brazilian sample during the COVID-19 initial quarantine [8]. [...]the papers published in the special issue "The relationship between nutrition and COVID-19” underlined the importance of nutrition in mitigating the mental and health-related impacts of the COVID-19 pandemic.

Diagnostic and therapeutic considerations in idiopathic systemic capillary leak syndrome: a case report

Background: Systemic capillary leak syndrome (SCLS) is a rare disorder which leads to severe shock. Typically, endothelial dysfunction leads to massive leakage of fluids from the intravascular compartment to the interstitial space, causing hemoconcentration, hypoalbuminemia, hypotension and potential organ failure. The syndrome may be idiopathic or triggered by disease, such as viral infections. The syndrome is often unrecognized and besides resuscitation, no effective treatments are known. Case Description: Here we describe a 46-year-old female with recurrent episodes of shock due to unrecognized SCLS, with the second episode being triggered by an asymptomatic COVID-19 infection. She was, besides resuscitation, treated with high dose vasopressors and intravenous immunoglobulins (IVIG). The case is complicated by compartment syndrome with infected muscle necrosis and eventually amputation of both lower legs. Moreover, the patient still has a chronic kidney insufficiency. In this case report we will discuss pittfalls and potential therapeutic options in SCLS treatment. Conclusions: Vasopressor use may aggravate ischemic complications in a hypovolemic condition and its use should therefore be discouraged in these patients. Cardiac output monitoring should be considered early. The use of IVIG might be beneficial in the acute phase as well as in preventing future episodes of shock. Whether the use of bevacizumab is also of value is yet unclear. © Journal of Emergency and Critical Care Medicine. All rights reserved.

FEATURES OF POST-VACCINATION HUMORAL IMMUNE RESPONSE IN THE PERSONS WHO UNDERWENT COVID-19 OF VARIOUS SEVERITY.

The studies on humoral immune response in the individuals who have undergone COVID-19 and vaccinated with anti-COVID vaccines allows us to assess the development of "hybrid" immunity, which contributes to understanding the mechanisms of its formation from the effector phase to the step of immunological memory. We assessed the relative and absolute contents of B cell populations and subpopulations, development of humoral immunity in the patients who suffered with COVID-19 of varying severity being thereafter vaccinated with "KoviVak" and "Sputnik V". The study involved volunteers (age 47.3+/-14.5 years) who beared COVID-19 asymptomatically (n = 32), at moderate severity (n = 21), or had severe form of the disease (n = 12), then being vaccinated with "KoviVak" and "Sputnik V" 6-9 months after their recovery. The groups of vaccinated persons consisted of those who beared severe disease being vaccinated with "KoviVak" (n = 6) or "Sputnik V" (n = 6);moderate cases, vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 11);asymptomatic cases vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 22). We have determined relative and absolute numbers of B lymphocytes (CD45+CD19+), B1 lymphocytes (CD45+CD5+CD19-CD27-), B2 lymphocytes (CD45+CD19+CD5-CD27-), total population of memory B cells (CD45+CD19+CD5-CD27+), non-switched (CD45+CD19+IgD+CD27+), and switched (CD45+CD19+IgD-CD27+) memory B cells;mature naive B lymphocytes (CD45+CD19+CD27-IgD+), plasmoblasts (CD45+CD19+ CD38+++IgD-CD27+), as well as presence of IgG to S(RBD)-SARS-CoV-2 protein. We have found that the humoral immunity among survivors of COVID-19 of varying severity is expressed for up to nine months. The largest number of volunteers who raised antibodies to SARS-CoV-2 S-protein was registered in the group of seriously ill patients. As soon as 1 month after "Sputnik V" vaccination and until the end of the observation, all the examined subjects in this group became seropositive. 4-5 months after injection of this vaccine, specific immunoglobulins were present in all patients who had asymptomatic or average-severity infection. All volunteers who received "KoviVak" had antibodies to the COVID-19 viral S protein from the beginning to the end of the study. Vaccination, especially with "KoviVak", contributed to the highest increase, both in relative and absolute numbers of memory B lymphocytes in asymptomatic patients. Less pronounced changes in the content of B lymphocytes in COVID-19 patients who had severe and moderate clinical course may be associated with higher levels of these cells prior to injection of the vaccines. A positive correlation was found between the number of memory B cells and presence of immunoglobulins to the S protein SARS-CoV-2 in all examined patients.Copyright © 2023 Russian Association of Allergologists and Clinical Immunologists, St. Petersburg Regional Branch (SPb RAACI). All rights reserved.

The Study of the Immune Status in Post-Covid Syndrome by Flow Cytometry

A novel coronavirus infection was described in 2019 in Wuhan, China. From the first months of the spread of the infection around the world, evidence began to appear that patients after recovery had various symptoms. Duration, intensity, and variability of symptoms vary among patients and are often not associated with the severity of the most acute illness. Recently the concept of post-COVID syndrome (postCOVID or long-COVID in the English-language literature) has acquired increasingly clear diagnostic criteria. Persistent symptoms and / or the appearance of delayed complications after 4 weeks or more from the onset of symptoms of an acute illness are commonly called post-COVID syndrome. The wide range of symptoms that can occur in patients with post-COVID syndrome is now a major health concern worldwide. A proper clinical evaluation will help determine the etiology and build a treatment plan. Longer studies aimed at identifying the effects of COVID-19, possible risk factors for their development, a detailed study of the pathogenetic mechanisms of SARS-CoV-2, and the development of treatment and rehabilitation methods to improve the mental and physical health of surviving patients are relevant elements of study for the foreseeable future. T-lymphocytes are a poorly studied population of T lymphocytes. These cells are more often localized in the mucous membranes of the body which have the properties of innate and acquired immunity. The main biological functions are cytolysis, immunoregulation which indicates an important immunocompetent role of this type of cell population in severe infectious diseases. This article provides information on the fraction of T-lymphocytes during the formation of adaptive immunity in patients with post-COVID syndrome.

Heart Rate Variability during Virtual Reality Activity in Individuals after Hospitalization for COVID-19: A Cross-Sectional Control Study

(1) Background: COVID-19 can lead to many complications, including cardiorespiratory complications and dysautonomia. This can be assessed by heart rate variability (HRV), which reflects the autonomic nervous system. There are different possibilities for physical rehabilitation after COVID, one of which that has been growing fast is the use of Virtual reality (VR) for rehabilitation. VR may represent an innovative and effective tool to minimize deficits that could lead to permanent disabilities in patients of outpatient rehabilitation services. The aim of this protocol is to establish whether practicing a task using a VR game with body movements influences physiological variables, such as heart rate, HRV, oxygen saturation, blood pressure, and perceptual variables during exercise in individuals post-hospitalization for COVID. (2) Methods: This cross-sectional study evaluated individuals divided into two groups, a post-hospitalization for COVID-19 group and a healthy control group. Subjects underwent one session of a VR task, and physiological variables, including HRV, were measured during rest, VR activity, and recovery. In addition, considering the influence of age in HRV and the impact of COVID-19, we divided participants by age. (3) Results: In all HRV indices and in both groups, an increase in sympathetic and a decrease in parasympathetic activity were found during VR. Additionally, the older post-COVID-19 group performed worse in non-linear indices, peripheral oxygen saturation, and rating of perceived exertion (RPE). (4) Conclusions: The VR game positively affects physiological variables and can therefore be utilized as a secure physical activity in both healthy individuals and individuals after hospitalization for COVID-19. COVID-19 affects the autonomic nervous system of older patients' post-hospitalization, which may be partly due to a higher BMI and the reduced exercise capacity in this population, affecting their ability to perform exercise activities. Other important observations were the higher RPE in COVID-19 patients during and after exercise, which may reflect altered physiological and autonomic responses. Taken together with the high reporting of fatigue after COVID-19, this is an important finding, and considering that RPE is usually lower during VR exercise compared to non-VR strengthens the potential for the use of VR in COVID-19 patients.