Immune and coagulation profiles in 3 adults with multisystem inflammatory syndrome.

INTRODUCTION: There is a paucity of information on the cytokine, complement, endothelial activation, and coagulation profiles of multisystem inflammatory syndrome in adults (MIS-A), a rare but serious complication following recovery from SARS-CoV-2 infection. We aim to examine the immune biomarker and coagulation profiles in association with the clinical presentation and course of MIS-A. METHOD: The clinical features of MIS-A patients admitted to our tertiary hospital were documented. Their levels of interleukin (IL)-1ß, IL-6, IL-10, IL-17, IL-18, interferon-α (IFN-α), IFN-γ, interferon gamma-induced protein 10 (IP-10), tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, complement activation product (complement 5a [C5a]), and endothelial biomarker intercellular adhesion molecule-1 (ICAM-1) levels were assayed. The haemostatic profile was assessed with standard coagulation testing and thromboelastography. RESULTS: Three male patients were diagnosed with MIS-A at our centre from January to June 2022 with a median age of 55 years. All had tested positive for SARS-CoV-2 12-62 days prior to MIS-A presentation, with gastrointestinal and cardiovascular systems as the most commonly involved. Levels of IL-6, IL-10, IL-18, IP-10 and MCP-1 were raised whereas IL-1ß, IFN-α, IFN-γ, IL-17 and TNF-α remained normal. Markedly elevated levels of C-reactive protein (CRP), ferritin and ICAM-1 were present in all. C5a was elevated in 2 patients. A hypercoagulable state was demonstrated by raised levels of D-dimer, factor VIII, von Willebrand factor antigen, and ristocetin cofactor with corresponding raised parameters in thromboelastography in the 2 patients who had their coagulation profile assessed. CONCLUSION: MIS-A patients demonstrate activation of pro-inflammatory cytokines, endotheliopathy, complement hyperactivation and hypercoagulability.

Autoimmune Rheumatic Disease Flares with Myocarditis Following COVID-19 mRNA Vaccination: A Case-Based Review.

Since the introduction of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccines, there have been multiple reports of post-vaccination myocarditis (mainly affecting young healthy males). We report on four patients with active autoimmune rheumatic diseases (ARDs) and probable or confirmed myocarditis following COVID-19 mRNA vaccination managed at a tertiary hospital in Singapore; we reviewed the literature on post-COVID-19 mRNA vaccination-related myocarditis and ARD flares. Three patients had existing ARD flares (two had systemic lupus erythematosus (SLE), one had eosinophilic granulomatosis polyangiitis (EGPA)), and one had new-onset EGPA. All patients recovered well after receiving immunosuppressants comprising high-dose glucocorticoids, cyclophosphamide, and rituximab. Thus far, only one case of active SLE with myocarditis has been reported post-COVID-19 mRNA vaccination in the literature. In contrast to isolated post-COVID-19 mRNA vaccination myocarditis, our older-aged patients had myocarditis associated with ARD flares post-COVID-19 vaccination (that occurred after one dose of an mRNA vaccine), associated with other features of ARD flares, and required increased immunosuppression to achieve myocarditis resolution. This case series serves to highlight the differences in clinical and therapeutic aspects in ARD patients, heighten the vigilance of rheumatologists for this development, and encourage the adoption of risk reduction strategies in this vulnerable population.

Evaluation of Patients with Vaccine Allergies Prior to mRNA-Based COVID-19 Vaccination.

During the initial rollout of coronavirus disease 2019 (COVID-19) vaccination in Singapore, the Ministry of Health (MOH) issued a recommendation that patients with a history of any previous vaccine allergy be referred to an allergist for further review of their suitability to proceed with mRNA-based COVID-19 vaccines. Patients fulfilling the above criterion were divided into three groups: immediate reaction (Group A), delayed reaction (Group B) and no/irrelevant reaction (Group C). They were subjected to either a skin prick test (SPT) and intradermal test (IDT) with polyethylene glycol (PEG) or polysorbate-containing products; direct injection with the Pfizer BNT162b2 vaccine in the allergy clinic; or injection at community vaccination centres, respectively. Groups A and B were also invited to complete a questionnaire survey on post-vaccination reactions, and blood sampling pre-vaccination and 1 h after the first dose of the BNT162b2 vaccine to measure immunoglobulin (Ig) G, IgM and IgE antibodies to the Pfizer BNT162b2 vaccine via ELISA assays immobilised with the BNT162b2 vaccine, as well as levels of allergic cytokines interleukin (IL)-4 and IL-33, complement C5a and the endothelial activation marker intercellular adhesion molecule-1 (ICAM-1). Groups A and B comprised 62 (20.5%) patients each. In Group A, two subjects (3.2%) with equivocal IDT results tolerated both doses of the BNT162b2 vaccine without major allergic reactions. The remaining 60 (96.8%) in Group A and 62 (100%) in Group B completed both doses of BNT162b2 vaccination without major adverse reactions. Among the 99 who completed the questionnaire survey, 13 (13%) patients reported mild allergic reactions after the first dose of the vaccine. Immunoglobulin (Ig) G and M antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine were detected in 67 subjects prior to vaccination. The presence of anti-Pfizer BNT162b2 IgG and IgM prior to vaccination did not result in major allergic reactions nor increases in Th2-related cytokines (IL-4, IL-33), complement activation products (C5a) or endothelial activation (ICAM-1). The majority of those with suspected reactions to non-COVID-19 polysorbate-containing vaccines tolerated the BNT162b2 vaccine. Excipient skin tests for PEG and polysorbate prior to vaccination are unnecessary.

Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long-term outcomes in COVID-19 patients.

Sustained hypercoagulability and endotheliopathy are present in convalescent COVID-19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID-19 patients were evaluated up to 16 months after recovery from COVID-19. These values were compared with a control group of healthy volunteers (n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID-19 acute ischaemic limb. Elevated D-dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D-dimer 0.34 FEU µg/mL (IQR 0.28, 0.46) (p < .001) and Factor VIII 150% (IQR 171, 203) (p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) (p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) (p = 0.01) and delayed lag time 2.4 min (1.42-2.97) (p = 0.0002) versus controls. Raised vWF:Ag and ICAM-1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) (p = 0.02) and ICAM-1 54.1 ng/mL (IQR 43.8, 64.1) (p = .004) than controls. IL-6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL-6 of 1.5 pg/mL (IQR 0.6, 3.0) (p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID-19 severity and COVID-19 vaccination preceding SARS-CoV-2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID-19.

Pseudo-Anaphylactic Reactions to Pfizer BNT162b2 Vaccine: Report of 3 Cases of Anaphylaxis Post Pfizer BNT162b2 Vaccination.

Anaphylactic reactions were observed after Singapore's national coronavirus disease 2019 (COVID-19) vaccination programme started in December 2020. We report the clinical and laboratory features of three patients in our institution who developed anaphylactic reactions after receiving the Pifzer BNT162b2 vaccine. IgM and IgG antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine, were detected in all subjects. Similarly, mild to high elevated levels of anti-polyethylene glycol (PEG) IgG (1035-19709 U/mL, vs. vaccine-naive < 265 U/mL, vaccine-tolerant < 785 U/mL) and IgM (1682-5310 U/mL, vs. vaccine-naive < 1011 U/mL, vaccine-tolerant < 1007 U/mL) were detected in two out of three patients via commercial ELISA. High levels of serum anaphylatoxin C3a (79.0 ± 6.3 µg/mL, mean ± SD, vs. normal < 10 µg/mL) were observed in all three patients during the acute phase of the reaction, while tryptase levels, a marker of mast cell activation, were not elevated. Finally, one patient with the highest levels of anti-PEG IgG, IgM, and anti-Pfizer BNT162b2 IgG and IgM exhibited an enhanced Th2 cytokine serum profile during an acute reaction, with high levels of IL-4 (45.7 pg/mL, vs. vaccine-naive/tolerant < 2.30 pg/mL), IL-33 (86.4 pg/mL, vs. vaccine-naive/tolerant < 5.51 pg/mL) and IL-10 (22.9 pg/mL, vs. vaccine-naive/tolerant < 12.49 pg/mL) diminishing over time following corticosteroid treatment. Taken together, we propose these cases of anaphylaxis described are driven by a complement activation-related pseudoallergy (CAPRA), rather than classical IgE-mediated mechanisms.

The Implementation of AI and AI-Empowered Imaging System to Fight Against COVID-19—A Review Implementation of Machine Learning Techniques for the Analysis of Transmission Dynamics of COVID-19 Data-Driven Decision Making in IoT Healthcare Systems—COVID-19: A Case Study Touch and Voice-Assisted Multilingual Communication Prototype for ICU Patients Specific to COVID’19 Cerebral Venous Thrombosis post BNT162b2 mRNA SARS-CoV-2 vaccination: A Black Swan Event

Summary COVID-19 has already affected the world with this deadly virus, resulting in over 3.5 lakh deaths. The behavior of this virus is extraordinarily peculiar and mutates frequently. So, the scientific community faces the problems to analyze and forecast the virus's growth and transmission capability. The combined effort of powerful Artificial intelligence and Image processing techniques to predict the initial pattern of COVID-19 disease identifies the most affected areas in each country through social networking information and predicts drug-protein interactions for making new drugs vaccines. However, AI-empowered X-Ray and computed tomography image acquisition and segmentation techniques help us identify and diagnose the COVID-19 affected patients with minimal contact. In this chapter, our primary motivation is to sum up the essential roles of some AI-driven techniques (Machine learning, Deep learning, etc.) and AI-empowered imaging techniques to analyze, predict, and diagnose against COVID-19 disease. An essential set of open challenges and future research issues on AI-empowered procedures for handling COVID-19 are also discussed in this chapter. Summary This paper mainly deals with the design of Machine Learning model for the analysis of transmission dynamics of Covid 19. The entire globe is affected because of Corona virus. Ventilator dependent, Severe Acute respiratory and quarantine care ICU patients frequently face difficulties for their most basic human interactions, namely communication due to either respiratory illness, language problem or intubated. ICU patients have serious implications with respect to physical and psychological due to non communication problems. Researchers have developed different types of services like Speech language Pathologist so that Augmentative and alternative communication assistance can be given to all health professionals and caretakers. A probabilistic model is designed to analyse the new cases and death cases. Using machine learning approach Regression model is designed and future predications are displayed. The adequacy of the model is discussed along with the residuals of new cased and death cases. PCF and APCAF are obtained. This paper mainly deals with a probabilistic model to analyse and predict the new cases and deaths of covid 19. A new transformation of analyzing stationarity is carried out and based on this forecasting is executed. Summary This research express an impression of automated decision-making techniques that have been suggested for scrutiny of data from IoT based healthcare systems. IoT data analytics plays a vital role in this modern era since data from connected devices reveal meaningful results with better insights for the future. The chapter involves the design of a decision-making system that collects data from IoT based healthcare systems, preprocess and analyzes data, and generates detailed information reports for better diagnosis. Data preprocessing methods such as data cleaning, munging, normalization, reduction, and removing noisy data are applied. The blend of IoT data with analytics technique results to be beneficial in healthcare systems. The collected IoT information like pulse rate, temperature, oxygen level and heart rate from connected devices can be used to analyze the need and severity in the preliminary stage itself using appropriate machine learning techniques. Multi Criteria Decision Making (MCDM) techniques such as SMART, WPM, and TOPSIS are also applied for conclusion production procedure to generate detailed informative diagnostic reports. Being healthcare data, the overall objective is to aid business organizations with better decision making processes through data analytics thereby deploying the right IoT strategy. The result of the next-generation expert systems can utilize the results for further analysis in diagnosis and treatment. Summary The proposed work deals with the design and development of touch and native voice-assisted prototype to enable the intuitive communication & interaction between health professionals and patients who are affected with Severe Acute Respiratory Infection (SARI), Ventilator-dependent and admitted in Quarantine care. It also ensures the development of the multilingual capability to communicate effectively in most speaking ten Indian languages, so that the patients will be relieved from pains etc., as their queries are being addressed by health professionals. In this prototype, touch based gesture patterns can be effectively used as an interactive module and helps the doctors to monitor and answer to the queries of ICU patients regularly by updating it to the caretakers such that the patients are at ease to express their emotions or pains. The proposed prototype will be made available and accessible in an open software repository. As per the existing methods patients express their needs through non-verbal communication methods and they could be missed out or misinterpreted resulting in symptoms that are poorly understood and the clinicians overestimate their ability to understand their communication feelings. These situations are eradicated by employing the use of ?Touch Voice of SARI? Application. Hence this can be considered as an assistive communication tool which replaces the nonverbal communication to a meaningful communication for ventilator patients and healthcare professionals.