Characterization of Adaptive Immune Responses to SARS-CoV-2 Updated Bivalent Booster

Bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and Omicron BA.4/5 spike proteins are successful in preventing infection from the original strain and Omicron variants, but the quality of adaptive immune responses is still not well documented. This study aims at characterizing adaptive immune responses to the bivalent booster vaccination in 46 healthy participants. Plasma and PBMC were collected prior and three weeks after bivalent booster. We measured anti-N, anti-S, and RBD IgM, IgA, IgG plasma titers against original, Omicron BA.1, and BA.5 variants (pending) as well as total anti-S IgG titers and surrogate Virus Neutralization capacity against the Alpha, Delta, and BA.1 variant. With spectral flow-cytometry we identified peripheral blood B-cells specific for the RBD of the S-protein of the original and BA.1 variants. T-cell-specific responses were assessed by cytokine release assay after stimulation with SARS-CoV-2 peptides from the original, BA.1, BA.4, and BA.5 variants (pending). Finally, we performed TRB and IGH repertoire studies on sorted CD4+, CD8+, CD19+ lymphocytes, to study breadth of SARS-CoV-2 specific clonotypes (pending). 27/46 participants were analyzed;9 had SARS-CoV-2 infection (COVID+), while 18 are infection naive (COVID-). In both groups, median time since last dose of SARS-CoV-2 vaccine (3rd or 4th) was 11 months. All subjects were positive for anti-S IgG prior to bivalent booster. The COVID + group displayed anti-S IgG pre-booster levels and neutralization against BA.1 higher than the COVID- group. Significant increase post-boost of total anti-S IgG and BA.1 neutralizing activity was detected in the COVID- but not in the COVID+ group;however, no difference in neutralization activity post-boost was detected between the two groups. Furthermore, the COVIDgroup showed significant increase in the frequency of CD19+ and CD27+ switched memory B-cells specific for BA.1 RBD in post-boost compared to pre-boost samples. However, post-boost frequencies of the same B-cells were higher in the COVID+ compared to the COVID- group. These preliminary findings confirm that among individual immunized with the original COVID-19 mRNAvaccine, prior COVID infection provides increased protection against SARS-CoV-2 variants. They also demonstrate that booster immunization with the bivalent vaccine induces robust adaptive immune responses against Omicron variant.[Formula presented][Formula presented]Copyright © 2023 Elsevier Inc.

Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Assessment of the Impact of the Egyvir on Rats Experimental Animals, a Preclinical Study for Sars-Cov-2 Treatment

Background: The SARS-COV-2 is a worldwide pandemic problem. We developed a herbal extract with potent in-vitro virucidal, anti-inflammatory and immunomodulatory effects called EGIVIR. Our aim is to assess the bioavailability and cytotoxicity of EGYVIR on different organs and biological systems in Sprague Dawley rats as a model of experimental animals.Methods: 128 rats were divided into 16 groups (8 rats each), where Egyvir was assessed in oral doses of 20, 30, and 40 mg/kg body weight, and by inhalation in 0.2, 0.3, and 0.4 mg/kg body weight, four times/day, compared to the control groups.Results: The Egyvir had no significant effect on the blood pressure, pulse, motor activity, histological, hematological, and coagulation profiles. Also, the blood levels of triglycerides, cholesterol, blood glucose, lactate dehydrogenase (LDH), and creatine phosphor kinase (CPK) were not significantly affected. Egyvir had no harmful effect on the kidney and liver functions, blood electrolytes levels and urinary levels of sodium, potassium, and chloride. There was no significant effect on the serum levels of interleukin-113 (IL -113), IL-2, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). Additionally, there was no significant change in the levels of Superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and malonaldehyde (MDA) in comparison to the control groups (P<0.05).Conclusion: Egyvir is considered a safe antiviral natural drug. It could be used for the treatment of SARS-COV-2 without any adverse effects when used with the recommended doses. However, these data are a preliminary step for validation in a clinical setting.

Hand Surgical Simulation in the Pandemic Era: A Systematic Review

Introduction: The COVID-19 pandemic and duty hour restrictions have illuminated a role for surgical simulation in trainees that permits meaningful technical experience outside the operating room. There is a need for the implementation of surgical simulation infrastructure adjacent to clinical training with practical considerations for complexity and cost. This systematic review analyzes surgical simulations that train hand surgical techniques and procedures with subjective or objective competency assessment. Method(s): A systematic review was conducted according to PRISMA- P guidelines using the PubMed, Medline, Scopus, Embase, Web of Science, and Cochrane databases. Selected search terms included procedures relevant to the field of hand surgery and various types of simulation training. Data, including skills and techniques taught and assessed, model type, equipment, cost, and emphasis placed in training for each article, were extracted. Result(s): Of 2,519 articles, 40 met inclusion criteria. Models were described as: synthetic benchtop/3D-printed (40.0%), animal (22.5%), cadaveric (20.0%), augmented and virtual reality (AR/ VR;12.5%), and other computer simulation (12.5%). Three models incorporated both a physical benchtop component and an AR/ VR component. The procedures most represented included tendon repair (30.0%), fracture fixation (27.5%), wrist arthroscopy (15.0%), and carpal tunnel release (15.0%). Sixty-five percent of articles emphasized the importance of surgical simulation in a surgeon's training. Conclusion(s): A diversity of surgical simulation models exist for the practice of various aspects of hand surgery. The existing literature demonstrates their utility for increasing expertise with surgical techniques and procedures in a low-risk setting.

Statistical Literacy—Misuse of Statistics and Its Consequences

Although statistical literacy has become a key competence in today's data-driven society, it is usually not a part of statistics education. To address this issue, we propose an innovative concept for a conference-like seminar on the topic of statistical literacy. This seminar draws attention to the relevance and importance of statistical literacy, and moreover, students are made aware of the process of science communication and are introduced to the peer review process for the assessment of scientific papers. In the summer term 2020, the seminar was conducted as a joint project by the University of Hamburg, the University of Muenster, and the Joachim Herz Foundation. In this article, we present the concept of the seminar and our experience with this concept in the summer term 2020.

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.

Predictors of poor outcomes in patients with pandemic viral infections (influenza AH1N1pdm09, COVID-19) on a ventilator.

Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

New Developments in Climate Change, Air Pollution, Pollen Allergy, and Interaction with SARS-CoV-2

In recent years, the environmental impacts of climate change have become increasingly evident. Extreme meteorological events are influenced by climate change, which also alter the magnitude and pattern of precipitations and winds. Climate change can have a particularly negative impact on respiratory health, which can lead to the emergence of asthma and allergic respiratory illnesses. Pollen is one of the main components of the atmospheric bioaerosol and is able to induce allergic symptoms in certain subjects. Climate change affects the onset, length, and severity of the pollen season, with effects on pollen allergy. Higher levels of carbon dioxide (CO2) can lead to enhanced photosynthesis and a higher pollen production in plants. Pollen grains can also interact with air pollutants and be affected by thunderstorms and other extreme events, exacerbating the insurgence of respiratory diseases such as allergic rhinitis and asthma. The consequences of climate change might also favor the spreading of pandemics, such as the COVID-19 one.

COMPARATIVE EFFECTS OF TOCILIZUMAB AND CYTOSORB ON BLOOD CYTOKIENE LEVELS IN PATIENTS WITH SARS-CoV-2 PNEUMONIA

Background/aims: SARS-CoV-2 is responsible of respiratory failure and also causes a massive release of inflammatory mediators such as IL-6, IL-1, CRP etc. This hyperinflammatory condition, often indicated as Cytokine Release Syndrome (CRS), could led to life-threatening events. The clinical course resembles septic shock and the elevated values of inflammatory mediators are associated with a higher viral load and reduced survival. The use of techniques aiming to contrast the surge of inflammatory mediators has been advocated in the treatment of this condition. Method(s): Four patients were retrospectively admitted in Intensive Care Unit with respiratory failure caused by SARS-CoV-2 infection. Two patients were treated with Tocilizumab (TCZ) alone, the others received TCZ in association with hemoadsorption (HA) treatment. The HA procedure was performed with CytoSorb responsible of removing hydrophobic molecules with a molecular weight of up to approximately 60 kDa including cytokines and other inflammatory mediators involved in CRS. Each procedure lasts 24 hours. Blood values of IL-6, C-reactive protein (CRP) and other biochemical variables were measured in two patients who received Tocilizumab (TCZ) alone and in other two in whom it was associated with hemoadsorption (TCZ- HA). All variables were measured before, during and after the treatment. The aim of the study is to assess the variations of IL-6 in patients with SARS-CoV-2 infection treated with TCZ alone or in association with hemoadsorption (HA). Result(s): All patients full-filled the criteria of severe SARS-CoV-2 infection. In all patients the administration of TCZ was followed by an increasing in IL-6 values. Its values remained elevated in patients given TCZ but sharply decreased in the following days in those treated also with HA. The percentage variations of IL-6 from the baseline between the two groups was +344% and +89% in the two patients treated with TCZ alone and - 56% and -15% in TCZ-HA group. Both TCZ and TCZ-HA were well tolerated. Conclusion(s): The increase of the IL-6 can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ- HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators. More experience is needed to identify the best candidate for TCZ or TCZ-HA.

Template for Extended Abstract contributions to INDOOR AIR 2022

This investigation presents results of Computational Fluid Dynamics (CFD) modelling of aerosol behaviour within an arbitrary 'realistic' 100m2 office environment, with dynamic and variable respiratory droplet release profile applied based on published findings (Morawska et al., 2009). A multitude of ventilation strategies and configurations have been applied to the base model to compare the effectiveness of reducing the concentration of suspended aerosols over time. A key finding of the investigation indicates a relatively low sensitivity to increasing outside air percentage, and that the benefit from this strategy is heavily dependent on the in-duct droplet decay factor. The application of local recirculating air filtration systems with MERV-13 filters mounted on occupant desks proved significantly more effectiveness than increasing outside air concentration from 25% to 100% in reducing the quantity of suspended aerosols. This highlights that the ventilation industry should perhaps focus on opportunities to integrate filtration systems into furniture, partitions, cabinetry etc., and that an appliance-based solution may be more beneficial for reducing COVID-19 transmission in buildings (and likely more straightforward) than modifications to central ventilation systems, particularly in the application of refurbishments and retrofits. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Clinical Features, Laboratory Findings Outcomes in Multisystem Inflammatory Syndrome (Mis-C) Following Covid-19 Infection - a Multicenter, Observational, Ambidirectional Cohort Study in Rio De Janeiro State, Brazil

Objectives: As of March 5th, 2022, around 1.585 cases of MIS-C and 98 deaths (6,4%) were reported in Brazil. The state of Rio de Janeiro State (RJ) having 94 cases (5,9%) and 4 deaths (4,2%)1.Our aim was to evaluate clinical and laboratory features, and management of MIS-C in seven pediatric hospitals in RJ, Brazil. Method(s): Multicenter, observational, ambidirectional cohort study in seven tertiary hospitals in RJ(Brazil), assessing medical charts of pediatric inpatients (0-18 years) diagnosed with MIS-C according to WHO/CDC criteria, from August, 2020 to February, 2022. Descriptive statistics were used to analyze distributions of continuous variables, frequencies, and proportions. Result(s): A total of 112 cases of MIS-C were enrolled. The mean age was 4.2 years and thre was male predominance (59,8%). All cases had a SARS-CoV-2 contact (29.5% close contact;31.3%:positive PCR;serology:43.8%).Only 12.5% had comorbidities. Length of stay (LOS) was 7 days.Median duration of fever was 8 days. Most common symptoms were: rash(67%);gastrointestinal (67%);conjunctivitis (42%);neurological(39.6%);cardiovascular(37.5%);cervical lymphadenopathy (36.6%), and shock/hypotension(28.6%).Co-infection occurred in 3 patients. Forty-four patients fulfilled criteria for Kawasaki disease. Most patients were admitted to PICU(12;62,5%) for amedian of 2 days. Respiratory distress was seen in 18,7%;hypotension:28,6%, and shock in 23,2%. Main laboratory findings were: high C-reactive protein in 95%;D-dimer:77%, anemia:77%, thrombocytosis:63%;transaminitis:43.8%, lymphopenia:38%;hypoalbuminemia:34%;thrombocytopenia: 29%;hypertriglyceridemia:28%, and high pro-BNP in 27%. Echocardiogram was performed in 91/112 patients;abnormal in 70,3%;exhibiting myocardial dysfunction( 25%);pericardial effusion(21%);coronary dilation/aneurysms(11%) and, valvulitis (14.5%). IVIG+corticosteroids (CTC) were administered in 59.8%(67/ 112);18.6%(18/112) IVIG only;10.7%(12/112) CTC only;3.4%(4/112)biologics, and 15(13.3%) received no treatment. ASA low dose in 77.7% (87/112) and moderate/high dose in 34.8%. Oxygen support was needed in 27,7%;vasoactive amines:18,7%;dialysis:5,3%, and transfusion:18,7%.One patient died from a cytokine storm syndrome. Conclusion(s): Our study reports a higher number of MIS-C cases in RJ than the number reported to Brazilian authorities, highlighting underreporting. Our patients were younger, had fewer comorbidities, cardiovascular/gastrointestinal/renal involvement, shortest LOS in ICU, and a higher frequency of myopericarditis.

COVID-19 ARDS MANAGEMENT IN AN INTENSIVE CARE WARD USING ANTI-CD6 MONOCLONAL ANTIBODY: A CASE SERIES

Background: Covid-19 ARDS is a common presentation in the emergency ward and needs quick assessment and treatment. Material and Methods: This case series was aggregated from patients admitted to the emergency ward, with a diagnosis of mild to moderate ARDS with impending cytokine release syndrome (CRS). Results: These 10 patients were treated with antiCD6 monoclonal antibody, Itolizumab as it had been given emergency use approval for critically ill patients on CRS. Of the 10 patients, 8 received Itolizumab on day 2 while 2 received it on day 1. Nine out of ten patients recovered and were discharged, while one patient died. Patients' progress was monitored by daily evaluation of patients' CRP and cytokine (IL-6) levels, LDH, and clinical and radiological assessment. All 10 patients were observed for oxygen delivery parameters including days of ventilation support, and total oxygen delivery. Conclusion: The administration of antiCD6 monoclonal antibody, itolizumab early has shown to reduce the duration of ventilation support to 5.4 days, total oxygen requirements to 12 days, and hospital stay to 13.3 days. [ FROM AUTHOR] Copyright of Journal of Cardiovascular Disease Research (Journal of Cardiovascular Disease Research) is the property of Journal of Cardiovascular Disease Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Atrial Torsades De Pointes Post Covid Myocarditis

Background: Among patients with COVID-19 infection, the risk of adverse cardiovascular outcome, particularly myocarditis and dysrhythmias remain elevated at least up to one year after infection. We present a case of atrial tachycardia and atrial Torsades de Pointes from COVID myocarditis, persisted 6 months after infection, which was successfully managed by ablation. Objective(s): A 25-year-old female presented with mild COVID-19 infection, Omicron variant, in May 2022. One month after, her Covid infection resolved;she presented with symptomatic atrial tachycardia, paroxysmal atrial fibrillation and flutter. ECG showed multiple blocked premature atrial contractions (PAC) (Figure 1A). Holter monitor showed PAC triggered atrial tachycardia degenerating to paroxysmal atrial fibrillation, atrial Torsades de Pointes. She has mild persistent troponin elevation. Echocardiography was normal. Cardiac MRI showed evidence of mild myocarditis with subepicardial late Gadolinium enhancement (LEG) along the lateral mid-apical left ventricular wall and edema. (Figure 1B). She was treated with Colchicine for 2 months. Repeat cardiac MRI 4 months after COVID infection showed resolution of edema and LGE. However, her symptomatic PAC and atrial tachycardia did not respond to betablocker and amiodarone. She underwent electrophysiology study. Activation mapping of PAC using CARTO revealed earliest activation at the right anterior atrial wall, with close proximity to tricuspid valve;unipolar signal showed QS pattern, bipolar signal showed 16 msec pre-PAC (Figure 1C and 1D). Mechanical pressure from ThermoCool SmartTouch ablation catheter (Biosense Webster Inc.) at this site suppressed the PAC. Radiofrequency ablation resulted with an initial acceleration and then disappearance of the PAC. We did not isolate pulmonary veins or ablate cavotricuspid isthmus. Post ablation, PAC and atrial fibrillation were not inducible on Isoproterenol. Method(s): N/A Results: Covid myocarditis can result in dysrhythmia that lingers long after Covid myocarditis has resolved. Covid myocarditis can be caused by direct viral invasion of myocytes or more commonly is inflammatory related to cytokine release and edema. Our case demonstrates that dysrhythmias can persist despite resolution of myocarditis. Catheter ablation can successfully to treat these arrhythmias. Conclusion(s): This case highlights the importance of recognizing cardiac dysrhythmia as possible the long-term cardiac complications of COVID-19, requiring specific treatment such as catheter ablation. [Formula presented]Copyright © 2023

Serotonin Release Assay: Functional Assay for Heparin- and Vaccine-Induced (Immune) Thrombotic Thrombocytopenia.

The serotonin release assay (SRA) has been the gold-standard assay for detection of heparin-dependent platelet-activating antibodies and integral for the diagnosis for heparin-induced thrombotic thrombocytopenia (HIT). In 2021, a thrombotic thrombocytopenic syndrome was reported after adenoviral vector COVID-19 vaccination. This vaccine-induced thrombotic thrombocytopenic syndrome (VITT) proved to be a severe immune platelet activation syndrome manifested by unusual thrombosis, thrombocytopenia, very elevated plasma D-dimer, and a high mortality even with aggressive therapy (anticoagulation and plasma exchange). While the platelet-activating antibodies in both HIT and VITT are directed toward platelet factor 4 (PF4), important differences have been found. These differences have required modifications to the SRA to improve detection of functional VITT antibodies. Functional platelet activation assays remain essential in the diagnostic workup of HIT and VITT. Here we detail the application of SRA for the assessment of HIT and VITT antibodies.

Extension of Lung Damage at Chest Computed Tomography in Severely Ill COVID-19 Patients Treated with Interleukin-6 Receptor Blockers Correlates with Inflammatory Cytokines Production and Prognosis.

Elevated inflammatory markers are associated with severe coronavirus disease 2019 (COVID-19), and some patients benefit from Interleukin (IL)-6 pathway inhibitors. Different chest computed tomography (CT) scoring systems have shown a prognostic value in COVID-19, but not specifically in anti-IL-6-treated patients at high risk of respiratory failure. We aimed to explore the relationship between baseline CT findings and inflammatory conditions and to evaluate the prognostic value of chest CT scores and laboratory findings in COVID-19 patients specifically treated with anti-IL-6. Baseline CT lung involvement was assessed in 51 hospitalized COVID-19 patients naive to glucocorticoids and other immunosuppressants using four CT scoring systems. CT data were correlated with systemic inflammation and 30-day prognosis after anti-IL-6 treatment. All the considered CT scores showed a negative correlation with pulmonary function and a positive one with C-reactive protein (CRP), IL-6, IL-8, and Tumor Necrosis Factor α (TNF-α) serum levels. All the performed scores were prognostic factors, but the disease extension assessed by the six-lung-zone CT score (S24) was the only independently associated with intensive care unit (ICU) admission (p = 0.04). In conclusion, CT involvement correlates with laboratory inflammation markers and is an independent prognostic factor in COVID-19 patients representing a further tool to implement prognostic stratification in hospitalized patients.

Impacts of the COVID-19 pandemic on enrollment in medications for opioid use disorder (MOUD) in Vancouver, Canada: An interrupted time series analysis.

BACKGROUND: In anticipation of COVID-19 related disruptions to opioid use disorder (OUD) care, new provincial and federal guidance for the management of OUD and risk mitigation guidance (RMG) for prescription of pharmaceutical opioids were introduced in British Columbia, Canada, in March 2020. This study evaluated the combined impacts of the COVID-19 pandemic and counteracting OUD policies on enrollment in medications for OUD (MOUD). METHODS: Using data from three cohorts of people with presumed OUD in Vancouver, we conducted an interrupted time series analysis to estimate the combined effects impact of the COVID-19 pandemic and counteracting OUD policies on the prevalence of enrollment in MOUD overall, as well as in individual MOUDs (methadone, buprenorphine/naloxone, slow-release oral morphine) between November 2018 and November 2021, controlling for pre-existing trends. In sub-analysis we considered RMG opioids together with MOUD. RESULTS: We included 760 participants with presumed OUD. In the post-COVID-19 period, MOUD and slow-release oral morphine prevalence rates showed an estimated immediate increase in level (+7.6%, 95% CI: 0.6%, 14.6% and 1.8%, 95% CI: 0.3%, 3.3%, respectively), followed by a decline in the monthly trend (-0.8% per month, 95% CI: -1.4%, -0.2% and -0.2% per month, 95% CI: -0.4, -0.1, respectively). There were no significant changes in the prevalence trends of enrollment in methadone, buprenorphine/naloxone, or when RMG opioids were considered together with MOUD. CONCLUSIONS: Despite immediate improvements in MOUD enrollment in the post-COVID-19 period, this beneficial trend reversed over time. RMG opioids appeared to have provided additional benefits to sustain retention in OUD care.

Lessons drawn from Shanghai for controlling highly transmissible SARS-CoV-2 variants: insights from a modelling study.

BACKGROUND: The continuous emergence of novel SARS-CoV-2 variants with markedly increased transmissibility presents major challenges to the zero-COVID policy in China. It is critical to adjust aspects of the policy about non-pharmaceutical interventions (NPIs) by searching for and implementing more effective ways. We use a mathematical model to mimic the epidemic pattern of the Omicron variant in Shanghai to quantitatively show the control challenges and investigate the feasibility of different control patterns in avoiding other epidemic waves. METHODS: We initially construct a dynamic model with a core step-by-step release strategy to reveal its role in controlling the spread of COVID-19, including the city-based pattern and the district-based pattern. We used the least squares method and real reported case data to fit the model for Shanghai and its 16 districts, respectively. Optimal control theory was utilized to explore the quantitative and optimal solutions of the time-varying control strength (i.e., contact rate) to suppress the highly transmissible SARS-CoV-2 variants. RESULTS: The necessary period for reaching the zero-COVID goal can be nearly 4 months, and the final epidemic size was 629,625 (95%CI: [608,049, 651,201]). By adopting the city-based pattern, 7 out of 16 strategies released the NPIs more or earlier than the baseline and ensured a zero-resurgence risk at the average cost of 10 to 129 more cases in June. By adopting the district-based pattern, a regional linked release can allow resumption of social activity to ~ 100% in the boundary-region group about 14 days earlier and allow people to flow between different districts without causing infection resurgence. Optimal solutions of the contact rate were obtained with various testing intensities, and higher diagnosis rate correlated with higher optimal contact rate while the number of daily reported cases remained almost unchanged. CONCLUSIONS: Shanghai could have been bolder and more flexible in unleashing social activity than they did. The boundary-region group should be relaxed earlier and more attention should be paid to the centre-region group. With a more intensive testing strategy, people could return to normal life as much as possible but still ensure the epidemic was maintained at a relatively low level.

Intermittent social isolation during adolescence increases ethanol preference in males and females and alters irritability-like behaviors and synaptic transmission in the CeA of adult males

Chronic stress during adolescence increases the susceptibility to many neuropsychiatric diseases in adulthood, including anxiety-like and alcohol drinking behaviors. Social isolation is a particularly profound stressor with increasing human relevance, especially during the COVID-19 pandemic, when millions of adolescents faced prolonged periods of isolation. However, preclinical rodent models of adolescent social stress have produced mixed results that are often sex, species and strain-dependent. Here we examined the effect of intermittent social isolation on alcohol intake and preference during adolescence (PND28-56) and its long-term effects and alcohol drinking on anxiety, irritability, and synaptic transmission in both male and female Wistar rats. To this goal, we developed and utilized a new model of social isolation and alcohol exposure whereby adolescent (PND28) male and female rats were intermittently socially isolated for 24h prior to 2-bottle choice (2BC) access to ethanol (20% v/v, 2h/session, Tues/Thur/Sat) vs. water, for 4 weeks. Two weeks later (young adults), all rats were tested for anxiety in the novelty induced hypophagia test and irritability-like behavior in the bottle brush test, and a subset was used to record spontaneous inhibitory GABAergic postsynaptic currents (sIPSCs) in the central nucleus of the amygdala (CeA). Additionally, we studied genetically selected Marchigian Sardinian alcohol-preferring (msP) rats to compare the effects of social isolation in a rat strain of increased alcohol preference vulnerability and high sensitivity to anxiety. Social isolation increased alcohol preference in both male and female Wistars when compared to the group-housed controls, starting from week 1 and throughout adolescence. All msP rats displayed escalation of drinking during week 1 and 2 and the effect of the isolation was observed starting from week 3 in males only. No isolation effects were observed in female msPs throughout the 4 weeks. Social isolation and alcohol drinking during adolescence increased aggressive-like behavior in male adult Wistar rats, but not females, and did not alter anxiety measures. Baseline frequency of sIPSCs was decreased in socially isolated male Wistar and msP adult rats vs. group-housed, while rise times, amplitudes, and decay times remained unchanged, indicating reduced basal presynaptic GABA release in the CeA. Together, these findings suggest that an intermittent social isolation produces increased alcohol preference in Wistar rats of both sexes and in male msPs, as well as synaptic changes in the CeA.Copyright © 2023

THE ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS (NETs) IN THE IMMUNOPATHOGENESIS OF SEVERE COVID-19: POTENTIAL IMMUNOTHERAPEUTIC STRATEGIES REGULATING NET FORMATION AND ACTIVITY.

The role of neutrophil granulocytes (NG) in the pathogenesis of COVID-19 is associated with the NG recruitment into inflammatory foci, activation of their functions and enhanced formation of neutrophil extracellular networks (NETs). In this review, we analyzed a large body of scientific literature devoted to the features of developing NETs, their role in the COVID-19 pathogenesis, a role in emerging immunothrombosis, vasculitis, acute respiratory distress syndrome, cytokine storm syndrome, and multi-organ lesions. Convincing data are presented clearly indicating about a profound role of NETs in the COVID-19 immunopathogenesis and associated severe complications resulting from intensified inflammation process, which is a key for the course of SARS-CoV-2 virus infection. The presented role of NGs and NETs, along with that of other immune system cells and pro-inflammatory cytokines, is extremely important in understanding development of overactive immune response in severe COVID-19. The scientific results obtained available now allow to identify an opportunity of regulatory effects on hyperactivated NGs, NETosis at various stages and on limiting a negative impact of pre-formed NETs on various tissues and organs. All the aforementioned data should help in creating new, specialized immunotherapy strategies designed to increase the odds of survival, reduce severity of clinical manifestations in COVID-19 patients as well as markedly reduce mortality rates. Currently, it is possible to use existing drugs, while a number of new drugs are being developed, the action of which can regulate NG quantity, positively affect NG functions and limit intensity of NETosis. Continuing research on the role of hyperactive NG and NETosis as well as understanding the mechanisms of regulating NET formation and restriction in severe COVID-19, apparently, are of high priority, because in the future the new data obtained could pave the basis for development of targeted approaches not only for immunotherapy aimed at limiting education and blocking negative effects already formed NETs in severe COVID-19, but also for immunotherapy, which could be used in combination treatment of other netopathies, primarily autoimmune diseases, auto-inflammatory syndromes, severe purulent-inflammatory processes, including bacterial sepsis and hematogenous osteomyelitis.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.