Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome.

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients. Objectives: We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity. Methods: Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases. Results: A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17-87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection. Conclusion: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.

IL-6 Serum Levels in COVID-19 Patients With Vertigo.

Introduction Dizziness and vertigo represent well-established symptoms of COVID-19. An overexpression of cytokines, a condition often described with the term "cytokine storm" or "hypercytokinemia", is a key characteristic of SARS-Cov-2 infection and plays a pivotal role in disease progression and prognosis. Among them, IL-6 is of major importance.  Purpose The purpose of this study is to investigate any probable IL-6 serum titer difference in COVID-19 patients with vertigo (V+) or without vertigo (V-) admitted to the COVID-19 internal medicine departments of Attikon University Hospital, Athens, Greece, within 12 months. Methods The sample consisted of 52 COVID-19 patients who were diagnosed between January 1, 2020, and December 31, 2020. Of those, 31 reported vertigos during their admission (V+), while the remaining 21 COVID-19 patients did not complain of such symptoms (V-). Results Higher IL-6 serum levels post-COVID-19 infections lead to higher incidence rates of vertigo symptoms (p<.005), regardless of gender and age (p.005).

Lichen planus after COVID-19 infection and vaccination.

Lichen planus (LP) is an inflammatory disorder believed to result from CD8 + cytotoxic T-cell (CTL)-mediated autoimmune reactions against basal keratinocytes. We present a review of LP following COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 7/2022. 36 articles were selected based on subject relevance, and references within articles were also screened. 39 cases of post-vaccination LP and 6 cases of post-infection LP were found among case reports and case series. 152 cases of post-vaccination LP and 12 cases of post-infection LP were found in retrospective and prospective studies. LP is a rare complication of COVID-19 infection and vaccination that may be mediated by overstimulation of T-cell responses and proinflammatory cytokine production. However, it does not represent a limitation against COVID-19 vaccination, and the benefits of vaccination considerably outweigh the risks.

Therapeutic Effect of Gegentang Granules on Mouse Model with hCoV-229E Pneumonia and Hanshi Yidu Xifei Syndrome

Objective：To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E（hCoV-229E）pneumonia with Hanshi Yidu Xifei syndrome in vivo. Method： Mice were randomly divided into normal group，infection group，cold-dampness group，model group，chloroquine phosphate group（0.18 g·kg-1），interferon-α2b（IFN-α2b）group（1.83×106 U·kg-1）， Gegentang granules high-dose and low-dose groups（6.6，3.3 g·kg-1）with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling，and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR），the pathological changes in lung tissue were evaluated by hematoxylin-eosin（HE）staining，the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay（ELISA），and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result：Comparing with model group，Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome，including listlessness，weakness of limbs，sticky stool，etc. Comparing with model group，Gegentang granules high-dose group significantly reduced lung index，histopathological score of interstitial lung and bronchus，and the level of serum motilin（P< 0.05，P<0.01），two doses of Gegentang granules could significantly increase the level of serum gastrin（P< 0.05，P<0.01），the percentage of CD4+ ，CD8+ T lymphocytes in peripheral blood（P<0.05，P<0.01），and the level of tumor necrosis factor-α（TNF-α）in lung tissue was significantly decreased（P<0.01），and the level of interleukin-6（IL-6）showed decreasing tendency. Conclusion： Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization，regulate the level of gastrointestinal hormones，decrease lung index and histopathological score，and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Mortality and Its Predictors in COVID-19 Patients With Pre-existing Interstitial Lung Disease.

Background The data on the impact of coronavirus disease 2019 (COVID-19) on interstitial lung disease (ILD) is still limited. To the best of our knowledge, there has been no study from India to date to assess the impact of COVID-19 in patients with preexisting ILD. We undertook this study to assess the clinical outcome of ILD patients admitted to our hospital with COVID-19. Methods In this retrospective observational study, records of reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with preexisting ILD who were admitted to the hospital in the period from May 1, 2020, to April 30, 2021, were obtained from the hospital database. The clinical outcomes of the patients were recorded. Univariate analysis was performed to find relation between various predetermined risk factors for mortality and those with significant p values (p<0.05) were subjected to multiple logistic regression to determine independent risk factors. Results In our study of 28 patients, the overall mortality was 35.7%. On comparing the parameters associated with increased mortality, there was no effect of age, gender, comorbidities, type of ILD, CT thorax findings on diagnosis, use of corticosteroids and antifibrotics in the past, spirometric findings on mortality. On multivariate analysis, the significant parameters were interleukin 6 (IL-6), p=0.02, OR=1.020 (1.006-1.043) and D-dimer, p=0.04, OR=2.14 (5.55-1.14). Conclusion COVID-19 in patients with pre-existing ILD has a comparatively higher mortality. D-dimer and IL-6 are significant predictors of mortality in ILD patients infected with COVID-19.

Syndrome of Inappropriate Antidiuretic Hormone Secretion-Induced Encephalopathy in a Patient With COVID-19.

Various electrolyte imbalances have been documented in coronavirus disease 2019 (COVID-19) patients who progress to severe acute respiratory syndrome coronavirus-2 infection. Patients with co-morbidities like diabetes, hypertension, obesity, ischemic heart disease, chronic kidney disease, and chronic obstructive pulmonary disease are more vulnerable to developing complications in the form of electrolyte disturbance. We report a case of acute severe hyponatremia in a middle-aged man who was admitted to the hospital with viral pneumonia due to a coronavirus-2 infection. A dramatic drop of plasma sodium was preceded by gastrointestinal symptoms and followed by encephalopathy. On clinical assessment his plasma sodium was found to be critically low, i.e. 105 mmol/L. His chest x-ray showed minimal pleural effusion. The patient was managed in the ICU and his serum sodium was normalized gradually with partial but rapid correction of this severe hyponatremia with hypertonic sodium chloride and followed by fluid restriction.

Pathophysiology of moderate to severe plaque psoriasis: anti-IL-17 towards disease modification.

Psoriasis is a chronic inflammatory disease that can be triggered by injury, trauma, infection and medications. Genetic and immunologic studies have highlighted the importance of the interleukin (IL)-23/T-helper 17 (Th17) pathway in systemic psoriasis pathogenesis. Main IL-23 is an upstream regulatory cytokine with direct effects on epidermal keratinocytes and other resident skin cells while IL-17, a downstream molecule, can activate inflammatory responses in different cells across a diversity of organs. Disease modification could be achieved with drugs that can slow down the biological processes that cause the persistent inflammation in moderate to severe psoriasis. Early intervention with anti-IL-17 and anti-IL-23 agents in new-onset moderate to severe plaque psoriasis might modify the natural course of the disease. Perhaps we are not simply seeing a pharmacologic and mechanistic effect of new-generation biologics but eventually a disease modification process. In this short report we underline the main available data which supports an important role for IL-17 blockade and address whether these new drugs targeting the IL-23/IL-17 axis could be disease-modifying agents in plaque psoriasis. This type of data gains more relevance in the current pandemic era, where chronic patients undergoing earlier treatment may have better outcomes and consequently avoid constant hospital visits.

Exogenous pulmonary surfactant: A review focused on adjunctive therapy for severe acute respiratory syndrome coronavirus 2 including SP-A and SP-D as added clinical marker.

Type I and type II pneumocytes are two forms of epithelial cells found lining the alveoli in the lungs. Type II pneumocytes exclusively secrete 'pulmonary surfactants,' a lipoprotein complex made up of 90% lipids (mainly phospholipids) and 10% surfactant proteins (SP-A, SP-B, SP-C, and SP-D). Respiratory diseases such as influenza, severe acute respiratory syndrome coronavirus infection, and severe acute respiratory syndrome coronavirus 2 infection are reported to preferentially attack type II pneumocytes of the lungs. After viral invasion, consequent viral propagation and destruction of type II pneumocytes causes altered surfactant production, resulting in dyspnea and acute respiratory distress syndrome in patients with coronavirus disease 2019. Exogenous animal-derived or synthetic pulmonary surfactant therapy has already shown immense success in the treatment of neonatal respiratory distress syndrome and has the potential to contribute efficiently toward repair of damaged alveoli and preventing severe acute respiratory syndrome coronavirus 2-associated respiratory failure. Furthermore, early detection of surfactant collectins (SP-A and SP-D) in the circulatory system can be a significant clinical marker for disease prognosis in the near future.

Does inflammation link stress to poor COVID-19 outcome?

Coronavirus disease 2019 (COVID-19) continues to ravage communities across the world. Despite its primary effect on the respiratory system, the virus does not solely impact those with underlying lung conditions as initially predicted. Indeed, prognosis is worsened (often fatal) in patients with pre-existing hyperinflammatory responses (e.g., hypertension, obesity and diabetes), yet the mechanisms by which this occurs are unknown. A number of psychological conditions are associated with inflammation, suggesting that these may also be significant risk factors for negative outcomes of COVID-19. In this review, we evaluate preclinical and clinical literature suggesting that chronic stress-induced hyperinflammation interacts synergistically with COVID-19-related inflammation, contributing to a potentially fatal cytokine storm syndrome. In particular, we hypothesize that both chronic stress and COVID-19-related hyperinflammation are a product of glucocorticoid insufficiency. We discuss the devastating effects of SARS-CoV-2 on structural and functional aspects of the biological stress response and how these induce exaggerated inflammatory responses, particularly interleukin (IL)-6 hypersecretion. We postulate that chronic stress should be considered a significant risk factor for adverse COVID-19-related health outcomes, given overlapping peripheral and central immune dysregulation in both conditions. We conclude by discussing how people with a history of chronic stress could mitigate their risk for COVID-19 complications, identifying specific strategies that can be implemented during self-isolation.

The Role of Interleukin-6 Inhibitors in the Treatment of COVID-19 Infections: A Case Series.

An outbreak of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection started in December 2019 in China that resulted in a global health emergency. The World Health Organization later named the disease as coronavirus disease 2019 (COVID-19). Currently, there is no effective treatment available and the data are evolving through continuous clinical trials and ongoing research. Severe infections present with hypoxemic respiratory failure from acute respiratory distress syndrome as one of the major complications. We report two cases of COVID-19 patients who initially presented with moderate to severe symptoms. Later, their clinical course worsened despite ongoing treatment with multiple medications such as hydroxychloroquine and azithromycin until they were started on tocilizumab. Within a short period after they were administered tocilizumab, their oxygen saturation improved and other inflammatory markers such as D-dimer levels, lactate dehydrogenase, and ferritin levels decreased. There is an increase in the amount of research citing the role of various cytokines in the pathophysiology of COVID-19. Targeting the inflammatory mediators in the pathogenesis, especially interleukin-6 pathway inhibitors, would improve overall morbidity and mortality, thus decreasing the burden on healthcare systems.