Single-Cell Genomics for Investigating Pathogenesis of Inflammatory Diseases.

Recent technical advances have enabled unbiased transcriptomic and epigenetic analysis of each cell, known as "single-cell analysis". Single-cell analysis has a variety of technical approaches to investigate the state of each cell, including mRNA levels (transcriptome), the immune repertoire (immune repertoire analysis), cell surface proteins (surface proteome analysis), chromatin accessibility (epigenome), and accordance with genome variants (eQTLs; expression quantitative trait loci). As an effective tool for investigating robust immune responses in coronavirus disease 2019 (COVID-19), many researchers performed single-cell analysis to capture the diverse, unbiased immune cell activation and differentiation. Despite challenges elucidating the complicated immune microenvironments of chronic inflammatory diseases using existing experimental methods, it is now possible to capture the simultaneous immune features of different cell types across inflamed tissues using various single-cell tools. In this review, we introduce patient-based and experimental mouse model research utilizing single-cell analyses in the field of chronic inflammatory diseases, as well as multi-organ atlas targeting immune cells.

Cannabinoids as Immune System Modulators: Cannabidiol Potential Therapeutic Approaches and Limitations.

Introduction: Cannabidiol (CBD) is the second most abundant Phytocannabinoid in Cannabis extracts. CBD has a binding affinity for several cannabinoid and cannabinoid-associated receptors. Epidiolex (oral CBD solution) has been lately licensed by the Food and Drug Administration (FDA) for the treatment of pediatric epileptic seizures. Methods: In this review, we discussed the most promising applications of CBD for chronic inflammatory conditions, namely CBD's anti-inflammatory effects during inflammatory bowel disease, coronavirus disease (antiviral effect), brain pathologies (neuroprotective and anti-inflammatory properties), as well as CBD immunomodulatory and antitumoral activities in the tumor microenvironment. Special focus was shed on the main therapeutic mechanisms of action of CBD, particularly in the control of the immune system and the endocannabinoid system. Results: Findings suggest that CBD is a potent immunomodulatory drug as it has manifested immunosuppressive properties in the context of sterile inflammation (e.g., inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases), and immunoprotective effects during viral infections (e.g. COVID-19) Similarly, CBD has exhibited a selective response toward cancer types by engaging different targets and signaling pathways. These results are in favor of the primary function of the endocannabinoid system which is homeostatic maintenance. Conclusion: The presented evidence suggests that the endocannabinoid system is a prominent target for the treatment of inflammatory and autoimmune diseases, rheumatoid diseases, viral infections, neurological and psychological pathologies, and cancer. Moreover, the antitumoral activities of CBD have been suggested to be potentially used in combination with chemo- or immunotherapy during cancer. However, clinical results are still lacking, which raises a challenge to apply translational cannabis research to the human immune system.

Concomitant Severe Psoriasis and Bullous Pemphigoid Induced by COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first isolated in Wuhan, China, is currently a pandemic. At the beginning of the pandemic, pulmonary issues were the most discussed and studied. However, now 3 years later, the role of the dermatologist has become increasingly central. Often the diversity in the presentation of these manifestations has made it difficult for the dermatologist to recognize them. In addition to the common symptoms involving fever, cough, dyspnea, and hypogeusia/hyposmia that have been widely discussed in the literature, much attention has been paid to dermatologic manifestations in the past year. The vaccination campaign has been the most important strategy to combat the COVID-19 pandemic. Specifically, two viral vector-based vaccines [Vaxzervria® (AstraZeneca; AZD1222) and COVID-19 Janssen® vaccine (Johnson & Johnson; Ad26.COV2. S)] and two mRNA-based vaccines [Comirnaty® (Pfizer/BioNTech; BNT162b2) and Spikevax® (Moderna; mRNA-1273)]. However, several cutaneous adverse reactions have been reported following vaccination, making the dermatologist's role critical. It is possible to group these adverse reactions according to a classification with six main clinical pictures: urticarial rash, erythematous/maculopapular/morbid rash, papulovesicular rash, chilblain-like acral pattern, livedo reticularis/racemose-like, and purpuric "vasculitic" pattern. Beyond this classification, there are several reports of other dermatologic manifestations associated with the infection, such as pityriasis rosea, herpes zoster, or, particularly, the worsening of pre-existing chronic inflammatory dermatologic diseases. Here we report the case of a 61-year-old patient who presented at our clinic with a diffuse psoriasiform eruption mixed with a concomitant blistering rash induced by COVID-19. The uniqueness of our case has two features: the first is the concomitance of the two events after infection that seems to be unprecedented; the second is the management of the patient that could help dermatology colleagues in the management of these conditions during infection.

Self-reported Impact of the Early 2020 COVID-19 Crisis on the Healthcare Pathway During and After Lockdown in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Practical Survey.

Introduction: Global lockdown in the context of the coronavirus disease 2019 (COVID-19) pandemic is an unprecedented experience. We report here the results of an anonymous questionnaire-based survey on the healthcare and control of chronic IMIDs (chronic immune-mediated inflammatory diseases) within the IMMINENT network during the French lockdown (March 17, 2020-May 11, 2020) and the 2-month period following the end of the lockdown (July 11, 2020). Methods: Two anonymous questionnaires were sent by email to 4500 patients who were followed in a university hospital for an IMID in the departments of gastroenterology, rheumatology, dermatology, pneumology, neurology, and internal medicine. Results: A total of 921/4500 (20.46%) responded to the first survey (impact of the lockdown), and 553/4500 (12.28%) to the second (impact at 2-months post-lockdown). Concerning the impact of the lockdown, 420/915 (45.9%) reported affected follow-up. Similarly, after the lockdown, 248/544 (45.6%) declared a negative impact on their follow-up. The repartition by departments of patients' perception of an altered follow-up during (P = .72) and at the end of the lockdown (P = .77) was not statistically different. Our study highlighted the effects of the COVID-19 pandemic and the restriction measures implemented on the self-reported impact felt by patients on the follow-up of their chronic IMIDs without significant differences among all departments. Conclusion: Our study is original by showing that patients, whatever the type of IMID, shared this same negative perception. This transdisciplinary study demonstrated the importance of a collaborative network among all departments.

Immune Response to COVID-19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review.

Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.

Physiological and Immunological Causes of the Susceptibility of Chronic Inflammatory Patients to COVID-19 Infection: Focus on Diabetes.

The coronavirus disease 2019 (COVID-19) pandemic has recently emerged, which was then spread rapidly in more than 190 countries worldwide so far. According to the World Health Organization, 3,232,062 global cases of COVID-19 were confirmed on April 30th with a mortality rate of 3.4%. Notably, the symptoms are almost similar to those of flu such as fever, cough, and fatigue. Unfortunately, the global rates of morbidity and mortality caused by this disease are more and still increasing on a daily basis. The rates for patients suffering from inflammatory diseases like diabetes, is even further, due to their susceptibility to the pathogenesis of COVID-19. In this review, we attempted to focus on diabetes to clarify the physiological and immunological characteristics of diabetics before and after the infection with COVID-19. We hope these conceptions could provide a better understanding of the mechanisms involved in COVID-19 susceptibility and increase the awareness of risk to motivate behavior changes in vulnerable people for enhancing the prevention. Up to now, the important role of immune responses, especially the innate ones, in the development of the worst signs in COVID-19 infection have been confirmed. Therefore, to better control patients with COVID-19, it is recommended to consider a history of chronic inflammatory diseases as well as the way of controlling immune response in these patients.

Potential Therapeutic Applications of Hydrogen in Chronic Inflammatory Diseases: Possible Inhibiting Role on Mitochondrial Stress.

Mitochondria are the largest source of reactive oxygen species (ROS) and are intracellular organelles that produce large amounts of the most potent hydroxyl radical (·OH). Molecular hydrogen (H2) can selectively eliminate ·OH generated inside of the mitochondria. Inflammation is induced by the release of proinflammatory cytokines produced by macrophages and neutrophils. However, an uncontrolled or exaggerated response often occurs, resulting in severe inflammation that can lead to acute or chronic inflammatory diseases. Recent studies have reported that ROS activate NLRP3 inflammasomes, and that this stimulation triggers the production of proinflammatory cytokines. It has been shown in literature that H2 can be based on the mechanisms that inhibit mitochondrial ROS. However, the ability for H2 to inhibit NLRP3 inflammasome activation via mitochondrial oxidation is poorly understood. In this review, we hypothesize a possible mechanism by which H2 inhibits mitochondrial oxidation. Medical applications of H2 may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19).