Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review

The novel coronavirus disease 2019 (COVID-19) is a global pandemic that continues to sweep across the world, posing an urgent need for effective therapies and prevention of the spread of the severe acute respiratory syndrome related to coronavirus-2 (SARS-CoV-2). A major hypothesis that is currently guiding research and clinical care posits that an excessive and uncontrolled surge of pro-inflammatory cytokines (the so-called “cytokine storm”) drives morbidity and mortality in the most severe cases. In the overall efforts made to develop effective and safe therapies (including vaccines) for COVID-19, clinicians are thus repurposing ready-to-use drugs with direct or indirect anti-inflammatory and immunomodulatory activities. Speculatively, there are many opportunities and challenges in targeting immune/inflammatory processes in the evolving settings of COVID-19 disease because of the need to safely balance the fight against virus and aggressive inflammation versus the suppression of host immune defenses and the risk of additional harms in already compromised patients. To this end, many studies are globally underway to weigh the pros and cons of tailoring drugs used for inflammatory-driven conditions to COVID-19 patient care, and the next step will be to summarize the growing clinical trial experience into clean clinical practice. Based on the current evidence, anti-inflammatory drugs should be considered as complementary approaches to anti-viral drugs that need to be timely introduced in the management of COVID-19 according to disease severity. While drugs that target SARS-CoV-2 entry or replication are expected to confer the greatest benefits at the early stage of the infection, anti-inflammatory drugs would be more effective in limiting the inflammatory processes that drive the worsening of the disease.

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Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666201023124843 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ahmed RG

Keyword(s):

Immune System ◽

Cellular Therapy ◽

Early Stage ◽

Control Strategies ◽

Vital Role ◽

Healthy Life ◽

Global Pandemic ◽

Maternal Immune System ◽

Perinatal Management ◽

Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

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Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing

Frontiers in Microbiology ◽

10.3389/fmicb.2021.707629 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rodrigo Cuiabano Paes Leme ◽

Raquel Bandeira da Silva

Keyword(s):

Bacterial Species ◽

Drug Repurposing ◽

Current Evidence ◽

Pharmacokinetic Studies ◽

Bacterial Populations ◽

Human Pharmacokinetic ◽

Inflammatory Drugs ◽

Anti Inflammatory

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs’ activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.

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The Impact of Armed Conflict on the Epidemiological Situation of COVID-19 in Libya, Syria and Yemen

Frontiers in Public Health ◽

10.3389/fpubh.2021.667364 ◽

2021 ◽

Vol 9 ◽

Author(s):

Mohamed A. Daw

Keyword(s):

Armed Conflict ◽

Early Stage ◽

Armed Conflicts ◽

Cumulative Number ◽

The Novel ◽

Global Pandemic ◽

Large Numbers ◽

Public Data ◽

Novel Coronavirus ◽

The Impact

Background: Since the Arab uprising in 2011, Libya, Syria and Yemen have gone through major internal armed conflicts. This resulted in large numbers of deaths, injuries, and population displacements, with collapse of the healthcare systems. Furthermore, the situation was complicated by the emergence of COVID-19 as a global pandemic, which made the populations of these countries struggle under unusual conditions to deal with both the pandemic and the ongoing wars. This study aimed to determine the impact of the armed conflicts on the epidemiology of the novel coronavirus (SARS-CoV-2) within these war-torn countries and highlight the strategies needed to combat the spread of the pandemic and its consequences.Methods: Official and public data concerning the dynamics of the armed conflicts and the spread of SARS-COV-2 in Libya, Syria and Yemen were collected from all available sources, starting from the emergence of COVID-19 in each country until the end of December 2020. Datasets were analyzed by a set of statistical techniques and the weekly resolved data were used to probe the link between the intensity levels of the conflict and the prevalence of COVID-19.Results: The data indicated that there was an increase in the intensity of the violence at an early stage from March to August 2020, when it approximately doubled in the three countries, particularly in Libya. During that period, few cases of COVID-19 were reported, ranging from 5 to 53 cases/day. From September to December 2020, a significant decline in the intensity of the armed conflicts was accompanied by steep upsurges in the rate of COVID-19 cases, which reached up to 500 cases/day. The accumulative cases vary from one country to another during the armed conflict. The highest cumulative number of cases were reported in Libya, Syria and Yemen.Conclusions: Our analysis demonstrates that the armed conflict provided an opportunity for SARS-CoV-2 to spread. The early weeks of the pandemic coincided with the most intense period of the armed conflicts, and few cases were officially reported. This indicates undercounting and hidden spread during the early stage of the pandemic. The pandemic then spread dramatically as the armed conflict declined, reaching its greatest spread by December 2020. Full-blown transmission of the COVID-19 pandemic in these countries is expected. Therefore, urgent national and international strategies should be implemented to combat the pandemic and its consequences.

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CLINICAL AND LABORATORY CHARACTERISTICS OF SARS-COV-2 INFECTION IN CHILDREN AND ADOLESCENTS

Revista Paulista de Pediatria ◽

10.1590/1984-0462/2021/39/2020231 ◽

2021 ◽

Vol 39 ◽

Author(s):

Marlos Melo Martins ◽

Arnaldo Prata-Barbosa ◽

Maria Clara de Magalhães-Barbosa ◽

Antonio José Ledo Alves da Cunha

Keyword(s):

Latin American ◽

Inflammatory Responses ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Current Evidence ◽

Cochrane Library ◽

Childhood And Adolescence ◽

Inflammatory Reactions ◽

One Year ◽

Novel Coronavirus

ABSTRACT Objective: To present the current evidence on clinical and laboratory characteristics of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during childhood and adolescence. Data source: This is a narrative review conducted in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Latin American and Caribbean Health Sciences Literature in the Virtual Health Library (LILACS/VHL), Scopus, Web of Science, Cochrane Library, portal of the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The terms used were SARS-CoV-2, COVID-19, novel coronavirus, child, newborn, and adolescent. Data synthesis: Unlike adults, most children infected by SARS-CoV-2 have mild or asymptomatic clinical presentations. Symptomatic children mainly have low fever and cough, with some associated gastrointestinal symptoms. Severe cases are rare and occur especially in infants under one year of age. Detection of viral particles in feces seems to be more persistent in children and can be used as a tool for diagnosis and control of the quarantine period. Different from adults, children can present distinct inflammatory responses, as has happened in new cases of Kawasaki-like syndrome associated with SARS-CoV-2 infection. Conclusions: Most children have asymptomatic or mild presentations, with a prevalence of fever, cough, and gastrointestinal symptoms. New cases with different systemic inflammatory reactions in children have been reported, with clinical manifestations distinct from those typically found in adults.

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Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

Mediators of Inflammation ◽

10.1155/2010/342328 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 18

Author(s):

Na-Young Park ◽

Giuseppe Valacchi ◽

Yunsook Lim

Keyword(s):

Oxidative Stress ◽

Wound Healing ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Wound Closure ◽

Inflammatory Responses ◽

Early Stage ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Anti Inflammatory

Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

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Negative pressure rooms and COVID-19

Journal of Perioperative Practice ◽

10.1177/1750458920949453 ◽

2020 ◽

Vol 31 (1-2) ◽

pp. 18-23

Author(s):

Sammy Al-Benna

Keyword(s):

Negative Pressure ◽

Health Care Professionals ◽

Healthcare Professionals ◽

Clinical Care ◽

Public Health Emergency ◽

Positive Pressure ◽

Global Pandemic ◽

Operating Theatres ◽

Novel Coronavirus ◽

Surrounding Areas

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 novel coronavirus disease (COVID-19), has rapidly developed into a global pandemic and public health emergency. The transmission and virulence of this new pathogen have raised concern for how best to protect healthcare professionals while effectively providing care to the infected patient requiring surgery. Although negative pressure rooms are ideal for aerosol-generating procedures, such as intubation and extubation, most operating theatres are generally maintained at a positive pressure when compared with the surrounding areas. This article compares negative and positive pressure rooms and the advantages of a negative pressure environment in optimising clinical care and minimising the exposure of patients and health care professionals to SARS-CoV-2.

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Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.660916 ◽

2021 ◽

Vol 12 ◽

Author(s):

Stefanie Krug ◽

Sadiya Parveen ◽

William R. Bishai

Keyword(s):

Immune Response ◽

Inflammatory Responses ◽

Lung Damage ◽

Tb Treatment ◽

Inflammatory Processes ◽

Clinical Models ◽

Human Immune Response ◽

Human Immune ◽

Anti Inflammatory ◽

Microbiological Cure

Following infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may prolong the TB treatment duration and permanently diminish the lung function of TB survivors. The host also expresses certain anti-inflammatory mediators which may play either beneficial or detrimental roles depending on the timing of their deployment. The balance between the timing and expression levels of pro- and anti-inflammatory responses plays an important role in the fate of infection. Interestingly, M. tuberculosis appears to manipulate both sides of the human immune response to remodel the host environment for its own benefit. Consequently, therapies which modulate either end of this spectrum of immune responses at the appropriate time may have the potential to improve the treatment of TB or to reduce the formation of permanent lung damage after microbiological cure. Here, we highlight host-directed TB therapies targeting pro- or anti-inflammatory processes that have been evaluated in pre-clinical models. The repurposing of already available drugs known to modulate these responses may improve the future of TB therapy.

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Non-steroidal anti-inflammatory drugs in the post-operative treatment of ophthalmic patients

Ophthalmology journal ◽

10.17816/ov2015345-48 ◽

2015 ◽

Vol 8 (3) ◽

pp. 45-48

Author(s):

Sergey Yurievich Astakhov ◽

Medeya Vakhtangovna Gobedzhishvili

Keyword(s):

Cataract Surgery ◽

Operative Treatment ◽

Cataract Extraction ◽

Eye Drops ◽

Treatment Results ◽

Before And After ◽

Inflammatory Processes ◽

Inflammatory Drugs ◽

Anti Inflammatory

Purpose: to analyze the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) after cataract extraction. To determine the NSAID’s role in post-operative inflammatory processes treatment. Results: the rationale of NSAIDs use before and after cataract surgery was validated. The NSAIDs efficacy in terms of post-op inflammation reduction was confirmed. Among NSAIDs benefits, the convenient and easy-to-use instillation regimen of Bromfenac 0.09% eye drops solution was highlighted.

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Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.620984 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yufei Xie ◽

Annemarie H. Meijer ◽

Marcel J. M. Schaaf

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Critical Role ◽

Model Systems ◽

Trinitrobenzene Sulfonic Acid ◽

Inflammatory Drugs ◽

Anti Inflammatory

Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

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