NF-κB and the Innate Immune Response in the Respiratory Distress Syndrome of the Newborn: Commentary on the article by Cheah et al. on page 616

ABSTRACT Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.

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100 IMMUNE RESPONSE AFTER HETEROLOGOUS SURFACTANT TREATMENT OF NEWBORNS WITH RESPIRATORY DISTRESS SYNDROME (RDS)

Pediatric Research ◽

10.1203/00006450-199009000-00124 ◽

1990 ◽

Vol 28 (3) ◽

pp. 293-293

Author(s):

Arend F Bos ◽

Sidarto Bambang Oetomo ◽

Lou De Ley ◽

Bengt Robertson ◽

Albert Okken

Keyword(s):

Immune Response ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Surfactant Treatment

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Tempering Macrophage plasticity for controlling SARS-CoV-2 infection for managing COVID-19 disease

10.31219/osf.io/g2vwm ◽

2020 ◽

Author(s):

Devinder Toor ◽

Aklank Jain ◽

Shivani Kalhan ◽

Harmesh Manocha ◽

Vivek Kumar Sharma ◽

...

Keyword(s):

Immune Response ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Failure ◽

Pulmonary Fibrosis ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Antiviral Immune Response ◽

Macrophage Plasticity

Hyper activation of macrophages contributes to acute respiratory distress syndrome, respiratory failure, and subsequent death of COVID-19 cases. Given this, tempering macrophage plasticity is paramount and the highest priority for the management of COVID-19 cases. In this context we here propose that either exchange or in situ re-programming of derailed Th17+ alveolar macrophages/ Slan+ DC with Th1 programmed counterpart would potentially mitigate or abolish pulmonary fibrosis. This approach is also anticipated to afford antiviral immune response and promote recovery in the patients and hold tremendous potential for managing severely infected patients by both curbing viruses and enhancing post-treatment recovery.

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COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6401341 ◽

2020 ◽

Vol 2020 ◽

pp. 1-34

Author(s):

Patrick C. Bradshaw ◽

William A. Seeds ◽

Alexandra C. Miller ◽

Vikrant R. Mahajan ◽

William M. Curtis

Keyword(s):

Immune Response ◽

Cell Death ◽

T Cell ◽

Energy Metabolism ◽

Respiratory Distress ◽

Ketogenic Diet ◽

Innate Immune Response ◽

Redox State ◽

Innate Immune ◽

Cytokine Storm

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.

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Functional alteration of innate T cells in critically ill Covid-19 patients

10.1101/2020.05.03.20089300 ◽

2020 ◽

Cited By ~ 8

Author(s):

Youenn Jouan ◽

Antoine Guillon ◽

Loïc Gonzalez ◽

Yonatan Perez ◽

Stephan Ehrmann ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Critically Ill ◽

Distress Syndrome ◽

Potential Contribution ◽

Innate T Cells ◽

Functional Alteration

AbstractCovid-19 can induce lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors in Covid-19-driven ARDS are poorly understood. Here, we dynamically analyzed the biology of innate T cells, a heterogeneous class (MAIT, γδT and iNKT cells) of T lymphocytes, presenting potent anti-infective and regulatory functions. Patients presented a compartmentalized lung inflammation paralleled with a limited systemic inflammation. Circulating innate T cells of critically ill Covid-19 patients presented a profound and persistent phenotypic and functional alteration. Highly activated innate T cells were detected in airways of patients suggesting a recruitment to the inflamed site and a potential contribution in the regulation of the local inflammation. Finally, the expression of the CD69 activation marker on blood iNKT and MAIT cells at inclusion was predictive of disease severity. Thus, patients present an altered innate T cell biology that may account for the dysregulated immune response observed in Covid-19-related acute respiratory distress syndrome.

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Rituximab Administration in Coronavirus Pandemic Era: A Mini-Review of Clinical Evidence

Journal of Iranian Medical Council ◽

10.18502/jimc.v4i2.6458 ◽

2021 ◽

Author(s):

Ahmad Shamabadi ◽

Hamidreza Mahmoudi ◽

Maryam Daneshpazhooh

Keyword(s):

Immune Response ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Cohort Studies ◽

B Cell ◽

Clinical Evidence ◽

Distress Syndrome ◽

Insufficient Evidence ◽

High Quality

Rituximab (RTX), as a B cell-depleting agent, is indicated in treating several malignancies and autoimmune diseases. The management of patients currently receiving RTX and patients starting the medication raised concerns in the pandemic era. Theoretically, suppressing the immune response at the beginning of coronavirus disease 2019 (COVID-19) enhances viral replication, but it prevents acute respiratory distress syndrome as the disease progresses. This review aims to investigate the results of RTX administration in patients during the pandemic era. There is insufficient evidence to definitively conclude on the safety of RTX during the pandemic. For this purpose, high-quality controlled cohort studies, as well as registry-based studies, would be helpful.

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The chance of COVID-19 infection after vaccination

Infectious Disorders - Drug Targets ◽

10.2174/1871526522666220105113829 ◽

2022 ◽

Vol 22 ◽

Author(s):

Ghazaleh Khalili-Tanha ◽

Majid Khazaei ◽

Saman Soleimanpour ◽

Gordon A Ferns ◽

Amir Avan

Keyword(s):

Genetic Diversity ◽

Immune Response ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Mild Form ◽

The World ◽

New Generation ◽

Pathogenic Infection

Abstract: The outbreak of COVID-19 that began in Wuhan, China, has constituted a new emerging epidemic that has spread around the world. There are some reports on illustrated the patients getting reinfected after recovering from COVID-19. Here we provide an overview of the biphasic cycle of COVID-19, genetic diversity, immune response and chance of reinfection after recovering from COVID-19. The new generation of COVID-19 is highly contagious and pathogenic infection can lead to acute respiratory distress syndrome. Whilst most patients suffer from a mild form of the disease, there is a rising concern that patients who recover from COVID-19 may be at risk of reinfection. The proportion of the infected population, is increasing worldwide; meanwhile, the rate and concern of reinfection by the recovered population are still high. Moreover, there are a few evidence on the chance of COVID-19 infection even after vaccination, which is around one per cent or less. Although the hypothesis of zero reinfections after vaccination has not been clinically proven, further studies should be performed on the recovered class in clusters to study the progression of the exposed with the re-exposed subpopulations to estimate the possibilities of reinfection and, thereby, advocate the use of these antibodies for vaccine creation.

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