scholarly journals Steroid harms if given early in COVID-19 viraemia

2021 ◽  
Vol 14 (2) ◽  
pp. e241105
Author(s):  
Kanupriya Arora ◽  
Prasan Kumar Panda
Keyword(s):  
Immune Response ◽  
Immune Regulation ◽  
Severe Disease ◽  
Preventive Measure ◽  
Disease Course ◽  
Supportive Treatment ◽  
Cytokine Storm ◽  
Adaptive Immune ◽  
The One ◽  
Anti Inflammation

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

2020 ◽  
Author(s):  
Amr H. Sawalha ◽  
Ming Zhao ◽  
Patrick Coit ◽  
Qianjin Lu
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Viral Entry ◽  
Viral Infections ◽  
Severe Disease ◽  
Disease Course ◽  
Vicious Cycle ◽  
Respiratory Complications ◽  
Disease Remission ◽  
Functional Receptor

SummaryInfection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

scholarly journals Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos A. Labarrere ◽  
Ghassan S. Kassab
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Global Economy ◽  
Rna Viruses ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Recognition Protein ◽  
Pattern Recognition Protein

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

scholarly journals COVID-19 and Cytokine Storm

2020 ◽  
Author(s):  
Mustafa Kurtuluş ◽  
İbrahim Pirim
Keyword(s):  
Immune Response ◽  
Host Response ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
Past Century ◽  
Viral Agent ◽  
Disease Course ◽  
Cytokine Storm ◽  
The Past ◽  
Novel Coronavirus

Although the etiopathogenesis of infections has been largely illuminated by technical and scientific developments in the past century; many issues are still not clear today. The word “there is no disease, there is a patient” is stil valid today. Because the immune response of the host is as important as the virulence of the pathogen in infections and disease course can vary a lot according to the person. Cytokine Storm is seen exactly in a group of diseases where the host response is very prominent. For this reason, Cytokine Storm Syndrome (CSS) is mostly mentioned. CSS emerging due to different inflammatory etiologies; it is an overwhelming systemic inflammation, hemodynamic imbalance, multiple organ failure, and potentially leading to death. After being first seen in Influenza in 2003 as a viral agent, CSS was seen in SARS-Cov, MERS-CoV and SARS-CoV2, which were found to be the las thuman disease from the Corona viridea family.The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. Uncontrolled production of pro-inflammatory mediators contributes to, acut respiratory distress syndrome (ARDS) and cytokine storm syndrome in COVID-19.

scholarly journals Immune Response to COVID-19

2021 ◽  
Author(s):  
Ricardo Wesley Alberca
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Multiple Organ ◽  
Disease Course ◽  
Angiotensin Converting Enzyme 2 ◽  
Damage And Failure ◽  
Adaptive Immune ◽  
General Aspects ◽  
Inflammatory Molecules ◽  
The Impact

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades the host’s cells via the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). ACE2 and TMPRSS2 molecules are highly expressed on the respiratory tract but are also expressed in other organs such as kidneys, heart, and intestine, which could partially explain the multiple organ infection, damage, and failure. During the COVID-19 disease course, patients may develop a dysregulation in the immune response, with an exacerbated production of pro-inflammatory molecules and hypercoagulation, which can collaborate to the increase in tissue damage and death. This chapter will cover general aspects of the innate and adaptive immune response during COVID-19, the impact of comorbidities on the immune response to SARS-CoV-2, and the immune response generated by COVID-19 vaccines.

scholarly journals Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Vincent J. Venditto ◽  
Dalia Haydar ◽  
Ahmed Abdel-Latif ◽  
John C. Gensel ◽  
Michael I. Anstead ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Lung Pathology ◽  
Disease Course ◽  
Immunomodulatory Effects ◽  
Therapeutic Success ◽  
Published Evidence ◽  
Potential Applications ◽  
Regulatory Functions ◽  
Immunomodulatory Therapies

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on timing with respect to the disease course. Azithromycin is an immunomodulatory drug that has been shown to have antiviral effects and potential benefit in patients with COVID-19. Multiple immunomodulatory effects have been defined for azithromycin which could provide efficacy during the late stages of the disease, including inhibition of pro-inflammatory cytokine production, inhibition of neutrophil influx, induction of regulatory functions of macrophages, and alterations in autophagy. Here we review the published evidence of these mechanisms along with the current clinical use of azithromycin as an immunomodulatory therapeutic. We then discuss the potential impact of azithromycin on the immune response to COVID-19, as well as caution against immunosuppressive and off-target effects including cardiotoxicity in these patients. While azithromycin has the potential to contribute efficacy, its impact on the COVID-19 immune response requires additional characterization so as to better define its role in individualized therapy.

scholarly journals Stochastic Model of the Adaptive Immune Response Predicts Disease Severity and Captures Enhanced Cross-Reactivity in Natural Dengue Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Hung D. Nguyen ◽  
Sidhartha Chaudhury ◽  
Adam T. Waickman ◽  
Heather Friberg ◽  
Jeffrey R. Currier ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Stochastic Model ◽  
Disease Severity ◽  
Secondary Infection ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Cross Reactivity ◽  
Adaptive Immune ◽  
Severe Manifestation

The dengue virus circulates as four distinct serotypes, where a single serotype infection is typically asymptomatic and leads to acquired immunity against that serotype. However, the developed immunity to one serotype is thought to underlie the severe manifestation of the disease observed in subsequent infections from a different serotype. We developed a stochastic model of the adaptive immune response to dengue infections. We first delineated the mechanisms initiating and sustaining adaptive immune responses during primary infections. We then contrasted these immune responses during secondary infections of either a homotypic or heterotypic serotype to understand the role of pre-existing and reactivated immune pathways on disease severity. Comparison of non-symptomatic and severe cases from heterotypic infections demonstrated that overproduction of specific antibodies during primary infection induces an enhanced population of cross-reactive antibodies during secondary infection, ultimately leading to severe disease manifestations. In addition, the level of disease severity was found to correlate with immune response kinetics, which was dependent on beginning lymphocyte levels. Our results detail the contribution of specific lymphocytes and antibodies to immunity and memory recall that lead to either protective or pathological outcomes, allowing for the understanding and determination of mechanisms of protective immunity.

scholarly journals Cell type-specific immune dysregulation in severely ill COVID-19 patients

2020 ◽  
Author(s):  
Changfu Yao ◽  
Stephanie A Bora ◽  
Tanyalak Parimon ◽  
Tanzira Zaman ◽  
Oren A Friedman ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Ventilatory Support ◽  
Adaptive Immune Response ◽  
Disease Course ◽  
B Cell Activation ◽  
Peripheral Blood Mononuclear ◽  
Mild Disease

Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.

scholarly journals The epidemiology, clinical presentation, and predictors of severe Tick-borne encephalitis in Lithuania, a highly endemic country: A retrospective study of 1040 patients

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241587
Author(s):  
Daiva Radzišauskienė ◽  
Jurgita Urbonienė ◽  
Gintaras Kaubrys ◽  
Saulius Andruškevičius ◽  
Dalius Jatužis ◽  
...  
Keyword(s):  
Immune Response ◽  
Retrospective Study ◽  
Clinical Presentation ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
University Hospital ◽  
Disease Course ◽  
Tick Borne Encephalitis ◽  
Vilnius University ◽  
Severity Of The Disease

Introduction In recent decades, the incidence of Tick-borne encephalitis (TBE) has been increasing and posing a growing health problem because of the high costs to the healthcare system and society. The clinical manifestations are well studied but there is a lack of research analyzing the severity of the disease. Objective The aim of this study was to analyze the epidemiology and clinical presentation of severe TBE, to identify the predictors for a severe disease course, and also predictors for meningoencephalomyelitic and severe meningoencephalitic/encephalitic forms. Methods A retrospective study was conducted in the Center of Infectious Diseases and the Center of Neurology at Vilnius University Hospital Santaros Klinikos in the years 2005–2017 to describe the clinical and epidemiological features of TBE in adults. Results 1040 patients were included in the study. A total of 152/1040 (14.6%) patients had a severe course. The highest proportion of severe cases, reaching 41.2%, was reported in the 70–79 year-old age group. A total of 36/152 (23.7%) severe patients presented meningoencephalomyelitis. Myelitic patients were older, were frequently infected in their living areas, and usually reported a monophasic disease course compared with severe meningoencephalitic/encephalitic patients. Severe meningoencephalitic/encephalitic patients, compared with non-severe meningoencephalitic/encephalitic, were older, less often noticed the tick bite, and often had a monophasic course. The sequelae on discharge were observed in 810/1000 (81%) of patients. Conclusions The prognostic factors associated with a severe disease course and severe meningoencephalitic form are: older age, comorbidities, a monophasic course, a fever of 40˚C and above, CRP more than 30 mg/l, CSF protein more than 1 g/l, delayed immune response of TBEV IgG, pathological findings in CT. Age above 60 years, presence of CNS disease, bulbar syndrome, pleocytosis 500x106/l and above, and delayed immune response of TBEV IgG are predictors of the most severe myelitic form.

scholarly journals Coronavirus Disease (COVID-19) Outbreak and Adaptive Immune System of the Body: A Review

2020 ◽  
Author(s):  
Amar Deep ◽  
Suchit Swaroop ◽  
Ajay Kumar ◽  
Sumit Rungta
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infection ◽  
Severe Disease ◽  
The Body ◽  
World Health ◽  
Cochrane Library ◽  
Research Database ◽  
First Line ◽  
Adaptive Immune

In December 2019, a severe disease with an unknown aetiology has appeared in a Wuhan City, Hubei province, China. Immediately, it was identified as novel Coronavirus Disease (COVID-19) that has spread globally and also called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and was characterised in China. As we know the presence of viruses with new genetic diversity in nature, it is unclear from where this virus has evolved and transmitted to humans at the first place. As the outbreak of COVID-19 progresses, epidemiological data is essential to guide situational awareness, and intervention strategies and also immune response in COVID-19. That’s why treatments dealing with the immune-pathology of SARS-CoV-2 infection is a major issue for focus now-a-days, while a rapid and well-coordinated immune response represent the first line of defence against the viral infection. Presently, limited data and information is available on the host innate and adaptive immune status of SARS-CoV-2 infected patients. Here, authors described that how the immune system plays the first line of defence against viral infection, and attempt to compile, accumulate and disseminate the immune response information on COVID-19 from the World Health Organisation (WHO), MEDLINE, Embase, Cochrane Library, Centers for Disease Control and Prevention COVID-19 Research Database and trials registries for the recognition in progress and finished studies, cohort, and from Randomised Controlled Trials (RCTs).

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