scholarly journals Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms

Author(s):  
Christian Muschitz ◽  
Anita Trummert ◽  
Theresa Berent ◽  
Norbert Laimer ◽  
Lukas Knoblich ◽  
...  

SummarySevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.

2019 ◽  
Vol 5 (3) ◽  
pp. 70 ◽  
Author(s):  
James Riddell ◽  
L. Joseph Wheat

Histoplasmosis is an endemic fungal infection that may affect both immune compromised and non-immune compromised individuals. It is now recognized that the geographic range of this organism is larger than previously understood, placing more people at risk. Infection with Histoplasma capsulatum may occur after inhalation of conidia that are aerosolized from the filamentous form of the organism in the environment. Clinical syndromes typically associated with histoplasmosis include acute or chronic pneumonia, chronic cavitary pulmonary infection, or mediastinal fibrosis or lymphadenitis. Disseminated infection can also occur, in which multiple organ systems are affected. In up to 10% of cases, infection of the central nervous system (CNS) with histoplasmosis may occur with or without disseminated infection. In this review, we discuss challenges related to the diagnosis of CNS histoplasmosis and appropriate treatment strategies that can lead to successful outcomes.


2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.


2020 ◽  
Vol 7 ◽  
Author(s):  
Georgina M. Ellison-Hughes ◽  
Liam Colley ◽  
Katie A. O'Brien ◽  
Kirsty A. Roberts ◽  
Thomas A. Agbaedeng ◽  
...  

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has led to 47 m infected cases and 1. 2 m (2.6%) deaths. A hallmark of more severe cases of SARS-CoV-2 in patients with acute respiratory distress syndrome (ARDS) appears to be a virally-induced over-activation or unregulated response of the immune system, termed a “cytokine storm,” featuring elevated levels of pro-inflammatory cytokines such as IL-2, IL-6, IL-7, IL-22, CXCL10, and TNFα. Whilst the lungs are the primary site of infection for SARS-CoV-2, in more severe cases its effects can be detected in multiple organ systems. Indeed, many COVID-19 positive patients develop cardiovascular complications, such as myocardial injury, myocarditis, cardiac arrhythmia, and thromboembolism, which are associated with higher mortality. Drug and cell therapies targeting immunosuppression have been suggested to help combat the cytokine storm. In particular, mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory ability, have shown promise in early clinical studies to avoid, prevent or attenuate the cytokine storm. In this review, we will discuss the mechanistic underpinnings of the cytokine storm on the cardiovascular system, and how MSCs potentially attenuate the damage caused by the cytokine storm induced by COVID-19. We will also address how MSC transplantation could alleviate the long-term complications seen in some COVID-19 patients, such as improving tissue repair and regeneration.


2021 ◽  
Vol 218 (3) ◽  
Author(s):  
Eric Song ◽  
Ce Zhang ◽  
Benjamin Israelow ◽  
Alice Lu-Culligan ◽  
Alba Vieites Prado ◽  
...  

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.


2021 ◽  
Vol 9 (1) ◽  
pp. 6-6
Author(s):  
Inderbir Padda ◽  
Nimrat Khehra ◽  
Urooj Jaferi ◽  
Dina Mosabbeh ◽  
Harshan Atwal ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its effects on the organ systems have been summarized in recent literature with predominant pulmonary characteristics as a hallmark of the COVID-19 virus. Considering its accelerated appearance from Wuhan, China, in December 2019, extrapulmonary effects have been reported globally of SARS-CoV-2 involving the central nervous system (CNS), cardiovascular, gastrointestinal, renal, and hematologic systems; thus, the potential mechanisms, pathophysiology, clinical characteristics, management, outcome, and case reports per organ system are summarized in depth. The authors interpreted articles composed of case reports, case-series, meta-analysis, cohort studies, retrospective studies, and narrative reviews focusing on COVID-19 confirmed cases and their effects on the organ systems. Prevalent clinical organ system complexities include pneumonia, acute respiratory distress syndrome (ARDS), pulmonary hypertension, pulmonary embolism, hypertension, cardiac arrhythmias, myocarditis progressing to fulminant myocarditis, anorexia, nausea, vomiting, diarrhea, liver dysfunction, encephalopathy, encephalitis, meningitis, intracerebral hemorrhage, acute kidney injury, and hypercoagulability causing stroke and disseminated intravascular coagulation (DIC). This comprehensive literature review article will help clinicians and researchers gain insight about SARS-CoV-2 and its diverse effects on multiple organ systems involved, therefore help implement prospective management and preventative measures.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Ashim Malhotra ◽  
Sundeep Bath ◽  
Fawzy Elbarbry

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson’s and Alzheimer’s disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment.


2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Syed Hassan ◽  
Fatima Khalid ◽  
Zaid Alirhayim ◽  
Syed Amer

Lithium toxicity is known to affect multiple organ systems, including the central nervous system. Lithium levels have been used in the diagnosis of toxicity and in assessing response to management. There is evidence that nonsteroidal anti-inflammatory medications (NSAIDs) can increase lithium levels and decrease renal lithium clearance. We present a case of lithium toxicity, which demonstrates this effect and also highlights the fact that lithium levels do not correlate with clinical improvement, especially the neurological deficit.


2019 ◽  
Vol 6 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Md Fakruddin

Diabetes Mellitus (DM), one of the most non-communicable diseases, is increasing day by day in an alarming way. More than 140 million people are suffering from diabetes throughout the world. It is not a single disease entity, but rather a group of metabolic disorders sharing the common underlying feature of hyperglycemia. Hyperglycemia in diabetes results from defects in insulin secretion, insulin action, or, most commonly, both. The chronic hyperglycemia and attendant metabolic deregulation may be associated with secondary damage in multiple organ systems, especially the kidneys, eyes, nerves, and blood vessels. The pathophysiology of diabetes is not fully elucidated. Insulin secretory dysfunction and insulin resistance or both is main candidate for this metabolic disorder, moreover various genetic and environmental factors may also involve in this process. Racial variations play also an important role as evidenced by various studies. However, the interrelationships between the molecular and metabolic mechanisms in these parameters contributing this life threatening disease still remain a mystery to the scientists. Journal of Current and Advance Medical Research 2019;6(1):59-63


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2131
Author(s):  
Daire J. Hurley ◽  
Mustapha Irnaten ◽  
Colm O’Brien

Glaucoma is the leading cause of irreversible blindness globally. With an aging population, disease incidence will rise with an enormous societal and economic burden. The treatment strategy revolves around targeting intraocular pressure, the principle modifiable risk factor, to slow progression of disease. However, there is a clear unmet clinical need to find a novel therapeutic approach that targets and halts the retinal ganglion cell (RGC) degeneration that occurs with fibrosis. RGCs are highly sensitive to metabolic fluctuations as a result of multiple stressors and thus their viability depends on healthy mitochondrial functioning. Metformin, known for its use in type 2 diabetes, has come to the forefront of medical research in multiple organ systems. Its use was recently associated with a 25% reduced risk of glaucoma in a large population study. Here, we discuss its application to glaucoma therapy, highlighting its effect on fibrotic signalling pathways, mitochondrial bioenergetics and NAD oxidation.


1993 ◽  
Vol 27 (12) ◽  
pp. 1463-1464 ◽  
Author(s):  
Daniel M. Witt ◽  
Allan J. Ellsworth ◽  
John H. Leversee

OBJECTIVE: To describe a potential drug interaction between amiodarone and clonazepam. CASE SUMMARY: A 78-year-old man with a history of congestive heart failure and coronary artery disease began taking amiodarone to suppress sustained ventricular tachycardia. Following the development of restless leg syndrome, therapy with clonazepam 0.5 mg qhs was initiated. Subsequently, the patient demonstrated signs and symptoms of benzodiazepine toxicity, which cleared following the discontinuation of clonazepam. DISCUSSION: Amiodarone is a Class III antiarrhythmic with an adverse-effect profile involving many different organ systems. It also has been shown to inhibit the metabolism of drugs cleared by oxidative microsomal enzymes. Clonazepam undergoes extensive hepatic metabolism, primarily by reduction and acetylation, and is therefore susceptible to altered disposition during concomitant administration of agents that inhibit hepatic microsomal enzymes. Hypothyroidism, occurring in up to 11 percent of patients treated with amiodarone, can also alter drug metabolism and sensitize the central nervous system, thus increasing the potential for toxicity. It is likely that a combination of these factors was responsible for the symptoms described in this patient. CONCLUSIONS: The complex pharmacologic profile of amiodarone and its effects on multiple organ systems necessitates close patient monitoring during concurrent administration of medications such as clonazepam, which are cleared by oxidative metabolism.


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