COVID-19: Cytokine storm modulation/blockade with oral polyvalent immunoglobulins (PVIG, KMP01D): A potential and safe therapeutic agent (Primum nil nocere)

2020 ◽  
Vol 58 (12) ◽  
pp. 678-686 ◽  
Author(s):  
Laura M. Sly ◽  
Peter Braun ◽  
Barry G. Woodcock
Keyword(s):  
Therapeutic Agent ◽  
Cytokine Storm ◽  
Nil Nocere ◽  
Polyvalent Immunoglobulins

scholarly journals Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2

2020 ◽  
Author(s):  
Russell M. Petrak ◽  
Nathan C. Skorodin ◽  
Nicholas W. Van Hise ◽  
Robert M. Fliegelman ◽  
Jonathan Pinsky ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Markers ◽  
Chart Review ◽  
Therapeutic Agent ◽  
P Value ◽  
Cytokine Storm ◽  
Multi Center Study ◽  
Center Study

AbstractBackgroundTocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2.MethodsWe evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between 3/13/20 and 4/16/20. This was a multi-center study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. In the absence of mechanical ventilation, the timing of the dose was related to the patient’s date of admission only.ResultsWe evaluated 145 patients. The average age was 58.1 years, 64% were male, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% expired, of which 43.9% were African American. Mechanical ventilation was required in 55.9%, of which 34.5% expired. Avoidance of MV (p value = 0.002) and increased survival (p value < 0.001) was statistically associated with early dosing.ConclusionsTocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill COVID-19 patients.SummaryUtilizing tocilizumab early in the treatment course of critically ill patients with COVID-19 resulted in significant decreases in mortality and the avoidance of mechanical ventilation.

scholarly journals COVID 19: AN OVERVIEW OF PATHOGENESIS, CYTOKINE STORM AND INTERFERONS AS A POTENTIAL DRUG THERAPY

2020 ◽  
pp. 1-2
Author(s):  
R. Ishwarya ◽  
V. Kishore Kumar ◽  
K.V Leela
Keyword(s):  
Respiratory Distress ◽  
Therapeutic Agent ◽  
Distress Syndrome ◽  
Infected Individual ◽  
Low Molecular Weight ◽  
Cytokine Storm ◽  
Novel Coronavirus ◽  
Respiratory Droplets ◽  
Intercellular Messenger ◽  
Made In

Novel Coronavirus (SARS-CoV-2) causing Coronavirus disease (COVID-19) has become a pandemic and has not been previously identified in humans. Transmission among humans occurs through respiratory droplets of infected individual. Patients infected with SARS-CoV-2 undergo acute respiratory distress because of Cytokine storm which serve as the major cause of morbidity and mortality in affected individuals. Cytokines are defined as non-structural proteins which are small with low molecular weight and have a greater regulatory influence in inflammation and immunity. They are considered as the intercellular messenger in the immune system. Therefore, this article provides a glimpse of advancements made in the area of SARS-CoV-2 infection where Cytokines may be a useful biomarker for both diagnostic and prognostic purpose and also as a therapeutic agent in targeting certain cytokines responsible for Acute Respiratory Distress Syndrome (ARDS) in SARS-CoV-2 infected patients.

Tocilizumab In Severe To Critical Confirmed COVID-19: A Case Series At Ulin Referral Hospital Of South Kalimantan

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Haryati Haryati ◽  
Fidya Rahmadhany Arganita ◽  
Widya Ramadhaniati
Keyword(s):  
Therapeutic Agent ◽  
Clinical Laboratory ◽  
Case Series ◽  
Absolute Lymphocyte Count ◽  
Clinical Severity ◽  
X Rays ◽  
Cytokine Storm ◽  
Laboratory Results ◽  
Before And After ◽  
New Type

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes pneumonia. The clinical severity of COVID-19 is related to the presence of a “cytokine storm” that causes overproduction of inflammatory mediators such as interleukin (IL)-6. Tocilizumab (TCZ) as an IL-6 inhibitor is subject of major studies as a potential therapeutic agent. This study reported 20 cases of COVID-19 patients being treated with the IL-6 inhibitor TCZ beside standard therapy. Patients were followed up on clinical, laboratory and chest x-rays before and after the administration of therapy which were report descriptively. The oxygen saturation of patients who survived shows rapid improvements. The laboratory results showed that CRP decreased after administration TCZ immediately. Meanwhile, other markers improve slowly, such as leucocytes, Neutrophyl Lymphocyte Ratio (NLR), Absolute Lymphocyte Count (ALC) and Lactate Dehydrogenase (LDH) but ferritin was tended to fluctuate. In chest X-ray’s, infiltrate bilateral on admission began to diminished until almost disappeared on the 14th day after TCZ. From 20 patients, 80% of patients survived with improvement in clinical, laboratory and chest X-rays, while the rest death with a good response on first therapy but fluctuated and worsened before death. Tocilizumab can be considered to provide clinical improvements in severe and critical COVID-19 patients.

scholarly journals Extracellular Vesicle-Based Therapy for COVID-19: Promises, Challenges and Future Prospects

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1373
Author(s):  
Vamika Karn ◽  
Shaista Ahmed ◽  
Lung-Wen Tsai ◽  
Rajni Dubey ◽  
Shreesh Ojha ◽  
...  
Keyword(s):  
Public Health ◽  
Therapeutic Agent ◽  
Distress Syndrome ◽  
Mortality Rates ◽  
Extracellular Vesicle ◽  
Therapeutic Strategies ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Alveolar Fluid Clearance ◽  
Future Prospects

The COVID-19 pandemic has become a serious concern and has negatively impacted public health and the economy. It primarily targets the lungs, causing acute respiratory distress syndrome (ARDS); however, it may also lead to multiple organ failure (MOF) and enhanced mortality rates. Hence, there is an urgent need to develop potential effective therapeutic strategies for COVID-19 patients. Extracellular vesicles (EVs) are released from various types of cells that participate in intercellular communication to maintain physiological and pathological processes. EVs derived from various cellular origins have revealed suppressive effects on the cytokine storm during systemic hyper-inflammatory states of severe COVID-19, leading to enhanced alveolar fluid clearance, promoted epithelial and endothelial recovery, and cell proliferation. Being the smallest subclass of EVs, exosomes offer striking characteristics such as cell targeting, being nano-carriers for drug delivery, high biocompatibility, safety, and low-immunogenicity, thus rendering them a potential cell-free therapeutic candidate against the pathogeneses of various diseases. Due to these properties, numerous studies and clinical trials have been performed to assess their safety and therapeutic efficacy against COVID-19. Hence, in this review, we have comprehensively described current updates on progress and challenges for EVs as a potential therapeutic agent for the management of COVID-19.

ACE2 as therapeutic agent

2020 ◽  
Vol 134 (19) ◽  
pp. 2581-2595
Author(s):  
Qiuhong Li ◽  
Maria B. Grant ◽  
Elaine M. Richards ◽  
Mohan K. Raizada
Keyword(s):  
Therapeutic Agent ◽  
Renin Angiotensin System ◽  
Peptide Hormone ◽  
Experimental Models ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
Overwhelming Evidence ◽  
Future Challenges

Abstract The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin–angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein–coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.

Gold as a Therapeutic Agent

1890 ◽  
Vol 30 (767supp) ◽  
pp. 12257-12257
Author(s):  
C. J. S. Thompson
Keyword(s):  
Therapeutic Agent

Low melatonin as a contributor to SARS-CoV-2 disease

2020 ◽  
Vol 3 (4) ◽  
pp. 558-576
Author(s):  
Seithikurippu R Pandi-Perumal ◽  
Daniel P Cardinali ◽  
Russel J Reiter ◽  
Gregory M Brown
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Pineal Gland ◽  
Oxygen Species ◽  
Cytokine Storm ◽  
Major Site ◽  
Immune Modulator ◽  
Inflammatory Agent ◽  
Site Of Action ◽  
Extrapineal Melatonin

That the pineal gland is a source of melatonin is widely known; however, by comparison, few know of the much larger pool of extrapineal melatonin. That pool is widely distributed in all animals, including those that do not have a pineal gland, e.g., insects.  Extrapineal melatonin is not released into the blood but is used locally to function as an antioxidant, anti-inflammatory agent, etc. A major site of action of peripherally-produced melatonin is the mitochondria where it neutralizes reactive oxygen species (ROS) that are generated during oxidative phosphorylation. Its role also includes major actions as an immune modulator reducing overreactions to foreign agents while simultaneously boosting immune processes. During a pandemic such as coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, melatonin is capable of suppressing the damage inflicted by the cytokine storm. The implications of melatonin in susceptibility and treatment of COVID-19 disease are discussed. 

Nil nocere? The nocebo phenomenon

2009 ◽  
Vol 64 (4) ◽  
pp. 697-727 ◽  
Author(s):  
Ferenc Köteles ◽  
György Bárdos
Keyword(s):  
Nil Nocere

Áttekintésünk célja a nocebo-jelenség átfogó ismertetése, valamint három, a szakirodalomban rendszerint különállóként kezelt jelenségkör (nocebo, egészséges személyek tünetbeszámolója, orvosilag nem megmagyarázott panaszok) rövid összehasonlítása. Elméletünk szerint e jelenségek között a kiváltó és fenntartó mechanizmusok szintjén annyira szoros a rokonság, hogy tárgyalásuk egységes fogalmi keretben (nem-specifikus egészségproblémák) lenne indokolt.Ennek bizonyítására áttekintjük a jelenségek mögött álló potenciális pszichofiziológiai mechanizmusokat (az elvárások különböző típusai; klasszikus kondicionálás; társas tanulás; stressz, szorongás, depresszió; szomatizáció; a tabletták anyaga; valós betegségek tünetei) és motivációs hátteret (kontrolligény és hibás oktulajdonítás; gyógyszerek hatásosságának megítélése; terápiás rezisztencia; bűntudat és önbüntetés; tömegjelenségek; másodlagos betegségelőnyök; tudatos szimuláció), illetve a fontosabb kapcsolódó diszpozicionális személyiségjellemzőket (női nem; neuroticizmus; testi folyamatok fokozott észrevételére való hajlam).Röviden összehasonlítjuk a nocebo- és a placebo-jelenséget, és ellenezzük azt a megközelítést, ami a kettőt egymás tükörképének tekinti.Végül összefoglaljuk és kiegészítjük a korábbi irodalomban található, a nocebo-hatás csökkentését célzó intervenciós lehetőségeket.

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