scholarly journals Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation during Acute Respiratory Distress: A Case Report and Literature Review

2020 ◽  
Vol 5 (3) ◽  
pp. 112 ◽  
Author(s):  
Faryal Farooqi ◽  
Naveen Dhawan ◽  
Richard Morgan ◽  
John Dinh ◽  
Kester Nedd ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Distress ◽  
Acute Phase ◽  
Current Evidence ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Acute Phase Reactants ◽  
Standard Drug ◽  
Therapeutic Benefits

COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic. The disease continues to pose a major therapeutic challenge. Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS). Cytokine release syndrome (or “cytokine storm”) is likely to be a contributing factor to ARDS in many patients. Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release. We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress. The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm. We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status. The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc). The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days. We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation. Ultimately, the patient was downgraded from the ICU and discharged within days. We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support. This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19. Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality—the cytokine storm. This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality. Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19.

scholarly journals Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Drug Research ◽  
2021 ◽  
Author(s):  
Ashif Iqubal ◽  
Farazul Hoda ◽  
Abul Kalam Najmi ◽  
Syed Ehtaishamul Haque
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Macrophage Activation ◽  
Fatality Rate ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Disease Condition ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

AbstractCoronavirus disease (COVID-19) emerged from Wuhan, has now become pandemic and the mortality rate is growing exponentially. Clinical complication and fatality rate is much higher for patients having co-morbid issues. Compromised immune response and hyper inflammation is hall mark of pathogenesis and major cause of mortality. Cytokine release syndrome (CRS) or cytokine storm is a term used to affiliate the situation of hyper inflammation and therefore use of anti-cytokine and anti-inflammatory drugs is used to take care of this situation. Looking into the clinical benefit of these anti-inflammatory drugs, many of them enter into clinical trials. However, understanding the immunopathology of COVID-19 is important otherwise, indiscriminate use of these drugs could be fetal as there exists a very fine line of difference between viral clearing cytokines and inflammatory cytokines. If any drug suppresses the viral clearing cytokines, it will worsen the situation and hence, the use of these drugs must be based on the clinical condition, viral load, co-existing disease condition and severity of the infection.

scholarly journals Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1067
Author(s):  
Oleksandr Oliynyk ◽  
Wojciech Barg ◽  
Anna Slifirczyk ◽  
Yanina Oliynyk ◽  
Vitaliy Gurianov ◽  
...  
Keyword(s):  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
C Reactive Protein ◽  
Treatment Results ◽  
Reactive Protein ◽  
Median Serum ◽  
D Dimer

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0–4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25–0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

scholarly journals Efficacy of tocilizumab in COVID-19: A review of the current evidence

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110303
Author(s):  
Walid Alam ◽  
Abdul Rahman Bizri
Keyword(s):  
Randomized Clinical Trials ◽  
Current Evidence ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Inflammatory Reactions ◽  
Health Measures ◽  
Clinical Trial Registries ◽  
Overwhelming Evidence ◽  
Clinical Benefits ◽  
Mixed Efficacy

As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative review that aims to review the current evidence provided by randomized clinical trials (RCT) for the use of tocilizumab in COVID-19. Electronic database searches were carried out in Medline, PubMed, Embase, Google Scholar, and ongoing clinical trial registries with the period set from January 1, 2020 to February 20, 2021. Prepublication manuscripts were found using the pre-print repository medRxiv. Keywords included “COVID-19,”“coronavirus,”“SARS-CoV-2,”“sepsis,”“pneumonia,”“cytokine storm,”“cytokine release syndrome,”“IL-6 inhibitors,” and “tocilizumab,” as exact phrases, and a combination of subject headings according to databases syntax. Only trials with a clear and well-defined methodology, at least 100 patients recruited, and which have had results published either after peer review or in pre-print were included. In hospitalized patients with severe COVID-19, who are hypoxic and have a CRP ≥ 75 mg/L, the current evidence favors the use of a combination of tocilizumab and corticosteroids to reduce mortality, among other clinical benefits. There is also overwhelming evidence of the good safety profile of tocilizumab with only few cases of neutropenia reported with a decrease in infection rates. Tocilizumab is currently thought to work through the inhibition of IL-6 receptors (IL-6R), preventing downstream activation of pro-inflammatory reactions and cytokine release syndrome.

scholarly journals Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

2021 ◽  
Vol 22 (15) ◽  
pp. 7914
Author(s):  
So Yeong Cheon ◽  
Bon-Nyeo Koo
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Immune Complex ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Organ Damage ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Pro Inflammatory Cytokines

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

scholarly journals Combined effects of Tocilizumab and Remdesivir in severe COVID- 19 patient with cytokine release syndrome: A case-report (Preprint)

2021 ◽  
Author(s):  
Sabahat Ali ◽  
Sundas Khalid ◽  
Maham Afridi ◽  
Samar Akhtar ◽  
Yousef S. Khader ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Virus Disease ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Treatment Regimens ◽  
Corona Virus

BACKGROUND Novel corona virus (nCoV) or Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to cause severe bilateral pneumonia and acute respiratory distress syndrome (ARDS) or Corona virus disease-2019 (COVID-19) in patients that can be debilitating and even fatal. With no drugs or vaccines available yet, a wide range of treatment regimens used are being repurposed. The need of the hour is to analyze various regimens available and devise a treatment plan most effective against SARS-CoV-2. OBJECTIVE Patient concerns: A 68-year-old hypertensive, diabetic male, exhibiting symptoms of cough and shortness of breath presented at the emergency department of our hospital. Diagnosis: Chest CT revealed bilateral ground glass opacities indicative of COVID-19 and the CT score of 24 indicated severe pulmonary pneumonia. He tested positive for COVID-19. METHODS Interventions: The treatment regimen included use of convalescent plasma, oxygen therapy, steroids, high dose antibiotics, broad spectrum antiviral Remdesivir, and anti-interleukin-6 monoclonal antibody/Tocilizumab at various stages of the disease. RESULTS Outcomes: Oxygen support was required at the time of admission. The patient initially developed cytokine release storm and mechanical ventilation was used to manage his condition. Supportive care and multiple treatment regimens were used to successfully recover the patient’s health. CONCLUSIONS Lessons: With a rapid increase in number of confirmed cases worldwide, COVID-19 has become a major challenge to our healthcare system. With no available vaccines currently, finding a combination of therapeutic drugs which are effective in reducing progression of disease is of utmost importance. CLINICALTRIAL Abbreviations:COVID-19=Corona virus disease 2019, nCoV=Novel corona virus (nCoV), SARS-CoV-2=Severe acute respiratory syndrome coronavirus 2, ARDS=acute respiratory distress syndrome, RT PCR= real-time polymerase chain reaction, SPO2= oxygen saturation, ICU=Intensive Care Unit, GGO=ground glass opacities, TDS=thrice daily, OD=once daily, BD= twice daily, CRS= cytokine release syndrome, CPAP=continuous positive airway pressure,FiO2= fraction of inspired oxygen, PEEP=positive end-expiratory pressure, PSV= pressure support ventilation.

scholarly journals Combination therapy of Tocilizumab and steroid for management of COVID-19 associated cytokine release syndrome: A single center experience from Pune, Western India

2021 ◽  
Author(s):  
Ameet Dravid ◽  
Reema Kashiva ◽  
Zafer Khan ◽  
Danish Memon ◽  
Aparna Kodre ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Combination Therapy ◽  
Fungal Infections ◽  
Infectious Complications ◽  
Western India ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Systemic Complications ◽  
Risk Of Death ◽  
Increased Risk

AbstractBackgroundCytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednisolone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for the treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroids in COVID-19 associated CRS.MethodsThis retrospective cohort study was conducted at a tertiary level private hospital in Pune, India between 2nd April and 2nd November 2020. All patients administered TCZ and steroids for treatment of CRS were included. The primary endpoint was incidence of all-cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of infectious complications. Baseline and time-dependent risk factors significantly associated with death were identified by Relative risk estimation.ResultsOut of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. Median age of the cohort was 57 (IQR: 46.5, 66) years. Almost 72 % patients had preexisting co-morbidities. Median time to TCZ administration since onset of symptoms was 9 days (IQR: 7, 11). 63% patients needed intensive care unit (ICU) admission. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Infectious complications like hospital acquired pneumonia, bloodstream bacterial and fungal infections were observed in 2.13 %, 2.13 % and 0.06 % patients respectively. Age ≥ 60 years (p=0.014), presence of co-morbidities like hypertension (p = 0.011), IL-6 ≥ 100 pg/ml (p = 0.002), D-dimer ≥ 1000 ng/ml (p < 0.0001), CT severity index ≥ 18 (p < 0.0001) and systemic complications like lung fibrosis (p = 0.019), cardiac arrhythmia (p < 0.0001), hypotension (p < 0.0001) and encephalopathy (p < 0.0001) were associated with increased risk of death.ConclusionsCombination therapy of TCZ and Steroids is likely to be safe and effective in the management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled clinical trials.

Inflammatory Biomarkers and Chronic Diseases: The Link to COVID-19.

2021 ◽  
pp. 1-8
Keyword(s):  
Fatal Outcome ◽  
Healthcare Systems ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Gm Csf ◽  
Immune Therapies ◽  
Medical Reports ◽  
Strong Body ◽  
True Measure

1. Abstract The COVID-19 disease and pandemic eruption have caused a major concern for patients and healthcare systems globally. Immunological therapies are among the areas that require a lot of attention as the immunological consequences of the infection are neither well defined nor well understood. All medical reports indicate that severe acute respiratory syndrome-coronavirus-2 infection has a fatal outcome often results from alveolar injury that impedes airway capacity and multi-organ failure. Both of these complications are associated with the hyper production of cytokines that is known by the term cytokine storm and also called cytokine release syndrome. Strong body of clinical reports show that both mild and severe forms of disease result in cytokine secretion through changes in circulating leukocyte subsets. This is accompanied by elevated level of cytokines production. The milieu of cytokines produced includes IL-6, IL-1β, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), IL-17, MCP-1, MCP-3 and IL-1ra. With no surprise immune-therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID-19) patients have become a focus of recent clinical trials. In this mini-review we are also highlighting the importance of monitoring closely the levels of the cytokines as a true measure for the patient`s status and immunity level.

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