scholarly journals Countermeasures to Coronavirus Disease 2019: Are Immunomodulators Rational Treatment Options—A Critical Review of the Evidence

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Daniel B Chastain ◽  
Tia M Stitt ◽  
Phong T Ly ◽  
Andrés F Henao-Martínez ◽  
Carlos Franco-Paredes ◽  
...  

Abstract Severe acute respiratory syndrome coronavirus 2 is associated with higher concentrations of proinflammatory cytokines that lead to lung damage, respiratory failure, and resultant increased mortality. Immunomodulatory therapy has the potential to inhibit cytokines and quell the immune dysregulation. Controversial data found improved oxygenation after treatment with tocilizumab, an interleukin-6 inhibitor, sparking a wave of interest and resultant clinical trials evaluating immunomodulatory therapies. The purpose of this article is to assess potential proinflammatory targets and review the safety and efficacy of immunomodulatory therapies in managing patients with acute respiratory distress syndrome associated with coronavirus disease 2019.

Folia Medica ◽  
2021 ◽  
Vol 63 (3) ◽  
pp. 321-328
Author(s):  
Viktoria Ilieva ◽  
Yordanka Yamakova

Introduction: The benefit of non-invasive ventilation (NIV) in cases of hypercapnic acute respiratory failure (ARF) has already been proven. Still, its safety and efficacy as a respiratory support method for patients with hypoxemic ARF hasn’t been studied so well.Aim: The aim of our study was to examine the safety and efficacy of NIV in hypoxemic ARF of primary lung origin.Materials and methods: This was a prospective observational cohort study of patients with hypoxemic ARF due to communityacquired pneumonia with or without acute respiratory distress syndrome (ARDS) treated using NIV. They were divided into four groups: pneumonia without ARDS, mild, moderate, or severe ARDS. Their clinical and ABG parameters were recorded before initiation of NIV, at 1 hour and 24 hours after ventilation onset and at transition to non-intensive NIV or before endotracheal intubation in NIV failure cases.Results: A total of 63 patients were included. NIV trial was successful in 85.71% of them, while 14.29% experienced NIV failure. In the general population, we observed a significant difference in PaO2/FiO2 only before transition to non-intensive NIV in comparison to the value at admission. This trend was seen in the patients with pneumonia without ARDS and moderate ARDS, but not in those with mild and severe ARDS. The clinical parameters showed improvement early in the course of treatment both in the entire study population and all subgroups.Conclusions: NIV is an effective and safe option for respiratory support in patients with severe CAP only when an adequate etiological treatment has been applied.


2021 ◽  
Vol 42 (1) ◽  
pp. 46
Author(s):  
Kasha P Singh ◽  
Joe Sasadeusz ◽  
Sharon R Lewin ◽  
Jennifer Audsley

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognised in late 2019, with over 30 000 000 cases and over 1 000 000 deaths reported by the end of September 2020. SARS-CoV-2 infection is usually associated with fever, cough, coryza, dyspnoea, anosmia, headache and fatigue and may cause pneumonia and hypoxemia. An excessive/dysregulated inflammatory response may lead to lung damage including acute respiratory distress syndrome (ARDS), coagulopathy and other complications. Mortality amongst hospitalised patients is higher in those needing intensive care. In Australia over 27 000 cases with 882 deaths had been reported by 30 September, most in Victoria. Two therapies have proven beneficial in treatment of hospitalised patients in expedited randomised placebo-controlled trials and are now in widespread use. Dexamethasone improved survival of those requiring respiratory support and the antiviral agent remdesivir decreased time to recovery in mild-moderate disease. Remdesivir was authorised by the Australian Therapeutic Goods Administration in July 2020. Over 200 other therapeutics are being tested for COVID-19 in more than 2000 clinical trials, and many more agents are in preclinical development. We review the evidence for some of the candidates for therapy in COVID-19.


2020 ◽  
Vol 41 (4) ◽  
pp. 217
Author(s):  
Kasha P Singh ◽  
Joe Sasadeusz ◽  
Sharon R Lewin ◽  
Jennifer Audsley

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognised in late 2019, with over 30000000 cases and over 1000000 deaths reported by the end of September 2020. SARS-CoV-2 infection is usually associated with fever, cough, coryza, dyspnoea, anosmia, headache and fatigue and may cause pneumonia and hypoxemia. An excessive/dysregulated inflammatory response may lead to lung damage including acute respiratory distress syndrome (ARDS), coagulopathy and other complications. Mortality amongst hospitalised patients is higher in those needing intensive care. In Australia over 27000 cases with 882 deaths had been reported by 30 September, most in Victoria. Two therapies have proven beneficial in treatment of hospitalised patients in expedited randomised placebo-controlled trials and are now in widespread use. Dexamethasone improved survival of those requiring respiratory support and the antiviral agent remdesivir decreased time to recovery in mild-moderate disease. Remdesivir was authorised by the Australian Therapeutic Goods Administration in July 2020. Over 200 other therapeutics are being tested for COVID-19 in more than 2000 clinical trials, and many more agents are in preclinical development. We review the evidence for some of the candidates for therapy in COVID-19.


2021 ◽  
pp. 30-41
Author(s):  
Tatyana Nikolaevna Tsyganova ◽  
Egor Egorov ◽  
Tamara Nikolaevna Voronina

COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, primarily affects lung tissue and disrupts gas exchange, leading to acute respiratory distress syndrome, systemic hypoxia, and lung damage. The search for methods of prevention and rehabilitation, especially after suffering from pneumonia caused by COVID-19, is on the agenda. This article discusses the possibilities of the interval hypoxic training (IHT) method for preventing infections by initiating nitric oxide production in the body. One of the main effects of IHT is the balanced stimulation of nitric oxide (NO) secretion. Over the past two decades, there has been an increasing interest in the function of nitric oxide (NO) in the human body. Nitric oxide plays a key role in maintaining normal vascular function and regulating inflammatory processes, including those leading to lung damage and the development of acute respiratory distress syndrome (ARDS). Our immune system destroys bacteria and viruses by oxidative burst, i.e. when oxygen accumulates inside the cell. This process also involves nitric oxide, a signaling molecule that has an antibacterial and antiviral effect, as well as regulates vascular tone and affects the permeability of the cell wall. Interval hypoxytherapy enhances endogenous oxidative protection and increases the amount of nitric oxide, thus allowing the body’s cells to resist infection more effectively. Mitochondrial NOS induction and mitochondrial NO synthesis increase under the action of pathogenic factors on the cell. By modulating the activity of mtNOS and the synthesis of mitochondrial NO, it is possible to increase the resistance to hypoxic effects. Interval hypo-hyperoxic training as an effective non-specific method of increasing the body’s defenses is indispensable not only in the prevention of viral infection, but also in rehabilitation after viral pneumonia, as well as as a method that reduces the severity of viral infection in the event of infection.


Author(s):  
Renat R. Gubaidullin ◽  
◽  
Aleksandr P. Kuzin ◽  
Vladimir V. Kulakov ◽  
◽  
...  

ntroduction. The COVID-19 pandemic caused an outbreak of viral lung infections with severe acute respiratory syndrome complicated with acute respiratory failure. Despite the fact that the pandemic has a lengthened run, none of the therapeutic approaches have proved to be sufficiently effective according to the evidence-based criteria. We consider the use of surfactant therapy in patients with severe viral pneumonia and acute respiratory distress syndrome (ARDS) as one of the possible methods for treating COVID-19 related pneumonia. Objective. To prove the clinical efficacy and safety of orally inhaled Surfactant-BL, an authorized drug, in the combination therapy of COVID-19 related ARDS. Materials and methods. A total of 38 patients with COVID-19 related severe pneumonia and ARDS were enrolled in the study. Of these, 20 patients received the standard therapy in accordance with the temporary guidelines for the prevention, diagnosis and treatment of the novel coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation, version 9. And 18 patients received the surfactant therapy in addition to the standard therapy. Surfactant-BL was used in accordance with the instructions on how to administer the drug for the indication – prevention of the development of acute respiratory distress syndrome. A step-by-step approach to the build-up of the respiratory therapy aggressiveness was used to manage hypoxia. We used oxygen inhalation via a face mask with an oxygen inflow of 5–15 l/min, highflow oxygen therapy via nasal cannulas using Airvo 2 devices, non-invasive lung ventilation, invasive lung ventilation in accordance with the principles of protective mechanical ventilation. Results and discussion. Significant differences in the frequency of transfers to mechanical ventilation, mortality, Intensive Care Unit (ICU) and hospitalization length of stay (p <0.05) were found between the groups. Patients receiving surfactant therapy who required a transfer to mechanical ventilation accounted for 22% of cases, and the mortality rate was 16%. In the group of patients receiving standard therapy without surfactant inhalation 45% were transferred to mechanical ventilation, and 35% died. For patients receiving surfactant therapy, the hospital stay was reduced by 20% on average, and ICU stay by 30%. Conclusion. The inclusion of surfactant therapy in the treatment of COVID-19 related severe pneumonia and ARDS can reduce the progression of respiratory failure, avoid the use of mechanical ventilation, shorten the ICU and hospitalization length of stay, and improve the survival rate of this patient cohort.


2021 ◽  
Vol 82 (6) ◽  
pp. 1-9
Author(s):  
M Gabrielli ◽  
F Valletta ◽  
F Franceschi ◽  

Ventilatory support is vital for the management of severe forms of COVID-19. Non-invasive ventilation is often used in patients who do not meet criteria for intubation or when invasive ventilation is not available, especially in a pandemic when resources are limited. Despite non-invasive ventilation providing effective respiratory support for some forms of acute respiratory failure, data about its effectiveness in patients with viral-related pneumonia are inconclusive. Acute respiratory distress syndrome caused by severe acute respiratory syndrome-coronavirus 2 infection causes life-threatening respiratory failure, weakening the lung parenchyma and increasing the risk of barotrauma. Pulmonary barotrauma results from positive pressure ventilation leading to elevated transalveolar pressure, and in turn to alveolar rupture and leakage of air into the extra-alveolar tissue. This article reviews the literature regarding the use of non-invasive ventilation in patients with acute respiratory failure associated with COVID-19 and other epidemic or pandemic viral infections and the related risk of barotrauma.


2021 ◽  
Author(s):  
Abhijit Duggal ◽  
Rachel kast ◽  
Emily Van Ark ◽  
Lucas Bulgarelli ◽  
Matthew Siuba ◽  
...  

Rationale: The acute respiratory distress syndrome (ARDS) is a heterogenous condition, and identification of subphenotypes may help in better risk stratification. Objectives: Identify ARDS subphenotypes using new simpler methodology and readily available clinical variables. Design: Retrospective Cohort Study of ARDS trials. Setting: Data from the U.S. ARDSNet trials and from the international ART trial. Participants: 3763 patients from ARDSNet datasets and 1010 patients from the ART dataset. Primary and secondary outcome measures: The primary outcome was 60-day or 28-day mortality, depending on what was reported in the original trial. K-means cluster analysis was performed to identify subgroups. For feature selection, sets. Sets of candidate variables were tested to assess their ability to produce different probabilities for mortality in each cluster. Clusters were compared to biomarker data, allowing identification of subphenotypes. Results: Data from 4,773 patients was analyzed. Two subphenotypes (A and B) resulted in optimal separation in the final model, which included nine routinely collected clinical variables, namely: heart rate, mean arterial pressure, respiratory rate, bilirubin, bicarbonate, creatinine, PaO2, arterial pH, and FiO2. Participants in subphenotype B showed increased levels of pro-inflammatory markers, had consistently higher mortality, lower number of ventilator-free days at day 28, and longer duration of ventilation compared to patients in the subphenotype A. Conclusions: Routinely available clinical data can successfully identify two distinct subphenotypes in adult ARDS patients. This work may facilitate implementation of precision therapy in ARDS clinical trials.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Braira Wahid ◽  
Noshaba Rani ◽  
Muhammad Idrees

Abstract After wreaking havoc on a global level with a total of 5,488,825 confirmed cases and 349,095 deaths as of May 2020, severe acute respiratory syndrome coronavirus 2 is truly living up to the expectations of a 21st-century pandemic. Since the major cause of mortality is a respiratory failure from acute respiratory distress syndrome, the only present-day management option is supportive as the transmission relies solely on human-to-human contact. Patients suffering from coronavirus disease 2019 (COVID-19) should be tested for hyper inflammation to screen those for whom immunosuppression can increases chances of survival. As more and more clinical data surfaces, it suggests patients with mild or severe cytokine storms are at greater risk of failing fatally and hence these cytokine storms should be targets for treatment in salvaging COVID-19 patients.


BMJ ◽  
2020 ◽  
pp. m1091 ◽  
Author(s):  
Tao Chen ◽  
Di Wu ◽  
Huilong Chen ◽  
Weiming Yan ◽  
Danlei Yang ◽  
...  

Abstract Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. Main outcome measures Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. Results The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. Conclusion Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.


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