scholarly journals Targeting MMP-Regulation of Inflammation to Increase Metabolic Tolerance to COVID-19 Pathologies: A Hypothesis

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 390
Author(s):  
Eugenio Hardy ◽  
Carlos Fernandez-Patron

Many individuals infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) develop no or only mild symptoms, but some can go on onto develop a spectrum of pathologies including pneumonia, acute respiratory distress syndrome, respiratory failure, systemic inflammation, and multiorgan failure. Many pathogens, viral and non-viral, can elicit these pathologies, which justifies reconsidering whether the target of therapeutic approaches to fight pathogen infections should be (a) the pathogen itself, (b) the pathologies elicited by the pathogen interaction with the human host, or (c) a combination of both. While little is known about the immunopathology of SARS-CoV-2, it is well-established that the above-mentioned pathologies are associated with hyper-inflammation, tissue damage, and the perturbation of target organ metabolism. Mounting evidence has shown that these processes are regulated by endoproteinases (particularly, matrix metalloproteinases (MMPs)). Here, we review what is known about the roles played by MMPs in the development of COVID-19 and postulate a mechanism by which MMPs could influence energy metabolism in target organs, such as the lung. Finally, we discuss the suitability of MMPs as therapeutic targets to increase the metabolic tolerance of the host to damage inflicted by the pathogen infection, with a focus on SARS-CoV-2.

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.


2020 ◽  
Vol 11 ◽  
Author(s):  
Federica Mannino ◽  
Alessandra Bitto ◽  
Natasha Irrera

The new coronavirus outbreak was first identified in Wuhan, China, in December 2019, and has turned out to be a global health emergency, affecting millions of people worldwide. Coronavirus disease 19 (COVID-19), caused by the SARS-CoV-2 virus, can manifest with flu-like symptoms and can be complicated by severe pneumonia with acute respiratory distress syndrome (ARDS); however a large percentage of infected individuals do not have symptoms but contribute to the spread of the disease. Severe acute respiratory syndrome coronavirus-2 infection has become a global public health emergency since no available treatment seems effective and it is hard to manage the several complications caused by an intense release of cytokines. This paper reviews the current options on drugs used to reduce the deadly effects of the cytokine storm.


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.


Author(s):  
Subhashis Debnath ◽  
Runa Chakravorty ◽  
Donita Devi

In December 2019, severe acute respiratory syndrome-coronavirus-2, a novel coronavirus, initiated an outbreak of pneumonia from Wuhan in China, which rapidly spread worldwide. The outbreak was declared as “a public health emergency of international concern” by the WHO on January 30, 2020, and as a pandemic on March 11, 2020. The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality.


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.


Perfusion ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 100-102
Author(s):  
Pauline H Go ◽  
Albert Pai ◽  
Sharon B Larson ◽  
Kalpaj Parekh

Iatrogenic tracheal injuries are rare but potentially serious complications of endotracheal intubation that frequently require lung isolation to repair. This is not tolerated in patients with severe respiratory failure. We describe a case in a patient with acute respiratory distress syndrome, repaired using veno-venous extracorporeal membrane oxygenation.


Author(s):  
Luciano Gattinon ◽  
Eleonora Carlesso

Respiratory failure (RF) is defined as the acute or chronic impairment of respiratory system function to maintain normal oxygen and CO2 values when breathing room air. ‘Oxygenation failure’ occurs when O2 partial pressure (PaO2) value is lower than the normal predicted values for age and altitude and may be due to ventilation/perfusion mismatch or low oxygen concentration in the inspired air. In contrast, ‘ventilatory failure’ primarily involves CO2 elimination, with arterial CO2 partial pressure (PaCO2) higher than 45 mmHg. The most common causes are exacerbation of chronic obstructive pulmonary disease (COPD), asthma, and neuromuscular fatigue, leading to dyspnoea, tachypnoea, tachycardia, use of accessory muscles of respiration, and altered consciousness. History and arterial blood gas analysis is the easiest way to assess the nature of acute RF and treatment should solve the baseline pathology. In severe cases mechanical ventilation is necessary as a ‘buying time’ therapy. The acute hypoxemic RF arising from widespread diffuse injury to the alveolar-capillary membrane is termed Acute Respiratory Distress Syndrome (ARDS), which is the clinical and radiographic manifestation of acute pulmonary inflammatory states.


Sign in / Sign up

Export Citation Format

Share Document