scholarly journals The Role of Acidosis in the Pathogenesis of Severe Forms of COVID-19

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 852
Author(s):  
Yury D. Nechipurenko ◽  
Denis A. Semyonov ◽  
Igor A. Lavrinenko ◽  
Denis A. Lagutkin ◽  
Evgenii A. Generalov ◽  
...  

COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient’s condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a “cytokine storm”. In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

2021 ◽  
Vol 22 (6) ◽  
pp. 3059
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Eugenio Garofalo ◽  
Andrea Bruni ◽  
Alessandro Vatrella ◽  
...  

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.


2021 ◽  
Vol 28 ◽  
Author(s):  
Amir Hossein Kheirkhah ◽  
Seyed Hossein Shahcheraghi ◽  
Malihe lotfi ◽  
Marzieh lotfi ◽  
Sanaz Raeisi ◽  
...  

: Given that conventional therapies are ineffective for COVID-19, obtained exosomes from stem cells have been proposed as a sustainable and effective treatment. Exosomes are subsets with lengths between 30 and 100 nanometers, and they can be secreted by different cells. Exosomes are containing different types of miRNAs, mRNAs, and different proteins. The role of immune system modulation of exosomes of mesenchymal stem cells has been studied and confirmed in more than one study. Exosome miRNAs detect and reduce cytokines that cause cytokine storms such as IL-7, IL-2, IL-6, etc. These miRNAs include miR-21, miR-24, miR-124, miR-145, etc. The risks associated with treatment with exosomes from different cells are relatively small compared to other treatments because transplanted cells do not stimulate the host immune system and also has reduced infection transmission. Due to the ineffectiveness of existing drugs in reducing inflammation and preventing cytokine storms, the use of immune-boosting systems may be suggested as another way to control cytokine storm.


Author(s):  
Claudia Matteucci ◽  
Antonella Minutolo ◽  
Emanuela Balestrieri ◽  
Vita Petrone ◽  
Marialaura Fanelli ◽  
...  

Abstract COVID-19 is characterized by immune-mediated lung injury and complex alterations of the immune system, such as lymphopenia and cytokine storm, that have been associated with adverse outcomes underlining a fundamental role of host response in SARS-CoV-2 infection and the pathogenesis of the disease. Thymosin alpha 1 (Tα1) is one of the molecules used in the management of COVID-19, since it is known to restore the homeostasis of the immune system during infections and cancer. Here we captured the interconnected biological processes regulated by Tα1 in CD8+ T cells under inflammatory conditions. Genes associated with cytokine signaling and production were found up-regulated in blood cells from COVID-19 patients and the ex-vivo treatment with Tα1 mitigated cytokines expression and inhibited lymphocytes activation in CD8+ T cell subset specifically, suggesting the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.


Author(s):  
William D Miller ◽  
Robert Keskey ◽  
John C Alverdy

Abstract Although sepsis has been characterized as a dysregulated immune response to an ongoing or suspected infection, the role of the microbiome as a key influencer of the septic response is emerging. The unavoidable disruption of the microbiome while treating sepsis with antibiotics can itself result in immune system dysregulation, further exacerbating the course and outcome of sepsis. Alterations in the gut microbiome as a result of sepsis and its treatment have been implicated in the organ dysfunction typical of sepsis across a wide variety of tissues including the lung, kidney and brain. A number of microbiota directed interventions are currently under investigation in the setting of sepsis including fecal transplant, the administration of dietary fiber in enteral feeding products and the use of antibiotic scavengers that are directed at attenuating the effects of antibiotics on the gut microbiota while allowing them to concentrate at the primary sites of infection. Taken together, the emerging role of the gut microbiome in sepsis touches various elements of the pathophysiology of sepsis and its treatment, and provides yet another reason to consider the judicious use of antibiotics via antibiotic stewardship programs.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 992-996
Author(s):  
Prasad Umakant Wallalwar ◽  
Pradnya Dandekar ◽  
Shweta Dadarao Parwe

The concept of Immunity is mentioned as ‘Vyadhikshamatwa’ in Ayurveda. In Ayurveda numbers of medicinal herbs are described under immunity-enhancing drugs category. The concept of immunity enhancer is explained under the category of Rasayan chikitsa in Ayurveda. These herbs are used in various diseases, especially by modulating the immune system. These herbs are called as Rasayan Dravyas. Ayurveda medical science comprises the herbs which are Rasayana and also which are non-Rasayana in nature. In Samhitas entirely enriched with enormous data of Rasayana medicinal herbs acting as immune modulators. The data of available Samhitas and researches show that these Rasayana herbs have immense potential as immune modulators. Advanced researches have proven that drugs like Guduchi, Haritaki, Ashwagandha, Brahmi, Jyotishmati act as a good immune enhancer. Theses herbs are mentioned in Ayurveda as Rasayana drugs. Experimental studies also have proven the role of Rasayana drugs as antioxidant, adoptogenic and having anti-stress activities. These Rasayana drugs as having immunity enhancer protect the health of a healthy person and protects them from any type of diseased condition. Charakacharya had mentioned Rasayanchikitsa adhyay as the first addhya of their chikitsasthan considering his aim as ‘Swasthasya Swasthya Rakshanam’. This means to protect the health of a healthy person as in priority by using immunity enhancer drugs as Rasayanas. This review article empowers such reviewed data on Rasayan medicinal herbs as a promising future target for immunotherapy.


Medicines ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 55
Author(s):  
Leonardo Freire-de-Lima ◽  
Aline Miranda Scovino ◽  
Camilla Cristie Barreto Menezes ◽  
Leonardo Marques da Fonseca ◽  
Jhenifer Santos dos Reis ◽  
...  

Coronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. Since 2019, several studies regarding the interplay between autoimmune diseases and COVID-19 infections is increasing all over the world. In addition, thanks to new scientific findings, we actually know better why certain conditions are considered a higher risk in both situations. There are instances when having an autoimmune disease increases susceptibility to COVID-19 complications, such as when autoantibodies capable of neutralizing type I IFN are present, and other situations in which having COVID-19 infection precedes the appearance of various autoimmune and autoinflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C), Guillain-Barré syndrome, and Autoimmune haemolytic anaemia (AIHA), thus, adding to the growing mystery surrounding the SARS-CoV-2 virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae. Herein, we discuss the role of host and virus genetics and some possible immunological mechanisms that might lead to the disease aggravation.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 923-927
Author(s):  
Anuradha Kishor Ingale ◽  
Pooja Shrivastav

The goal of Ayurveda is prevention is better than cure. There are a total of 9152 COVID-19 cases reported in India (till April 13, 2020), 308 people were died because of this disease, and 856 patients were treated successfully in our Country. This virus can easily affect or harm those individuals who have an infection, less immunity and especially who all have been aged more than sixty. Most of the countries are worried only for their people's life (health). In contrast, the developing countries like India that has a large population have to consider about the livelihood for people like Below Poverty Line (BPL) or those living in slum areas, equally with their life. The main aim of the article is to aware the people not only Urban but also among Rural and needy individuals to adopt the Ayurveda lifestyle during Covid19 outbreak. For this to study various methods which are described in Ayurveda for boosting immunity among various individuals. This study is a review type of article. All information and references have been collected and compiled from various available Ayurvedic classics texts. Research articles are also searched from various websites related to Covid19 outbreak and its effect on needy individuals. All matters have been analysed for some discussion, and an attempt has been made to rule out some conclusions. During this lockdown, people are mostly living a sedentary lifestyle which not only weakens their immune system but also make them more susceptible to infections. Hence Ayurveda is a science of life that is mainly focusing on strengthening persons by boosting their immune system through improving our lifestyle by using medicines, diets, meditation and activities like Yoga. This article will give insights about poor people and effective strategy to threat COVID-19 through Ayurveda in India.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
J. R. Thiele ◽  
J. Zeller ◽  
H. Bannasch ◽  
G. B. Stark ◽  
K. Peter ◽  
...  

C-reactive protein (CRP) is a pentraxin that has long been employed as a marker of inflammation in clinical practice. Recent findings brought up the idea of CRP to be not only a systemic marker but also a mediator of inflammation. New studies focused on structural changes of the plasma protein, revealing the existence of two distinct protein conformations associated with opposed inflammatory properties. Native, pentameric CRP (pCRP) is considered to be the circulating precursor form of monomeric CRP (mCRP) that has been identified to be strongly proinflammatory. Recently, a dissociation mechanism of pCRP has been identified on activated platelets and activated/apoptotic cells associated with the amplification of the proinflammatory potential. Correspondingly, CRP deposits found in inflamed tissues have been identified to exhibit the monomeric conformation by using conformation-specific antibodies. Here we review the current literature on the causal role of the dissociation mechanism of pCRP and the genesis of mCRP for the amplification of the proinflammatory potential in inflammatory reactions such as atherosclerosis and ischemia/reperfusion injury. The chance to prevent the formation of proinflammatory mediators in ubiquitous inflammatory cascades has pushed therapeutic strategies by targeting pCRP dissociation in inflammation. In this respect, the development of clinically applicable derivatives of the palindromic compound 1,6-bis(phosphocholine)-hexane (1,6-bis PC) should be a major focus of future CRP research.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1761
Author(s):  
Bahareh Hafezi ◽  
Lily Chan ◽  
Jason P. Knapp ◽  
Negar Karimi ◽  
Kimia Alizadeh ◽  
...  

Cytokine storm syndrome is a cascade of escalated immune responses disposing the immune system to exhaustion, which might ultimately result in organ failure and fatal respiratory distress. Infection with severe acute respiratory syndrome-coronavirus-2 can result in uncontrolled production of cytokines and eventually the development of cytokine storm syndrome. Mast cells may react to viruses in collaboration with other cells and lung autopsy findings from patients that died from the coronavirus disease that emerged in 2019 (COVID-19) showed accumulation of mast cells in the lungs that was thought to be the cause of pulmonary edema, inflammation, and thrombosis. In this review, we present evidence that a cytokine response by mast cells may initiate inappropriate antiviral immune responses and cause the development of cytokine storm syndrome. We also explore the potential of mast cell activators as adjuvants for COVID-19 vaccines and discuss the medications that target the functions of mast cells and could be of value in the treatment of COVID-19. Recognition of the cytokine storm is crucial for proper treatment of patients and preventing the release of mast cell mediators, as impeding the impacts imposed by these mediators could reduce the severity of COVID-19.


Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.


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