scholarly journals Antibiotics Against COVID-19 and Mitochondria? Urgent Thinking Out of the Box

2020 ◽  
Author(s):  
Jaroslaw Tyszka ◽  
Karolina Kobos ◽  
Aleksandra Tyszka
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Local Health ◽  
Antiviral Immune Response ◽  
Health Authorities ◽  
Treatment Data ◽  
The Moment ◽  
The Impact

Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

scholarly journals Modelling the impact of delaying vaccination against SARS-CoV-2 assuming unlimited vaccine supply

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Marcos Amaku ◽  
Dimas Tadeu Covas ◽  
Francisco Antonio Bezerra Coutinho ◽  
Raymundo Soares Azevedo ◽  
Eduardo Massad
Keyword(s):  
Mathematical Model ◽  
Vaccination Campaign ◽  
Vaccination Rate ◽  
Sao Paulo ◽  
The State ◽  
São Paulo ◽  
Health Authorities ◽  
The World ◽  
The Moment ◽  
The Impact

Abstract Background At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far. Methods We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations. Results The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole. Conclusions Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.

scholarly journals The Role of Micronutrients in Support of the Immune Response against Viral Infections

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3198 ◽  
Author(s):  
Francesco Pecora ◽  
Federica Persico ◽  
Alberto Argentiero ◽  
Cosimo Neglia ◽  
Susanna Esposito
Keyword(s):  
Fatty Acids ◽  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Optimal Function ◽  
The Impact

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

scholarly journals Sex differences in severity and mortality from COVID-19: are males more vulnerable?

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajay Pradhan ◽  
Per-Erik Olsson
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Basic Research ◽  
Contributing Factors ◽  
High Infection ◽  
Males And Females

Abstract Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

scholarly journals Skin Immune Landscape: Inside and Outside the Organism

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Florence Abdallah ◽  
Lily Mijouin ◽  
Chantal Pichon
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Skin Surface ◽  
Negative Influence ◽  
Background Information ◽  
Symbiotic Relationship ◽  
Skin Microbiota ◽  
Effector Cells ◽  
Skin Immune System ◽  
The Impact

The skin is an essential organ to the human body protecting it from external aggressions and pathogens. Over the years, the skin was proven to have a crucial immunological role, not only being a passive protective barrier but a network of effector cells and molecular mediators that constitute a highly sophisticated compound known as the “skin immune system” (SIS). Studies of skin immune sentinels provided essential insights of a complex and dynamic immunity, which was achieved through interaction between the external and internal cutaneous compartments. In fact, the skin surface is cohabited by microorganisms recognized as skin microbiota that live in complete harmony with the immune sentinels and contribute to the epithelial barrier reinforcement. However, under stress, the symbiotic relationship changes into a dysbiotic one resulting in skin disorders. Hence, the skin microbiota may have either positive or negative influence on the immune system. This review aims at providing basic background information on the cutaneous immune system from major cellular and molecular players and the impact of its microbiota on the well-coordinated immune responses in host defense.

scholarly journals Potential Reasons for Unresponsiveness to Anti-PD1 Immunotherapy in Young Patients with Advanced Melanoma

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1318
Author(s):  
Devayani Machiraju ◽  
Sarah Schäfer ◽  
Jessica C. Hassel
Keyword(s):  
Overall Survival ◽  
Immune System ◽  
Treatment Approach ◽  
Young Patients ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Advanced Melanoma ◽  
Age Dependent ◽  
Melanoma Patients ◽  
The Impact

The impact of age on the clinical benefit of anti-PD1 immunotherapy in advanced melanoma patients has been evolving recently. Due to a reduced immune function in elderly patients, young patients with a robust immune system are theoretically expected to benefit more from the treatment approach. However, in contrast to this hypothesis, recent studies in patients with metastatic melanoma have demonstrated that immunotherapy, especially with anti-PD1 treatment, is less effective in patients below 65 years, on average, with significantly lower responses and reduced overall survival compared to patients above 65 years of age. Besides, data on young patients are even more sparse. Hence, in this review, we will focus on age-dependent differences in the previously described resistance mechanisms to the treatment and discuss the development of potential combination treatment strategies for enhancing the anti-tumor efficacy of anti-PD1 or PDL1 treatment in young melanoma patients.

scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2

2021 ◽  
Vol 23 (1) ◽  
pp. 280
Author(s):  
Sabrina Sales Martinez ◽  
Yongjun Huang ◽  
Leonardo Acuna ◽  
Eduardo Laverde ◽  
David Trujillo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Viral Infections ◽  
Selenium Deficiency ◽  
The Novel ◽  
Stress Studies ◽  
History Of ◽  
The Impact ◽  
Nutritional Strategies ◽  
Healthy Immune System

Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. This review examines viral infections, including the novel SARS-CoV-2, in the context of selenium, in order to inform potential nutritional strategies to maintain a healthy immune system.

scholarly journals The Impact of Radiation-Induced DNA Damage on cGAS-STING-Mediated Immune Responses to Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8877
Author(s):  
Quinn Storozynsky ◽  
Mary M. Hitt
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Treatment Strategies ◽  
Cytotoxic T Cell ◽  
Innate Immune Signaling ◽  
Therapeutic Outcomes ◽  
Wide Range ◽  
Radiation Induced ◽  
Nuanced Understanding ◽  
The Impact

Radiotherapy is a major modality used to combat a wide range of cancers. Classical radiobiology principles categorize ionizing radiation (IR) as a direct cytocidal therapeutic agent against cancer; however, there is an emerging appreciation for additional antitumor immune responses generated by this modality. A more nuanced understanding of the immunological pathways induced by radiation could inform optimal therapeutic combinations to harness radiation-induced antitumor immunity and improve treatment outcomes of cancers refractory to current radiotherapy regimens. Here, we summarize how radiation-induced DNA damage leads to the activation of a cytosolic DNA sensing pathway mediated by cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING). The activation of cGAS–STING initiates innate immune signaling that facilitates adaptive immune responses to destroy cancer. In this way, cGAS–STING signaling bridges the DNA damaging capacity of IR with the activation of CD8+ cytotoxic T cell-mediated destruction of cancer—highlighting a molecular pathway radiotherapy can exploit to induce antitumor immune responses. In the context of radiotherapy, we further report on factors that enhance or inhibit cGAS–STING signaling, deleterious effects associated with cGAS–STING activation, and promising therapeutic candidates being investigated in combination with IR to bolster immune activation through engaging STING-signaling. A clearer understanding of how IR activates cGAS–STING signaling will inform immune-based treatment strategies to maximize the antitumor efficacy of radiotherapy, improving therapeutic outcomes.

scholarly journals Coronavirus Disease 2019 (COVID-19) and Nutritional Status: The Missing Link?

2020 ◽  
Author(s):  
Renata Silverio ◽  
Daniela Caetano Gonçalves ◽  
Márcia Fábia Andrade ◽  
Marilia Seelaender
Keyword(s):  
Body Composition ◽  
Immune System ◽  
Nutritional Status ◽  
Immune Responses ◽  
Lean Mass ◽  
Severe Disease ◽  
Cytokine Storm ◽  
Risk Of Infection ◽  
Elderly Individuals ◽  
The Impact

ABSTRACT Coronavirus disease 2019 (COVID-19) is an emerging disease that has reached pandemic status by rapidly spreading worldwide. Elderly individuals and patients with comorbidities such as obesity, diabetes, and hypertension show a higher risk of hospitalization, severe disease, and mortality by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These patients frequently show exacerbated secretion of proinflammatory cytokines associated with an overreaction of the immune system, the so-called cytokine storm. Host nutritional status plays a pivotal role in the outcome of a variety of different infectious diseases. It is known that the immune system is highly affected by malnutrition, leading to decreased immune responses with consequent augmented risk of infection and disease severity. Body composition, especially low lean mass and high adiposity, has consistently been linked to worsened prognosis in many different diseases. In this review, evidence concerning the impact of nutritional status on viral infection outcomes is discussed.

scholarly journals Collision between Two Pandemics: Obesity and COVID-19 Viral Infection

2021 ◽  
pp. 27-37
Author(s):  
Jehan Saad Alrahimi
Keyword(s):  
Immune System ◽  
Chronic Inflammation ◽  
Complex Disease ◽  
Viral Infections ◽  
Host Cells ◽  
Organ Injury ◽  
Primary Immune Response ◽  
Type I ◽  
Novel Coronavirus ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 (COVID-19). The principal risk factor for the development of serious forms of COVID-19 was found to be the precarious metabolic health. There are several mechanisms that are implicated in the seriousness of COVID-19 ranging from attenuation of immune system function to chronic inflammation. It is important to keep in mind that obesity is a complex disease when discussing the relation between obesity and the severity of COVID-19. An increasing body of proof links obesity to COVID-19. Obesity has an obvious role in the high incidence, symptoms severity and mortality rates of viral infections seen in obese patients. Adipose tissue shows a high expression of the angiotensin-converting enzyme 2 (ACE2), the receptor for entry of SARS-CoV-2 into host cells, so obese population exhibit higher vulnerability to COVID-19. The primary immune response is offered mainly by type-I interferon (IFN-I) that is suppressed in COVID-19. The pro-inflammatory state associated with obesity produces imbalance of the inflammatory response to COVID-19, as the cytokine storm found in subjects with serious disease form. Obesity is considered as chronic inflammation of low degree, so it shows a capacity for pathogenic immune amplification. In this review, the effect of obesity on the immune system is described. The authors described the dysfunctional immune responses caused by obesity that lead to organ injury in COVID-19 infection and impair the ability of patient to combat the virus. Further research is required to assess the impact of obesity control, immunonutrition and physical exercise in SARS-CoV-2 infection.

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