[Low dose radiotherapy for COVID-19 pneumopathy: Biological rationale and literature review].
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ABSTRACT:
SUBMITTER: Miran C
PROVIDER: S-EPMC8040522 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:The COVID-19 pandemic outbreak has set the emergency services in developing countries on major alert, as the installed response capacities are easily overwhelmed by the constantly increasing high demand. The deficit of intensive care unit beds and ventilators in countries like Peru is forcing practitioners to seek preventive or early interventional strategies to prevent saturating these chronically neglected facilities. CASE PRESENTATION:A 64-year-old patient is reported after presenting with COVID-19 pneumonia and rapidly progressing to deteriorated ventilatory function. Compassionate treatment with a single 1?Gy dose to the bilateral whole-lung volume was administered, with gradual daily improvement of ventilatory function and decrease in serum inflammatory markers and oxygen support needs, including intubation. No treatment-related toxicity developed. Procedures of transport, disinfection, and treatment planning and delivery are described. CONCLUSION:Whole-lung low-dose radiotherapy seems to be a promising approach for avoiding or delaying invasive respiratory support. Delivered low doses are far from meeting toxicity ranges. On-going prospective trials will elucidate the effectiveness of this approach.
| S-EPMC7439803 | biostudies-literature
Project description:The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients. However, IFN nebulization is currently not standard in Europe and the United States. Therefore, our group has set up a project aimed to evaluate the possibility to nebulize IFN-β-1b (a drug currently used in Europe to treat multiple sclerosis via subcutaneous injections) and to assess the safety of this new mode of administration in SARS-CoV-2 infected patients. We present here literature data that allowed us to build our hypothesis and to develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to gain first pre-clinical and clinical experience of IFN-β-1b nebulization. After validation of the nebulization method and verification of droplet size compatible with nebulization, the method has been applied to four intensive care patients treated at our university hospital, for whom none of the COVID-19 therapies initially used in France led to significant clinical improvement. All patients exhibited negative viral carriage and experienced clinical improvement 7-16 days after having initiated nebulized IFN-β-1b inhalation therapy. No side effects were observed. All patients were alive within a 90-days follow-up. Although it is not possible to draw firm conclusions on treatment efficacy based on this case report, our study shows that pulmonary IFN-β-1b administration is feasible, with a good safety profile. This procedure, which presents the advantage of directly targeting the lungs and reducing the risks of systemic side effects, may represent a promising therapeutic strategy for the care of patients with severe COVID-19. However, our preliminary observation requires confirmation by randomized controlled trials.
| S-EPMC7734101 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Global health authorities working on the COVID-19 outbreak continue to explore methods to reduce the rate of its transmission to healthy individuals. Treatment protocols thus far have focused on social distancing and masking, treatment with antivirals early in infection, and steroids to reduce the inflammatory response. An alternative approach is therapy with low dose radiation (LDR), which has several advantages compared to the current drugs and medicines. To date more than 10 case reports and pilot clinical trial preliminary outcome are available from different countries. These reports cover a wide range of patient conditions and LDR treatment strategies. Although one report showed the failure to observe the improvement of COVID-19 patients after LDR therapy, the majority showed some clinical improvement, and demonstrated the safety of LDR for COVID-19 patients, particularly with 0.5 Gy. This review aims to summarize the potential rationales and mechanisms of LDR therapy for COVID-19 patients, and its current clinical status and potential use.
| S-EPMC8429076 | biostudies-literature
Project description:Radiotherapy (RT) affects anti-tumor immunity. However, the exact impact of RT on anti-tumor immune response differs among cancer types, RT dose and fractions, patients' innate immunity, and many other factors. There are conflicting findings on the optimal radiation dose and fractions to stimulate effective anti-tumor immunity. High-dose radiotherapy (HDRT) acts in the same way as a double-edged sword in stimulating anti-tumor immunity, while low-dose radiotherapy (LDRT) seems to play a vital role in modulating the tumor immune microenvironment. Recent preclinical data suggest that a 'hybrid' radiotherapy regimen, which refers to combining HDRT with LDRT, can reap the advantages of both. Clinical data have also indicated a promising potential. However, there are still questions to be addressed in order to put this novel combination therapy into clinical practice. For example, the selection of treatment site, treatment volume, the sequencing of high-dose radiotherapy and low-dose radiotherapy, combined immunotherapy, and so on. This review summarizes the current evidence supporting the use of HDRT + LDRT, explains possible immune biology mechanisms of this 'hybrid' radiotherapy, raises questions to be considered when working out individualized treatment plans, and lists possible avenues to increase efficiency in stimulating anti-tumor immunity using high-dose plus low-dose radiotherapy.
| S-EPMC9319172 | biostudies-literature
Project description:BackgroundHospitalized COVID-19 patients are at high risk of venous thromboembolism (VTE). Standard doses of anticoagulant prophylaxis may not be sufficiently effective for the prevention of VTE. The objective of this systematic-review and meta-analysis was to compare the efficacy and safety of high-dose versus low-dose thromboprophylaxis in hospitalized patients with COVID-19.Material and methodsMEDLINE and EMBASE were searched up to October 2021 for randomized clinical trials (RCTs) comparing high-dose with low-dose thromboprophylaxis in hospitalized adult patients with COVID-19. The primary efficacy outcome was the occurrence of VTE and the primary safety outcome was major bleeding.ResultsA total of 5470 patients from 9 RCTs were included. Four trials included critically ill patients, four non-critically ill patients, and one included both. VTE occurred in 2.9% of patients on high-dose and in 5.7% of patients on low-dose thromboprophylaxis (relative risk [RR] 0.53; 95% confidence intervals [CIs], 0.41-0.69; I2 = 0%; number needed to treat for an additional beneficial outcome, 22). Major bleeding occurred in 2.5% and 1.4% of patients, respectively (RR 1.78; 95% CI, 1.20-2.66; I2 = 0%; number needed to treat for an additional harmful outcome, 100). All-cause mortality did not differ between groups (RR 0.97; 95% CI, 0.75-1.26; I2 = 47%). The risk of VTE was significantly reduced by high-dose thromboprophylaxis in non-critically ill (RR 0.54; 95% CI, 0.35-0.86; I2 = 0%), but not in critically ill patients (RR 0.69; 95% CI, 0.39-1.21; I2 = 36%).DiscussionIn hospitalized patients with COVID-19, high-dose thromboprophylaxis is more effective than low-dose for the prevention of VTE but increases the risk of major bleeding.
| S-EPMC9244067 | biostudies-literature
Project description:PurposeThe respiratory disease COVID-19 reached global pandemic status in 2020. Excessive inflammation is believed to result in the most severe symptoms and death from this disease. Because treatment options for patients with severe COVID-19 related pulmonary symptoms remain limited, whole-lung low-dose radiation therapy is being evaluated as an anti-inflammatory modality. However, there is concern about the long-term risks associated with low-dose pulmonary irradiation. To help quantify the benefit-risk balance of low-dose radiation therapy for COVID-19, we estimated radiation-induced lifetime risks of both lung cancer and heart disease (major coronary events) for patients of different sexes, treated at ages 50 to 85, with and without other relevant risk factors (cigarette smoking and baseline heart disease risk).Methods and materialsThese estimates were generated by combining state-of-the-art radiation risk models for lung cancer and for heart disease together with background lung cancer and heart disease risks and age/sex-dependent survival probabilities for the U.S.PopulationResultsEstimated absolute radiation-induced risks were generally higher for lung cancer compared with major coronary events. The highest estimated lifetime radiation-induced lung cancer risks were approximately 6% for female smokers treated between ages 50 and 60. The highest estimated radiation-induced heart disease risks were approximately 3% for males or females with high heart disease risk factors and treated between ages 50 and 60.ConclusionsThe estimated summed lifetime risk of lung cancer and major coronary events reached up to 9% in patients with high baseline risk factors. Predicted lung cancer and heart disease risks were lowest in older nonsmoking patients and patients with few cardiac risk factors. These long-term risk estimates, along with consideration of possible acute reactions, should be useful in assessing the benefit-risk balance for low-dose radiation therapy to treat severe COVID-19 pulmonary symptoms, and suggest that background risk factors, particularly smoking, should be taken into account in such assessments.
| S-EPMC8078051 | biostudies-literature
Project description:Subacute thyroiditis (SAT), potentially caused by severe acute respiratory syndrome coronavirus 2 infection, has been reported as a complication of COVID-19 since 2020. The clinical characteristics and outcomes of SAT after COVID-19 remain incompletely defined. Therefore, we aimed to collect and survey case reports of SAT after COVID-19. We performed a systematic search of PubMed/MEDLINE, Web of Science, and Google Scholar. The keywords and MeSH terms used for the searches were "subacute thyroiditis" and "COVID-19." A total of 38 patients from 26 case reports, case series, and letters on SAT associated with COVID-19 were included and analyzed. The most frequent SAT symptom was neck pain (27 cases), followed by fever (22 cases). Of the 25 cases with information on the duration between onset of COVID-19 symptoms and onset of SAT symptoms, the shortest was simultaneous occurrence, and the longest was 4 months. In most cases, patients developed SAT at several days or weeks after the onset of COVID-19. All patients with SAT recovered with no severe complications or sequelae. Clinicians should be aware of the possibility of SAT development in patients with neck pain and fever following COVID-19. Further research is necessary to determine the relationship between SAT and COVID-19.
| S-EPMC9709026 | biostudies-literature
Project description:BackgroundCOVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19.Study design and methodsThis multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.
| S-EPMC7317159 | biostudies-literature
Project description:Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, aiming to identify novel candidate imprinted genes. Using our approach, we recovered ~30% of the known human imprinted genes, further 168 candidates were identified, 61 of which with at least three hemimethylated CpGs shared by more than two tissue types. Thirty-four of these candidate genes are members of the protocadherins cluster on 5q31.3; in mice, protocadherin genes have non-imprinted monoallelic randomic expression, which might be the case in humans. Among the remaining 27 genes, ZNF331 was recently validated as an imprinted gene, and six of them have been reported as candidates, supporting our prediction. Five candidates (CCDC166, ARC, PLEC, TONSL and VPS28) map to 8q24.3, and might constitute a novel imprinted cluster. Additionally, we performed a comprehensive compilation of known human and mice imprinted genes from literature and databases, and a comparison among high-throughput imprinting studies in humans. The screening for hemimethylated CpGs shared by multiple human tissues, together with the extensive review, appears as a useful approach to reveal candidate imprinted genes.
2017-09-26 | GSE103413 | GEO
Project description:BackgroundAs SARS-CoV-2 continues to spread worldwide, it has already resulted in over 110 million cases and 2.5 million deaths. Currently, there are no effective COVID-19 treatments, although numerous studies are under way. SARS-CoV-2, however, is not the first coronavirus to cause serious outbreaks. COVID-19 can be compared with previous human coronavirus diseases, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), to better understand the development of treatments.MethodsDatabases Medline, Embase and WHO COVID-19 was systematically searched on 9 February 2021 for studies reporting on therapeutic effect of COVID-19 treatments. Clinical trials, case reports, observational studies and systematic reviews in the English language were eligible.Results1416 studies were identified and 40 studies were included in this review. Therapies included are: remdesivir, convalescent plasma, hydroxychloroquine, lopinavir/ ritonavir, interferon, corticosteroids, cytokine storm inhibitors and monoclonal antibodies. Remdesivir, convalescent plasma and interferon seems to provide some clinical benefits such as faster recovery time and reduced mortality, but these effects are not clinically significant. Some corticosteroids are effective in reducing mortality in severe COVID-19 patients. Hydroxychloroquine do not convey any beneficial, and therapies such as cytokine storm inhibitors and monoclonal antibodies were also not effective and require further investigation.ConclusionsThere is no single therapy effective against COVID-19. However, a combination of therapies administered at different stages of infection may provide some benefit. This conclusion is reflected in the limited effects of these treatments in previous human coronaviruses.
| S-EPMC8068411 | biostudies-literature