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1.
Biomed Phys Eng Express ; 8(6)2022 09 05.
Article in English | MEDLINE | ID: covidwho-1992047

ABSTRACT

Objective.The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs.Approach.A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses.Main results.Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%.Significance.An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.


Subject(s)
COVID-19 , Radiotherapy Planning, Computer-Assisted , COVID-19/radiotherapy , Humans , Lung/diagnostic imaging , Monte Carlo Method , Radiology, Interventional , Radiotherapy Planning, Computer-Assisted/methods
2.
An Acad Bras Cienc ; 94(4): e20210056, 2022.
Article in English | MEDLINE | ID: covidwho-1963128

ABSTRACT

The extreme demand on health systems due to the COVID-19 pandemic has led to reconsider hypofractionation. Although the best clinical efficacy of these schemes is being demonstrated, the biological bases have not been established. Thus, after validating basic clinical parameters, through complementary in vitro models, we characterized the cellular and molecular mechanisms of hypofractionation protocols. Cell cultures of human lung cancer cell line A549 were irradiated with 0, 2, 4, 8, 12, 16 and 20 Gy. The clastogenic, cytotoxic, proliferative and clonogenic capacities and bystander effect were evaluated. In addition, we assessed survival and toxicity in a retrospective study of 49 patients with lung cancer. Our findings showed that the greater efficacy of ablative regimens should not only be attributed to events of direct cell death induced by genotoxic damage, but also to a lower cell repopulation and the indirect action of clastogenic factors secreted. These treatments were optimal in terms of 1- and 2-year overall survival (74 and 65%, respectively), and progression-free survival at 1 and 2 years (71 and 61%, respectively). The greater efficacy of high doses per fraction could be attributed to a multifactorial mechanism that goes beyond the 4Rs of conventional radiotherapy.


Subject(s)
COVID-19 , Lung Neoplasms , COVID-19/radiotherapy , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Pandemics , Radiation Dose Hypofractionation , Retrospective Studies
3.
In Vivo ; 36(4): 1959-1965, 2022.
Article in English | MEDLINE | ID: covidwho-1904088

ABSTRACT

AIM: To evaluate the feasibility and tolerability of low-dose radiotherapy (LDRT) delivered to both lungs in the treatment of SARS-CoV-2-immune-mediated pneumonia in the COLOR-19 study (NCT0437747). PATIENTS AND METHODS: From May 2020 to April 2021 at Brescia University Radiation Oncology Department, three patients with COVID-19-related pneumonia were treated with LDRT according to the COLOR-19 protocol. All patients were treated with a single fraction at the average prescription dose of 0.7 Gy to both lungs. RESULTS: Three patients were enrolled (two males and one female, aged 61-81 years) and underwent LDRT. Despite LDRT being safely performed without significant side-effects, two patients died (one 81-year-old male due to septic shock secondary to Escherichia coli infection and one 79-year-old male, already in poor condition, due to worsening of COVID-19). The remaining female patient (61 years old) underwent LDRT for less severe COVID-19: her clinical condition and chest X-ray improved, and she was discharged home completely asymptomatic 27 days after hospital admission. Blood levels of C-reactive protein and ferritin generally decreased after LDRT. CONCLUSION: Early results of the COLOR-19 study demonstrate the feasibility of LDRT for therapy of COVID-19-related pneumonia; no conclusions on the efficacy have been reached due to poor accrual.


Subject(s)
COVID-19 , COVID-19/radiotherapy , Female , Humans , Lung , Male , Middle Aged , SARS-CoV-2 , Treatment Outcome
4.
Radiother Oncol ; 166: 133-136, 2022 01.
Article in English | MEDLINE | ID: covidwho-1895399

ABSTRACT

This is a paired prospective comparative cohort study with 58 patients, in order to analyze the clinical LD-WLI in patients with moderate or severe COVID19 pneumonia. The results of this study show that the Radiotherapy could be an option to improve the clinical response for patients with COVID-19.


Subject(s)
COVID-19 , COVID-19/radiotherapy , Cohort Studies , Humans , Lung/radiation effects , Prospective Studies , SARS-CoV-2 , Treatment Outcome
5.
Exp Dermatol ; 31(7): 1109-1115, 2022 07.
Article in English | MEDLINE | ID: covidwho-1868642

ABSTRACT

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up to 8 consecutive days. Primary outcomes were safety and efficacy, defined as persistent or painful erythema and 28-day mortality. Comparisons were made via non-parametric exact tests. Patients in treatment (n = 15) and placebo (n = 15) arms had similar demographics. No adverse events occurred. Twenty eight-day mortality was 13.3% in treatment vs. 33.3% in placebo arms (p = 0.39). NB-UVB phototherapy in hospitalized COVID-19 patients was safe. Decreased mortality was observed in treated patients but this was statistically non-significant. Given its low-cost, scalability, and adjunctive nature, NB-UVB has the potential to improve COVID-19 outcomes. Continuation of this trial is warranted.


Subject(s)
COVID-19 , Ultraviolet Therapy , COVID-19/radiotherapy , Humans , Phototherapy , Prospective Studies , Treatment Outcome
6.
J Biophotonics ; 15(8): e202200058, 2022 08.
Article in English | MEDLINE | ID: covidwho-1802312

ABSTRACT

It is postulated that the inflammatory process resulting from SARS-CoV-2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti-inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID-19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID-19 and the anti-inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID-related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re-established after 10 treatment sessions with photobiomodulation.


Subject(s)
Ageusia , COVID-19 , Low-Level Light Therapy , Olfaction Disorders , Ageusia/etiology , Anosmia , COVID-19/complications , COVID-19/radiotherapy , Humans , Olfaction Disorders/complications , SARS-CoV-2 , Smell , Taste Disorders/complications
7.
Radiother Oncol ; 171: 25-29, 2022 06.
Article in English | MEDLINE | ID: covidwho-1768476

ABSTRACT

BACKGROUND AND PURPOSE: To evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. MATERIAL AND METHODS: We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement (oxygen saturation ≤93% on room air). Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was a radiological response assessed as severity and extension scores at days +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/FiO2 index (SAFI), at day +3 and +7. Descriptive analyses were summarized as means with standard deviation (SD) and/or medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. RESULTS: Forty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (44%) previously received an anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. The extension score improved significantly (p = 0.02) on day +7. Mean baseline extension score was 13.7 (SD ± 4.9) with a score of 12.2 (±5.2) at day 3, and 12.4 ± 4.7 at day 7. No differences were found in the severity score. SAFI improved significantly on day +3 and +7 (p < 0.01). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7. Significant decrease was found in C-reactive protein on day +7 (p = 0.02) and in lymphocytes counts on day +3 and +7 (p = 0.02). The median number of days in hospital after RT was 11 (range 4-78). With a median follow-up of 60 days after LD-RT, 26 (63%) patients were discharged, 11 (27%) died because of COVID respiratory failure and 4 (10%) died of other causes. CONCLUSIONS: LD-RT is a feasible and well-tolerated treatment that could lead to rapid clinical improvement. Large randomized trials would be required to establish the efficacy of LD-RT to treat COVID-19 pneumonia.


Subject(s)
COVID-19 , Aged , C-Reactive Protein , COVID-19/radiotherapy , Humans , Middle Aged , Prospective Studies , SARS-CoV-2 , Treatment Outcome
8.
Int J Radiat Biol ; 98(10): 1532-1541, 2022.
Article in English | MEDLINE | ID: covidwho-1751954

ABSTRACT

Purpose: Low-dose radiation therapy (LDRT) is an evidence-based anti-inflammatory treatment. In anti-COVID-19, our study suggests that low to moderate dose radiation of < 1.5 Gy can inhibit the induction of inflammatory cytokine and attenuate the ACE2 depression induced by spike protein in human bronchial epithelial cells in COVID-19 infection. Our study provided further mechanistic evidence to support LDRT as a cost-effective treatment for COVID-19 to relieve the severe inflammatory reaction and lung injury. Methods and materials: A cellular model was created by treating human bronchial epithelial cells (BEP2D) with SARS-CoV-2 spike protein. We used the qRT-PCR and ELISA analysis to identify the production of inflammatory cytokines. The BEP2D control cells and the spike-treated cells were irradiated using a single low to moderate dose radiation of 0.5 Gy, 1 Gy, and 1.5 Gy. The inflammatory cytokines and ACE2 expression were detected at different time points. Results: The soluble SARS-CoV-2 spike protein stimulated the formation of inflammatory cytokines IL-6 and TNF-α while reducing the ACE2 protein expression in human bronchial epithelial cells. A single low to moderate dose exposure of 0.5 Gy, 1 Gy, and 1.5 Gy could attenuate the IL-6 and TNF-α induction and rescue the depression of ACE2 by spike protein. Moreover, the spike protein increased the proteolytic degradation of ACE2 protein by promoting NEDD4-mediated ubiquitination of ACE2. Conclusions: The low-dose radiation can attenuate ACE2 depression and inflammatory response produced in the targeted human bronchial epithelial cells by spike protein. This coordinating effect of LDRT may relieve the severe inflammatory reaction and lung injury in COVID-19 patients.


Subject(s)
COVID-19 , Lung Injury , Angiotensin-Converting Enzyme 2 , COVID-19/radiotherapy , Cytokines/metabolism , Epithelial Cells/metabolism , Humans , Interleukin-6/metabolism , Lung Injury/metabolism , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Tumor Necrosis Factor-alpha/metabolism
9.
Cells ; 11(3)2022 01 29.
Article in English | MEDLINE | ID: covidwho-1667055

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide with over 260 million people infected and more than 5 million deaths, numbers that are escalating on a daily basis. Frontline health workers and scientists diligently fight to alleviate life-threatening symptoms and control the spread of the disease. There is an urgent need for better triage of patients, especially in third world countries, in order to decrease the pressure induced on healthcare facilities. In the struggle to treat life-threatening COVID-19 pneumonia, scientists have debated the clinical use of ionizing radiation (IR). The historical literature dating back to the 1940s contains many reports of successful treatment of pneumonia with IR. In this work, we critically review the literature for the use of IR for both diagnostic and treatment purposes. We identify details including the computed tomography (CT) scanning considerations, the radiobiological basis of IR anti-inflammatory effects, the supportive evidence for low dose radiation therapy (LDRT), and the risks of radiation-induced cancer and cardiac disease associated with LDRT. In this paper, we address concerns regarding the effective management of COVID-19 patients and potential avenues that could provide empirical evidence for the fight against the disease.


Subject(s)
COVID-19/radiotherapy , Lung/radiation effects , Pneumonia, Viral/radiotherapy , Radiation, Ionizing , SARS-CoV-2/radiation effects , COVID-19/epidemiology , COVID-19/virology , Humans , Lung/virology , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Prognosis , Radiation Dosage , Radiotherapy Dosage , Risk Factors , SARS-CoV-2/physiology
10.
Radiat Oncol ; 17(1): 10, 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1643167

ABSTRACT

BACKGROUND: Low dose radiotherapy (LDRT) of whole lungs with photon beams is a novel method for treating COVID-19 pneumonia. This study aimed to estimate cancer risks induced by lung LDRT for different radiotherapy delivery techniques. METHOD: Four different radiotherapy techniques, including 3D-conformal with anterior and posterior fields (3D-CRT AP-PA), 3D-conformal with 8 coplanar fields (3D-CRT 8 fields), eight fields intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy using 2 full arcs (VMAT) were planned on the CT images of 32 COVID-19 patients with the prescribed dose of 1 Gy to the lungs. Organ average and maximum doses, and PTV dose distribution indexes were compared between different techniques. The radiation-induced cancer incidence and cancer-specific mortality, and cardiac heart disease risks were estimated for the assessed techniques. RESULTS: In IMRT and VMAT techniques, heart (mean and max), breast (mean, and max), and stomach (mean) doses and also maximum dose in the body were significantly lower than the 3D-CRT techniques. The calculated conformity indexes were similar in all the techniques. However, the homogeneity indexes were lower (i.e., better) in intensity-modulated techniques (P < 0.03) with no significant differences between IMRT and VMAT plans. Lung cancer incident risks for all the delivery techniques were similar (P > 0.4). Cancer incidence and mortality risks for organs located closer to lungs like breast and stomach were higher in 3D-CRT techniques than IMRT or VMAT techniques (excess solid tumor cancer incidence risks for a 30 years man: 1.94 ± 0.22% Vs. 1.68 ± 0.17%; and women: 6.66 ± 0.81% Vs. 4.60 ± 0.43%: cancer mortality risks for 30 years men: 1.63 ± 0.19% Vs. 1.45 ± 0.15%; and women: 3.63 ± 0.44% Vs. 2.94 ± 0.23%). CONCLUSION: All the radiotherapy techniques had low cancer risks. However, the overall estimated risks induced by IMRT and VMAT radiotherapy techniques were lower than the 3D-CRT techniques and can be used clinically in younger patients or patients having greater concerns about radiation induced cancers.


Subject(s)
COVID-19/radiotherapy , Neoplasms, Radiation-Induced/prevention & control , Radiotherapy Planning, Computer-Assisted , Adult , Aged , Breast/radiation effects , COVID-19/pathology , Female , Heart/radiation effects , Heart Disease Risk Factors , Humans , Iran , Lung/pathology , Lung/radiation effects , Male , Middle Aged , Neoplasms, Radiation-Induced/diagnosis , Neoplasms, Radiation-Induced/etiology , Organs at Risk/radiation effects , Pneumonia, Viral/radiotherapy , Prognosis , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/methods , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Risk Assessment , SARS-CoV-2
11.
J Med Imaging Radiat Sci ; 53(2 Suppl): S44-S50, 2022 06.
Article in English | MEDLINE | ID: covidwho-1587208

ABSTRACT

BACKGROUND: Palliative radiotherapy (RT) is effectively used to relieve cancer related symptoms. The demand for these services is increasing worldwide. Rapid response clinics have been developed as a means to streamline the palliative RT radiotherapy process and increase efficiency and improve patient experiences. Key components to successful rapid response palliative RT are access to care, streamlined services and innovation. To successfully implement a rapid response RT programme, it is essential to identify gaps between currently provided care and ideal or enhanced care. The aims of this work are to audit the current palliative RT workflow at our institution both prior to and during the coronavirus pandemic. This work reports the impact of covid-19 on rate of palliative RT referrals and proposes a radiographer led, MR guided rapid response workflow to reduce wait times METHODS: A retrospective audit of palliative radiotherapy booking forms was completed over a two yearperiod (2019-2020) to assess the current pathway both prior to and during the covid-19 pandemic. This audit identified patients who had received urgent/emergency spinal RT in the specified timeframe. Further data on these patients was collected using departmental oncology information systems to form a detailed analysis of the pathway and wait times. Data was recorded and analysed using Microsoft Excel. RESULTS: A total of 813 patients met the inclusion criteria for this audit. Data was reported for 2019 and 2020 separately to determine any significant impact caused by the covid-19 pandemic. In 2020 there was an 11.5% increase in referrals for palliative radiotherapy with an equal portion (81%) of total referrals in each year being for single fractions. Timelines from referral to treatment delivery were reported, with those patients receiving same day single fraction RT palliative radiotherapy undergoing further analysis to determine the amount of time spent in the department. Mean wait time for these patients was 5 hours and 20 minutes in 2019 but increased by 20.9% in 2020. CONCLUSIONS: The increasing demand for palliative RT due to rising global cancer rates and extended life expectancy due to advanced systemic treatments may lead to increased wait times. An increase in both referrals and mean wait time was seen during the covid-19 pandemic. Improving efficiency and access to care is essential for this population. The MR Linac could play a role in streamlining palliative RT workflows due to its ability to employ a scan, plan and treat model in a single session. This work forms preliminary support for the development of a trial one stop palliative program on the MR Linac.


Subject(s)
COVID-19 , Neoplasms , COVID-19/radiotherapy , Humans , Neoplasms/radiotherapy , Palliative Care , Pandemics , Retrospective Studies
12.
J Photochem Photobiol B ; 226: 112357, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1510060

ABSTRACT

Mitochondrial antiviral signaling (MAVS) protein mediates innate antiviral responses, including responses to certain coronaviruses such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have previously shown that ultraviolet-A (UVA) therapy can prevent virus-induced cell death in human ciliated tracheal epithelial cells (HTEpC) infected with coronavirus-229E (CoV-229E), and results in increased intracellular levels of MAVS. In this study, we explored the mechanisms by which UVA light can activate MAVS, and whether local UVA light application can activate MAVS at locations distant from the light source (e.g. via cell-to-cell communication). MAVS levels were compared in HTEpC exposed to 2 mW/cm2 narrow band (NB)-UVA for 20 min and in unexposed controls at 30-40% and at 100% confluency, and in unexposed HTEpC treated with supernatants or lysates from UVA-exposed cells or from unexposed controls. MAVS was also assessed in different sections of confluent monolayer plates where only one section was exposed to NB-UVA. Our results showed that UVA increases the expression of MAVS protein. Further, cells in a confluent monolayer exposed to UVA conferred an elevation in MAVS in cells adjacent to the exposed section, and also in cells in the most distant sections which were not exposed to UVA. In this study, human ciliated tracheal epithelial cells exposed to UVA demonstrate increased MAVS protein, and also appear to transmit this influence to confluent cells not exposed to UVA, likely via cell-cell signaling.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/radiation effects , Ultraviolet Rays , Adaptor Proteins, Signal Transducing/immunology , COVID-19/immunology , COVID-19/radiotherapy , COVID-19/virology , Cell Communication/immunology , Cell Communication/radiation effects , Cells, Cultured , Epithelial Cells/immunology , Epithelial Cells/radiation effects , Host Microbial Interactions/immunology , Host Microbial Interactions/radiation effects , Humans , Immunity, Innate/radiation effects , Photobiology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction/immunology , Signal Transduction/radiation effects , Trachea/cytology , Ultraviolet Therapy
13.
Lasers Med Sci ; 37(3): 1921-1929, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1482226

ABSTRACT

We are currently facing a pandemic that continuously causes high death rates and has negative economic and psychosocial impacts. Therefore, this period requires a quick search for viable procedures that can allow us to use safe and non-invasive clinical tools as prophylactic or even adjuvant methods in the treatment of COVID-19. Some evidence shows that photobiomodulation therapy (PBMT) can attenuate the inflammatory response and reduce respiratory disorders similar to acute lung injury (ALI), complications associated with infections, such as the one caused by the new Coronavirus (SARS-CoV-2). Hence, the aim of the present study was to evaluate the influence of PBMT (infrared low-level laser therapy) on the treatment of ALI, one of the main critical complications of COVID-19 infection, in an experimental model in rats. Twenty-four male Wistar rats were randomly allocated to three experimental groups (n = 8): control group (CG), controlled ALI (ALI), and acute lung injury and PBM (ALIP). For treatment, a laser equipment was used (808 nm; 30 mw; 1.68 J) applied at three sites (anterior region of the trachea and in the ventral regions of the thorax, bilaterally) in the period of 1 and 24 h after induction of ALI. For treatment evaluation, descriptive histopathological analysis, lung injury score, analysis of the number of inflammatory cells, and expression of interleukin 1 ß (IL-1ß) were performed. In the results, it was possible to observe that the treatment with PBMT reduced inflammatory infiltrates, thickening of the alveolar septum, and lung injury score when compared to the ALI group. In addition, PBMT showed lower immunoexpression of IL-1ß. Therefore, based on the results observed in the present study, it can be concluded that treatment with PBMT (infrared low-level laser therapy) was able to induce an adequate tissue response capable of modulating the signs of inflammatory process in ALI, one of the main complications of COVID-19.


Subject(s)
COVID-19 , Low-Level Light Therapy , Animals , COVID-19/radiotherapy , Low-Level Light Therapy/methods , Lung/pathology , Male , Rats , Rats, Wistar , SARS-CoV-2
14.
Int J Radiat Oncol Biol Phys ; 112(1): 197-211, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1469874

ABSTRACT

PURPOSE: Low-dose whole lung radiation therapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection, and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling, and mechanisms of action. METHODS AND MATERIALS: Female C57BL/6 mice were treated with intranasal bleomycin sulfate (7.5 or 11.25 units/kg, day 0) and then exposed to whole lung radiation therapy (0.5, 1.0, or 1.5 Gy, or sham; day 3). Bodyweight was measured daily, and lung tissue was harvested for histology and flow cytometry on day 10. Computed tomography lung imaging was performed before radiation (day 3) and pre-endpoint (day 10). RESULTS: Bleomycin caused pneumonitis of variable severity, which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight, and a proportion of these mice exhibited less severe histopathologic lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. In addition, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells (DCs), and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of nonaerated lung in left than right lungs, and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric, or radiologic readouts of bleomycin-induced pneumonitis. CONCLUSIONS: Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose, and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ DCs, and neutrophil-DC hybrids.


Subject(s)
Pneumonia , Radiotherapy , Animals , Bleomycin , COVID-19/radiotherapy , Disease Models, Animal , Female , Humans , Lung/diagnostic imaging , Mice , Mice, Inbred C57BL , Pneumonia/chemically induced , Weight Loss
15.
Vopr Virusol ; 66(4): 252-258, 2021 09 17.
Article in Russian | MEDLINE | ID: covidwho-1431290

ABSTRACT

This review presents the literature data of new approaches for the treatment of COVID-19 with low doses of radiation (LDR). In addition, data on the use of LDR for the treatment of various disorders, in particular pneumonia, a number of inflammatory processes of various etiology, as well as Alzheimer's disease are discussed. The mechanisms of LDR action are briefly described, associated with the activation of the immune system and antiinflammatory response due to the effect on the processes of oxidative stress, which is reflected in an increase in the activity of cytokines (interleukin- (IL-) 6), changes in the expression of a number of genes (such as P53 and NF-κB (p65)) and long non-coding RNAs (ncRNAs) (the authors' own data are presented). Based on the analysis of the material presented, it can be assumed that further clinical trials of the effect of MDR (5-10 cGy) on patients with COVID-19, who are at different stages of the disease, will reveal the optimal conditions for the development and use of an effective treatment regimen.


Subject(s)
COVID-19 , Oxidative Stress/radiation effects , SARS-CoV-2/metabolism , COVID-19/metabolism , COVID-19/radiotherapy , Humans , Interleukin-6/metabolism , RNA, Long Noncoding/metabolism , Transcription Factor RelA/metabolism
16.
Br J Radiol ; 94(1126): 20210187, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1430508

ABSTRACT

OBJECTIVES: The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. METHODS: From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. RESULTS: All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. CONCLUSION: The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. ADVANCES IN KNOWLEDGE: LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials.


Subject(s)
COVID-19/radiotherapy , Pneumonia, Viral/radiotherapy , Adult , Aged , Early Warning Score , Feasibility Studies , Female , Humans , Male , Middle Aged , Pandemics , Pilot Projects , Pneumonia, Viral/virology , Radiotherapy Dosage , SARS-CoV-2
17.
Photochem Photobiol ; 98(2): 461-470, 2022 03.
Article in English | MEDLINE | ID: covidwho-1394005

ABSTRACT

Most recently, severe acute respiratory syndrome coronavirus-2 has triggered a global pandemic without successful therapeutics. The goal of the present study was to define the antiviral effect and therapeutic action of blue light irradiation in SARS-CoV-2-infected cells. Vero cells were infected with SARS-CoV-2 (NCCP43326) or mock inoculum at 50 pfu/well. After blue light irradiation, the inhibitory effect was assessed by qPCR and plaque reduction assay. When Vero cells were irradiated to blue light ranging from 1.6 to 10 J cm-2 , SARS-CoV-2 replication was inhibited by up to 80%. The antiviral effect of blue light irradiation was associated with translation suppression via the phosphorylation of eIF2α by prolonging endoplasmic reticulum (ER) stress. The levels of LC3A/B and Beclin-1, which are key markers of autophagy, and the levels of PERK and PDI for ER stress were highly increased, whereas caspase-3 cleavage was inhibited after blue light irradiation in the later stage of infection. Our data revealed that blue light irradiation exerted antiviral and photo-biogoverning activities by prolonging ER stress and stimulating autophagy progression during viral infection. The findings increase our understanding of how photo-energy acts on viral progression and have implications for use in therapeutic strategies against COVID-19.


Subject(s)
COVID-19 , Animals , COVID-19/radiotherapy , Chlorocebus aethiops , Pandemics , SARS-CoV-2 , Vero Cells , Virus Replication
18.
Arch Toxicol ; 95(10): 3425-3432, 2021 10.
Article in English | MEDLINE | ID: covidwho-1321732

ABSTRACT

Coronavirus variants are gaining strongholds throughout the globe. Despite early signals that SARS-CoV-2 coronavirus case numbers are easing up in the United States and during the middle of a (not so easy) vaccination roll out, the country has passed a grim landmark of 600,000 deaths. We contend that these numbers would have been much lower if the medical community undertook serious investigations into the potential of low doses of radiation (LDRT) as a mainstream treatment modality for COVID-19 pneumonia. LDRT has been posited to manifest anti-infectious and anti-inflammatory properties at doses of 0.3-1.0 Gy via the activation of the Nrf-2 pathway. Although some researchers are conducting well-designed clinical trials on the potential of LDRT, the deep-rooted, blind, and flawed acceptance of the Linear No-Threshold (LNT) model for ionizing radiation has led to sidelining of this promising therapy and thus unimaginable numbers of deaths in the United States.


Subject(s)
COVID-19/radiotherapy , Dose-Response Relationship, Radiation , Humans , NF-E2-Related Factor 2 , Radiotherapy Dosage
19.
Respir Med ; 186: 106531, 2021 09.
Article in English | MEDLINE | ID: covidwho-1300990

ABSTRACT

The covid-19 pandemic has been affecting many countries across the world and lost precious lives. Most patients suffer from respiratory disease which progresses to the severe acute respiratory syndrome, termed as SARS-CoV-2 pneumonia. A systemic inflammatory response occurs in SARS-CoV-2 pneumonia severely ill patients, The inflammation process if uncontrolled has a detrimental effect, and the release of cytokines play an important role leading to lung fibrosis. Radiation therapy used in low doses has an anti-inflammatory and immunomodulatory effect. Its low cost, wider availability, and decreased risk of acute side effects can reduce the burden on the health care system.


Subject(s)
COVID-19/radiotherapy , Radiotherapy/methods , Severe Acute Respiratory Syndrome/radiotherapy , COVID-19/complications , COVID-19/virology , Cytokines/metabolism , Disease Progression , Humans , Inflammation , Inflammation Mediators/metabolism , Macrophages , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/radiotherapy , Radiotherapy Dosage , SARS-CoV-2 , Severe Acute Respiratory Syndrome/etiology , Severity of Illness Index
20.
Strahlenther Onkol ; 197(11): 1010-1020, 2021 11.
Article in English | MEDLINE | ID: covidwho-1298545

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.


Subject(s)
COVID-19/radiotherapy , Radiotherapy, Conformal/methods , SARS-CoV-2 , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , C-Reactive Protein/analysis , COVID-19/diagnostic imaging , COVID-19/mortality , COVID-19/therapy , Cause of Death , Combined Modality Therapy , Comorbidity , Dexamethasone/therapeutic use , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lung/radiation effects , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/radiotherapy , Lung Diseases, Interstitial/therapy , Male , Oxygen/blood , Oxygen/therapeutic use , Oxygen Inhalation Therapy , Partial Pressure , Prospective Studies , Radiotherapy Dosage , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
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