Treatment Of COVID-19 Pneumonia Research Articles

Dexamethasone Vs methylprednisolone In treating Covid-19 pneumonia: A meta-analysis of randomized trials

Dexamethasone Vs methylprednisolone In treating Covid-19 pneumonia: A meta-analysis of randomized trials

Saying No to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia

Saying No to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia

Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms

IntroductionThymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital.MethodsThe primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%).ResultsThe length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients.ConclusionThymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.

Bioengineered Neutrophil Extinguisher Targets Cascade Immune Pathways of Macrophages for Alleviating Cytokine Storm in Pneumonia.

Cytokine storm is a common complication of COVID-19 pneumonia and has been proven to contribute to high mortality rates. However, current treatment approaches exhibit limited potential to balance immune response and overproduction of inflammatory cytokines, leading to poor therapeutic outcomes. Herein, a smart bioengineered neutrophil, Extinguisher, composed of live neutrophils encapsulating the liposome formulation of NF-κB suppressor MLN4924 and STING inhibitor H-151 (Lip@MH), is developed for alleviating the hyperinflammatory cytokine storm. Extinguisher inherits motility and chemotaxis characteristics of neutrophils, allowing for the specific delivery and sustained release of Lip@MH within inflamed tissues. Subsequently, Lip@MH effectively transports anti-inflammatory agents into macrophages and synergistically inhibits inflammatory pathways of NF-κB and STING, leading to decreased production of cytokines. In vivo studies demonstrate that Extinguisher not only selectively accumulates at the site of pneumonia caused by Pseudomonas aeruginosa-induced acute lung injury but inhibits the production of inflammatory factors through regulating NF-κB/STING signaling pathways, thereby effectively calming cytokine storm. Importantly, Extinguisher significantly improves therapeutic benefits and survival in mice with acute pneumonia. Therefore, Extinguisher represents an appropriate combination of cell therapy and immunoregulation for cytokine storm intervention and may bring insights into the treatment of COVID-19 pneumonia.

Multicentre study on the accuracy of lung ultrasound in the diagnosis and monitoring of respiratory sequelae in the medium and long term in patients with COVID-19.

Lung ultrasound (LUS) has proven to be a more sensitive tool than radiography (X-ray) to detect alveolar-interstitial involvement in COVID-19 pneumonia. However, its usefulness in the detection of possible pulmonary alterations after overcoming the acute phase of COVID-19 is unknown. In this study we proposed studying the utility of LUS in the medium- and long-term follow-up of a cohort of patients hospitalized with COVID-19 pneumonia. This was a prospective, multicentre study that included patients, aged over 18 years, at 3 ± 1 and 12 ± 1 months after discharge after treatment for COVID-19 pneumonia. Demographic variables, the disease severity, and analytical, radiographic, and functional clinical details were collected. LUS was performed at each visit and 14 areas were evaluated and classified with a scoring system whose global sum was referred to as the "lung score." Two-dimensional shear wave elastography (2D-SWE) was performed in 2 anterior areas and in 2 posterior areas in a subgroup of patients. The results were compared with high-resolution computed tomography (CT) images reported by an expert radiologist. A total of 233 patients were included, of whom 76 (32.6%) required Intensive Care Unit (ICU) admission; 58 (24.9%) of them were intubated and non-invasive respiratory support was also necessary in 58 cases (24.9%). Compared with the results from CT images, when performed in the medium term, LUS showed a sensitivity (S) of 89.7%, specificity (E) 50%, and an area under the curve (AUC) of 78.8%, while the diagnostic usefulness of X-ray showed an S of 78% and E of 47%. Most of the patients improved in the long-term evaluation, with LUS showing an efficacy with an S of 76% and E of 74%, while the X-ray presented an S of 71% and E of 50%. 2D-SWE data were available in 108 (61.7%) patients, in whom we found a non-significant tendency toward the presentation of a higher shear wave velocity among those who developed interstitial alterations, with a median kPa of 22.76 ± 15.49) versus 19.45 ± 11.39; p = 0.1). Lung ultrasound could be implemented as a first-line procedure in the evaluation of interstitial lung sequelae after COVID-19 pneumonia.

Safety of Tocilizumab and Remdesivir in Treating COVID-19 Pneumonia in Premature Twins.

Safety of Tocilizumab and Remdesivir in Treating COVID-19 Pneumonia in Premature Twins.

Steroid exposure and outcome in COVID-19 pneumonia.

Corticosteroids are used to treat COVID-19 pneumonia. However, the optimal dose is unclear. This study describes the association between corticosteroid exposure with disease severity and outcome in COVID-19 pneumonia. This is a single-centre retrospective, observational study including adult ICU patients who received systemic corticosteroids for COVID-19 pneumonia between March 2020 and March 2021. We recorded patient characteristics, disease severity, total steroid exposure, respiratory support and gas exchange data, and 90 day survival. We included 362 patients. We allocated patients to groups with increasing disease severity according to the highest level of respiratory support that they received: high flow oxygen or continuous positive airway pressure (HFNO/CPAP) in 12.7%, invasive mechanical ventilation (IMV) in 61.6% and extracorporeal membrane oxygenation (ECMO) in 25.7%. For these three groups the median (IQR) age was 61 (54-71) vs 58 (50-66) vs 46 (38-53) years respectively (p<0.001); median (IQR) APACHE II scores were 12 (9-15) vs 14 (12-18) vs 15 (12-17) respectively (p=0.006); median (IQR) lowest PaO2/FiO2 ratio was 15.1 (11.8-21.7) vs 15.1 (10.7-22.2) vs 9.5 (7.9-10.9) kPa respectively (p<0.001). Ninety-day mortality was 9% vs 27% vs 37% (p=0.002). Median (IQR) dexamethasone-equivalent exposure was 37 (24-62) vs 174 (86, 504) vs 535 (257, 1213) mg (p<0.001_. 'Pulsed' steroids were administered to 26% of the IMV group and 48% of the ECMO group. Patients with higher disease severity who received pulse steroids had a higher 90-day mortality. Corticosteroid exposure increased with the severity of Covid-19 pneumoonia. Pulsed dose steroids were used more frequently in patients receiving greater respiratory support. Future studies should address patient selection and outcomes associated with pulsed dose steroids in patients with severe and deteriorating COVID-19 pneumonia.

Two surgical cases of pneumothorax after treatment for COVID-19 pneumonia

Two surgical cases of pneumothorax after treatment for COVID-19 pneumonia

"Efficacy of tocilizumab in treatment of COVID-19 pneumonia: A case-control study from a tertiary care hospital".

We read with interest the article titled “Letter to Editor in response to article ‘Efficacy of Tocilizumab in treatment of COVID-19 pneumonia: A case–control study from a tertiary care hospital’ published in Lung India.”[1] We have the following comments to offer: Since tocilizumab was costly, not easily available during the pandemic and had significant adverse effects, its usage was based on criteria comprising clinical and laboratory markers and radiological opacities. These criteria were not uniform and were based on a few studies[2,3] published during the period of this study and quoted by the authors. In this study, the authors have not specified any such criteria or guidelines for intervention with tocilizumab. Also, during the time period of this study, tocilizumab was used in moderate, severe and critical patients and rapidly progressive cases in studies from abroad[2]and in India.[3] It is not understood how tocilizumab was used in 13 mild cases in this study. Moreover, mortality in mild cases and control was 6.25% and 7.5%, respectively, in this study. This unusually high mortality rate in mild cases needs further elaboration. The authors have calculated the inflammatory score based on biological reference interval, which does not give a proper correlation of disease severity with inflammatory markers. Since there were data available for various inflammatory markers in this retrospective study, the authors should have either used mean values with standard deviation using their own data or used the weighted mean difference values mentioned in a meta-analysis by Zeng F, et al.,[4] which has been quoted as a reference in this study. The authors have found better outcomes with tocilizumab with an inflammatory score of less than 3 in this study and have concluded that a lower level of inflammatory score may be used as a predictor of outcome with tocilizumab. In the discussion, the authors have supported this finding by quoting a study by Olewicz-Gawlik et al.[5] In fact, this referenced study has not been interpreted correctly. In this study, the serum concentrations of inflammatory markers before the administration of tocilizumab did not predict the outcome, whereas interleukin-6 (IL-6) and lactate dehydrogenase (LDH) measurements after the administration of tocilizumab seemed to be of predictive value. Because higher levels of inflammatory markers, especially C-reactive protein (CRP) and IL-6, are associated with poor outcome[6] and CRP levels above 75 mg/ml are taken as one of the criteria for initiating treatment with tocilizumab,[7] this contrasting finding in this study needs elaboration. The study has found the role of tocilizumab in reducing mortality in those with low Sequential Organ Failure Assessment (SOFA) score. The authors have quoted a study by Guaraldi G et al.,[8] in support of this observation. In fact, this study has adjusted SOFA score between cases and controls for the assessment of the efficacy of tocilizumab and does not mention the correlation of low SOFA score with reduced mortality. This requires further elaboration by the authors. Tocilizumab has significant adverse effects, and the same has not been studied with no mention of adverse effects and overall safety. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

The chest X-ray radiologic severity index as a determinant of the severity of COVID-19 pneumonia: study based on the duration of treatment and inpatient rooms.

The chest X-ray examination is an imaging modality that is widely used in screening for COVID-19 pneumonia. The problems with treating COVID-19 pneumonia patients are the high incidence and severity of the disease and the limitations of treatment room facilities. The chest X-ray RadiologicSeverity Index is expected to assist clinicians in obtaining the relationship between the extent of lesions on X-ray and the duration of treatment and hospitalization for COVID-19 pneumonia patients. This study used an observational method using a retrospective approach. The research subjects were COVID-19 pneumonia patients from March 2020 to April 2021 who were hospitalized at Doctor Kariadi General Hospital Semarang. A total of 105 subjects confirmed positive RT-PCR and received serial X-ray examination services during treatment. The calculation of the RSI value was carried out on all X-ray chest X-rays and then statistically analyzed using the paired T test and Mann-Whitney methods.There was no significant relationship between the value of RSI1 and the duration of hospitalization with p = 0.566, as well as the value of RSI2 with the duration of hospitalization with p = 0.715. There is a significant relationship between the values of RSI1 and RSI2 with the use of the intensive care unit with p < 0.000, respectively. There was a significant relationship between the values of RSI1 and RSI2 with the use of ventilators in treatment, with p < 0.000. Furthermore RSI1 and RSI2 have a good result as predictor of intensive care and ventilator usage. The chest X-ray RSI has no significant relationship with the duration of hospitalization. The value of the chest X-ray RSI has a significant relationship with the use of intensive care rooms and the use of ventilators in treatment. The increase in the RSI value can describe the severity of the disease so that it plays a role in planning the treatment room.

Low Dose Radiotherapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19): Final Results

Purpose/Objective(s)To evaluate the results of LD-RT to lungs in the management of patients with COVID-19 pneumonia.Materials/MethodsWe conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement. Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was 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.ResultsForty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (47%) previously received any antiCOVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. Extension score improved significantly (p=0.02) on day +7 and SAFI 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). 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.ConclusionLD-RT is a feasible and well-tolerated treatment that may lead to rapid clinical improvement. Large randomized trials should be done to establish the efficacy of LD-RT to treat COVID-19 pneumonia.

EP06.01-008 COVID-Protected Pathways for Image Guided Lunc Cancer Intervention During the COVID-19 Pandemic: A Cohort Study

EP06.01-008 COVID-Protected Pathways for Image Guided Lunc Cancer Intervention During the COVID-19 Pandemic: A Cohort Study

Predictors of COVID-19 Disease Course and Pulmonary Insult

Background: The novel coronavirus disease COVID-19 first appeared in Wuhan, Hubei. It is crucial to identify patients who are susceptible to severe forms of the disease. Imaging has an important role in the confirmation and treatment of COVID-19 pneumonia. Aim: To assess the predictors of the COVID-19 disease course and pulmonary insult. Methods: Our retrospective investigation included 115 patients with COVID-19, with a median age of 49.1-66.3 years old, at King Hussein Medical Center, Amman, Jordan. Patients were assigned into one of two groups based on the disease course: group I (n=63) included patients with moderate disease and group II (n=52) included patients with severe disease. Computed tomography (CT) scores of pulmonary insult were determined. Baseline CT findings showed ground-glass opacity, consolidation, crazy-paving pattern and reticular shadow. Each lung region was scored using the five-grade scale to calculate the CT score. Independent factors of moderate COVID-19 were evaluated using binary logistic regression. Multivariate logistic regression was used to predict the CT score in COVID-19. Results: The independent factors for the COVID-19 disease course were baseline CT score (P &lt; 0.05) and C-reactive protein (CRP) (P&lt; 0.05). The factors for pulmonary insult were age, neutrophil, lymphocyte and CRP levels and CT score (P &lt; 0.05). The cut-off value for CRP was 19.0 and the cut-off value for CT score was 9.0. Conclusion: Age, baseline CT score, CRP, neutrophil and lymphocyte percentages may predict the CT score of pulmonary insult. A CRP value of more than 19 and baseline CT score of more than 9 were independent factors of severe COVID-19 disease. Keywords: COVID-19, moderate, severe, pulmonary insult, computed tomography score, neutrophil, lymphocyte, CRP, age.

Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies

Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. All patients demonstrated undetectable baseline anti-SARS-CoV-2 immunoglobulin levels before CP. Each patient received at least a complete course of remdesivir and at least one unit of CP. Previous anti-CD20 therapy resulted in a more prolonged SARS-CoV-2 PCR positivity compared to other causes of B-cell lymphopenia (p = 0.004). Timing of CP therapy showed a significant impact on the clinical outcome. Simultaneous use of remdesivir and CP reduced time period for oxygen weaning after diagnosis (p = 0.017), length of hospital stay (p = 0.007), and PCR positivity (p = 0.012) compared to patients who received remdesivir and CP consecutively. In addition, time from the diagnosis to CP therapy affected the length of oxygen dependency (p < 0.001) and hospital stay (p < 0.0001). In those cases where there were at least 10 days from the diagnosis to plasma administration, oxygen dependency was prolonged vs. patients with shorter interval (p = 0.006). In conclusion, the combination of inhibition of viral replication with passive immunization was proved to be efficient and safe. Our results suggest the clear benefit of early, combined administration of remdesivir and CP to avoid protracted COVID-19 disease among patients with HMs and B-cell lymphopenia.

Successful Systemic Heparinization for Treatment of Acute Arterial Occlusion of Tibial Artery and Aortic Mural Thrombi in a Patient With COVID-19 Infection: A Case Report

The present case report described a 60-year-old woman who developed multiple isolated acute arterial occlusions of the left anterior tibial artery, peroneal artery, and posterior tibial artery with aortic mural thrombi in the infrarenal aorta during treatment of COVID-19 pneumonia. The patient underwent conservative treatment by systemic heparinization and switched to low molecular weight heparin. She experienced clinical improvement within hours of medical treatment and complete resolution of the tibial artery thrombosis after two weeks of treatment. The aortic mural thrombi was evaluated by computed tomography angiography (CTA) abdomen and lower extremities and resolved after six weeks of anticoagulant administration. Keywords: Acute limb ischemia; Aortic mural thrombi; Thrombosis; COVID-19

Ultraviolet-coupled advanced oxidation processes for anti-COVID-19 drugs treatment: Degradation mechanisms, transformation products and toxicity evolution.

Remdesivir (RDV), dexamethasone (DEX) and hydroxychloroquine (HCQ) were widely used in the treatment of COVID-19 pneumonia, possibly causing environmental risks and drug-resistance viruses. This study elucidated the degradation mechanisms and potential toxicity risks of the three anti-COVID-19 drugs by UV and ultraviolet-coupled advanced oxidation processes (UV/AOPs). All the drugs could be degraded by more than 98% within 3 min under the following optimal conditions: pH of 5.0 and drug-to-oxidant (H2O2) molar ratio of 1:200. Combined with density functional theory (DFT) analysis and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS), twenty-four transformation products (TPs) were detected and the main degradation pathways were investigated. Based on bacterial luminescence inhibition test and the peak-area evolution of TPs, RDV and HCQ showed an obvious toxicity-increase region when TPs were generated in large quantities, while the toxicity of DEX continued to decline during degradation processes. By QSAR predictions, the main contributors to the toxicity evolution during the UV/AOPs were predicted. Halogen-containing TPs showed significantly higher toxicity than other TPs, and thus the chlorine-containing structure in HCQ presented the potential toxicity. Appropriate reaction parameters and adequate reaction time for the UV/AOPs could eliminate the toxicity of TPs and ensure environmental safety. This study could play a positive role in the treatment of anti-COVID-19 drugs and their environmental hazard assessment.

Possible effects of the exposure to ionizing radiation on the patients recovered from COVID-19

The aim. To conduct an analytical literature review on the possible impact of SARS-CoV-2 on the radiosensitivity of the human body and justify the relevance of radiobiological research in this area.&#x0D; Materials and methods. Analysis of data from biological dosimetry / indication of radiation lesions of human peripheral blood T-lymphocyte chromosomes under medical irradiation for comparison with radiosensitivity in the patients recovered from COVID-19 (Scopus International Scientific Metric Database, IAEA guidelines, 2011).&#x0D; Results. With the ongoing COVID-19 pandemic, forecasting and clarifying of the mechanisms of distant effects resulting from interactions between ionizing radiation and the SARS-CoV-2 virus play an important role. The difficulty in solving this problem is caused by the fact that the global science has no exhaustive information on the possible influence of this virus on radiation-induced effects. The attention of the professional community is drawn to the possible impact of SARS-CoV-2 on the radiosensitivity of the body of patients recovered from COVID-19 and a hypothesis is first proposed regarding the mechanism on how to increase it based on the development of systemic long-term inflammation. Therefore, clinical trials of low-dose radiotherapy for the treatment of COVID-19-related pneumonia involve preliminary radiobiological studies to answer the following question: does the SARS-CoV-2 virus affect the radiosensitivity of the human body? Long-term experience of the author of this paper in biodosimetric (cytogenetic) studies allows her to recommend the peripheral blood lymphocyte test system with chromosome aberration’s analysis as the most radiosensitive cell model.&#x0D; Conclusions. Clinical trials of low-dose radiotherapy for the treatment of COVID-19 pneumonia involve a preliminary radiobiological study to answer the following question: does the SARS-CoV-2 virus affect the radiosensitivity of the human body? The most optimal approach for the solution of this problem is the use of test-system of human peripheral blood lymphocytes’ culture with the subsequent cytogenetic analysis. It will allow investigating changes in the “dose-effect” “cell cycle stage-effect” dependencies, as well as changes in individual radiosensitivity under the influence of SARS-CoV-2 virus

Favipiravir for the treatment of COVID-19 pneumonia: Can we predict the response to treatment?

Early experience with favipiravir in the treatment of COVID-19 is promising, but no clinical data have been published in medical journals. This study aimed to review the experience with favipiravir treatment for COVID-19 pneumonia and to examine whether there are any predictors of treatment response. Fifty-six patients with severe or progressive pneumonia associated with COVID-19 who were treated with favipiravir monotherapy for at least five days were included in this retrospective study. Treatment response was defined as clinical recovery without any need for admission into the intensive care unit and/or anti-cytokine therapy. The demographic, clinical, laboratory and radiographic features of the patients were compared between favipiravir-responders and non-responders. Of the 56 patients, 34 patients (60.7%) responded to treatment and recovered. There was no difference in the demographic, clinical, and radiographic findings between the responders and non-responders. The inflammatory biomarkers were also similar except for the CRP levels on the day favipiravir was started [74 (36-111) vs. 118.5 (46.5-203) mg/L, respectively, p = 0.043]. There was also a significant difference in the median time to defervescence [1 (1-2) vs. 3.5 (1.75-9.25) days, respectively]. Of clinical interest, 27 (79.4%) and 31 (91.2%) of the responders became afebrile within two and four days, respectively. The response rate was lower in patients who presented severe pneumonia associated with respiratory failure. Patients with non-severe pneumonia at admission and whose fever resolved within two days of treatment are more likely to improve with favipiravir.

Low-dose Radiation Therapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19). Final results of a prospective phase I–II trial

Background and purposeTo evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. Material and methodsWe 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. ResultsForty-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. ConclusionsLD-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.

Research on the mechanism of berberine in the treatment of COVID-19 pneumonia pulmonary fibrosis using network pharmacology and molecular docking

Purpose Pulmonary fibrosis caused by COVID-19 pneumonia is a serious complication of COVID-19 infection, there is a lack of effective treatment methods clinically. This article explored the mechanism of action of berberine in the treatment of COVID-19 (Corona Virus Disease 2019, COVID-19) pneumonia pulmonary fibrosis with the help of the network pharmacology and molecular docking.Methods We predicted the role of berberine protein targets with the Pharmmapper database and the 3D structure of berberine in the Pubchem database. And GeneCards database was used in order to search disease target genes and screen common target genes. Then we used STRING web to construct PPI interaction network of common target protein. The common target genes were analyzed by GO and KEGG by DAVID database. The disease-core target gene-drug network was established and molecular docking was used for prediction. We also analyzed the binding free energy and simulates molecular dynamics of complexes.Results Berberine had 250 gene targets, COVID-19 pneumonia pulmonary fibrosis had 191 gene targets, the intersection of which was 23 in common gene targets. Molecular docking showed that berberine was associated with CCl2, IL-6, STAT3 and TNF-α. GO and KEGG analysis reveals that berberine mainly plays a vital role by the signaling pathways of influenza, inflammation and immune response.Conclusion Berberine acts on TNF-α, STAT3, IL-6, CCL2 and other targets to inhibit inflammation and the activation of fibrocytes to achieve the purpose of treating COVID-19 pneumonia pulmonary fibrosis.