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1.
Eur J Med Res ; 27(1): 68, 2022 May 15.
Article in English | MEDLINE | ID: covidwho-1849783

ABSTRACT

BACKGROUND: Dermatomyositis is a rare idiopathic inflammatory disease with diverse presentations that can have varying degrees of cutaneous and systemic involvement. This phenotypic heterogeneity makes DM a therapeutic challenge. Some therapeutic drugs, such as hormones and immunosuppressants, have poor therapeutic effects. In recent years, tofacitinib has been reported to be effective in the treatment of dermatomyositis. CASE PRESENTATION: We report a case of anti-MDA5 antibody-positive dermatomyositis that was relieved after treatment with tofacitinib, during which gallbladder gangrene and suppurative cholecystitis occurred. After cholecystectomy, we continued to use tofacitinib and achieved a good therapeutic effect. CONCLUSIONS: Tofacitinib is effective in the treatment of anti-MDA5 antibody-positive dermatomyositis, but the risk of infection is increased. It can still be used after infection control. Close follow-up should be performed during the use of tofacitinib.


Subject(s)
Cholecystitis , Dermatomyositis , Lung Diseases, Interstitial , Autoantibodies , Cholecystitis/complications , Cholecystitis/drug therapy , Dermatomyositis/complications , Dermatomyositis/drug therapy , Humans , Interferon-Induced Helicase, IFIH1 , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/drug therapy , Piperidines , Pyrimidines
2.
J Infect Chemother ; 28(7): 1029-1032, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1783494

ABSTRACT

A recent study reported that patients with interstitial lung disease (ILD) are at increased risk of death from coronavirus disease 2019 (COVID-19). However, there are no studies on the outcome of COVID-19 patients with preexisting ILD treated with corticosteroids or antiviral drugs. We extracted 26 patients with preexisting ILD by medical records and HRCT pattern. Of 503 patients with COVID-19, we selected 52 patients as control matched for age and sex. Twenty out of the 26 ILD patients (76.9%) received corticosteroid therapy, and 23 patients (88.5%) also received antiviral treatment with remdesivir or favipiravir. Although no statistical difference was found, the proportion of severe patients in ILD group tended to be higher than in non-ILD group (23.1% vs. 42.3%; p = 0.114). Also, mortality rate in ILD group tended to be higher than in non-ILD patients (11.5% vs. 3.8%; p = 0.326). In univariate analysis to evaluate risk factors for severe condition, diagnosis of idiopathic pulmonary fibrosis, usual interstitial pneumonia pattern, and honeycomb lung were not risk factors of severe disease. Treatment with corticosteroids, antiviral drugs, and immunosuppressive agents may affect the outcome of COVID-19 patients with ILD.


Subject(s)
COVID-19 , Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Idiopathic Pulmonary Fibrosis/complications , Lung , Lung Diseases, Interstitial/drug therapy , Retrospective Studies , Tomography, X-Ray Computed
4.
J Infect Chemother ; 28(2): 321-325, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1521285

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.


Subject(s)
COVID-19 , Lung Diseases, Interstitial , Adrenal Cortex Hormones/therapeutic use , Humans , Hypoxia/drug therapy , Lung , Lung Diseases, Interstitial/drug therapy , SARS-CoV-2
6.
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
8.
Int J Mol Sci ; 22(12)2021 Jun 09.
Article in English | MEDLINE | ID: covidwho-1264471

ABSTRACT

Interstitial lung diseases (ILDs) comprise different fibrotic lung disorders characterized by cellular proliferation, interstitial inflammation, and fibrosis. The JAK/STAT molecular pathway is activated under the interaction of a broad number of profibrotic/pro-inflammatory cytokines, such as IL-6, IL-11, and IL-13, among others, which are increased in different ILDs. Similarly, several growth factors over-expressed in ILDs, such as platelet-derived growth factor (PDGF), transforming growth factor ß1 (TGF-ß1), and fibroblast growth factor (FGF) activate JAK/STAT by canonical or non-canonical pathways, which indicates a predominant role of JAK/STAT in ILDs. Between the different JAK/STAT isoforms, it appears that JAK2/STAT3 are predominant, initiating cellular changes observed in ILDs. This review analyzes the expression and distribution of different JAK/STAT isoforms in ILDs lung tissue and different cell types related to ILDs, such as lung fibroblasts and alveolar epithelial type II cells and analyzes JAK/STAT activation. The effect of JAK/STAT phosphorylation on cellular fibrotic processes, such as proliferation, senescence, autophagy, endoplasmic reticulum stress, or epithelial/fibroblast to mesenchymal transition will be described. The small molecules directed to inhibit JAK/STAT activation were assayed in vitro and in in vivo models of pulmonary fibrosis, and different JAK inhibitors are currently approved for myeloproliferative disorders. Recent evidence indicates that JAK inhibitors or monoclonal antibodies directed to block IL-6 are used as compassionate use to attenuate the excessive inflammation and lung fibrosis related to SARS-CoV-2 virus. These altogether indicate that JAK/STAT pathway is an attractive target to be proven in future clinical trials of lung fibrotic disorders.


Subject(s)
Janus Kinases/metabolism , Lung Diseases, Interstitial/pathology , STAT Transcription Factors/metabolism , Cellular Senescence , Endoplasmic Reticulum Stress , Humans , Interleukins/metabolism , Janus Kinases/antagonists & inhibitors , Janus Kinases/genetics , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/metabolism , Protein Kinase Inhibitors/therapeutic use , STAT Transcription Factors/antagonists & inhibitors , STAT Transcription Factors/genetics , Signal Transduction
10.
Respirology ; 26(6): 604-611, 2021 06.
Article in English | MEDLINE | ID: covidwho-1207464

ABSTRACT

The year 2020 was one like no other, as we witnessed the far-reaching impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic. Yet despite an unprecedented and challenging year, global research in interstitial lung disease (ILD) continued to break new grounds. Research progress has led to an improved understanding in new diagnostic tools and potential biomarkers for ILD. Studies on the role of antifibrotic therapies, newer therapeutic agents, supportive care strategies and the impact of coronavirus disease 2019 (COVID-19) continue to reshape the management landscape of ILD. In this concise review, we aim to summarize the key studies published in 2020, highlighting their impact on the various aspects of ILD.


Subject(s)
COVID-19 , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Animals , Biomarkers , COVID-19/complications , Humans , Lung Diseases, Interstitial/complications , Phenotype , SARS-CoV-2
11.
Medicina (Kaunas) ; 57(3)2021 Mar 18.
Article in English | MEDLINE | ID: covidwho-1167652

ABSTRACT

The COVID-19 pandemic dramatically changed medical care. Healthcare professionals are faced with new issues. Patients who survived COVID-19 have plenty of different continuing symptoms, of which the most common are fatigue and breathlessness. It is not well known how to care for patients with persistent or worsening respiratory symptoms and changes on chest X-ray following COVID-19 pneumonia. In this article, we talk about a subgroup of patients with organizing pneumonia following COVID-19 pneumonia that could be effectively treated with systemic glucocorticoids. It is important that patients with COVID-19 pneumonia be followed-up at least three weeks after diagnosis, in order to recognize early lung damage. We are providing a management algorithm for early diagnosis of lung diseases after COVID-19 pneumonia.


Subject(s)
COVID-19/complications , Lung Diseases, Interstitial/diagnosis , Algorithms , Biopsy , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/physiopathology , Computed Tomography Angiography , Disease Management , Early Diagnosis , Glucocorticoids/therapeutic use , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/physiopathology , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Pulmonary Diffusing Capacity , SARS-CoV-2 , Spirometry , Tomography, X-Ray Computed , Walk Test
12.
PLoS One ; 15(10): e0239692, 2020.
Article in English | MEDLINE | ID: covidwho-840912

ABSTRACT

BACKGROUND: SARS-Cov2 infection may trigger lung inflammation and acute-respiratory-distress-syndrome (ARDS) that requires active ventilation and may have fatal outcome. Considering the severity of the disease and the lack of active treatments, 14 patients with Covid-19 and severe lung inflammation received inhaled adenosine in the attempt to therapeutically compensate for the oxygen-related loss of the endogenous adenosine→A2A adenosine receptor (A2AR)-mediated mitigation of the lung-destructing inflammatory damage. This off label-treatment was based on preclinical studies in mice with LPS-induced ARDS, where inhaled adenosine/A2AR agonists protected oxygenated lungs from the deadly inflammatory damage. The treatment was allowed, considering that adenosine has several clinical applications. PATIENTS AND TREATMENT: Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio<300 received off-label-treatment with 9 mg inhaled adenosine every 12 hours in the first 24 hours and subsequently, every 24 days for the next 4 days. Fifty-two patients with analogue features and hospitalized between February and April 2020, who did not receive adenosine, were considered as a historical control group. Patients monitoring also included hemodynamic/hematochemical studies, CTscans, and SARS-CoV2-tests. RESULTS: The treatment was well tolerated with no hemodynamic change and one case of moderate bronchospasm. A significant increase (> 30%) in the PaO2/FiO2-ratio was reported in 13 out of 14 patients treated with adenosine compared with that observed in 7 out of52 patients in the control within 15 days. Additionally, we recorded a mean PaO2/FiO2-ratio increase (215 ± 45 vs. 464 ± 136, P = 0.0002) in patients receiving adenosine and no change in the control group (210±75 vs. 250±85 at 120 hours, P>0.05). A radiological response was demonstrated in 7 patients who received adenosine, while SARS-CoV-2 RNA load rapidly decreased in 13 cases within 7 days while no changes were recorded in the control group within 15 days. There was one Covid-19 related death in the experimental group and 11in the control group. CONCLUSION: Our short-term analysis suggests the overall safety and beneficial therapeutic effect of inhaled adenosine in patients with Covid-19-inflammatory lung disease suggesting further investigation in controlled clinical trials.


Subject(s)
Adenosine/adverse effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine/administration & dosage , Administration, Inhalation , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Female , Hospitalization , Humans , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Retrospective Studies , SARS-CoV-2
13.
BMJ Open Respir Res ; 7(1)2020 09.
Article in English | MEDLINE | ID: covidwho-788168

ABSTRACT

Reviews of COVID-19 CT imaging along with postmortem lung biopsies and autopsies indicate that the majority of patients with COVID-19 pulmonary involvement have secondary organising pneumonia (OP) or its histological variant, acute fibrinous and organising pneumonia, both well-known complications of viral infections. Further, many publications on COVID-19 have debated the puzzling clinical characteristics of 'silent hypoxemia', 'happy hypoxemics' and 'atypical ARDS', all features consistent with OP. The recent announcement that RECOVERY, a randomised controlled trial comparing dexamethasone to placebo in COVID-19, was terminated early due to excess deaths in the control group further suggests patients present with OP given that corticosteroid therapy is the first-line treatment. Although RECOVERY along with other cohort studies report positive effects with corticosteroids on morbidity and mortality of COVID-19, treatment approaches could be made more effective given that secondary OP often requires prolonged duration and/or careful and monitored tapering of corticosteroid dose, with 'pulse' doses needed for the well-described fulminant subtype. Increasing recognition of this diagnosis will thus lead to more appropriate and effective treatment strategies in COVID-19, which may lead to a further reduction of need for ventilatory support and improved survival.


Subject(s)
Coronavirus Infections/physiopathology , Cryptogenic Organizing Pneumonia/diagnosis , Diagnostic Errors , Hypoxia/physiopathology , Lung/diagnostic imaging , Pneumonia, Viral/physiopathology , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/etiology , Cryptogenic Organizing Pneumonia/physiopathology , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Hypoxia/etiology , Lung/pathology , Lung/physiopathology , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Tomography, X-Ray Computed
14.
Clin Rheumatol ; 39(11): 3171-3175, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-730357

ABSTRACT

We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither of them had a history of autoimmune disease. Chest computed tomography scans before the antiviral therapy showed bilateral multiple patchy ground-glass opacities (GGO) consistent with COVID-19 pneumonia. The GGO regressed over the course of the antiviral treatment; however, new non-segmental patchy consolidations emerged, which resembled those of interstitial lung disease (ILD), specifically collagen vascular disease-associated ILD. We tested the patients' sera for autoantibodies and discovered that both patients had high anti-SSA/Ro antibody titers. In Case 1, the patient recovered with antiviral therapy alone. However, in Case 2, the patient did not improve with antiviral therapy alone but responded well to corticosteroid therapy (methylprednisolone) and made a full recovery. The relationship between some immunological responses and COVID-19 pneumonia exacerbation has been discussed previously; our discovery of the elevation of anti-SSA/Ro antibodies suggests a contribution from autoimmunity functions of the immune system. Although it is unclear whether the elevation of anti-SSA/Ro antibodies was a cause or an outcome of aggravated COVID-19 pneumonia, we hypothesize that both patients developed aggravated the COVID-19 pneumonia due to an autoimmune response. In COVID-19 lung injury, there may be a presence of autoimmunity factors in addition to the known effects of cytokine storms. In patients with COVID-19, a high level of anti-SSA/Ro52 antibodies may be a surrogate marker of pneumonia severity and poor prognosis.


Subject(s)
Antibodies, Antinuclear/immunology , Coronavirus Infections/immunology , Lung Diseases, Interstitial/immunology , Pneumonia, Viral/immunology , Respiratory Insufficiency/immunology , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Benzamidines , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Female , Glucocorticoids/therapeutic use , Guanidines/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Male , Methylprednisolone/therapeutic use , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/drug therapy , Pregnenediones/therapeutic use , Pyrazines/therapeutic use , Recovery of Function , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/immunology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed
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