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1.
Polish Annals of Medicine ; 28(2):244-249, 2021.
Article in English | EMBASE | ID: covidwho-1957648

ABSTRACT

I nt r o duc t i o n: First cases of a disease called coronavirus disease 2019 (CO-VID-19), caused by a novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the coronavirus family, were detected in December 2019. The disease is manifested by a variety of symptoms and can run a different course: from oligosymptomatic or asymptomatic to the development of acute respiratory failure and even death. Ai m: The aim of this paper is to provide critical analysis of the potential pulmonary complications after COVID-19 infection. Ma t e r i a l a nd me t ho ds: We have provided the systematic literature review based on which we have discussed the pathophysiology of COVID-19, its outco-mes, risk factors and pulmonary complications. R e s u l t s a n d d i s c u s s i o n: The organs that are most often affected by a SARS--CoV-2 infection are the lungs. An infection with this virus can lead to a severe respiratory tract illness, both in the acute phase and as a complication after a rela-tively mild case. There are numerous observations of patients convalescing from COVID-19 who suffer from the interstitial pulmonary disease with fibrosis. There are also reported cases of spontaneous pneumothorax after COVID-19. Co nc l us i o ns: It should be borne in mind that other late complications may appear with time.

2.
Int Immunopharmacol ; 111: 109088, 2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1956180

ABSTRACT

OBJECTIVE: The aim of this study was to address the association between interstitial lung disease and the risk for severity and mortality among patients with coronavirus disease 2019 (COVID-19). METHODS: The electronic databases of PubMed, Web of Science and EMBASE were systematically searched. The pooled effect size with 95 % confidence interval (CI) was computed by a random-effects meta-analysis model. Heterogeneity test, sensitivity analysis, subgroup analysis, meta-regression analysis, Begg's test and Egger's test were performed. RESULTS: A total of sixteen eligible studies with 217,260 COVID-19 patients were enrolled in this meta-analysis. The findings based on adjusted effect estimates indicated that pre-existing interstitial lung disease was significantly associated with higher risk for COVID-19 severity (pooled effect = 1.34 [95 % CI: 1.16-1.55]) and mortality (pooled effect = 1.26 [95 % CI: 1.09-1.46]). Consistent results were observed in the subgroup analysis stratified by sample size, age, the percentage of male patients, study design, setting, the methods for adjustment and the factors for adjustment. The results of meta-regression demonstrated that sample size, age and region might be the potential sources of heterogeneity. Sensitivity analysis exhibited that our results were stable and robust. No publication bias was observed in Egger's test and Begg's test. CONCLUSION: This meta-analysis on the basis of adjusted effect estimates demonstrated that pre-existing interstitial lung disease was independently associated with significantly higher risk for COVID-19 severity and mortality.

3.
Annals of Thoracic Medicine ; 17(3):137-144, 2022.
Article in English | ProQuest Central | ID: covidwho-1954267

ABSTRACT

Post-COVID lung impairment and diseases are major public health concern in the pandemic of COVID-19. Multiple etiological factors can lead to post-COVID respiratory symptoms, with post COVID fibrosis or diffuse parenchymal lung disease being the major concern. We searched PubMed database for English literature related to post-COVID lung disease and we summarized the existing evidence on radiological, physiological, and histopathological aspects of post-COVID lung diseases. We suggest a guidance on the evaluation of these patients and highlight management considerations including general care, pulmonary rehabilitation, and lung transplantation. We also explain gaps in knowledge and awaited ongoing research results, especially in the field of drug therapies including corticosteroids and antifibrotics.

4.
Hum Genomics ; 16(1): 20, 2022 06 13.
Article in English | MEDLINE | ID: covidwho-1951361

ABSTRACT

The increased resolution of single-cell RNA-sequencing technologies has led to major breakthroughs and improved our understanding of the normal and pathologic conditions of multiple tissues and organs. In the study of parenchymal lung disease, single-cell RNA-sequencing has better delineated known cell populations and identified novel cells and changes in cellular phenotypes and gene expression patterns associated with disease. In this review, we aim to highlight the advances and insights that have been made possible by applying these technologies to two seemingly very different lung diseases: fibrotic interstitial lung diseases, a group of relentlessly progressive lung diseases leading to pulmonary fibrosis, and COVID-19 pneumonia, an acute viral disease with life-threatening complications, including pulmonary fibrosis. We discuss changes in cell populations and gene expression, highlighting potential common features, such as alveolar cell epithelial injury and aberrant repair and monocyte-derived macrophage populations, as well as relevance and implications to mechanisms of disease and future directions.


Subject(s)
COVID-19 , Pulmonary Fibrosis , COVID-19/genetics , Humans , Lung/pathology , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/pathology , RNA , Single-Cell Analysis
5.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927893

ABSTRACT

Rationale: Over 350,000,000 people have had SARS-CoV-2 infection worldwide. COVID-19 poses many challenges in the management of patients causing a long-term and significant burden on the healthcare system. Understanding the long-term complications is a challenge that the healthcare community and patients will face. To our knowledge, this is one of the largest retrospective analyses with the aim to understand the functional lung sequelae of the disease. Methods: We retrospectively reviewed 782 survivors who had COVID-19 diagnosed by RT-PCR and followed up at an outpatient pulmonary clinic in Hartford, Connecticut, USA, from March 2020 to June 2021. Data included patient's age, sex, comorbidities, pulmonary function tests (PFT), the maximal requirement of low-flow oxygen (LF), high-flow nasal cannula (HFNC), non-invasive ventilation (NIV) and mechanical ventilation (MV). We performed an adjusted logistic regression model to evaluate if severity of disease according to maximal oxygen support is associated with DLCO<80% in follow-up. SPSS IBM was used for the statistical modeling. Results: Of the 782 patients evaluated, 314 patients had PFT results available post COVID-19 for analysis. The mean age was 58.9±14.5 years, and of the total number of patients, 200 were female (63.7%). Other demographics are as follows: 156 (49.7%) were obese, 129 (41.2%) had asthma, 48 (15.3%) had COPD, 5 (1.6%) had Interstitial Lung Disease, 35 (11.1%) had anemia, 70 (22.3%) had diabetes mellitus, 164 (52.2%) had hypertension, 26 (8.3%) had heart failure. Only 14 (4.4%) required MV, 14 (4.5%) NIV, 29 (9.2%) HFNC, 94 (29.9%) LF and 153 (51.9%) remained on room air. Altered DLCO was seen in 107 patients (34.1%), 189 (60.1%) had normal DLCO, and 18 (5.7%) did not have DLCO, of which the latter were excluded from the analysis. Maximal oxygen support was associated with DLCO<80% on unadjusted analysis (p=0.003). However, it was not associated with DLCO<80% (p=0.2) when adjusted. Other variables associated with a higher risk of DLCO<80% were age (p<0.001) and COPD (p<0.028). Asthma was associated with lower risk of developing DLCO<80% (p<0.001). Conclusion: Patients with post-acute sequelae of SARS-CoV-2 infection can develop DLCO<80%, which may contribute to long-term symptoms. Altered DLCO was not associated with maximal oxygen support in the adjusted logistic regression analysis. However, this may be due to the low number of cases requiring MV or NIV, resulting in selection bias, given there was a higher mortality rate in patients requiring positive pressure ventilation. Additionally, age and COPD were correlated with DLCO<80%.

6.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927892

ABSTRACT

Rationale: SARS-CoV-2 has affected millions worldwide. Among those individuals infected with this coronavirus, most recover without hospitalization. However, COVID-19 is characterized by chronic lung failure and death in a significant number of hospitalized patients. Indeed, there is growing evidence that SARS-CoV-2 causes ARDS leading to lung fibrosis that shares similarities with interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis (IPF). Herein, we addressed the hypothesis that fatal COVID-19, PASC, and ILDs share key biomarkers of interest in lung fibrosis. Methods: This study included 9 fatal COVID-19 and 13 PASC cases, who received lung transplants due COVID-19 associated lung failure. Clinical characteristics such as duration of mechanical ventilation, length of hospitalization, age, sex, and BMI were evaluated in each patient. Autopsy and explanted lung samples were subjected to histopathological and/or immunohistochemical (IHC) analysis for key biomarkers of interest in lung fibrosis including bromodomain-containing protein-4(BRD4), interferon alpha 2(IFNα2), interleukin-1(IL-11), growth differentiation factor 15(GDF15), and keratin 8(KRT8). COVID-19 and PASC lung samples were also compared with lung samples from fatal ARDS due to other causes (i.e., non-COVID-19 ARDS).Results: In the fatal COVID-19 patient group, the mean age was 60.6(50-71) years-old and included 6 males and 3 females. In the transplanted-PASC patient group, the mean age was 46(31-71) years-old and included 12 males and 2 females. The average BMI was 28.3(21-35.5) for fatal COVID-19 and 25.2(19-29.5) for PASC. In fatal COVID-19, comorbidities included hypertension(22%), diabetes(44%), immunocompromised status(11%). The mean duration of mechanical ventilation was 23(8-65) days while hospitalization was 25(8-67) days. Conversely, PASC patients averaged 168(71-539) days from diagnosis to transplant date. The SARS-CoV-2 ARDS survivors that developed chronic lung failure had diffuse interstitial fibrosis frequently with organization into a non-specific interstitial fibrosis (NSIP) pattern. Key IHC findings in fatal COVID-19 and in PASC lung samples included BRD4, IFNalpha2, and IL-11 receptor alpha (IL-11RA) protein expression, which were markedly increased in several cell types most notably macrophages or myeloid cells localized in the alveolar space in COVID-19 lung samples. Although these markers were detected in non-COVID-19 ARDS the levels of each were markedly lower than that detected in the COVID-19 lung samples.Conclusions: These data suggest that key profibrotic pathways in the lung are shared among COVID-19 and chronic fibrotic ILDs. The identification of these pathways provides the impetus to further explore treatment strategies which might survival benefit to chronically ventilated COVID-19 patients and mitigate the need from lung transplantation in PASC patients.

7.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927825

ABSTRACT

Introduction: Antifibrotic drugs, including nintedanib and pirfenidone, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Pirfenidone blocks the synthesis of TGF-beta and does appear to increase the risk of CV or bleeding events. Nintedanib is a Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitor and may increase the risk of bleeding. Bleeding events were reported in 10% of patients in clinical trials (despite excluding patients at risk of bleeding including those on con-current anticoagulation (AC) or antiplatelet (AP) therapy. Consequently, nintedanib is relatively contraindicated for patients with IPF on anticoagulation or antiplatelet therapy. However, results from real-life data demonstrate that 17.8% of our patients with IPF are on anticoagulation or antiplatelet therapy. The overall incident of bleeding events in those patients taking either or with nintedanib is similar to that reported for Nintedanib alone. We describe two patients with antifibrotic and anticoagulation therapy to highlight how to manage these patients. Case 1. A 67-year-old female with history of acute pulmonary embolism secondary to COVID-19 on anticoagulation therapy presents for workup of acute respiratory distress syndrome or suspected exacerbation of underlying IPF-usual interstitial pneumonia. Patient treated as IPF with pirfenidione. Case 2. A 69-year-old man with a history of atrial fibrillation on anticoagulation therapy presents for follow-up of progressive fibrosing interstitial lung disease secondary to hypersensitivity pneumonitis. Nintedanib initiated for progressive fibrosing lung disease. Discussion: Concomitant use of anticoagulation and/or antiplatelet therapy with antifibrotics doesn't increase bleeding risk. Conclusion. Anticoagulation and/or antiplatelet therapy should not be a reason to withhold antifibrotic therapy in patients with IPF.

8.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927815

ABSTRACT

Introduction: Interstitial lung disease (ILD) comprises a heterogeneous group of diseases affecting the lung interstitium often associated with significant morbidity and mortality. The Australasian Interstitial Lung Disease Registry (AILDR) launched in 2016 with the concurrent aims to: a) provide a valuable resource for high quality ILD research to further understanding of ILD and b) improve care for ILD patients across Australia and NZ. Consisting initially of four pilot sites, over time the registry has expanded to 21 sites across Australasia. Methods: Consecutive ILD patients attending any of the registered ILD centres across Australia and NZ are eligible to enrol in the AILDR following provision of informed consent. Comprehensive data including demographics, ILD diagnosis, objective functional markers (baseline and subsequent tests) and treatment parameters are collected and stored on a secure online platform. We report data from the AILDR since initiation in May 2016 to 30th September 2021 inclusive. Results: In total 2140 participants were enrolled from 16 sites at a mean rate of 43/month (mean age 65.8±13.3years;1185 (55.4%) male;982 (45.9%) ever-smokers;mean BMI 29.4±5.9kg/m2). Baseline functional parameters demonstrated mean FVC 85.6±21.7% predicted, mean DLCO 60.5±19.4%predicted, and mean six-minute walk test (6MWT) distance 434.3±126.5metres. ILD diagnoses included: idiopathic pulmonary fibrosis (IPF) n=545 (30.3%), connective tissue disease associated ILD (CTD-ILD) n=326 (18.1%), chronic hypersensitivity pneumonitis (CHP) n=155 (8.6%), sarcoidosis n=120 (6.7%) and unclassifiable ILD n=190 (10.6%). Patients with IPF were more likely to be male (n=403, 73.9%, p<0.001) and older (72.6±8.3years, p<0.001) compared to all other ILD subtypes. A female predominance was observed for CHP (n=92, 59%, p=0.001) and CTD-ILD (n=206, 63%, p<0.001). Baseline functional parameters were lowest for those with CHP (FVC 76.8±22.4% predicted, DLCO 54.1±16.9% predicted), significantly lower comparable to the IPF group (FVC 84.8±19.6%predicted, DLCO 58.7±17.8%predicted, p<0.001). The highest baseline functional parameters were observed in those with sarcoidosis. Conclusion: We demonstrate the feasibility of a bi-national ILD registry evidenced by steady recruitment despite the COVID-19 pandemic. In this study, lower functional baseline parameters were detected in the CHP group suggesting priority research should be afforded to this group. Through a routine approach across Australasia, the AILDR aims to improve standardisation of diagnosis and management of ILD patients.

9.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927756

ABSTRACT

Introduction: Antisynthetase syndrome is a rare autoimmune disease. Clinical characteristics include interstitial lung disease (ILD), myositis, Raynaud's phenomenon, mechanic's hands, and arthritis. The condition is characterized by antibodies targeting an aminoacyl transfer RNA synthetase. Compared to other inflammatory myopathies, there is a higher prevalence and increased severity of ILD. Case Report: A 34-year-old female with a history of polycystic ovarian syndrome presented with progressive dyspnea during her third trimester of pregnancy. Initial computed tomography angiography (CTA) chest showed widespread multifocal and multilobar ground-glass opacities and nodular areas of consolidation. COVID-19 testing was negative. She went into preterm labor and delivered her baby at 30 weeks. About 10 days after delivery, her respiratory symptoms worsened. Transbronchoscopic lung biopsy was nondiagnostic. She subsequently underwent surgical lung biopsy which revealed organizing pneumonia and interstitial fibrosis. Laboratory studies revealed a high Jo-1 antibody of 1033U (normal less than 20U), positive ANA, creatine kinase 186 U/L, as well as aldolase 22.3 U/L leading to a diagnosis of antisynthetase syndrome. The patient continued to be dyspneic and developed increased oxygen requirements. Treatment was initiated with 1 dose of 125 mg of methylprednisolone followed by 1 g of methylprednisolone for 3 days, after which she was continued on oral prednisone. She was additionally started on 250 mg of mycophenolate mofetil. Despite these therapies she continued to have increased oxygen requirements, eventually requiring noninvasive positive pressure ventilation and ultimately intubation with mechanical ventilation. Chest x-ray demonstrated worsening bilateral patchy infiltrates. Given her clinical deterioration, she underwent 5 treatments of plasma exchange after which she received 1000 mg of rituximab. The patient improved on this therapy and was able to be extubated after 3 days. Her oxygen requirements subsequently decreased and she was discharged on a prednisone taper;mycophenolate with a goal dose of 1000 mg twice daily;and plan for continued rituximab infusions. At 2 months follow-up, the patient was doing well without the need for supplemental oxygen. Discussion: This case demonstrates a rare disease in a peripartum patient. A high suspicion for antisynthetase syndrome is required to initiate autoimmune testing, particularly since there can be ILD predominant phenotypes without significant evidence of a myositis. Treatment is not standardized but typically consists of corticosteroids and other immunosuppressive agents. In severe cases of antisynthetase syndrome that are refractory to initial corticosteroid therapy, therapeutic plasma exchange can be performed.

10.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927721

ABSTRACT

Introduction: First synthesized in 1869, Hydroxyurea is known for its efficacy in treating myeloproliferative disorders, cervical cancer, and sickle cell disease. Usually well-tolerated, Hydroxyurea has numerous documented adverse effects, including bone marrow suppression, fevers, gastrointestinal upset, anorexia, and maculopapular rash. In addition, one rare side effect is interstitial pneumonitis, a potentially devastating complication if overlooked. We present one such case of Hydroxyurea-induced interstitial pneumonitis. Case Description: A 65-year-old man with a six-month diagnosis of Chronic Granulocytic Leukemia (CGL) on Hydroxyurea developed acute hypoxemic respiratory failure saturating 80% on room air with HR 102, RR 24, and increasing oxygen requirements (10 Lpm) after being admitted with complaints of worsening dyspnea, fatigue, and productive cough with yellow/green sputum. Physical examination was notable for cachexia, ill appearance, generalized weakness, hoarse voice, tachycardia, tachypnea, diffusely diminished breath sounds, and scattered rales on auscultation of lung fields. Initial imaging was notable for bilateral airspace disease and pulmonary opacities on chest radiography and bilateral pneumonia (concerning for COVID-19 pneumonia), mediastinal adenopathy, and splenomegaly on chest computed tomography. Initial laboratory results were notable for leukocytosis 62.5 th/uL, lactic acidosis 2.5 mmol/L, procalcitonin level 4.95 ng/mL, and negative COVID-19 PCR test. Prompt initiation of Vancomycin/Cefepime therapy ensued upon collection of blood cultures in light of possible sepsis. Flagyl, Valacyclovir, and Posaconazole were added to antimicrobial coverage, along with steroid therapy, due to minimal clinical improvement. Tachycardia with significant oxygen requirements alternating between BiPAP and heated high flow nasal cannula with FiO2 ranging from 70-85% persisted. Daily imaging also showed worsening airspace disease. Negative viral, bacterial, and fungal cultures led to subsequent discontinuation of Hydroxyurea therapy due to suspicion of medicationinduced pneumonitis. Three days after cessation of Hydroxyurea, the patient's oxygen requirements began to decrease and imaging revealed interval resolution of pneumonitic changes in the absence of antimicrobial therapy. The patient was later transitioned to Ruxolitinib for his underlying CGL prior to his discharge home without the need for home oxygen therapy. Discussion: Thought to be caused by hypersensitivity pneumonitis, pulmonary toxicity from Hydroxyurea can easily be misdiagnosed. Unfortunately, while much is known about the pancytopenic, gastrointestinal, and cutaneous side effects of Hydroxyurea, few cases in the literature highlight the potentially fatal interstitial pneumopathy caused by Hydroxyurea, first reported in 1999. Thus, this case serves as an additional contribution to the minutiae of literature detailing Hydroxyurea's adverse pulmonary side effect profile. (Figure Presented).

11.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927719

ABSTRACT

We present a case with significant diagnostic and therapeutic challenges;a 57 year old female with history of bi-ventricular failure status post Left Ventricular Assisted Device (LVAD) in 2020 and Rheumatoid Arthritis (RA) who presented with Shortness of breath and refractory hypoxemia, Computerized tomography(CT) showed dense ground glass opacity and superimposed traction bronchiectasis which was not present in a prior CT. The management included high FiO2 therapy High flow nasal cannula (HFNC), initial heart failure measures with diuresis and antibiotics treatment were attempted, the clinical and radiological diagnosis of acute exacerbation (AE) of connective tissue disease associated interstitial lung disease (CTD-ILD) with progressive fibrosing phenotype was made, The decision of therapeutic pulse corticosteroids with Rituximab was based on the degree of severity of acute exacerbation, following treatment, the course of the disease was reversed with complete oxygen weaning with impressive clinical and radiological response. The case is considered puzzling from multiple aspects, first the complex comorbidities, LVAD placement made heart failure the main differential diagnosis (DD), the absence of interstitial infiltrate in the old CT made the initial diagnosis of AE of ILD less likely, other DD as Covid-19 pneumonia, pulmonary embolism, bacterial pneumonia were worked up. Another major dilemma was the optimal management of the life threatening hypoxemia in the setting of new CT findings. Connective tissue disease associated ILD is a diffuse parenchymal lung disease characterized by both inflammation and fibrosis. The progressive fibrosing phenotype carries poor prognosis, even worse is the prognosis of AE that characterized by marked deterioration and alveolar abnormalities with high mortality. There is extremely limited data of optimal treatment of AE and lack of blinded randomized controlled trials. Management is mainly supportive care, oxygen therapy is considered the cornerstone, otherwise no formal therapeutic strategy. The potential reported therapies included corticosteroids, immunosuppressant, anticoagulants, antibodies targeted therapy with no conclusive evidence. Although corticosteroids were described based on anecdotal evidence but recently published case series described novel combination of treating AE with combination of pulse steroid, Rituximab and plasma exchange resulting in promising outcome. In our case we followed the regimen of pulse steroids in combination with Rituximab which lead to satisfactory results in short interval. The rational of steroids use for its potent anti-inflammatory properties and since AE is linked to autoimmune antibody-driven inflammation, treatment with Rituximab causes Bcell depletion, the impressive clinical outcome of our patient signals a promising therapeutic potentials in treating fatal AE. (Figure Presented).

12.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927718

ABSTRACT

Introduction: Recognition of myositis-associated interstitial lung disease (ILD) has been increasing due to the recent identification of specific antibodies that are linked to a particular phenotype of myositis-ILD such as antisynthetase syndrome. The anti-Ro52 antibody has been found in multiple connective tissue diseases but its association with ILD is unclear. In fact, the literature on the phenotype of patients with an isolated anti-Ro52 antibody is very scarce. Case Presentation: A 57-year-old retired firefighter with history of gastroesophageal reflux presented to the hospital with a 4-week history of cough and progressive dyspnea with no other symptoms. He had presented to an urgent care facility where he tested negative for SARs-CoV-2 and was given antibiotics and inhalers without a clinical response. Patient required 2L/min of oxygen on admission. He had no other signs of autoimmune disease or other organ involvement. Chest CT showed peripheral ground glass opacities with basilar reticulations and bronchiectasis (Figure 1). WBC and CPK were normal and aldolase was mildly elevated. Initial serologies revealed an ANA 1:320 and a weakly positive p-ANCA with negative PR3/MPO antibodies. Patient was started on prednisone 60 mg and discharged five days later on mycophenolate mofetil (MMF) and 2L/min of oxygen. At 2-week follow-up, his extensive autoimmune panel showed a high titer of Anti-Ro52 antibody. An in depth ILD questionnaire revealed a family history of lupus and the remote use of a short course of steroids 20 years ago after a biceps biopsy showed polymyositis. On chart review, 10 years ago the patient had elevated CPK levels of 255 to 404, in the context of a nonspecific flank pain that resolved without intervention. At his 3-month follow-up, the patient still required 40mg of prednisone, reported dyspnea on exertion and required oxygen with ambulation. Rituximab was added to his regimen and his symptoms significantly improved;at 6-month follow-up, his FVC% improved from 53% to 70% and the patient was no longer on oxygen. Prednisone was titrated down to 10mg and he was continued on MMF 3g/day and Rituximab every 6 months. Discussion: We present a patient with Anti-Ro52 antibody myositisassociated ILD who required 3 immunosuppressive agents to control his disease. This case adds to the very scarce literature on ILD secondary to Anti-Ro52 antibody and highlights the importance of an extensive antibody testing for patients with ILD of unclear etiology, for diagnostic and therapeutic purposes. Further studies describing the phenotype of these patients are warranted. (Figure Presented).

13.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927716

ABSTRACT

Introduction: Antisynthetase syndrome(ASS) is a rare autoimmune disease characterized by myositis, arthritis, cutaneous findings and interstitial lung disease (ILD). In 15-30% cases of ASS, ILD can be the presenting feature making this a very challenging diagnosis to make, especially during the COVID 19 pandemic. We present a unique case of ILD as presenting feature of ASS. Case: A 31 yr old female, never smoker, with asthma and obesity was referred to the pulmonary clinic for dyspnea of 2 months. Dyspnea was on exertion, associated with cough and pleuritic chest pain. Oxygen saturation on exam was 91% at rest and 86% on exertion. PCR and antibodies for COVID was negative. CXR showed bilateral infiltrates. She was treated with several courses of antibiotics and steroids. Her symptoms improved with steroids yet returned when course completed. Chest CT revealed bilateral parenchyma opacities with sparing of the lung apices. This was repeated 3 months after her course of antibiotics and steroids which revealed worsening of ground glass opacities, now diffuse with areas of organizing pneumonia. Bronchoalveolar lavage showed alveolar macrophages with a mixture of acute and chronic inflammatory cells. PFTs revealed severe restrictive lung disease. Infectious work up including bacterial, viral and fungal causes was negative. Complete blood count with differential was normal. B-type natriuretic peptide, creatine kinase, liver function test, basic metabolic panel, HIV and fungal serologies were unrevealing. A rheumatologic work up revealed elevated ESR (48), CRP (6.9), aldolase (48) with positive anti OJ antibodies. She underwent VATs with wedge lung biopsy which revealed cellular non specific interstitial pneumonia (NSIP). She was diagnosed with ASS and started on a gradual taper of high dose steroids and steroid sparing agent Mycophenolate Mofetil. With time her respiratory symptoms improved and she no longer required supplemental oxygen. She was enrolled in pulmonary rehabilitation and encouraged to loose weight as her BMI of 55 could preclude lung transplantation if needed. Discussion: ASS is a rare autoimmune connective tissue disorder characterized by myositis, polyarthritis, cutaneous findings and ILD. It occurs more commonly in women with average age of onset in 50s. ILD has been reported in 69-100% with NSIP being most common followed by cryptogenic organizing pneumonia and UIP. Treatment consists of steroids, with or without a steroid-sparing agent. Timely diagnosis of ASS is imperative for patients presenting with ILD as delay can lead to progression of ILD which serves as a predictor for morbidity and mortality. (Figure Presented).

14.
International Journal of Computer Assisted Radiology and Surgery ; 17(SUPPL 1):S13-S14, 2022.
Article in English | EMBASE | ID: covidwho-1926067

ABSTRACT

Purpose Coronavirus disease 2019 (Covid-19) may cause dyspnoea, whereas Interstitial Lung Diseases (ILD) may lead to the loss of breathing ability. In both cases, chest X-Ray is typically one of the initial studies to identify the diseases as they are simple and widely available scans, especially in under-development countries. However, the assessment of such images is subject to a high intraobserver variability because it depends on the reader's expertise, which may expose patients to unnecessary investigations and delay the diagnosis. Content-based Image Retrieval (CBIR) tools can bridge such a variability gap by recovering similar past cases to a given reference image from an annotated database and acting as a differential diagnosis CAD-IA system [1]. The main CBIR components are the feature extraction and the query formulation. The former represents the compared images into a space where a distance function can be applied, and the latter relies on the k-Nearest Neighbor (kNN) method to fetch the most similar cases by their distances to the query reference. In this study, we examine the quality of Covid-19 and ILD deep features extracted by a modified VGG-19 Convolutional Neural Network (CNN) [2] following the perspective of the Voronoi frontiers induced by kNN, which is at the core of the CBIR query formulation component. Methods We curated a dataset of annotated chest X-Rays from our PACS/HIS systems following a retrospective study approved by the institutional board. A set of 185 Covid-19 and 307 ILD cases from different patients was selected, being Covid-19 cases confirmed by RT-PCR tests and ILD images included after the analysis of two thoracic radiologists. We also added 381 images of ''Healthy'' lungs (without Covid-19 or ILD) to enrich the dataset. The resulting set includes 873 X-Rays (mean age 60.49 ± 15.21, and 52.58% females). We cast the DICOM images into PNG files by using the Hounsfield conversion and a 256 Gy-scale window. The files were scaled to 224 × 224 images and fed into a modified VGG-19 version we implemented [2]. Our version includes the stack of convolutional layers and five new layers after the block5-pool, namely: GlobalAveragePooling2D, BatchNormalization, a dense layer with 128 units and ReLU, a dropout layer with ratio 0.6, and a final dense layer with three neurons for classification. The Adam function was used to minimize cross-entropy, whereas batch size and epochs were set to 36 and 100, respectively. All layers start with ImageNet weights that were frozen until block4-pool so that only the remaining layers were updated. We fed the CNN with images and labels (i.e., {Covid-19, ILD, Healthy}) so that our feature extraction procedure was oriented towards those classes rather than autoencoders. The flattened outputs of the last max-pooling layer were collected as feature vectors of dimensionality d = 512. We clean and preprocess those vectors before applying the kNN-based search mechanism. First, we scaled the dimensions into the [0,1] interval. Then, we perform a reduction by using the Principal Component Analysis (PCA). The number of reduced dimensions was determined by the intrinsic dimensionality of the features, estimated by the mean (l) and standard deviation (r) of the pairwise distance distribution as the value μ2/2.σ2. Finally, the reduced vectors were also scaled into the [0,1] interval. The experiments were performed in a 3854 core 1.5 GHz GPU NVidia TitanX 12 GB RAM, and an Intel(R) Xeon(R) CPU 2.00 GHz, 96 GB RAM. The code was implemented under Tensorflow (v.2.1.0) and R (v4.1.2). Results We used two Principal Components to reduce the vectors according to the estimated intrinsic dimensionality. Figure 1 shows the Voronoi frontiers induced by kNN with a smooth separation between the three classes, which creates a search space in which CBIR searches are expected to be accurate. We quantify such behavior through a kNNbased classification on the two experimental settings (i.e., 10-folds and Holdout) by using the scaled features with and without dimensionality reductio . able 1 summarizes the results with the following findings: • The accuracy measures increased with the neighborhood (k = 1 vs. k = 5) in all experimental cases, • Covid-19 cases were more difficult to label than ILD according to F1 and RC, • The kNN hit-ratio (TP) for Covid-19 was comparable to the very first diagnosis stored into the PACS/HIS systems by readers on duty regarding the Holdout cases (readers' mean ∗ 63% vs. KNN ∼ 59%), • Searches over the reduced data were ∼ 4 9 faster, and • While dimensionality reduction was just as suitable as nonreduced data in the 10-folds evaluation, it expressively enhanced the kNN performance for the Holdout test (e.g., 0.68 vs. 0.82, k = 1 and F1). This result shows the side-effects of searching high-dimensional spaces with kNN (the ''curse of dimensionality''), which requires pre-processing the vectors or defining other query criteria to browse the data. Conclusion This study has discussed feature extraction for Covid-19 and ILD images from the perspective of kNN queries, the query formulation component within CBIR systems. Although we used cross-validation and one external batch to mitigate overfitting, a practical limitation was the size of the CNN training set. Still, our approach showed promising results in the extraction of suitable features for CBIR environments.

15.
Acta Medica (Hradec Kralove) ; 65(1): 37-40, 2022.
Article in English | MEDLINE | ID: covidwho-1924737

ABSTRACT

Anti-melanoma differentiation-associated gene-5 (MDA-5) antibody is an autoantibody found in patients with dermatomyositis. These antibody-positive patients are clinically characterized by complications of rapidly progressive interstitial pneumonia resistant to treatment and with poor prognosis. We describe herein a patient with MDA-5 antibody-positive interstitial lung disease, which progressed rapidly to death after a period of slow progress. Recently, attention has been paid to the similarities in clinical courses and CT images between MDA-5 antibody-positive interstitial lung disease and coronavirus disease 2019 (COVID-19)-associated pneumonia. Patients with MDA-5 antibody do not always have diffuse and evenly distributed bilateral opacities at the time of first presentation. This patient had significant laterality of such opacities. It should be considered that MDA-5 antibody-positive patients with such laterality in opacities might progress rapidly. Chest physicians, dermatologists, and dermatologists need to be aware of the characteristics of the disease for optimal treatment choices.


Subject(s)
COVID-19 , Dermatomyositis , Lung Diseases, Interstitial , Autoantibodies , COVID-19/complications , Dermatomyositis/complications , Humans , Lung Diseases, Interstitial/complications
16.
Cureus ; 14(5): e25085, 2022 May.
Article in English | MEDLINE | ID: covidwho-1924638

ABSTRACT

This is a case report of a patient who developed acute progressive shortness of breath that started two days following the administration of Shingrix and Pneumovax vaccinations. Eight days after the onset of his symptoms he was diagnosed with acute interstitial pneumonitis based on CT scan of the chest which later appeared to be consistent with the diagnosis of antisynthetase syndrome in light of findings consistent with mechanic's hands on examination, elevated Anti-Jo-1 antibody titers and aldolase on laboratory studies.

17.
Respir Care ; 2022 Jul 05.
Article in English | MEDLINE | ID: covidwho-1924457

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) related chronic lung changes secondary to severe disease have become well known. The aim of this study was to determine the risk factors that affect the development of interstitial lung disease in subjects with COVID-19 pneumonia who were hospitalized. METHODS: Patients hospitalized with COVID-19 pneumonia between June 2020 and March 2021 were retrospectively analyzed. Smoking histories, comorbidities, reverse transcriptase polymerase chain reaction test results, laboratory parameters at the time of the diagnosis, oxygen support, the use of corticosteroids with dosage and duration data, the need for ICU care were recorded. High-resolution computed tomographies (HRCT) were obtained for study population in their 3-6 months follow-up visit. The subjects were classified as having residual parenchymal lung disease if a follow-up HRCT revealed parenchymal abnormalities except pure ground-glass opacities (the residual disease group). The control group consisted of the subjects with normal chest radiograph or HRCT in their follow-up visit or the presence of pure ground-glass opacities. Two groups were compared for their demographic and clinical abnormalities, laboratory parameters, treatment regimens, and the need for ICU care. RESULTS: The study included 446 subjects. The mean ± SD age was 58.4 ± 13.87 years, with 257 men (57.6%). Although 55 subjects had normal HRCT features on their follow-up HRCT, 157 had abnormal lung parenchymal findings. Univariate logistic regression analysis revealed statistically significant results for age, sex, corticosteroid treatment, and the need for ICU care for predicting interstitial lung disease development (P < .001, P = .003, P < .001, and P < .001, respectively). Also, the residual disease group had significantly higher leukocyte and neutrophil counts and lower lymphocyte counts (P < .001, P < .001, P = .004, respectively). Correlated with these findings, neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios were significantly higher in the residual disease group (P < .001 and P = .008, respectively). CONCLUSIONS: Residual parenchymal disease was observed 3-6 months after discharge in one third of the subjects hospitalized with COVID-19 pneumonia. It was observed that interstitial lung disease developed more frequently in older men and in those subjects with more-severe disease parameters.

18.
J Transl Autoimmun ; 5: 100160, 2022.
Article in English | MEDLINE | ID: covidwho-1914737

ABSTRACT

Introduction: SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications. Auto-antibodies are identified in approximately 50% of hospitalized COVID-19 patients. Objectives: To determine the global incidence of myositis-related auto-antibodies (non Jo1-RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics, and to describe the clinical and laboratory features of these patients. Study design: A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected inflammatory myopathy. The incidence of positive results for the MSA was expressed as absolute value per year for the reference population. Immunoblot analysis, indirect immunofluorescence and HLA typing of 36 patients with positivity for MSAs were collected and analyzed. Results: We observed MSA positive in 28 patients in 2020 and 36 patients in 2021, representing a mean increase of 6-fold respect to previous years since 2015 (range, 0 to 19). In 2020, the most common antibody detected was anti-MDA5 (68%). In contrast, in 2021 the most common antibodies were anti-PL7 and/or anti-PL12 (69%). All patients in 2021 with positive anti-synthetases were fully vaccinated, 4 had previous documented infection, with median time from vaccine to MSA positivity of 5 months. Eight out of 36 patients (22%) reported clinical onset after SARS-CoV-2 vaccination and 6 out of 36 (17%) presented clinical and/or radiological worsening after SARS-CoV-2 vaccination. All patients presented with a known human leukocyte antigen (HLA)-DRB1* allele associated with ASS. The most prevalent alleles identified were DRB1*03:01, DRB1*04, DRB1*11:01, corresponding to 70% (16/23) of our cohort. Conclusions: Our preliminary data show an increased incidence of anti-synthetase antibodies during COVID-19 pandemic and SARS-CoV-2 vaccination associated to HLA DRB1* risk allele. Differential profiles of MSA specificities were observed: mainly against RNA-sensors in 2020 and against RNA-synthetases in 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the occurrence of this autoimmune syndrome.

19.
Chest ; 2022 Jun 29.
Article in English | MEDLINE | ID: covidwho-1914239

ABSTRACT

TOPIC IMPORTANCE: Advances in our understanding of interstitial lung disease (ILD) pathophysiology and natural history have led to the development of guidelines for the diagnosis and management of several of these complex diseases. The demographics of ILD are not restricted to older adults. Connective tissue disease ILD, familial pulmonary fibrosis and post-COVID-19 fibrosis may affect women of child bearing age. Recent trials have excluded pregnant women, thereby limiting the applicability of contemporary therapeutic advances to these patients. REVIEW FINDINGS: This review synthesizes the current knowledge of pregnancy outcomes in those with ILD, with a focus on connective tissue disease ILD, and potential management implications for patients with ILD who are pregnant or considering pregnancy. SUMMARY: Pregnancy considerations for patients with ILD include the need for preconception counselling and planning to ensure disease stability, medication and vaccination optimization, and multidisciplinary involvement of a patients' pulmonologist, obstetrician and, when indicated, rheumatologist and genetic counsellor. Evidence to date suggests that women with ILD can have safe and healthy pregnancies but complications may occur in those with severe ILD.

20.
Respirol Case Rep ; 10(8): e0995, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1913889

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is a very effective method of preventing infection and is recommended for people having recovered from coronavirus disease 2019 (COVID-19). In this novel case report, we describe two patients with post-COVID-19 pneumonia who experienced acute respiratory failure and new bilateral ground-glass opacities several days after receiving SARS-CoV-2 vaccination. Both patients were treated with methylprednisolone pulse therapy and recovered from the disease successfully. Indeed, post-COVID-19 patients can gain benefits from the vaccine, but vaccination at the early stage of recovery from COVID-19 might be a risk for certain populations. These cases highlight a potential association between vaccination, interstitial lung disease and worsening of post-COVID-19 pneumonia. Further investigation and research examining the relationship between the timing of SARS-CoV-2 vaccination and potential risks in post-COVID-19 patients is recommended.

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