[Follow-up of patients after COVID-19 pneumonia. Pulmonary sequelae]. / Seguimiento de los pacientes después de neumonía por COVID-19. Secuelas pulmonares.

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2 that has caused an unprecedented pandemic with a high rate of morbidity and mortality worldwide. Although most cases are mild, there are a considerable number of patients who develop pneumonia or even acute respiratory distress syndrome (ARDS). After having recovered from the initial disease, many patients continue with various symptoms (fatigue, dry cough, fever, dyspnea, anosmia, and chest pain, among others.), which has led to consider the possible existence of "post-COVID-19 syndrome". Although the definition and validity of this syndrome are not clear yet, several studies report that individuals who have recovered from COVID-19 may have persistent symptoms, radiological abnormalities, and compromised respiratory function. Current evidence suggests that there is a large number of pulmonary sequelae after COVID-19 pneumonia (interstitial thickening, ground glass opacities, crazy paving pattern, and bronchiectasis, among others.). Likewise, it seems that pulmonary function tests (spirometry, DLCO, 6MWT, and measurement of maximum respiratory pressures), in addition to high-resolution computed axial tomographies (CAT scan), are useful for the assessment of these post-COVID-19 pulmonary sequelae. This review aims to describe the possible pulmonary sequelae after COVID-19 pneumonia, as well as to suggest diagnostic procedures for their correct assessment and follow-up; thus, allowing proper management by a multidisciplinary medical team.

COVID-19 es la enfermedad causada por el virus SARS-CoV-2, la cual ha ocasionado una pandemia sin precedentes, con gran cantidad de infectados y muertos en el mundo. Aunque la mayoría de los casos son leves, existe una cantidad considerable de pacientes que desarrollan neumonía o, incluso, síndrome de distrés respiratorio agudo (SDRA). Luego de recuperarse del cuadro inicial, muchos pacientes continúan con diversos síntomas (fatiga, tos seca, fiebre, disnea, anosmia, dolor torácico, entre otras), lo que ha llevado a considerar la posible existencia del "síndrome pos-COVID-19". Aunque la definición y validez de este síndrome aún no son claras, varios estudios reportan que los individuos recuperados de la COVID-19 pueden tener persistencia de síntomas, anormalidades radiológicas y compromiso en la función respiratoria. La evidencia actual sugiere que existe gran cantidad de secuelas pulmonares despues de una neumonía por COVID-19 (engrosamiento intersticial, infiltrado en vidrio esmerilado, patrón en empedrado, bronquiectasias, entre otras.). De igual forma, parece ser que las pruebas de función pulmonar (espirometría, prueba de difusión pulmonar de monóxido de carbono, prueba de caminata de seis minutos y la medición de las presiones respiratorias máximas), además de la tomografía axial computarizada de alta resolución, son útiles para evaluar las secuelas pulmonares pos-COVID-19. En esta revisión se pretende describir las posibles secuelas a nivel pulmonar posteriores a neumonía por COVID-19, así como sugerir procedimientos diagnósticos para su correcta evaluación y seguimiento, que permitan el manejo adecuado por parte de un equipo médico multidisciplinario.

Are Interstitial Lung Abnormalities a Prognostic Factor of Worse Outcome in COVID-19 Pneumonia?

PURPOSE: To assess the association between interstitial lung abnormalities (ILAs) and worse outcome in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19)-related pneumonia. MATERIALS AND METHODS: The study included patients older than 18 years, who were admitted at the emergency department between February 29 and April 30, 2020 with findings of COVID-19 pneumonia at chest computed tomography (CT), with positive reverse-transcription polymerase chain reaction nasal-pharyngeal swab for SARS-CoV-2, and with the availability of prepandemic chest CT. Prepandemic CTs were reviewed for the presence of ILAs, categorized as fibrotic in cases with associated architectural distortion, bronchiectasis, or honeycombing. Worse outcome was defined as intensive care unit (ICU) admission or death. Cox proportional hazards regression analysis was used to test the association between ICU admission/death and preexisting ILAs. RESULTS: The study included 147 patients (median age 73 y old; 95% CIs: 71-76-y old; 29% females). On prepandemic CTs, ILA were identified in 33/147 (22%) of the patients, 63% of which were fibrotic ILAs. Fibrotic ILAs were associated with higher risk of ICU admission or death in patients with COVID-19 pneumonia (hazard ratios: 2.73, 95% CIs: 1.50-4.97, P =0.001). CONCLUSIONS: In patients affected by COVID-19 pneumonia, preexisting fibrotic ILAs were an independent predictor of worse prognosis, with a 2.7 times increased risk of ICU admission or death. Chest CT scans obtained before the diagnosis of COVID-19 pneumonia should be carefully reviewed for the presence and characterization of ILAs.

Impact of COVID-19 pneumonia on interstitial lung disease: semi-quantitative evaluation with computed tomography.

OBJECTIVES: To evaluate the CT scores and fibrotic pattern changes in interstitial lung disease (ILD) patients, with and without previous COVID-19 pneumonia. METHODS: Patients with ILD (idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated ILD (CTD-ILD)) were retrospectively enrolled in the study which consisted of patients who had COVID-19 pneumonia while the control group had not. All patients had two CT scans, initial and follow-up, which were evaluated semi-quantitatively for severity, extent, and total CT scores, fibrosis patterns, and traction bronchiectasis. RESULTS: A total of 102 patients (pneumonia group n = 48; control group n = 54) were enrolled in the study. For both groups, baseline characteristics were similar and CT scores were increased. While there was a 4.5 ± 4.6 point change in the total CT score of the COVID-19 group, there was a 1.2 ± 2.7 point change in the control group (p < 0.001). In the IPF subgroup, the change in total CT score was 7.0 points (95% CI: 4.1 to 9.9) in the COVID-19 group and 2.1 points (95% CI: 0.8 to 3.4) in the control group. Seven patients (14.6%) in the COVID-19 group progressed to a higher fibrosis pattern, but none in the control group. CONCLUSIONS: Semi-quantitative chest CT scores in ILD patients demonstrated a significant increase after having COVID-19 pneumonia compared to ILD patients who had not had COVID-19 pneumonia. The increase in CT scores was more prominent in the IPF subgroup. There was also a worsening in the fibrosis pattern in the COVID-19 group. KEY POINTS: • The impact of COVID-19 pneumonia on existing interstitial lung diseases and fibrosis is unclear. • COVID-19 pneumonia may worsen existing interstitial lung involvement with direct lung damage and indirect inflammatory effect. • COVID-19 pneumonia may affect existing lung fibrosis by triggering inflammatory pathways.

Multi Level Approach for Segmentation of Interstitial Lung Disease (ILD) Patterns Classification Based on Superpixel Processing and Fusion of K-Means Clusters: SPFKMC.

During the COVID-19 pandemic, huge interstitial lung disease (ILD) lung images have been captured. It is high time to develop the efficient segmentation techniques utilized to separate the anatomical structures and ILD patterns for disease and infection level identification. The effectiveness of disease classification directly depends on the accuracy of initial stages like preprocessing and segmentation. This paper proposed a hybrid segmentation algorithm designed for ILD images by taking advantage of superpixel and K-means clustering approaches. Segmented superpixel images adapt the better irregular local and spatial neighborhoods that are helpful to improving the performance of K-means clustering-based ILD image segmentation. To overcome the limitations of multiclass belongings, semiadaptive wavelet-based fusion is applied over selected K-means clusters. The performance of the proposed SPFKMC was compared with that of 3-class Fuzzy C-Means clustering (FCM) and K-Means clustering in terms of accuracy, Jaccard similarity index, and Dice similarity coefficient. The SPFKMC algorithm gives an accuracy of 99.28%, DSC 98.72%, and JSI 97.87%. The proposed Fused Clustering gives better results as compared to traditional K-means clustering segmentation with wavelet-based fused cluster results.

Factors Affecting the Risk of Interstitial Lung Disease Development in Hospitalized Patients With COVID-19 Pneumonia.

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.

Can home rehabilitation impact impulse oscillometry and lung ultrasound findings in patients with scleroderma-associated interstitial lung disease? A pilot study.

OBJECTIVE: Exercise has been demonstrated to be beneficial for improving physical capacity and quality of life in people with scleroderma, although knowledge of its impact on the respiratory system is limited. This study evaluated the impact of therapist-oriented home rehabilitation (TOHR) on impulse oscillometry (IOS) and lung ultrasound (LUS) findings in patients with scleroderma-associated interstitial lung disease (ILD). RESULTS: Twelve women with scleroderma underwent spirometry, IOS, and LUS before and after performing TOHR. Regarding spirometry, a normal pattern and restrictive damage were observed in five (41.7%) and seven (58.3%) participants pre-TOHR and post-TOHR, respectively. For IOS, an abnormal result was detected in nine (75%) pre-TOHR participants and six (50%) post-TOHR participants. Heterogeneity of resistance between 4-20 Hz (R4-R20) > 20% of the predicted value was observed in eight (66.7%) pre-TOHR participants and three (25%) post-TOHR participants (P = 0.031). An abnormal LUS result was observed in nine (75%) participants both pre-TOHR and post-TOHR. The main change observed was B-lines > 2, which was noted in nine (75%) participants both pre-TOHR and post-TOHR. Our findings suggest that TOHR for women with scleroderma-associated ILD improves the resistance and reactance measured by IOS, including small airway disease. Trial Registration ClinicalTrials.gov ID: NCT05041868 Registered on: 13th September 2021.

[The role of artificial intelligence in assessing the progression of fibrosing lung diseases].

INTRODUCTION: The widespread use of artificial intelligence (AI) programs during the COVID-19 pandemic to assess the exact volume of lung tissue damage has allowed them to train a large number of radiologists. The simplicity of the program for determining the volume of the affected lung tissue in acute interstitial pneumonia, which has density indicators in the range from -200 HU to -730 HU, which includes the density indicators of "ground glass" and reticulation (the main radiation patterns in COVID-19) allows you to accurately determine the degree of prevalence process. The characteristics of chronic interstitial pneumonia, which are progressive in nature, fit into the same density framework. Аim. To аssess AI's ability to assess the progression of fibrosing lung disease using lung volume counting programs used for COVID-19 and chronic obstructive pulmonary disease. RESULTS: Retrospective analysis of computed tomography data during follow-up of 75 patients with progressive fibrosing lung disease made it possible to assess the prevalence and growth of interstitial lesions. CONCLUSION: Using the experience of using AI programs to assess acute interstitial pneumonia in COVID-19 can be applied to chronic interstitial pneumonia.

Mesalazine induced interstitial pneumonitis in the COVID era.

Mesalazine is the most widely used aminosalicylate for induction and maintenance of remission in patients with mild-to-moderate ulcerative colitis (UC). Drug-induced hypersensitivity pneumonitis is considered very rare (<1/10.000 patients). Due to its rarity and the scarce cases reported, mesalazine-induced lung injury needs to be highly suspected in a patient with onset of respiratory symptoms and UC under treatment with salicylates. It should make the clinician formulate a differential diagnosis that includes not only infections (tuberculosis, bacterial...) or the inflammatory bowel disease itself, but also the current coronavirus disease 2019 (COVID-19) since their clinical and radiological manifestations may be very similar.

Metabolic characteristics in patients with COVID-19 and no-COVID-19 interstitial pneumonia with mild-to-moderate symptoms and similar radiological severity.

BACKGROUND AND AIMS: It is known that the highest COVID-19 mortality rates are among patients who develop severe COVID-19 pneumonia. However, despite the high sensitivity of chest CT scans for diagnosing COVID-19 in a screening population, the appearance of a chest CT is thought to have low diagnostic specificity. The aim of this retrospective case-control study is based on evaluation of clinical and radiological characteristics in patients with COVID-19 (n = 41) and no-COVID-19 interstitial pneumonia (n = 48) with mild-to-moderate symptoms. METHODS AND RESULTS: To this purpose we compared radiological, clinical, biochemical, inflammatory, and metabolic characteristics, as well as clinical outcomes, between the two groups. Notably, we found similar radiological severity of pneumonia, which we quantified using a disease score based on a high-resolution computed tomography scan (COVID-19 = 18.6 ± 14.5 vs n-COVID-19 = 23.2 ± 15.2, p = 0.289), and comparable biochemical and inflammatory characteristics. However, among patients without diabetes, we observed that COVID-19 patients had significantly higher levels of HbA1c than n-COVID-19 patients (COVID-19 = 41.5 ± 2.6 vs n-COVID-19 = 38.4 ± 5.1, p = 0.012). After adjusting for age, sex, and BMI, we found that HbA1c levels were significantly associated with the risk of COVID-19 pneumonia (odds ratio = 1.234 [95%CI = 1.051-1.449], p = 0.010). CONCLUSIONS: In this retrospective case-control study, we found similar radiological and clinical characteristics in patients with COVID-19 and n-COVID-19 pneumonia with mild-to-moderate symptoms. However, among patients without diabetes HbA1c levels were higher in COVID-19 patients than in no-COVID-19 individuals. Future studies should assess whether reducing transient hyperglycemia in individuals without overt diabetes may lower the risk of SARS-CoV-2 infection.

A new standard scoring for interstitial pneumonia based on quantitative analysis of ultrasonographic data: A study on COVID-19 patients.

OBJECTIVE: To assess the effectiveness of 3 novel lung ultrasound (LUS)-based parameters: Pneumonia Score and Lung Staging for pneumonia staging and COVID Index, indicating the probability of SARS-CoV-2 infection. METHODS: Adult patients admitted to the emergency department with symptoms potentially related to pneumonia, healthy volunteers and clinical cases from online accessible databases were evaluated. The patients underwent a clinical-epidemiological questionnaire and a LUS acquisition, following a 14-zone protocol. For each zone, a Pneumonia score from 0 to 4 was assigned by the algorithm and by an expert operator (kept blind with respect to the algorithm results) on the basis of the identified imaging signs and the patient Lung Staging was derived as the highest observed score. The output of the operator was considered as the ground truth. The algorithm calculated also the COVID Index by combining the automatically identified LUS markers with the questionnaire answers and compared with the nasopharyngeal swab results. RESULTS: Overall, 556 patients were analysed. A high agreement between the algorithm assignments and the expert operator evaluations was observed, both for Pneumonia Score and Lung Staging, with the latter having sensitivity and specificity over 92% both in the discrimination between healthy/sick patients and between sick patients with mild/severe pneumonia. Regarding the COVID Index, an area under the curve of 0.826 was observed for the classification of patients with/without SARS-CoV-2. CONCLUSION: The proposed methodology allowed the identification and staging of patients suffering from pneumonia with high accuracy. Moreover, it provided the probability of being infected by SARS-CoV-2.

Chest CT texture-based radiomics analysis in differentiating COVID-19 from other interstitial pneumonia.

PURPOSE: To evaluate the potential role of texture-based radiomics analysis in differentiating Coronavirus Disease-19 (COVID-19) pneumonia from pneumonia of other etiology on Chest CT. MATERIALS AND METHODS: One hundred and twenty consecutive patients admitted to Emergency Department, from March 8, 2020, to April 25, 2020, with suspicious of COVID-19 that underwent Chest CT, were retrospectively analyzed. All patients presented CT findings indicative for interstitial pneumonia. Sixty patients with positive COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) and 60 patients with negative COVID-19 RT-PCR were enrolled. CT texture analysis (CTTA) was manually performed using dedicated software by two radiologists in consensus and textural features on filtered and unfiltered images were extracted as follows: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. Nonparametric Mann-Whitney test assessed CTTA ability to differentiate positive from negative COVID-19 patients. Diagnostic criteria were obtained from receiver operating characteristic (ROC) curves. RESULTS: Unfiltered CTTA showed lower values of mean intensity, MPP, and kurtosis in COVID-19 positive patients compared to negative patients (p = 0.041, 0.004, and 0.002, respectively). On filtered images, fine and medium texture scales were significant differentiators; fine texture scale being most significant where COVID-19 positive patients had lower SD (p = 0.004) and MPP (p = 0.004) compared to COVID-19 negative patients. A combination of the significant texture features could identify the patients with positive COVID-19 from negative COVID-19 with a sensitivity of 60% and specificity of 80% (p = 0.001). CONCLUSIONS: Preliminary evaluation suggests potential role of CTTA in distinguishing COVID-19 pneumonia from other interstitial pneumonia on Chest CT.

Case Report: Systemic Sclerosis After Covid-19 Infection.

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. The acute phase of the infection may in certain individuals be followed by another longer phase of disease (long COVID) of unknown etiology probably associated in certain cases with autoimmune activation. It has been shown that COVID-19 can trigger autoantibody production and in genetically predisposed patients may cause the onset or exacerbation of autoimmune diseases. We are reporting a case of mild COVID-19 infection complicated by autoantibody production and cutaneous and gastrointestinal symptoms and subsequently diagnosed with systemic sclerosis (SSc). A 47-year-old man with no history of any autoimmune diseases and in good health became sick together with his family on the 12th of November with mild symptoms: tiredness, fever, cough, and sore throat. Oropharyngeal swab for SARS-CoV-2 tested positive. He was isolated at home and did not require hospitalization. Three weeks later he presented with clinical manifestation compatible with suspicion of SSc. He briefly presented with skin rush, periorbital edema and conjunctivitis, vomiting, dysphagia, burning sensation in the skin, above all in the fingertips and around the mouth, puffy fingers, Raynaud's phenomenon, pain at the fingertip of the middle finger where a depressed area was noticed without a clear ulceration. ANA showed a strongly positive nucleolar pattern. Anti-PM/Scl 75 and PM/Scl 100 resulted positive. High-resolution computed tomography (HCRT) showed early stage of interstitial lung disease (ILD). The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical and radiological pictures according to the ACR/EULAR classification (scores: puffy finger, 2; ILD, 2; Raynaud's phenomenon, 3; SSc related antibodies, 3; total 10). There are several cases described in the medical literature of possible new onset of SLE after COVID-19 infection. This is the first case that describes a possible new onset of SSc. Conclusion: SARS-CoV-2 may trigger systemic sclerosis.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

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.