The inspiratory activity of respiratory center and respiratory muscles strength after COVID-19.

The respiratory pump that provides pulmonary ventilation includes the respiratory center, peripheral nervous system, chest and respiratory muscles. The aim of this study was to evaluate the activity of the respiratory center and the respiratory muscles strength after COVID-19 (COronaVIrus Disease 2019). Methods. The observational retrospective cross-sectional study included 74 post-COVID-19 patients (56 (76%) men, median age - 48 years). Spirometry, body plethysmography, measurement of lung diffusing capacity (DLCO), maximal inspiratory and expiratory pressures (MIP and MEP), and airway occlusion pressure after 0.1 sec (P0.1) were performed. In addition, dyspnea was assessed in 31 patients using the mMRC scale and muscle strength was assessed in 27 of those patients using MRC Weakness scale. Results. The median time from the COVID-19 onset to pulmonary function tests (PFTs) was 120 days. The total sample was divided into 2 subgroups: 1 - P0.1 <= 0.15 kPa (norm), 2 - > 0.15 kPa. The lung volumes, airway resistance, MIP, and MEP were within normal values in most patients, whereas DLCO was reduced in 59% of cases in both the total sample and the subgroups. Mild dyspnea and a slight decrease in muscle strength were also detected. Statistically significant differences between the subgroups were found in the lung volumes (lower) and airway resistance (higher) in subgroup 2. Correlation analysis revealed moderate negative correlations between P0.1 and ventilation parameters. Conclusion. Measurement of P0.1 is a simple and non-invasive method for assessing pulmonary function. In our study, an increase in P0.1 was detected in 45% of post-COVID-19 cases, possibly due to impaired pulmonary mechanics despite the preserved pulmonary ventilation as well as normal MIP and MEP values.Copyright © Savushkina O.I. et al., 2023.

Scientific rationale of Indian AYUSH Ministry advisory for COVID-19 prevention, prophylaxis, and immunomodulation

The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.

Autoimmune pulmonary alveolar proteinosis in an adolescent girl with rapidly progressive dyspnea

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.

Effects of Post COVID-19 Pneumonia on the Prognosis of Trauma Patients undergoing Treatment in a Tertiary Care Hospital

Background: In the light of post severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) Pneumonias playing a role in the long-term respiratory complications in patients subsequently involved in trauma, a study was conducted to assess the post COVID-19 Pneumonias on the prognosis of trauma patients in a Tertiary care Hospital of Telangana. Aim of the Study: To identify the post COVID-19 pneumonia and respiratory complications, their severity, factors affecting the management of trauma patients and the long-term sequelae. Materials: 42 patients categorized on American Association for the Surgery of Trauma (AAST) injury scoring scales were included. Patients aged between 18 and 70 years were included. Patients with previous history of post COVID-19 lung disease for 09 months or above were included. Pulmonary function tests like FEV1, FVC, TLC and DLCO were performed and analyzed. The CT scan signs were based on the involvement of the lung parenchyma as: Normal CT (no lesion), minimal (0-10%), moderate (11-25%), important (26-50%), severe (51-75%), and critical (>75%). Result(s): 42 patients with trauma with either COVID-19 disease affecting the lungs or RTPCR positive were included. There were 29 (69.04%) male patients and 13 (30.95%) female patients with a male to female ratio of 2.23:1. The mean age among the men was 41.55+/-3.25 years and 38.15+/-4.10 years in female patients. There were 33/42 patients with positive RTPCR test and 09/42 were negative for RTPCR test for COVID-19. Conclusion(s): Recovery from COVID-19 disease especially with lung parenchyma changes during the active state has shown to affect adversely the morbidity of post trauma surgeries. Preoperative assessment of Lung function tests such as FEV1, FVC, TLC and DLCO would guide the surgeon and the anesthetist in the surgical management of such patients.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Clinical and respiratory function outcomes 6-months following diagnosis of COVID-19

Introduction/Aim: As health systems emerge through successive waves of COVID-19, focus shifts to the management of Post-COVID-19 conditions. The aim of this prospective observational study was to characterise and evaluate the respiratory sequelae affecting patients 6-months post-diagnosis of COVID-19. SIGNFICANT MODELLING PREDICTORS Outcome Predictors MMRC>= 1 Disease severity Moderate: OR 16.5 +/- 1.02 (SE) p = 0.006 Impaired DLCO (%predicted) Disease severity B=-1.51+/-0.67 (SE) p = 0.010 Impaired TLC (%predicted) D-Dimer B= -0.305 +/- 0.001 (SE), p = 0.05 TLC below LLN Diabetes B=-1.28 +/- 0.32 (SE), p = 0.044 Methods: Patients were evaluated for symptom burden and lung function at 6-months post-diagnosis of COVID-19 in an outpatient setting. Result(s): Fifty-eight (45 inpatients and 13 outpatients;median age 59 years, 28 females) patients attended 6-month clinic appointment. Whilst nearly half (28,48.3%) were asymptomatic at 6-months, 24 (41.3%) patients reported a modified medical research council dyspnoea scale (MMRC) >= 1 and 21 (36.2%) patient-reported fatigue (n= 21, 36.2%). Reduced TLC (n= 11/50, 22.0%) and DLCO (n = 12/51, 23.5%) were common at 6-months. Results of predictive modelling analyses are described in adjacent table. Conclusion(s): Patients presenting with increased disease severity are at risk of persistent dyspnoea and impaired diffusion capacity, 6-months following acute COVID-19 illness. Research guided management of this growing at risk cohort, while paramount, poses a formidable challenge to stretched healthcare systems.

The inspiratory activity of respiratory center and respiratory muscles strength after COVID-19.

The respiratory pump that provides pulmonary ventilation includes the respiratory center, peripheral nervous system, chest and respiratory muscles. The aim of this study was to evaluate the activity of the respiratory center and the respiratory muscles strength after COVID-19 (COronaVIrus Disease 2019). Methods. The observational retrospective cross-sectional study included 74 post-COVID-19 patients (56 (76%) men, median age - 48 years). Spirometry, body plethysmography, measurement of lung diffusing capacity (DLCO), maximal inspiratory and expiratory pressures (MIP and MEP), and airway occlusion pressure after 0.1 sec (P0.1) were performed. In addition, dyspnea was assessed in 31 patients using the mMRC scale and muscle strength was assessed in 27 of those patients using MRC Weakness scale. Results. The median time from the COVID-19 onset to pulmonary function tests (PFTs) was 120 days. The total sample was divided into 2 subgroups: 1 - P0.1 <= 0.15 kPa (norm), 2 - > 0.15 kPa. The lung volumes, airway resistance, MIP, and MEP were within normal values in most patients, whereas DLCO was reduced in 59% of cases in both the total sample and the subgroups. Mild dyspnea and a slight decrease in muscle strength were also detected. Statistically significant differences between the subgroups were found in the lung volumes (lower) and airway resistance (higher) in subgroup 2. Correlation analysis revealed moderate negative correlations between P0.1 and ventilation parameters. Conclusion. Measurement of P0.1 is a simple and non-invasive method for assessing pulmonary function. In our study, an increase in P0.1 was detected in 45% of post-COVID-19 cases, possibly due to impaired pulmonary mechanics despite the preserved pulmonary ventilation as well as normal MIP and MEP values.Copyright © Savushkina O.I. et al., 2023.

Longitudinal Follow-up of Pulmonary Function in Patients Hospitalized with Pulmonary Covid-19

Purpose of Study: The post-acute sequelae of COVID-19, as a multisystemic disease have been described in adults. Although some studies have described the pulmonary complications up to 3 months post-COVID infection, longitudinal data on pulmonary sequalae are sparse. The objective of this review was to summarize the findings of studies that included a longitudinal follow-up of patients with moderate to severe pulmonary COVID-19 infection. Methods Used: We performed a literature search using Pubmed, Google Scholar and Medline using key words: "pulmonary function test", PFT?, "long-COVID", longitudinal? and sequalae?. We included studies of adult patients (>18 years of age) who had been hospitalized with acute COVID-19 infection and had at least two follow-ups with PFT measurements, including one follow-up at least 6 months post-infection. Studies that did not account for co-morbidities and other lung diseases or those which only included one-time follow-up were excluded. Summary of Results: Five studies satisfied our inclusion criteria (See Table). The studies showed persistent lung injury for at least 3 months after discharge, with decreased forced expiratory volume (FEV1), total lung capacity (TLC), forced vital capacity (FVC), diffusion vital capacity of the lungs for carbon monoxide (DCLO) and carbon monoxide transfer coefficient (KCO). Although these values improved at 6 and 12 months of follow-up, those with more severe disease continued to have decreased DLCO suggestive of restrictive lung damage. Studies that included symptomatic assessment revealed that a minority of patients continued with fatigue and dyspnea uf to 12 months after the infection. The limitations of the studies include availability of data from a single center, small sample size and the variability in controlling for different co-morbidities. In addition, baseline PFT measurement before COVID-19 infection was not available for most patients. Most of the studies were done at the time that the Delta variant was dominant, therefore the data may not be applicable to other variants. Conclusion(s): Our literature review shows that some adult patients hospitalized with acute covid pulmonary infection continue to have abnormal PFTs for up to 12 months after infection. Although PFTs improve overtime, a minority of patients with more severe disease on admission continue with abnormal functional abnormalities, specifically restrictive ventilatory pattern with impaired DLCO at 12 months of follow-up. It is important that patients hospitalized with moderate to severe pulmonary COVID-19 infection be followed up and managed for at least 12 months after the initial infection. Larger prospective studies including different variants of COVID-19 that take into account various co-morbidities and different management strategies are warranted.

Pulmonary function in non-hospitalized adults and children after mild Covid-19

Objective Asesmentof lung function impairment after mild SARS-CoV-2 infection in non-hospitalized children and adults. Additionally focusing on previous and persistent symptoms due to Covid-19 as well as current respiratory tract infection status. Methods Patients aged 6-60 years were recruited by telephone after laboratory-confirmed positive PCR result for SARS-CoV-2. Excluding criteria were hospitalization during Covid-19, pre-existing lung diseases (bronchial asthma, COPD) and smoking within the last five years. Pulmonary function testing was performed 4-12 weeks after infection, including Multiple-breath washout (LCI), spirometry (FEV?, FVC, Tiffeneau-Index) and diffusion capacity testing (DLCO, TLC;Hb corrected). All patients answered a questionnaire regarding previous and persistent symptoms. To gather information about the current infection status, a pharyngeal swab was taken to detect common respiratory bacterial and viral pathogens using a multiplex PCR approach. Patients with abnormalities in pulmonary function were invited to a follow up testing three months later. Results 110 patients, 90 adults and 20 children, were included. 44 adults and 17 children had at least one abnormal value in pulmonary function tests after an average of 7.7 weeks (range 4.3-11.3) to confirmed SARS-Cov-2 infection. Among these 44 adults, 33 reported pulmonary symptoms during Covid-19 and 19 persistent respiratory symptoms. No abnormalities in DLCO were found in adults. At the second pulmonary function testing 12.5 weeks (range 11.0-16.7) on average after the first appointment, improvement was shown in 61,7% ( n=29 of 47) with previous abnormal LCI, in 69,2% (n=9 of 13) with prior abnormal FVC and in 4 of 5 children with abnormal DLCO. No large correlation was detected between impaired pulmonary function and multiplex PCR results. Conclusion Mild lung function impairment was shown at the first appointment, particularly in LCI, but not equally measured in the entirety of lung function tests. Pulmonary function results were not affected by current infection status and partially mismatching with stated persisting symptoms. Within 3 months, most initially abnormal values improved, and self- perceived health status increased. Long term pulmonary function impairment was rarely detected after mild, non-hospitalized Covid-19 course. .

Dermatomyositis with Specific Autoantibodies Appearing after Sars-Cov-2 Infection or Mrna Vaccination: Hints at a Shared Pathogenetic Mechanism

Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.

Pulmonary function and functional capacity at 3, 6 and 12 months in COVID-19 patients and effect of physical activity on recovery

BACKGROUND: Long-term sequelae due to Coronavirus disease 2019 (COVID-19) are now under investigation. Aim of this study was to evaluate the one-year clinical impact of COVID-19 on respiratory function and relation with physical activity. METHOD(S): One hundred four patients were evaluated 3, 6 and 12 months after SARS-CoV-2 diagnosis. Clinical conditions, symptomatology, 6-minute walking test (6MWT), pulmonary function test with spirometry and diffusing capacity of carbon monoxide (DLCO) were analyzed. RESULT(S): Eighty-six (82.7%) patients referred at least one symptom at 3 months, 46 (44.2%) at 6 months and 24 (23.1%) at 12 months. At the 3-months visit, patients with moderate COVID showed a slight decrease of distance at the 6MWT, with an improvement at 12 months (P=0.04). Patients with severe COVID-19 showed a recovery of SpO2 at rest (P<0.001), DLCO (P=0.001), DLCO/VA (P=0.002), forced vital capacity (P=0.01) and 6MWT distance (P=0.002) at 6 and 12 months. Patients with critical COVID-19 showed a remarkable reduction of DLCO at 3 months (65+/-21%). Then a subsequent gradual improvement of DLCO was recorded (78+/-18% at 6 months, 85+/-16% at 12 months, P=0.01). Patients with DLCO<80% of predicted at 12 months were older (P=0.02), with higher prevalence of cardio-vascular disease (P=0.006), diabetes (P=0.01) and critical COVID-19 (P=0.003). The improvement of 6MWT distance and DLCO during the three visits did not correlate with physical activity. CONCLUSION(S): Patients with COVID-19 lung involvement showed a progressive improvement in respiratory function and physical performance at 6 and 12 months after acute disease.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Long-Term Sequelae of severe COVID-19: Outpatient assessment of radiological and pulmonary function tests

Objective: Identify lung sequelae of COVID-19 through radiological and pulmonary function assessment. Design(s): Prospective, longitudinal, cohort study from March 2020 to March 2021. Setting(s): Intensive Care Units (ICU) in a tertiary hospital in Portugal. Patient(s): 254 patients with COVID-19 admitted to ICU due to respiratory illness. Intervention(s): A chest computed tomography (CT) scan and pulmonary function tests (PFT) were performed at 3 to 6 months. Main variables of interest: CT-scan;PFT;decreased diffusion capacity of carbon monoxide (DLCO). Result(s): All CT scans revealed improvement in the follow-up, with 72% of patients still showing abnormalities, 58% with ground glass opacities and 62% with evidence of fibrosis. PFT had abnormalities in 94 patients (46%): thirteen patients (7%) had an obstructive pattern, 35 (18%) had a restrictive pattern, and 58 (30%) had decreased DLCO. There was a statistically significant association between abnormalities in the follow-up CT scan and older age, more extended hospital and ICU stay, higher SAPS II and APACHE scores and invasive ventilation. Mechanical ventilation, especially with no lung protective parameters, was associated with abnormalities in PFT. Multivariate regression showed more abnormalities in lung function with more extended ICU hospitalization, chronic obstructive pulmonary disease (COPD), chronic kidney disease, invasive mechanical ventilation, and ventilation with higher plateau pressure, and more abnormalities in CT-scan with older age, more extended ICU stay, organ solid transplants and ventilation with higher positive end-expiratory pressure (PEEP). Conclusion(s): Most patients with severe COVID-19 still exhibit abnormalities in CT scans or lung function tests three to six months after discharge.Copyright © 2023

Rituximab in the Treatment of Idiopathic Inflammatory Myopathies with Interstitial Lung Disease, Long-Term Follow-Up

Background. Interstitial lung disease (ILD) is the common internal organ manifestation of idiopathic inflammatory myopathies (IIM) that can severely affect the course and prognosis of the disease. Rituximab (RTX) has been used to treat IIM, including variants with ILD. Objectives. To describe the course of disease in IIM patients with ILD, treated with RTX in long-term follow-up. Methods. Our prospective study included 35 pts with IIM fulfilling Bohan and Peter criteria and having ILD. The mean age was 51.8+/-11.9 years, female-26 pts (74%);24 (68.5%) with antisynthetase syndrome, 5 (14.3%) dermatomyositis (DM), 5 (14.3%) with a-Pm/Scl overlap myositis and 1 (2,9%) with a-SRP necrotizing myopathy were included. 25 (71,4% ) patients had nonspecific interstitial pneumonia, 9 (25,7%) organizing pneumonia (OP) and 1 (2,9%) OP, transformed to diffuse alveolar damage. All pts had the standard examination including manual muscle testing (MMT), creatinkinase (CK) anti-Jo-1 antibodies (anti-Jo-1) assay;forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) evaluation as well as high-resolution computed tomography (HRCT) scanning of the chest were performed at baseline, and 36 and more months. The median disease duration was 3.2 [0.16-18] years, 21 (60%) of pts were positive for a-Jo-1 antibody. All pts received prednisolone at a mean dose of 24.3+/-13 mg/day, immunosupressants at inclusion received 25 (71%) pts: cyclophosphamide 18 , mycophenolate mofetil 6 and comdination 1;Rituximab (RTX) was administered in case of severe course of disease and intolerance or inadequate response to GC and other immunosuppressive drugs. Results. The mean follow-up period after the first infusion of RTX was 47.2+/-11.9 months. Pts received 1-11 courses of RTX . The cumulative mean dose of RTX was 4.6 +/-2.5g. MMT 8 increased from 135.8+/-13.5 to 148.75+/-3.5 (p=0.000001). CK level decreased DELTACK - 762 u/l(median 340;25th% 9;75th% 821). anti-Jo-1 decreased from 173.4+/-37 to 96.5+/-79 u/ml (p=0.00002), FVC increased from 82+/-22.6 to 96,9+/-22% (p=0.00011). DLCO increased from 51.4+/-15.2 to 60+/-77.8% (p=0.0001). The mean prednisone dose was reduced from 24.3+/-13 to 5.7+/-2.4 mg/day. 3 pts died: ILD progression was the cause of death in 1 case, 1 bacterial pneumonia and COVID19 pneumonia. Conclusions. The results of this study confirm the positive effect of RTX in IIM patients with ILD (increase of muscle strength and improve lung function, decrease in anti-Jo-1 levels) and also its good steroid-sparing effect. RTX could be considered as an effective drug for the complex therapy of IIM patients with ILD when standard therapy is ineffective or impossible.

COVID-19 in patients with Pulmonary Alveolar Proteinosis A European multicenter study

Background: Interruption of GM-CSF signaling leads to Pulmonary Alveolar Proteinosis (PAP), occasionally to lung infections and relates to the impaired ability of lung macrophages to catabolize phagocytized surfactant and handle microbes. COVID-19 is associated with worse prognosis in lung disorders. We hypothesized that PAP patients would be at increased risk for COVID-19 and poor outcome. Aim and objectives: This multi-center, retrospective, European study aimed to investigate prevalence and clinical consequences of COVID-19 in PAP and the impact of iGM-CSF treatment on hospitalization or death. Method(s): All patients with PAP and COVID-19 diagnosed and followed-up in 11 referral European centers from January 24th 2020 to August 31st 2021 were included. Prevalence, clinical course and outcome were investigated. Result(s): COVID-19 developed in 34/255 (13.3%) of patients, mostly adults (91.2%), all with autoimmune (a)PAP;all patients were infected before the preventive option of vaccination was available;11 (35.5%) were hospitalized, of whom almost half were in the ICU;3 (27%) of hospitalized patients either died or underwent lung-transplant;these three patients had worse DLCO% predicted (p=0.019) and had more often arterial hypertension (AH) (p=0.012), and a smoking history (p=0.002). All patients with mild disease treated at home survived. Among children, 3 developed COVID-19 with good outcome. Conclusion(s): PAP patients experienced similar rates of COVID-19 with the general population but increased rates of hospitalizations and deaths, underscoring the vulnerability of this population and the necessity of preventive measures to avoid infection. If infected, secondary prophylaxis with monoclonal antibodies and the impact of iGM-CSF must be considered.

Respiratory Outcomes in COVID-19 patients 3-6 months after admission to Public Health Hospital Maciel. Montevideo, Uruguay. A Follow up Cohort Study

To date, millions of people worldwide have recovered from COVID19, but concern remains on long-term impairment. We aimed to determine 3-6 months respiratory outcomes in a Latin American Public Health Hospital. Method(s): COVID-19 patients referred (April-June 2021,gamma variant breakdown) were enrolled, recalling epidemiology, demographic, comorbidities, laboratory, radiology, treatment and outcomes, performing spirometry, lung volumes, diffusing capacity (DLCO), walking test (6MWT);values< 80% of predicted were considered abnormal. Logistic regression analysis were performed to evaluate covariates associated with DLCO abnormality. Result(s): 56 patients followed 6 months make up the cohort. 56,9 +/- 13,0 years, 58,9% female,46,4% ever smokers, 42,9% obesity (BMI >30), 37,5% hypertension, 23,2% diabetes, 16,1% heart disease, 16,1% asthma. 64% dyspnea (MRC>1), 50% fatigue, sit to stand Sp02% 94,7 +/- 3,9. Lymphocites103 /muL 413,3 +/- 625,7,D-dimer ng/ml 3050,9 +/-7226,1,ferritin ng/ml 641,8 +/- 1173,4, 21.4% radiology abnormality, 35.7% admitted to ICU, days stay 17,1 +/- 10,5. 3 vs 6 months: TLC 5,3 +/- 1,9 vs 5,16 +/- 2,3 p=0.05;FVC 3,10 +/- 0,9 vs 3,16 +/- 1,0 p=0.04;DLCO:17,2 +/- 6,0 vs 17,8 +/- 6,2 7 p=0.006;Sp02% in 6MWT 90,1 +/- 98,2 vs 91,1 +/- 3,6 p=0.05. 6 months: dyspnea 28.6%, fatigue 26.8%, abnormality in: FVC 12,5%,FEV1 16,1%,DLCO 58,9%,distance 6MW 28,6%. Abnormal DLCO correlations: age > 65 p=0.02,smoking p=0.04,heart disease p=0.04,dyspnea MRC>1 p=0.002, persistent fatigue p=0.05. Conclusion(s): At 6 months some COVID-19 patients maintain symptoms and impaired DLCO and are the main target for further follow up and intervention.

The outcome of pulmonary function tests and high-resolution computed tomography of chest in post-coronavirus disease 2019-confirmed cases after 3 months of recovery

Background: Coronavirus disease (COVID-19) is a recently prevalent infectious disease that is caused by a virus from the coronavirus family and causes acute respiratory syndrome. It is a pandemic catastrophe that has affected more than 60 million people around the world and has caused about 1.5 million deaths, as reported by the WHO. This disease affects the respiratory system and leads to different forms of symptoms and signs. Pneumonia is a common cause for hospitalization, with most patients treated in hospital wards and others requiring ICU. Although the number of complete recoveries from COVID-19 has increased, there is still concern about complications associated with the disease that appear after recovery. The studies that have looked at past types and other forms of coronavirus epidemics, such as SARS have shown that some cases had respiratory complications from the infection after being full recovered, as 36 and 30% of the entire study population had clinical and high-resolution computed tomography (HRCT) changes at 3 and 6 months after recovery, respectively. Mostly, the abnormalities seen in pulmonary function test (PFT) results are sequelae of diffusion capacity defect. In recovered cases of Middle East respiratory syndrome, 36% of patients showed HRCT sequelae at follow-up of 6 weeks, because of fibrosis. Data on COVID-19 indicate that prolonged disease and persistent symptoms show post-PFT affection and follow-up radiographic changes after recovery from COVID-19 as interstitial pulmonary changes and a degree of pulmonary vasculopathy. In recovered cases of COVID-19, capacity of diffusion is the commonest defect in lung function, followed by the restrictive pattern defects on spirometry;both are related to the degree of severity of pneumonic COVID-19. PFTs (involving spirometry as well as diffusion capacity) are considered as routine follow-up examinations for some of the recovered cases, especially severe cases. Rehabilitation programs of the respiratory system are an option strategy that might be considered. This study aims to show changes in pulmonary function and HRCT of chest in post-COVID-19-infected patients to detect long-term effects on the lungs after 3 months as obstructive or restrictive, or both, lung diseases. Patients and Methods: The study was conducted on 100 confirmed PCR-positive COVID-19 cases that were admitted to Ain Shams University Isolation Hospitals, and the follow-up was performed in the outpatient clinic. PCR samples (Combined nasopharyngeal and oropharyngeal swab) were taken after 3 months from discharge of patients above the age of 18 years who become negative with clinical improvement. PFT [spirometry and diffusion for carbon monoxide (DLCO)] and chest HRCT were done. All patients' clinical data were recorded, and CT chest imaging data of these patients were correlated with the clinical data. Result(s): A total of 100 patients were included in this study, where males represented 58% and female represented 42%. The mean+/-SD age of cases in this study was 45.05 +/- 11.80 years and ranged from 20 to 79 years. CT chest severity score (SS) of abnormality in COVID-19-infectedd patients based on HRCT chest findings before and after 3 months from treatment showed a highly significant correlation (P=0.000). The results of PFT in the studied group after 3 months of discharge showed restrictive pattern in 14.9%, obstructive pattern in 17.8%, and both obstructive and restrictive patterns in 5.9% of the total number of cases. There was a significant correlation between DLCO abnormality findings and age of studied group (P=0.032), a significant correlation between abnormality findings on PFT and HRCT chest SS after discharge of the studied group (P0.001). There was a significant correlation between abnormality findings of DLCO and HRCT chest SS after 3 months of the studied group (P=0.000) and before treatment (P=0.001), whereas there was no significant correlation between other findings of PFT and HRCT chest SS after 3 months and before. There was a significant correlation between H

Proteomic determinants of disease, mortality and sequelae in COVID-19 patients requiring invasive mechanical ventilation

Introduction: The molecular mechanisms linked to the pathology of severe COVID-19 and its outcomes are poorly described. Aim(s): To analyze the proteomic profile of bronchial aspirates (BAS) samples from critically ill COVID-19 patients in order to identify factors associated with the disease and its prognosis. Method(s): Multicenter study including 74 critically ill non-COVID-19 and COVID-19 patients. BAS was obtained by bronchoaspiration after invasive mechanical ventilation (IMV) initiation. Proximity extension assay (PEA) technology was used for proteomic profiling. Random forest (RF) statistical models were used to predict the variable importance. Result(s): After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-alpha showed differences between COVID-19 and non-COVID-19 patients. Reduced levels of ENTPD2 and PTN were observed in non-survivors, even after adjustment. AGR2, NQO2, IL-1alpha, OSM and TRAIL, were the top five strongest predictors for ICU mortality and were used to build a prediction model. PTN (HR=4.00) ENTPD2 (HR=2.14) and the prediction model (HR=6.25) were associated with higher risk of death. In survivors, FCRL1, NTF4 and THOP1 correlated with lung function (DLCO levels) 3-months after hospital discharge. Similar findings were observed for Flt3L and THOP1 and radiological features (TSS). The proteins identified are expressed in immune and non-immune lung cells. A poor control of viral infectivity and an inappropriate reparative response seems to be linked to the disease and fatal outcomes, respectively. Conclusion(s): In critically ill COVID-19 patients, specific proteomic profiles are associated with the pathology, mortality and lung sequelae.

Respiratory outcomes 3-month following COVID-19- related hospitalisation: a Tunisian prospective study

Background: Despite recovery from COVID-19,concern remains that some organs, including the lungs, might have long-term impairment following infection. Aim(s): Assess symptoms,pulmonary function,exercise capacity and chest HRCT changes in non-intubated patients hospitalised with severe COVID19 pneumonia at 3months. Method(s): In this prospective,longitudinal study,patients admitted to hospital for severe COVID19 who did not require mechanical ventilation were prospectively followed up at 3months after discharge from respiratory department Rabta Hospital of Tunis. During the follow-up,patients were interviewed and underwent pulmonary function tests(PFT),chest high-resolution CT(HRCT)and 6-min walk distance test(6MWT). PFT included:diffusing capacity of the lungs for carbon monoxide (DLCO);forced vital capacity(FVC);forced expiratory volume in 1 second (FEV1) and total lung capacity (TLC). Result(s): Between June 1st, and august 31, 2021;47 patients (mean age 56 +/- 12 years;sex ratio 0.74)were included. At 3 months, the most common persistent symptoms were dyspnea(78.7%),cough(46.8%),fatigue(36.2%) and anxiety(17%). Abnormal HRCT findings were pulmonary fibrosis (4%),ground glass opacities(42.5%) and consolidation(32%). Median FVC, FEV1 and TLC were respectively 97% (53-119%), 87.5% (30-120%) and 87% (72- 127%). DLCO was below the lower limit of normal in 12.7% of patients. During 6MWT, the average walked distance was 480 meters [120-680];22 patients (46.8%) showed reduced physical capacity. Conclusion(s): At 3 months after severe COVID pneumonia,a substantial number of patients still have respiratory symptoms with radiological and functional impairment. A long-term monitoring is mandatory.

Circulating calprotectin correlates with DLCO in patients four months after COVID-19

Background: After 4 months we have shown, that DLCO is lower in severe COVID-19 patients compared to nonsevere (Guler SA, et al. Eur Respir J. 2021 Apr 29;57(4):2003690). Contributing factors are unclear. Calprotectin is an inflammatory marker released by activated neutrophils and is increased in acute severe COVID-19. Aim(s): We hypothesized that circulating calprotectin correlates with persistent lung functional impairment after COVID-19. Method(s): Calprotectin serum levels were measured in 124 patients (50% male) 4 months after COVID-19 (NCT04581135). Calprotectin was correlated with clinical parameters (Spearman's correlation). Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models. Result(s): Post-ICU patients (72% male) compared to non-ICU were significantly older (age 59.4 +/- 13.6 vs 49.2 +/- 13.1 years) and more obese (BMI 28.7 +/- 4.5 vs 25.2 +/- 6.0 kg/m2) (p=0.001, each) compared to non-ICU. DLCO was lower in post-ICU patients (75.96 +/- 19.05 %-predicted) compared to non-ICU (p<0.01). Calprotectin was significantly higher in post-ICU patients (2.74 +/- 1.15 mug/ml) compared to non-ICU (1.81 +/- 0.94 mug/ml, p<0.001). In unadjusted analysis, calprotectin correlated with DLCO (r=-0.350, p<0.001) and FVC (r=-0.417, p<0.001). In MLR adjusted for age, sex and BMI, calprotectin correlates with DLCO (R2=0.276, p<0.001). Calprotectin significantly predicted DLCO (beta=-6.463, p=0.001). Conclusion(s): Serum calprotectin is higher in post-ICU patients compared with non-ICU 4 months after COVID-19. The relationship between calprotectin levels and DLCO suggests a potential role for calprotectin in persisting lung functional impairment.

Interstitial changes after severe SARS-CoV-2 Infection

Introduction and aim: COVID19 pandemic caused by SARS-CoV-2 is associated with high morbidity and mortality rate worldwide,producing inflammation that can lead to persistent parenchymal lesions. The aim was to analyse the medium-long term evolution of patients with severe COVID19. Method(s): Follow-up of a cohort of 97 COVID19 patients admitted to intensive care unit from March 2020 to June 2021,requiring invasive/non-invasive mechanical ventilation (IMV/NIMV) and/or high-flow nasal cannula (HFNC). They were clinically evaluated in the Interstitial Diseases consult at 4-6 weeks after discharge with spirometry (SP),CO diffusion capacity (DLCO) and thoracic ultrasound (TU);those suggestive of mild interstitial changes (IC) were evaluated at 3 months and moderate-severe ones at 6 months with HRCT,SP and DLCO. Result(s): Mean age was 61+/-15 years (61% male) and hospital stay was 26+/-17 days.93% used HFNC,57% NIMV and 31% IMV. At 4-6 week after discharge assessment showed 45% dyspnea and 33% crackles. SP was normal in 63%,with mild DLCO disorders in 36% and 77% pathological TU. The most frequent abnormality on HRCT was ground glass. After clinical-functional and ultrasound-radiological evaluation at 4-6 weeks after COVID19,37% of cases were discharged,another 2% at 3 months,22% at 6 months and 7% at 12 months. The remaining 32% are still being followed up for persistent IC(6 receiving home oxygen therapy,6 treated with steroids and 4 with antifibrotic). Conclusion(s): Most patients with severe COVID19 infection have after discharge IC with mild clinical-functional impact at 4-6 weeks,although one third have persistent changes after 12 months. Medium to long-term follow-up of postCOVID19 patients is necessary to identify those with permanent abnormalities.

Clinical and functional characteristics of the post-COVID period (6-month follow-up).

Respiratory symptoms and functional disorders are registered in patients who suffered from COVID-19 (COronaVIrus Disease 2019). Aim. Clinical and functional evaluation of the respiratory system during 6-month follow-up in patients who had moderate and severe COVID-19. Methods. 80 patients were included in the cohort observational prospective study. Patients were examined in 46 (36 - 60) days from the onset of symptoms of COVID-19 and in 93 (89 - 103) and 180 (135 - 196) days at the 2nd and 3rd stages respectively. At all stages, symptoms, dyspnea level, and quality of life were analyzed using validated questionnaires, and a 6-minute step test was performed. At the 2nd and 3rd stages, we assessed spirometric parameters, total lung capacity, carbon monoxide diffusing capacity (DLCO), and high resolution computed tomography scans of chest organs. Results. At the 1st stage of the study, 62% of patients complained of fatigue, muscle weakness, 61% of patients had dyspnea of variable severity. At the 3rd stage of the study, 43% and 42% of patients had the same complaints respectively. The prevalence of moderate COVID-19 form in patients with 35 (25 - 45)% lung damage and severe COVID-19 form with 75 (62 - 75)% of lung damage was established. At the 2nd stage, a DLCO < 80% level was recorded in 46% of patients with 35 (25 - 45)% lung damage and in 54% of patients with 75 (62 - 75)%. At the 3rd stage, DLCO < 80% was diagnosed in 51.9% and 48.1% of patients with of 35 (25 - 45)% and 75 (62 - 75)% lung damage respectively. The level of DLCO < 60% was found in 38,5% and 35,5% of patients with moderate and severe lung damage at the 2nd and 3rd stages of the study respectively. Conclusion. The symptoms were reported less frequently during the 6-month follow-up after COVID-19. 77% and 87% of patients had DLCO < 80% in 93 (89 - 103) and 180 (135 - 196) days after the disease onset, respectively. 38.5% and 35.5% of those patients, predominantly having suffered COVID-19 in severe form, had DLCO < 60% at 93 (89 - 103) and 180 (135 - 196) days, respectively. This calls for a continuous observation and regular examinations after COVID-19.Copyright © 2022 Leshchenko I.V., Glushkova T.V.