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.

Association between Type 2 Diabetes Mellitus and Covid-19 Severity: A Literature Review

We conducted a review and evaluated the already documents reports for the relationship among diabetes and COVID-19. The review outcome shows that the COVID-19 severity seems to be greater among patients with diabetes as comorbidity. So, strict glycemic control is imperative in patients infected with COVID-19. Thus, world-wide diabetes burden and COVID-19 pandemic must be deliberated as diabetes increases the COVID-19 severity. Established on this, it is precise significant to follow specific treatment protocols and clinical management in COVID-19 patients affected with diabetes to prevent morbidity and mortality.Copyright © 2023 The Authors.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

Impact of admission viral load on respiratory outcomes in hospitalized SARS-CoV-2 infected patients with cancer and without cancer: A 2-, 4- and 6-months follow-up prospective study.

BACKGROUND: This prospective follow-up study aimed to determine the temporal changes in respiratory outcomes over 6 months period in patients with and without cancer hospitalized for severe COVID-19 and to determine the associated risk factors based on admission viral load. METHODS: All adult patients hospitalized with a confirmed diagnosis of severe SARS-CoV-2 infection were investigated using rRT-PCR on nasopharyngeal swab specimens. Patients were divided into three arbitrary groups according to their cycle threshold (CT) values obtained at admission as high (CT<25.0), medium (CT between 25.0 and 30.0), and low (CT>30.0) viral load. Patients had pulmonary function tests, chest high-resolution computed tomography (HRCT), and a 6-minute walking time distance measured at each follow-up visit. RESULTS: This follow-up study had a total of 112 participants, of which 75 were cancer-free and 37 had active cancer. Overall, 29.5% had a low viral load, compared to 48.2% who had a high viral load, and 22.3% had a medium viral load. For patients who did not have cancer, the mean age was 57.3 (SD 15.4) and for those who had cancer, it was 62.3 (SD 18.4). Most patients had overall better temporal changes in pulmonary function and tolerance, as well as exercise capacity, even though severe and chronic respiratory abnormalities persisted in a fraction of the patients. In patients without cancer who had a high viral load, we have seen a substantial reduction in diffusion capacity of the lungs for carbon monoxide (DLCO) predicted value with a median of 65 (IQR 63-70) while in patients with cancer, it was 60 (IQR 56-67) at 2 months. At 4 and 6 months, the predicted DLCO values for patients without cancer were 65 (IQR 61-70), whereas the predicted DLCO values for patients with active cancer were 62 (IQR 60-67) and 67 (59-73). Importantly, radiological abnormalities persisted in 22 (29%) non-cancer patients and 16 (43%) cancer patients. Multivariate regression analysis showed an increased odds ratio of impaired HRCT associated with a high viral load of 3.04 (95% CI:1.68-6.14; p < 0.001) for patients without cancer and 5.07 (95% CI: 4.04-10.8; p < 0.0001) for patients with cancer. The CT pneumonia score at hospitalization was 2.25 (95% CI:1.76-3.08; p = 0.041) and 2.85 (95% CI:1.89-5.14; p = 0.031) for non-cancer and cancer patients respectively. CONCLUSIONS: The evidence of persistent pulmonary abnormalities and radiographic changes was found in both patient groups who had high viral load at hospital admission and suggesting that SARS-CoV-2 viral load might serve as a useful indicator to predict the development of respiratory complications in patients with COVID-19.

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.

A Case of Ocular Myasthenia Gravis Seen by Rheumatology as Suspected Mononeuritis Multiplex in an Adult Male Shortly after Pfizerbiontech Sars-Cov-2 Vaccination

Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of newonset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARSCOV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link.

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.

Predictors of outcomes in patients hospitalised with COVID-19 pneumonitis

Introduction/Aim: Medium and long-term impacts of COVID-19 pneumonitis are being increasingly recognised. Our study aimed to evaluate outcomes of hospitalised COVID-19 patients with moderate-to-severe respiratory compromise. Method(s): Patients admitted to a tertiary centre with COVID-19 pneumonitis (March 2020-October 2022) were followed in the Post-COVID Respiratory Clinic at 6-24 weeks. Baseline demographics, admission details, pulmonary function tests (PFTs), and clinic data were collected. Univariable and multivariable logistic regression were performed to investigate for predictors of persisting respiratory symptoms (dyspnoea, cough, chest pain) and functional limitation (self-reported). Result(s): 125 patients (64.8%male, 63.2+/-16.7years, 42.5% former/current smokers, BMI 31.0+/-8.0kg/m2, 49.6% fully vaccinated) with median follow-up time of 85 [interquartile range (IQR) 64-131] days were included. Pre-existing conditions included lung disease (29.6%), immunocompromise (15.2%), diabetes (24.8%) and hypertension (43.6%). 35.2% required ICU care (14.4% mechanical ventilated, 4% ECMO), 44.8% received high flow nasal prong oxygen and/or continuous positive airway pressure (CPAP). At initial clinic follow up, 65.4% had persisting X-ray changes. Mean predicted FEV1, FVC, DLCO were 86.8+/-20.7%, 85.3+/-20.3%, 82.2+/-19.8% respectively. Symptoms included dyspnoea (63.2%), fatigue (24.2%), cognitive dysfunction (12.9%) and musculoskeletal complaints (10.5%). Univariate predictors of continued respiratory and/or functional disability included age [odds ratio (OR) 1.03, 95%confidence interval (CI) 1.01-1.06, p = 0.01), prior lung disease (OR2.98, 95%CI 1.05-8.48, p = 0.04), hypertension OR2.61, 95%CI 1.09-6.22, p = 0.03) and length of hospital stay (LOHS) (OR1.03, 95%CI 1.00-1.07, p = 0.04). On multivariable analysis, only LOHS was independently predictive of continued respiratory and functional limitations (OR1.03, 95%CI 1.00-1.07, p = 0.02). Conclusion(s): Patients recovering from COVID-19 pneumonitis have a large burden of disability at follow-up. Older age, hypertension, lung disease and LOHS are risk factors for delayed recovery.

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor therapy: An Italian center experience

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a triple CFTR modulator combination, has proved to be highly effective in Phe508del homozygous and Phe508del/minimal function compound heterozygous people with cystic fibrosis (PwCF).We report preliminary data on the realworld effectiveness and safety of ELX/TEZ/IVA after 6 months of treatment. Method(s):We collected prospective data on PwCF who started ELX/TEZ/IVA and evaluated changes in pulmonary function (spirometry and lung clearance index [LCI]), nutritional status (body mass index [BMI]), sweat chloride, and rate of hospitalization from baseline to 6 months of treatment. Result(s): Between August 2021 and October 2021, ELX/TEZ/IVAwas started in 24 PwCF (12 female,10 Phe508del-homozygous, median age 20.5 (range 13-37), all with pancreatic insufficiency). After 6 months of treatment, all respiratory function indicators improved (median change: +16% percentage predicted forced expiratory volume in 1 second, +12% percentage predicted forced vital capacity, +23% percentage predicted forced expiratory flow at 25/75%, -2 lung clearance index). Improvement was also observed in BMI (+0.41 z-score) and sweat chloride concentrations (-54 mMol/L, 6 PwCF had Cl concentrations within the limit of normality) (Table 1). Over a 6-month period, only one hospitalization due to pulmonary exacerbations was observed, compared with 22 hospitalizations observed in the 6 months before starting ELX/TEZ/IVA (rate per 100 patient-months 15.3 vs 0.7, rate ratio 0.05, 95% CI, 0.01-0.29). Treatment was well tolerated, with only mild and transient adverse events consisting of headache (n = 4), cutaneous rash (n = 2), and mild hemoptysis (n = 2). One PwCF had intestinal subocclusion and required hospitalization. One patient had liver function test elevation after 6 months of therapy during an Changes in clinical variables and sweat test results from baseline through 6 months in patients treated with elexacaftor, tezacaftor and ivacaftor. Data are medians (interquartile ranges). Baseline vs 6 months compared usingWilcoxon signed-rank test. ppFEV1, percentage predicted forced expiratory volume in 1 second;ppFVC, percentage predicted forced vital capacity;ppFEV25/75, percentage predicted forced expiratory flow at 25/75%;LCI, lung clearance index;BMI, body mass index;Cl, chloride. (Table Presented) episode of SARS-COV2 infection, which required adjustment of the dose administered. Conclusion(s): Our data confirm that ELX/TEZ/IVA treatment is safe, well tolerated, and effective in PwCF. ELX/TEZ/IVA improved pulmonary function and nutritional status and remarkably reduced hospitalization rate. Our data indicate that introduction of ELX/TEZ/IVA in CF care will radically change the natural history of and management approach to the disease.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

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 sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Virtual spirometry training is comparable to face-to-face training learning outcomes

Introduction: In response to COVID-19 restrictions, the Queensland Health Spirometry Training Program initiated virtual (V) workshops, as an alternative to face-to-face (F2F) training. The program included online pre-reading, a practical skills workshop (V or F2F), and a post-workshop workplace portfolio assessment. The aims of this study were to compare F2F and virtual training (1) portfolio assessment outcomes, and (2) post-workshop confidence with spirometry practice. Method(s): (1) Between 2019 and 2022, health practitioners (HP) who attended F2F or virtual workshops submitted a post-workshop workplace portfolio. The portfolio spirometry reports were assessed against the ATS/ERS spirometry standards (Graham et al., 2019). Three spirometry trials in each report were scored for acceptability criteria: fast start of test (SOT 1), start of test sharp peak (SOT 2), middle of test (MOT) and end of forced expiration (EOFE). Repeatability criteria (FEV 1 and FVC), technical comments and interpretation were also assessed. Mean scores for each criterion were compared between F2F and virtual workshop portfolio tests, using univariable linear regression analysis. (2) After F2F or virtual training, participants rated their confidence levels with spirometry performance, understanding the test, and quality assurance, using a 5-point Likert scale (very confident to not confident). Result(s): 138 HPs attended either F2F or virtual workshops and 62 portfolios were assessed. There were no significant differences (all p values >0.05) in the portfolio scores between F2F (n = 30) and virtual (n = 32) training for spirometry acceptability, repeatability, and reporting criteria. Post-workshop confidence levels with spirometry performance, understanding the test, and quality assurance were not significantly different (all p values >0.05) between the two training formats (n = 138). Comparison of scores between F2F (n = 30) versus V (n = 32) Scoring criteria Maximal score Mean difference 95% CI p value Acceptability SOT 1 3 0.014 -0.130 0.158 0.848 SOT 2 3 -0.023 -0.169 0.124 0.758 MOT 3 -0.024 -0.162 0.114 0.731 EOFE 3 0.053 -0.038 0.143 0.250 Repeatability FEV 1 1 0.039 -0.009 0.087 0.111 FVC 1 0.024 -0.035 0.084 0.421 Reporting Comments 2 0.019 -0.175 0.213 0.846 Interpretation 1 0.059 -0.009 0.127 0.087 Conclusion(s): This study provides confidence that the virtual spirometry training did not significantly impact learning outcomes compared with the F2F format.

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. .

Ultrasonic personal spirometer appears accurate and feasible for remote monitoring

Introduction/Aim: Home spirometry may improve respiratory disease monitoring and management and mitigate the decline in testing exacerbated by COVID-19. Smartphone-connected spirometers could allow patients to conduct spirometry independently without the need to travel to lung function clinics. This study assessed the accuracy of a personal spirometer and the feasibility of unsupervised home spirometry. Method(s): Subjects (19-88 years) with (n = 44) and without (n = 20) respiratory disease, were recruited and supervised to perform spirometry on a standard desktop spirometer (MGC Diagnostics) and a personal ultrasonic spirometer (SpiroHome) in the clinical laboratory. Unsupervised testing was subsequently conducted using the SpiroHome at the subjects' home (2 tests/week for 3 weeks). Subjects returned to the clinic to conduct an exit survey which assessed their willingness to adopt a personal spirometer into their long-term care plan. Comparisons between desktop and personal spirometry, as well as supervised and unsupervised spirometry, were compared by Bland-Altman analysis (%Bias +/- CI) and Pearson's correlation. Result(s): The proportion of tests meeting American Thoracic Society/European Respiratory Society criteria (80%) remained constant across clinic and home spirometry sessions for subjects who completed 3 weeks of home testing (p = 0.73, Fisher's exact test, n = 61). Supervised spirometry on the SpiroHome (n = 56) reliably measured FEV 1 (-3.12+/-27.01%;r=0.98, p < 0.0001) and FVC (-0.38+/-22.91%;r=0.99, p < 0.0001) producing a small underestimation compared to desktop spirometry. Unsupervised home spirometry (when performed <24 hrs from the clinic appointment) on the SpiroHome (n = 51) produced a small underestimation of FEV 1 (-2.41+/-35.57%;r=0.96, p < 0.0001) and a slight overestimation of FVC (0.08+/-24.70%;r=0.98, p < 0.0001) compared with supervised manoeuvres in the clinical laboratory. Conclusion(s): Findings indicate that lung function assessed by SpiroHome compares well with in-clinic standard desktop spirometry across a range of diseases and severities in both the clinic and home settings. A larger cohort of subjects are being recruited to confirm the accuracy and the overall utility of personal spirometry.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

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.

Comparing the Effects of Endurance and Resistance Training Programs on some Pulmonary, Functional, and Quality of Life Indicators in Patients with COVID-19 Discharged from Hospital.

Background and purpose: The present study investigated the effect of six weeks of endurance and resistance training on pulmonary indices, physical performance, and quality of life in COVID-19 patients after discharge from hospital. Materials and methods: Thirty six patients with COVID-19 (mean age: 38.76±0.98 years, mean weight: 81.86±2.88 kg) were selected. At the beginning and end of the study, pulmonary (FEV1, FVC, FEV1/FVC, and MVV), physical (6-minute walk test), quality of life (SF-36), and anthropometry tests were performed. The patients were divided into three groups: Endurance training (45 minutes at 60-75% estimated HR), Resistance training (45 minutes at 40-70% of I-RM), and controls. The intervention was conducted for 6 weeks (3 sessions). One-way ANOVA test was used for statistical analysis. Results: Findings indicated a significant increase in FEV1 (P=0.029), FVC (P=0.047), FEV1/FVC (P=0.043) in the endurance training group compared to the control group, while difference was observed in MVV (P=0.041) and FEV1/FVC (P=0.022) between endurance training and resistance training groups. The 6-minute test distance increased in the endurance training (P=0.0001) and resistance training (P=0.001) groups compared to the control group, but no difference was observed between the training groups (P=0.48). Endurance and resistance training programs induced significant improvements in physical performance (P=0.024 and P=0.09, respectively) and general health (P=0.022 and P=0.015, respectively) dimensions compared to the control group. Conclusion: Moderate-intensity endurance training can improve pulmonary function, physical performance, and quality of life in patients with COVID-19 after discharge from hospital and can be used in rehabilitation programs of these patients. [ FROM AUTHOR] Copyright of Journal of Mazandaran University of Medical Sciences (JMUMS) is the property of Mazandaran University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The role of spirometry in the management of post-COVID respiratory symptoms

Background: The COVID-19 pandemic is considered as a major challenge of the 21st century medicine around the world. Prolonged post-COVID symptoms of the respiratory system remain a topical issue: dry annoying cough, respiratory failure, and discomfort in the lung projection area. Thus, in COVID-infected patients, the assessment of respiratory system functional state with postcoid respiratory symptoms is undoubtedly important that is the aim of our study. Method(s): To achieve this aim, 56 patients (18 to 65 years of age, 33-females, 23-males) with post-COVID respiratory symptoms who referred to the Scientific Research Institute of Allergology, Asthma and Clinical Immunology (Tskaltubo, Georgia) for further diagnosis and treatment were involved in the study. Result(s): Respiratory status: external respiratory functioning status and spirometry features were assessed using computer spirometry -Spirolab 3. Analysis of the results showed that in the above patients, defects in forced expiratory time (FET < 6 min) were observed. According to the basic parameters of spirometry, the slight changes in FEV1;FVC FEV1/VC (Tiffeneau-Pinelli index) were revealed;Only 6 (10%) patients showed a mild obstruction, 4 of irreversible type and only 2 patients had reversible broncho-obstruction. In addition, mild restriction was determined in only 5 (9%) patients. Restrictive changes were detected in patients with a history of severe course of COVID infection and CT severity scores 12-21. Significant changes were observed in the PEF-peak expiratory flow rate in 35 (61%) patients the PEF index was reliably lower, by 70% or more, compared to the norm. Conclusion(s): Obstruction of medium and small bronchus was also reported in the majority of patients. MEF50%, MEF25% indicators were reliably reduced, undoubtedly indicating the importance of COVID 19 infection in the development and course of respiratory symptoms. The study reaffirmed the need for spirometry in the management and monitoring of COVID infection. Information on changes in spirometry parameters in COVID patients and patients with post-COVID respiratory symptoms is still scarce, however, the study in this area is undoubtedly promising.

Cardiopulmonary long-term effects in patients after hospitalization due to COVID-19 infection

Background: Multiple studies have described acute effects of the Covid-19 infection on the heart, but little is known about the long-term cardiac and pulmonary effects and complications after recovery. The aim of this analysis was to deliver a comprehensive report of symptoms and possible long-term impairments after hospitalization because of Covid-19 infection as well as to try to identify predictors for Long-Covid. Method(s): This was a prospective, multicenter registry study. Patients with verified Covid-19 infection, who were treated as in-patients at our dedicated Covid hospital (Clinic Favoriten), have been included in this study. In all patients, testing was performed approximately 6 months post discharge. During the study visit the following tests and investigations were performed: Detailed patient history and clinical examination, transthoracic echocardiography, electrocardiography, cardiac magnetic resonance imaging (MRI), chest computed tomography (CT) scan, lung function test and a comprehensive list of laboratory parameters including cardiac bio markers. Result(s): Between July 2020 and October 2021, 150 patients were recruited. Sixty patients (40%) were female and the average age was 53.5+/-14.5 years. Of all patients, 92% had been admitted to our general ward and 8% had a severe course of disease, requiring admission to our intensive care unit. Six months after discharge the majority of patients still experienced symptoms and 75% fulfilled the criteria for Long-Covid. Only 24% were completely asymptomatic (figure 1). Echocardiography detected reduced global longitudinal strain (GLS) in 11%. Cardiac MRI revealed pericardial effusion in 18%. Furthermore, cardiac MRI showed signs of former peri-or myocarditis in 4%. Pulmonary CT scans identified post-infectious residues, such as bilateral ground glass opacities and fibrosis in 22%. Exertional dyspnea was associated with either reduced forced vital capacity measured during pulmonary function tests in 11%, with reduced GLS and/or diastolic dysfunction, thus providing evidence for a cardiac and/or pulmonary cause. Independent predictors for Long-Covid were markers of a more severe disease course like length of in-hospital stay, admission to an intensive care unit, type of ventilation as well as higher NT-proBNP and/or troponin levels. Conclusion(s): Even 6 months after recovery from Covid-19 infection, the majority of previously hospitalized patients still suffer from at least one symptom, such as chronic fatigue and/or exertional dyspnea. While there was no association between fatigue and cardiopulmonary abnormalities, impaired lung function, reduced GLS and/or diastolic dysfunction were significantly more prevalent in patients presenting with exertional dyspnea. On chest CT approximately one fifth of all patients showed post infectious changes in chest CT including evidence for myo-and pericarditis as well as accumulation of pericardial effusions.

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.