Long-term pulmonary sequelae in adolescents post-SARS-CoV-2 infection.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes long-term pulmonary sequelae in adults, but little is known about pulmonary outcomes in pediatrics. OBJECTIVE(S): The aim of this study was to describe long-term subjective and objective pulmonary abnormalities after SARS-CoV-2 infection in pediatric populations. METHODS: Single-center, retrospective cohort of patients seen in post-coronavirus disease 2019 (COVID-19) pulmonary clinic in 2021. Subjects evaluated had persistent pulmonary symptoms 4 weeks or more after initial infection. Clinical testing included a 6-min walk test (6MWT), chest X-ray, pre- and postbronchodilator spirometry, plethysmography, and diffusion capacity. Patients were followed 2-to-3-months after the initial visit with repeat testing. The primary outcome was the presence of abnormal pulmonary function testing. Secondary measures included variables associated with pulmonary outcomes. RESULTS: Eighty-two adolescents were seen at a median of 3.5 months postinfection, with approximately 80% reporting two or more symptoms at clinic presentation (cough, chest pain, dyspnea at rest, and exertional dyspnea). At follow-up (~6.5 months) exertional dyspnea persisted for most (67%). Spirometry was normal in 77% of patients, but 31% had a positive bronchodilator response. No abnormalities were noted on plethysmography or diffusion capacity. Clinical phenotypes identified included inhaled corticosteroid responsiveness, paradoxical vocal fold motion disorder, deconditioning, and dysautonomia. Multivariable modeling demonstrated that obesity, anxiety, and resting dyspnea were associated with reduced 6MWT, while female sex and resting dyspnea were associated with higher Borg Dyspnea and Fatigues scores. CONCLUSIONS: This is the largest study to date of pediatric patients with long-term pulmonary sequelae post-COVID-19. Identified clinical phenotypes and risk factors warrant further study and treatment.

Characteristics, risk factors, and outcomes associated with readmission in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: We aimed to determine the characteristics, risk factors, and outcomes associated with readmission in COVID-19 patients. METHODS: PubMed, Embase, Web of Science, and Scopus databases were searched to retrieve articles on readmitted COVID-19 patients, available up to September 25, 2021. All studies comparing characteristics of readmitted and non-readmitted COVID-19 patients were included. We also included articles reporting the reasons for readmission in COVID-19 patients. Data were pooled and meta-analyzed using random or fixed-effect models, as appropriate. Subgroup analyses were conducted based on the place and duration of readmission. RESULTS: Our meta-analysis included 4823 readmitted and 63,413 non-readmitted COVID-19 patients. The re-hospitalization rate was calculated at 9.3% with 95% Confidence Interval (CI) [5.5%-15.4%], mostly associated with respiratory or cardiac complications (48% and 14%, respectively). Comorbidities including cerebrovascular disease (Odds Ratio (OR) = 1.812; 95% CI [1.547-2.121]), cardiovascular (2.173 [1.545-3.057]), hypertension (1.608 [1.319-1.960]), ischemic heart disease (1.998 [1.495-2.670]), heart failure (2.556 [1.980-3.300]), diabetes (1.588 [1.443-1.747]), cancer (1.817 [1.526-2.162]), kidney disease (2.083 [1.498-2.897]), chronic pulmonary disease (1.601 [1.438-1.783]), as well as older age (1.525 [1.175-1.978]), male sex (1.155 [1.041-1.282]), and white race (1.263 [1.044-1.528]) were significantly associated with higher readmission rates (P < 0.05 for all instances). The mortality rate was significantly lower in readmitted patients (OR = 0.530 [0.329-0.855], P = 0.009). CONCLUSIONS: Male sex, white race, comorbidities, and older age were associated with a higher risk of readmission among previously admitted COVID-19 patients. These factors can help clinicians and policy-makers predict, and conceivably reduce the risk of readmission in COVID-19 patients.

Statistical analysis of the Hungarian COVID-19 victims.

With the wide spread of Coronavirus, most people who infected with the COVID-19, will recover without requiring special treatment. Whereas, elders and those with underlying medical problems are more likely to have serious illnesses, even be threatened with death. Many more disciplines try to find solutions and drive master plan to this global trouble. Consequently, by taking one particular population, Hungary, this study aims to explore a pattern of COVID-19 victims, who suffered from some underlying conditions. Age, gender, and underlying medical problems form the structure of the clustering. K-Means and two step clustering methods were applied for age-based and age-independent analysis. Grouping of the deaths in the form of two different scenarios may highlight some concepts of this deadly disease for public health professionals. Our result for clustering can forecast similar cases which are assigned to any cluster that it will be a serious cautious for the population.

Pathological Features in 100 Deceased Patients With COVID-19 in Correlation With Clinical and Laboratory Data.

Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 post-mortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.

Tobacco use disorder and the lungs.

This narrative review provides a summary of the impact of tobacco smoking on the respiratory system and the benefits of smoking cessation. Tobacco smoking is one of the leading preventable causes of death world-wide and a major risk factor for lung cancer and chronic obstructive pulmonary disease. Smoking is also associated with an increased risk of respiratory infections and appears to be related to poorer outcomes among those with COVID-19. Non-smokers with second-hand smoke exposure also experience significant adverse respiratory effects. Smoking imposes enormous health- and non-health-related costs to societies. The benefits of smoking cessation, in both prevention and management of respiratory disease, have been known for decades and, to this day, cessation support remains one of the most important cost-effective interventions that health professionals can provide to people who smoke. Cessation at any age confers substantial health benefits, even in smokers with established morbidities. As other treatments for chronic respiratory disease advance and survival rates increase, smoking cessation treatment will become even more relevant. While smoking cessation interventions are available, the offer of these by clinicians and uptake by patients remain limited.

Risk Factors for Death Among 120,804 Hospitalized Patients with Confirmed COVID-19 in São Paulo, Brazil.

São Paulo is a state in Brazil with one of the highest numbers of confirmed and severe cases of coronavirus disease (COVID-19), with an incidence of 294 hospitalizations per 100,000 inhabitants. We report the clinical characteristics and outcomes of 120,804 hospitalized patients with confirmed COVID-19 from February 26 to October 10, 2020, in São Paulo. Characteristics of patients who died and survived were compared using a survival analysis. The median age was 60 years (interquartile range [IQR], 47-72), 67,821 (56.1%) were men, and 61,659 (51.0%) were white. Most hospitalized patients (79,812; 66.1%) reported one or more comorbidities, 41,708 (34.5%) hospitalized patients were admitted to intensive care units, and 33,079 (27.4%) died. Men (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.18-1.25), elderly individuals (HR, 3.85; 95% CI, 3.68-4.02), and patients with chronic cardiovascular disease including hypertension (HR, 1.05; 95% CI, 1.02-1.08), chronic lung disease (HR, 1.38; 95% CI, 1.31-1.45), diabetes mellitus (HR, 1.14; 95% CI, 1.11-1.18), and chronic neurological disease (HR, 1.48; 95% CI, 1.41-1.55) were at higher risk for death from COVID-19.

Nuclear factor-kappa B and its role in inflammatory lung disease.

Nuclear factor-kappa B, involved in inflammation, host immune response, cell adhesion, growth signals, cell proliferation, cell differentiation, and apoptosis defense, is a dimeric transcription factor. Inflammation is a key component of many common respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and acute respiratory distress syndrome. Many basic transcription factors are found in NF-κB signaling, which is a member of the Rel protein family. Five members of this family c-REL, NF-κB2 (p100/p52), RelA (p65), NF-κB1 (p105/p50), RelB, and RelA (p65) produce 5 transcriptionally active molecules. Proinflammatory cytokines, T lymphocyte, and B lymphocyte cell mitogens, lipopolysaccharides, bacteria, viral proteins, viruses, double-stranded RNA, oxidative stress, physical exertion, various chemotherapeutics are the stimulus responsible for NF-κB activation. NF-κB act as a principal component for several common respiratory illnesses, such as asthma, lung cancer, pulmonary fibrosis, COPD as well as infectious diseases like pneumonia, tuberculosis, COVID-19. Inflammatory lung disease, especially COVID-19, can make NF-κB a key target for drug production.

Validation of the Withings ScanWatch as a Wrist-Worn Reflective Pulse Oximeter: Prospective Interventional Clinical Study.

BACKGROUND: A decrease in the level of pulse oxygen saturation as measured by pulse oximetry (SpO2) is an indicator of hypoxemia that may occur in various respiratory diseases, such as chronic obstructive pulmonary disease (COPD), sleep apnea syndrome, and COVID-19. Currently, no mass-market wrist-worn SpO2 monitor meets the medical standards for pulse oximeters. OBJECTIVE: The main objective of this monocentric and prospective clinical study with single-blind analysis was to test and validate the accuracy of the reflective pulse oximeter function of the Withings ScanWatch to measure SpO2 levels at different stages of hypoxia. The secondary objective was to confirm the safety of this device when used as intended. METHODS: To achieve these objectives, we included 14 healthy participants aged 23-39 years in the study, and we induced several stable plateaus of arterial oxygen saturation (SaO2) ranging from 100%-70% to mimic nonhypoxic conditions and then mild, moderate, and severe hypoxic conditions. We measured the SpO2 level with a Withings ScanWatch on each participant's wrist and the SaO2 from blood samples with a co-oximeter, the ABL90 hemoximeter (Radiometer Medical ApS). RESULTS: After removal of the inconclusive measurements, we obtained 275 and 244 conclusive measurements with the two ScanWatches on the participants' right and left wrists, respectively, evenly distributed among the 3 predetermined SpO2 groups: SpO2≤80%, 80%

How to Manage COVID-19 Vaccination in Immune-Mediated Inflammatory Diseases: An Expert Opinion by IMIDs Study Group.

Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.

TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2.

Introduction: The COVID-19 pandemic remains aglobal challenge. While there are mRNA agents on the horizon as apotential prevention, adefinitive drug therapy is an unmet medical need. The hyperinflammatory response, known as the 'cytokine storm', is chiefly responsible for complications and deaths. The binding of spike-glycoprotein of SARS-CoV-2 to TLR4 receptors has been documented in several studies and has been found to play arole in hyperinflammation; hence, there is an interest in TLR4 as apotential drug target.Areas covered: This review discusses the neurological and respiratory complications of SARS-CoV-2 infection and progresses to examine the role of the 'cytokine storm' and the involvement of TLR4 receptors in these complications. The possibility of using TLR4 modulators to curb the complications are considered and finally, ashort perspective on future potential drug treatments is offered. Various databases were searched including Pub-Med, Google Scholar, and Medline. The search mainly included research articles, meta-analysis, retrospective studies, reports, and systematic reviews.Expert opinion: TLR4 modulators are being investigated in clinical trials for COVID-19. Challenges in terms of structural diversity of the agents, their natural origin, and efficacy demand extensive research.

COVID-19 and Acute Cervical Spinal Cord Injury-Case Report of 2 Patients: Do We Need to Rethink Our Standard Treatment Strategy?

STUDY DESIGN: This was a case series. OBJECTIVE: The authors sought to examine the high-risk population of COVID-positive patients with acute cervical spinal cord injury (SCI) in a large level 1 trauma and tertiary referral center. SUMMARY OF BACKGROUND DATA: There are limited studies regarding the surgical management of patients with acute SCI in the setting of the recent coronavirus pandemic. METHODS: The authors describe the cases of 2 patients who died from COVID-related complications after acute cervical SCI. RESULTS: Patients with SCI are at increased risk of pulmonary complications. COVID-19 infection represents a double hit in this patient population, increasing potential morbidity and mortality in the perioperative time frame. Careful consideration must be made regarding the timing of potential surgical intervention in the treatment of acute SCI. CONCLUSIONS: Nationwide database of COVID-positive patients with acute spinal cord injury should be collected and analyzed to better understand how to manage acute SCI in the COVID-19 era. The authors recommend preoperative discussion in patients with acute cervical SCI with COVID-19, specifically emphasizing the increased risk of respiratory complications and mortality.

Association of alpha-1-antitrypsin deficiency with vitamin D status: who is most at risk of getting severe COVID-19?

INTRODUCTION: Coronavirus disease 2019 (COVID-19), a new disease that we do not know yet how to treat, is rapidly evolving and has forced us to stay indoors. Surprisingly, a broad range of symptoms has been reported since COVID-19 emergence. Individual variations in susceptibility to SARS-CoV-2 can be due to non-genetic and genetic factors. Alpha-1-antitrypsin deficiency (AATD) is an inherited condition that is associated with an increased risk of liver and lung diseases which may increase susceptibility to COVID-19 infection. At the same time, there could be a possibility of developing non-hereditary AATD. DISCUSSION: In addition to some evidence showing the role of vitamin D deficiency in COVID-19 pathology, it has been recognized that there is a biological link between AAT and vitamin D. Therefore, here we offer a new perspective that lower vitamin D levels in COVID-19 patients can cause acquired AATD that provide a condition with more disease severity and a higher risk of death. As a consequence, COVID-19 individuals with vitamin D deficiency may have a higher risk of morbidity and mortality. CONCLUSION: Therefore, early vitamin D and AAT assessments and optimal interventions could be helpful to prevent severe COVID-19 outcomes.

Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome.

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.

A Systematic Review and Meta-Analysis of Cancer Patients Affected by a Novel Coronavirus.

BACKGROUND: Cancer patients with coronavirus disease 2019 (COVID-19) have been reported to have double the case fatality rate of the general population. METHODS: A systematic search of PubMed, Embase, and Cochrane Central was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio (OR) and forest plots (random-effects model) were constructed for both primary and secondary outcomes. RESULTS: This systematic review of 38 studies and meta-analysis of 181 323 patients from 26 studies included 23 736 cancer patients. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (n = 165 980, OR = 2.54, 95% confidence interval [CI] = 1.47 to 4.42), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated. Among cancer subtypes, the mortality was highest in hematological malignancies (n = 878, OR = 2.39, 95% CI = 1.17 to 4.87) followed by lung cancer (n = 646, OR = 1.83, 95% CI = 1.00 to 3.37). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of comorbidities. There was insufficient data to assess the association of COVID-19-directed therapy and survival outcomes in cancer patients. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.

[Group Training of Patients with Chronic Lung Diseases under Outpatient Conditions - Recommendations of the Working Group Lung Sports in Germany and the German Airways League]. / Ambulanter Lungensport und körperliches Training bei Patienten mit Atemwegs- und Lungenkrankheiten.

To improve acceptance and use of physical training by patients with chronic lung diseases, recommendations for performing lung exercises on an outpatient basis in a group setting are given by experts in physical training, sports therapists and pulmonologists. The evidence-based positive effects of physical training were analyzed for asthma , COPD, interstitial lung diseases, cystic fibrosis, lung carcinoma, and pulmonary hypertension. The requirements for lung exercises in outpatient groups as well as compensation by care providers were given on the basis of legal regulations. Furthermore, the main items of the training units as well as supervision by specially trained group leaders in relation to the severity of the underlying lung disease are described. Finally, aspects of safety of the participating patients are discussed, including the prevention of infection with corona-2-virus.

Looking beyond pulmonary disease in COVID-19: A lesson from patients with cystic fibrosis.

Coronavirus disease 2019 (COVID-19) caused more than 52.775.271 million confirmed cases, 1.293.106 deaths, globally, and afflicted 208 countries, areas, or territories; and almost three months have passed since the World Health Organisation (WHO) declared COVID-19 as a pandemic. Despite the dramatic and global impact of the Coronavirus, the knowledge about the SARS-CoV-2 infection has been improved remarkably. Herein, we provided the rationale for SARS-CoV-2 infection as endothelial dysfunction rather than respiratory disease. Accordingly, we strongly invited the researchers to look beyond pulmonary injury and shift their attention from respiratory disease to endothelial disorder. This strategy could be particularly relevant to identifying therapeutic weapons stabilizing the endothelium rather than the lungs.

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020) : Statement of the Austrian Society of Pneumology (ASP).

The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV­2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.