Delta Variant in the COVID-19 Pandemic: A Comparative Study on Clinical Outcomes Based on Vaccination Status.

BACKGROUND: As the global battle against the COVID-19 pandemic endures, the spread of the Delta variant has introduced nuanced challenges, prompting a nuanced examination. MATERIALS AND METHODS: We performed a multilevel logistic regression analysis encompassing 197 patients, comprising 44 vaccinated individuals (V group) and 153 unvaccinated counterparts (UV). These patients, afflicted with the Delta variant of SARS-CoV-2, were hospitalized between October 2021 and February 2022 at the COVID-19 department of a University Centre in Cluj-Napoca, Romania. We compared patient characteristics, CT lung involvement, Padua score, oxygen saturation (O2 saturation), ventilation requirements, dynamics of arterial blood gas (ABG) parameters, ICU admission rates, and mortality rates between the two groups. RESULTS: The UV group exhibited a statistically significant (p < 0.05) proclivity toward developing a more severe form of infection, marked by elevated rates of lung involvement, oxygen requirement, ICU admission, and mortality. CONCLUSION: Our findings underscore the substantial efficacy of the vaccine in diminishing the incidence of severe disease, lowering the rates of ICU admissions, and mitigating mortality among hospitalized patients.

Laboratory Diagnostics Accuracy for COVID-19 versus Post-COVID-19 Syndrome in Lung Disease Patients with Multimorbidity.

The laboratory tests and identification of risk factors such as comorbidities are essential in the management, treatment and prognosis of patients with chronic respiratory diseases. Performing rigorous monitoring among patients with post-COVID-19 syndrome and early identification of risk factors associated with poor prognosis are crucial in improving patient outcomes. In the present study, 182 patients diagnosed with COVID-19 and PCI during 2020-2022 were included. A clinical and epidemiological evaluation was performed for each patient. Laboratory tests at admission included complete blood count, Erythrocyte Sedimentation Rate (ESR) and biochemical tests. Receiver operating curve (ROC) and area under the curve (AUC) were calculated to compare the diagnostic performance of each parameter. Regarding comorbidities, arterial hypertension, diabetes mellitus and obesity were the most frequent ones. In the case of chronic lung diseases, asthma and Chronic Obstructive Pulmonary Disease (COPD) were the most frequent. Pleurisy was found especially in patients with PCI Variations in serum LDH values were observed, especially in severe forms of COVID-19 in 2020, with a mean value of 481.44 U/L, compared to patients with PCI, whose mean values (122 U/L) were within the biological range of reference. High neutrophil/lymphocyte ratio (NLR) values quantified in this study were especially associated with moderate and severe forms of COVID-19 and also PCI. The Spearman correlation coefficient was determined to measure the correlations between the clinical parameters of all investigated subjects. A value of p < 0.05 was considered statistically significant. The statistical results indicated that serum lactate dehydrogenase (LDH), glucose and C-reactive protein (CRP) are sensitive markers with a diagnostic role in COVID-19, and lymphocyte (Ly) count, CRP, ESR and glucose were evidenced to be target markers in PCI. LDH values were observed to be statistically significant (p < 0.005) in patients with COVID-19 and obesity evaluated in 2021, while Ly count was statistically significant (p = 0.05) in patients with PCI and arterial hypertension. Regarding comorbidities, it has been observed that obesity, arterial hypertension and cardiovascular diseases represent risk factors in COVID-19/PCI, associated especially with the severe forms of the disease.

Non-Pharmacological Intervention for Personalizing Sleep Quality through Gentle Rocking Motion.

INTRODUCTION: Achieving restorative sleep is crucial for overall well-being, yet sleep difficulties affect a substantial portion of the adult population. Sleep disturbances are associated with diminished quality of life, physical complaints, cognitive impairment, and emotional regulation challenges. OBJECTIVE: This study explores the influence of an innovative experimental bed designed to generate rocking motions on sleep parameters. METHODS: A prospective observational study enrolled 60 adult participants, assessing their sleep on a regular stationary bed and the Inoveris bed, providing gentle rocking movements. Polysomnography was conducted, recording electroencephalography, electrooculogram, electromyogram, respiratory effort, and other parameters. RESULTS: The rocking bed significantly increased total sleep time (TST) and reduced N1 sleep stage duration (p < 0.001). Participants also experienced a quicker transition to the N2 sleep stage (p = 0.01), indicative of a faster shift from wakefulness to deeper sleep. Additionally, rocking led to a higher percentage of N1 sleep stages (p = 0.01) and a significant increase in N3 sleep stage duration (p = 0.004). While some results lacked statistical significance, notable trends in the rocking bed group have clinical relevance, consistently improving sleep parameters, including increased TST. The rocking bed also showed a trend towards higher sleep efficiency (SE) and sleep duration percentage, hinting at a potential overall enhancement in sleep quality. CONCLUSION: This study contributes valuable insights into the potential benefits of rocking motions on sleep architecture. Despite variations in outcomes across studies, our results underscore the potential of rocking beds as a non-pharmacological intervention for enhancing sleep quality. Notable improvements in total sleep time (TST), N1 sleep stage reduction, and accelerated transitions to deeper sleep stages highlight the clinical relevance of rocking interventions. Further research, collaboration, and addressing the identified limitations will advance our understanding of the therapeutic applications of rocking motions in sleep science.

Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review.

Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking's role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords 'smoking', 'long COVID', and 'post-acute COVID' to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID.

Speaking of the "Devil": Diagnostic Errors in Interstitial Lung Diseases.

Interstitial lung diseases are respiratory diseases, which affect the normal lung parenchyma and can lead to significant pulmonary fibrosis, chronic respiratory failure, pulmonary hypertension, and ultimately death. Reuniting more than 200 entities, interstitial lung diseases pose a significant challenge to the clinician, as they represent rare diseases with vague and insidious respiratory symptoms. As such, there are many diagnostic errors that can appear along the journey of the patient with ILD, which leads to significant delays with implications for the prognosis and the quality of life of the patient.

Exploring the Role of Biomarkers Associated with Alveolar Damage and Dysfunction in Idiopathic Pulmonary Fibrosis-A Systematic Review.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases (ILDs), marked by an ongoing, chronic fibrotic process within the lung tissue. IPF leads to an irreversible deterioration of lung function, ultimately resulting in an increased mortality rate. Therefore, the focus has shifted towards the biomarkers that might contribute to the early diagnosis, risk assessment, prognosis, and tracking of the treatment progress, including those associated with epithelial injury. METHODS: We conducted this review through a systematic search of the relevant literature using established databases such as PubMed, Scopus, and Web of Science. Selected articles were assessed, with data extracted and synthesized to provide an overview of the current understanding of the existing biomarkers for IPF. RESULTS: Signs of epithelial cell damage hold promise as relevant biomarkers for IPF, consequently offering valuable support in its clinical care. Their global and standardized utilization remains limited due to a lack of comprehensive information of their implications in IPF. CONCLUSIONS: Recognizing the aggressive nature of IPF among interstitial lung diseases and its profound impact on lung function and mortality, the exploration of biomarkers becomes pivotal for early diagnosis, risk assessment, prognostic evaluation, and therapy monitoring.

A Debate on Surgical and Nonsurgical Approaches for Obstructive Sleep Apnea: A Comprehensive Review.

Regular and unobstructed breathing during the night is the prerequisite for an undisturbed and restful sleep. The most prevalent nocturnal breathing disturbance with morbid consequences is obstructive sleep apnea syndrome. The prevalence of obstructive sleep apnea (OSA) is increasing, and a significant number of patients with OSA are undiagnosed. On the other hand, the "obesity epidemic" is a growing concern globally. A sleep test is required to diagnose sleep apnea and to individualize therapy. A multidisciplinary approach is the key to success. This narrative review presents a debate on whether surgery is a friend or a foe in the treatment of sleep apnea. Depending on the type and severity of the apnea, the causal factor, and the presence of obesity and hypercapnia as well as the associated pathologies, the optimal therapeutic method is determined for each individual case. The article concludes that each case is unique, and there is no ideal method. Positive pressure ventilation, although a therapeutic gold standard, has its disadvantages extensively discussed in this paper. Nevertheless, it is necessary prior to any surgical intervention, either for the curative treatment of the causal factor of apnea or for elective surgery for another condition. The anesthetic risks associated with the presence of apnea and obesity should not be neglected and should form the basis for decision making regarding surgical interventions for the treatment of sleep apnea.

HPLC Analysis and Risk Assessment of 15 Priority PAHs in Human Blood Serum of COPD Patient from Urban and Rural Areas, Iasi (Romania).

One of the leading risk factors for environmental health problems is air pollution. The World Health Organization (WHO) reports that this risk factor is associated with one of every nine deaths worldwide. Epidemiological studies conducted in this field have shown a solid connection between respiratory pathology and polycyclic aromatic hydrocarbon (PAH) exposure. COPD and asthma are respiratory diseases that were shown to have a strong association with exposure to PAHs. The purpose of the present study was to assess the serum levels of 15 PAHs in 102 COPD patients and to evaluate the results according to the residence environment of the investigated subjects. Analyses were carried out using a high-performance liquid chromatograph Nexera X2-Shimadzu Japan, which was equipped with an LC-30AD pump and an SIL-30AC autosampler. Spiked matrices, procedure blanks, spiked controls, and calibration standards in the acetonitrile were used as quality-assurance samples. Benzo(a)pyrene is the main representative of PAHs and was determined in higher concentrations in subjects with COPD versus the control group from the urban area (0.90/0.47 ng/mL) and rural area (0.73/0.44 ng/mL). The values obtained for the Benzo(a)pyrene-equivalent factor indicate a higher carcinogenic potential for patients diagnosed with COPD in urban areas compared to those in rural areas. These results could be due to traffic and vehicle emissions. This research identifies the need for legislative action to decrease semi-volatile organic compounds, especially PAHs, mainly in urban cities, in order to improve environmental management and health conditions.

Prognostic Role of Clinical Features of Moderate Forms of COVID-19 Requiring Hospitalization.

INTRODUCTION: We aimed to characterize the clinical features of moderate forms of COVID-19 requiring hospitalization and potentially identify predictors for unfavorable outcomes. METHODS: Pooled anonymized clinical data from 452 COVID-19 patients hospitalized in two regional Romanian respiratory disease centers during the Alpha and Delta variant outbreaks were included in the analysis. RESULTS: Cough and shortness of breath were the most common clinical features; older patients exhibited more fatigue and dyspnea and fewer upper airway-related symptoms such as smell loss or sore throat. The presence of confusion, shortness of breath and age over 60 years were significantly associated with worse outcomes (odds ratios 5.73, 2.08 and 3.29, respectively). CONCLUSION: The clinical picture on admission may have a prognostic role for moderate forms of COVID-19. Clear clinical definitions and developing adequate informational infrastructure allowing complex data sharing and analysis might be useful for fast research response should a similar outbreak occur in the future.

Understanding perceived addiction to and addictiveness of electronic cigarettes among electronic cigarette users: a cross-sectional analysis of the International Tobacco Control Smoking and Vaping (ITC 4CV) England Survey.

BACKGROUND AND AIMS: The addictive potential of electronic cigarettes (e-cigarettes) remains to be fully understood. We identified patterns and correlates of perceived addiction to e-cigarettes and perceived addictiveness of e-cigarettes relative to tobacco cigarettes (relative addictiveness) in dual users as well as exclusive e-cigarette users. DESIGN, SETTING AND PARTICIPANTS: Observational study using cross-sectional survey data from England (2016) from the International Tobacco Control Project (ITC) Four Country Smoking and Vaping (4CV) survey. The study comprised 832 current e-cigarette users who had been vaping for at least 4 months. MEASUREMENTS: Perceived addiction to e-cigarettes and relative addictiveness of e-cigarettes were examined. Socio-demographic factors were age, gender and education; markers of addiction included urge to vape, time to first vape after waking and nicotine strength used; vaping and smoking characteristics included frequency and duration of e-cigarette use, intention to quit, adjustable power or temperature, enjoyment, satisfaction relative to tobacco cigarettes and tobacco cigarette smoking status. FINDINGS: A total of 17% of participants reported feeling very addicted to e-cigarettes, while 40% considered e-cigarettes equally/more addictive than tobacco cigarettes. Those who felt very addicted had higher odds of regarding e-cigarettes as more addictive than tobacco cigarettes (odds ratio 3.4, 95% confidence interval 2.3-5.1). All markers of addiction, daily use and enjoyment were associated with higher perceived addiction, whereas time to first vape after waking, daily vaping and perceiving vaping as less satisfying than smoking were associated with relative addictiveness. CONCLUSIONS: Markers of addiction to e-cigarettes appear to correspond with perceived addiction to e-cigarettes, suggesting that self-reported perceived addiction might serve as an indicator of addiction. Prevalence both of markers of addiction and perceived addiction were comparatively low overall, suggesting a limited but relevant addictive potential of e-cigarettes. Additionally, positive and negative reinforcement, reflected here by enjoyment and relative satisfaction, might play a role in e-cigarette addiction.

Recognising the importance of chronic lung disease: a consensus statement from the Global Alliance for Chronic Diseases (Lung Diseases group).

BACKGROUND: Chronic respiratory diseases are disorders of the airways and other structures of the lung, and include chronic obstructive pulmonary disease (COPD), lung cancer, asthma, bronchiectasis, interstitial lung diseases, occupational lung diseases and pulmonary hypertension. Through this article we take a broad view of chronic lung disease while highlighting (1) the complex interactions of lung diseases with environmental factors (e.g. climate change, smoking and vaping) and multimorbidity and (2) proposed areas to strengthen for better global patient outcomes. CONCLUSION: We suggest new directions for the research agenda in high-priority populations and those experiencing health disparities. We call for lung disease to be made a research priority with greater funding allocation globally.

The Risk of Sarcoidosis Misdiagnosis and the Harmful Effect of Corticosteroids When the Disease Picture Is Incomplete.

Sarcoidosis is a complex granulomatous disease of unknown etiology. Due to the heterogeneity of the disease, the diagnosis remains challenging in many cases, often at the physician's discretion, requiring a thorough and complex investigation. Many other granulomatous diseases have the potential to mimic sarcoidosis, whether infectious, occupational, or autoimmune diseases and starting an unnecessary corticosteroid treatment can worsen the patient's prognosis, leading to side effects that can be harder to treat than the actual disease.

Assessment of Some Risk Factors and Biological Predictors in the Post COVID-19 Syndrome in Asthmatic Patients.

Long COVID-19 or post-COVID infection (PCI) refers to the prolongation of symptoms in people who have been infected with the SARS-CoV-2 virus. Some meta-analysis studies have shown that patients with comorbidities, such as diabetes, obesity or hypertension, have severe complications after infection with the SARS-CoV-2 virus. The presence of chronic respiratory diseases such as bronchial asthma, COPD, pulmonary hypertension or cystic fibrosis increases the risk of developing severe forms of the COVID-19 disease. The risk of developing the severe form of COVID-19 was observed in patients with bronchial asthma being treated with corticosteroids, but also in those hospitalized with severe asthma. The biological variables determined in patients with PCI infection showed changes, especially in the hematological parameters, but also in some inflammatory markers. The aim of this study was to investigate some biological predictors in post-COVID-19 infection in patients with asthma and various comorbidities. In the case of patients diagnosed with moderate and severe forms of COVID-19, the variation in biological tests has shown high concentrations for serum glucose, lactate dehydrogenase and C-reactive protein. Additionally, the calculation of the relative risk (RR) based on the associated comorbidities in patients with PCI points to higher values for patients with asthma, hypertension, diabetes and obesity (RR moderate/severe form = 0.98/1.52), compared to patients with PCI and asthma (RR moderate/severe form = 0.36/0.63). Based on the statistical results, it can be concluded that the alanine aminotransferase (ALT) activity (p = 0.006) and the age of patients (p = 0.001) are the variables that contribute the most to the separation of the four classes of comorbidities considered.

Role of pulmonary rehabilitation in chronic obstructive pulmonary disease - a historical perspective.

Introduction: Pulmonary rehabilitation is known as an effective therapy for patients with chronic obstructive pulmonary disease (COPD). This article is a brief introduction into the history of medical and pulmonary rehabilitation, presenting the evolution of applied therapies and methods from ancient to present times. It also highlights the role of physical effort in the prevention and treatment of lung diseases, with special consideration to COPD. Methods: For this literature review, the international databases Medline and Scopus were used to identify relevant articles, between January 1981 to December 2021; eighty articles were considered: thirty-six reviews, eight original research and six general articles which met the criteria for inclusion. A total of thirty references were excluded because they were not relevant. Results: Available published data suggest a rich history of rehabilitation reaching for thousands of years even though it was developed as a medical branch only in the 20th century. Pulmonary rehabilitation is currently an important component of the management of COPD patients, with a positive impact on symptoms, frequency of exacerbations, severity and mortality rates. Conclusions: Even though this type of intervention is known to be beneficial for this type of patients more studies need to be conducted in this field.

Polycyclic Aromatic Hydrocarbons Induced by Smoking and Air Pollution: Correlation with Oxidative Stress in Chronic Obstructive Pulmonary Disease Patients.

Oxidative stress is induced by tobacco smoking and is also associated with exposure to air pollution, which are two of the most important risk factors for chronic obstructive pulmonary disease (COPD). The aim of this study was to correlate tobacco use and exposure to air pollution with oxidative stress markers useful in clinical practice in patients with COPD. A total of 102 patients were included and the levels of polycyclic aromatic hydrocarbons (PAHs), malondialdehyde, uric acid and number of packs-years (PY) were determined. Also, six different ratios were used to assess the source of exposure. The results obtained in this study show an admission of pollutants according to smoking status (former smokers/smoker/non-smokers) quantified in average total concentrations for the group of patients with COPD of 4.12 ng/mL, 6.76 ng/mL, 6.04 ng/mL. The six ratios used show that in COPD, the content of PAHs in the blood could be a result of diesel emissions and fuel combustion. Uric acid levels were lower in the smoker group of COPD patients (mean = 5.21 mg/dL), which indicates that oxidative stress is intensified with each cigarette smoked. Additionally, high concentrations of malondialdehyde were quantified for smoking patients diagnosed with COPD (mean = 2.72 µmol/L) compared to former smokers (mean = 2.43 µmol/L) and non-smoking (mean = 2.32 µmol/L) patients, which is another indicator of the implication of smoking in oxidative stress in COPD patients.

The Lipid Profile and Biochemical Parameters of COPD Patients in Relation to Smoking Status.

Tobacco consumption is the most incriminated and studied risk factor for Chronic obstructive pulmonary disease (COPD), but other factors such as air pollution, are also linked to this disease. One of the known aspects of this chronic lung disease is that its occurrence is mainly due to the chronic inflammation of the airways. Lipid metabolism seems to be affected by smoking, with studies showing a correlation between this habit and high levels of triglycerides and low levels of high-density lipoprotein cholesterol (HDL-CHOL). Uric acid concentration is thought to reflect the antioxidative capacity of the body because it is the most abundant aqueous antioxidant. The aim of this study was to investigate the lipid profile and biochemical parameters of COPD patients in relation to smoking status. The present study was conducted between 2020 and 2021 in the Clinical Hospital of Pneumology in Iasi, Romania. Patients diagnosed with COPD (n = 52) were included and divided in three groups depending on their smoking status: non-smokers, smokers and ex-smokers. The obtained results show low correlations between COPD stages and serum uric acid concentrations (r = 0.4; p ˂ 0.05), smoking status (smoker/non-smoker/ex-smoker) and total serum cholesterol values (r = 0.45; p ˂ 0.05), but also between serum urea concentrations and the number of packs-years for the smoker/ex-smoker groups (r = 0.45, p ˂ 0.05). Smoking was associated with changes in the lipid profile of smokers and ex-smokers, along with increased low-density lipoprotein cholesterol (LDL-CHOL) and low serum uric acid values.

Beyond the European Union Tobacco Products Directive: smokers' and recent quitters' support for further tobacco control measures (2016-2018).

BACKGROUND: Several measures recommended by the WHO Framework Convention on Tobacco Control have not been implemented in the European Union, despite changes in the legislation such as the Tobacco Products Directive (TPD). This study aims to understand smokers' and recent quitters' levels of support for tobacco control measures that go beyond the TPD during and after its implementation. METHODS: Data from wave 1 (2016, n=6011) and wave 2 (2018, n=6027) of the EUREST-PLUS International Tobacco Control Policy Evaluation Project Six European Countries Survey, a cohort of adult smokers in Germany, Greece, Hungary, Poland, Romania, Spain were used to estimate the level of support for seven different tobacco control measures, overall and by country. RESULTS: In 2018, the highest support was for implementing measures to further regulate tobacco products (50.5%) and for holding tobacco companies accountable for the harm caused by smoking (48.8%). Additionally, in 2018, 40% of smokers and recent quitters supported a total ban on cigarettes and other tobacco products within ten years, if assistance to quit smoking is provided. Overall, support for tobacco control measures among smokers and recent quitters after the implementation of the TPD remained stable over time. CONCLUSION: There is considerable support among smokers and recent quitters for tobacco control measures that go beyond the current measures implemented. A significant percentage of smokers would support a ban on tobacco products in the future if the government provided assistance to quit smoking. This highlights the importance of implementing measures to increase smoking cessation in conjunction with other policies.

Secondhand Smoke Exposure in European Countries With Different Smoke-Free Legislation: Findings From the EUREST-PLUS ITC Europe Surveys.

INTRODUCTION: Exposure to secondhand smoke (SHS) poses serious and extensive health and economic-related consequences to European society and worldwide. Smoking bans are a key measure to reducing SHS exposure but have been implemented with varying levels of success. We assessed changes in the prevalence of self-reported SHS exposure and smoking behavior in public places among smokers in six European countries and the influence of the country's type of smoking ban (partial or total ban) on such exposure and smoking behavior. AIMS AND METHODS: The EUREST-PLUS ITC Europe Surveys were conducted among adult smokers in Germany, Greece, Hungary, Poland, Romania, and Spain in 2016 (Wave 1, n = 6011) and 2018 (Wave 2, n = 6027). We used generalized estimating equations models to assess changes between Waves 1 and 2 and to test the interaction between the type of smoking ban and (1) self-reported SHS exposure, (2) self-reported smoking in several public places. RESULTS: A significant decrease in self-reported SHS exposure was observed in workplaces, from 19.1% in 2016 to 14.0% in 2018 (-5.1%; 95% CI: -8.0%; -2.2%). Self-reported smoking did not change significantly inside bars (22.7% in Wave 2), restaurants (13.2% in Wave 2) and discos/nightclubs (34.0% in W2). SHS exposure in public places was significantly less likely (adjusted odds ratio = 0.35; 95% CI: 0.26-0.47) in the countries with total bans as compared to those countries with partial bans. CONCLUSION: The inverse association between smoking in public places and smoking bans indicates an opportunity for strengthening smoke-free legislation and protecting bystanders from exposure to SHS in public places. IMPLICATIONS: Prevalence of smokers engaging in and being exposed to smoking in public places varied by type of smoke-free legislation across six European Union countries in our study; those with total smoke bans reported significantly less exposure to SHS than those with partial or no bans. Our results indicate room for improvement, not only to decrease the prevalence of exposure to SHS in Europe but also to diminish the variability between countries through common, more restrictive smoke-free legislation, and importantly, strong and sustained enforcement.

Unravelling data for rapid evidence-based response to COVID-19: a summary of the unCoVer protocol.

INTRODUCTION: unCoVer-Unravelling data for rapid evidence-based response to COVID-19-is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic. METHODS AND ANALYSIS: From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients' baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded. ETHICS AND DISSEMINATION: After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer's activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications.