The natural history of symptomatic COVID-19 during the first wave in Catalonia

The natural history of coronavirus disease 2019 (COVID-19) has yet to be fully described. Here, we use patient-level data from the Information System for Research in Primary Care (SIDIAP) to summarise COVID-19 outcomes in Catalonia, Spain. We included 5,586,521 individuals from the general population. Of these, 102,002 had an outpatient diagnosis of COVID-19, 16,901 were hospitalised with COVID-19, and 5273 died after either being diagnosed or hospitalised with COVID-19 between 1st March and 6th May 2020. Older age, being male, and having comorbidities were all generally associated with worse outcomes. These findings demonstrate the continued need to protect those at high risk of poor outcomes, particularly older people, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death were lower for younger populations, there is a need to limit their role in community transmission

Characteristics and outcomes of over 300,000 patients with COVID-19 and history of cancer in the United States and Spain

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin’s lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n ¼ 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.</p

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study

Background: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I2 value was less than 0·4. Findings: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12–2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22–3·95]), chest pain or angina (1·15 [1·05–1·26]), and hear

Power domination sets and centralities in the European airport network

A power domination set in a network is a subset of its nodes such that by applying a simple set of rules all nodes are monitored. The concept was introduced in the context of electrical networks but has been extended and studied for other networks and families of graphs. It has been shown that this problem is NP-complete and thus, for large networks, optimization methods like simulated annealing, threshold acceptance or genetic algorithms could be useful to find near-optimal solutions. In this TFG we introduce a new threshold acceptance algorithm to find power domination sets in graphs and we apply it to analyze these sets in relation to airport centralities and cascade failures in the European airport network. To start with, the cited network is analyzed using a few distinct centrality definitions, including a classical degree centrality, betweenness centrality PageRank, etc. to find the most connected nodes and have an overview of the whole network. An alternative outlook of the local connectivity between nodes is given by finding communities. These groups of nodes are identified according to their strong local associations, in opposition to weaker associations with the rest of the nodes. Having characterised the network from different perspectives, cascade failures are modelled to detect vulnerabilities on the network by comparing the effects of different airport closures. A comparison is assessed based on the effect of the failure of airports depending on their classification. Failing nodes could belong to power dominations sets or be nodes selected from high, medium or low connectivity levels. The main result is a complete insight on how the system is affected from the failure of nodes according to their properties and how the parameters used to tune the model affect this analysis.Un conjunt dominador en potència (power dominating set) en una xarxa és un subconjunt de nodes que poden monitoritzar la totalitat de la xarxa a partir d’un conjunt de regles senzilles. El concepte s’introduí en el context de les xarxes elèctriques, però s’ha estès i estudiat per a altres xarxes i famílies de grafs. S’ha demostrat que aquest problema és NP-complet pel que, per xarxes grans, mètodes d’optimització com la recuita simulada (simulated annealing), threshold accepting o algorismes genètics constitueixen eines útils per poder trobar solucions òptimes o quasi-òptime

Venous or arterial thrombosis and mortality among COVID-19 cases: a European network cohort study

Background: There are limited data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We estimated the incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and death among COVID-19 cases; and to assess the impact of these events on hospitalization and mortality. Methods: A distributed network cohort using primary care records from Netherlands, Italy, Spain and the UK; and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed from a diagnosis of COVID-19 or positive RT-PCR test on or after 1st September 2020. Outcomes included VTE, ATE, hospitalization, and mortality up to 90-days after index date. We estimated cumulative incidences for the study outcomes. Multi-state models were used to study the association between VTE/ATE occurrence and hospitalization and mortality. Results: Overall, 909,473 COVID-19 cases and 32,329 patients hospitalised with COVID-19 were studied. Cumulative 90-day incidence of VTE ranged from 0.2% to 0.8%, and up to 4.5% for those hospitalised. For ATE, estimates ranged from 0.1% to 0.8%, increasing to 3.1% among those hospitalised. Mortality ranged between 1.1% and 2.0%, rising to 14.6% for hospitalised patients. VTE and ATE were associated with worse outcomes. For example, VTE and ATE whilst outpatient resulted in adjusted HR for death of 4.42 [3.07-6.36] and 3.16 [2.65-3.75] respectively. Conclusions and Relevance: Risks of VTE and ATE were up to one percent among COVID-19 cases, but increase with age, among males, and for those hospitalized. Their occurrence is associated with excess mortality, underling the importance of effective treatment strategies that reduce their frequency

Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study

Background: There are few data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We aimed to estimate the incidence of venous thromboembolism, arterial thromboembolism, and death among COVID-19 cases and to assess the impact of these events on the risks of hospitalisation and death. Methods: We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. Findings: Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07–6·36] for those not hospitalised and 1·63 [1·39–1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65–3·75] and 1·93 [1·57–2·37]). Interpretation: Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency. Funding: European Medicines Agency

Background rates of five thrombosis with thrombocytopenia syndromes of special interest for COVID-19 vaccine safety surveillance:Incidence between 2017 and 2019 and patient profiles from 38.6 million people in six European countries

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) has been reported among individuals vaccinated with adenovirus‐vectored COVID‐19 vaccines. In this study, we describe the background incidence of non‐vaccine induced TTS in six European countries. METHODS: Electronic medical records from France, the Netherlands, Italy, Germany, Spain, and the United Kingdom informed the study. Incidence rates of cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction or ischemic stroke, all with concurrent thrombocytopenia, were estimated among the general population of persons in a database between 2017 and 2019. A range of additional potential adverse events of special interest for COVID‐19 vaccinations were also studied in a similar manner. FINDINGS: A total of 38 611 617 individuals were included. Background rates ranged from 1.0 (95% CI: 0.7–1.4) to 8.5 (7.4–9.9) per 100 000 person‐years for DVT with thrombocytopenia, from 0.5 (0.3–0.6) to 20.8 (18.9–22.8) for PE with thrombocytopenia, from 0.1 (0.0–0.1) to 2.5 (2.2–2.7) for SVT with thrombocytopenia, and from 1.0 (0.8–1.2) to 43.4 (40.7–46.3) for myocardial infarction or ischemic stroke with thrombocytopenia. CVST with thrombocytopenia was only identified in one database, with incidence rate of 0.1 (0.1–0.2) per 100 000 person‐years. The incidence of non‐vaccine induced TTS increased with age, and was typically greater among those with more comorbidities and greater medication use than the general population. It was also more often seen in men than women. A large proportion of those affected were seen to have been taking antithrombotic and anticoagulant therapies prior to their event. INTERPRETATION: Although rates vary across databases, non‐vaccine induced TTS has consistently been seen to be a very rare event among the general population. While still remaining very rare, rates were typically higher among older individuals, and those affected were also seen to generally be male and have more comorbidities and greater medication use than the general population

COVID-19 in patients with autoimmune diseases : characteristics and outcomes in a multinational network of cohorts across three countries

Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center (CUIMC) (United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. Outcomes were death and complications within 30 days of hospitalisation. We studied 133 589 patients diagnosed and 48 418 hospitalised with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalised vs diagnosed patients with COVID-19. Compared with 70 660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% vs 6.3% to 24.6%). Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality

Thirty-day outcomes of children and adolescents with COVID-19: An international experience

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017–2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%–7.6%), famotidine (9.0%–28.1%), and antithrombotics such as aspirin (2.0%–21.4%), heparin (2.2%–18.1%), and enoxaparin (2.8%–14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19