Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US.

OBJECTIVE: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. DESIGN: International network cohort study. SETTING: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. PARTICIPANTS: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. MAIN OUTCOME MEASURES: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. RESULTS: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. CONCLUSIONS: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study.

INTRODUCTION: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. METHODS: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. RESULTS: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. CONCLUSION: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

Comparing the Clinical Characteristics and Mortality of Residential and Non-Residential Older People with COVID-19: Retrospective Observational Study.

Nursing homes have accounted for a significant part of SARS-CoV-2 mortality, causing great social alarm. Using data collected from electronic medical records of 1,319,839 institutionalised and non-institutionalised persons ≥ 65 years, the present study investigated the epidemiology and differential characteristics between these two population groups. Our results showed that the form of presentation of the epidemic outbreak, as well as some risk factors, are different among the elderly institutionalised population with respect to those who are not. In addition to a twenty-fold increase in the rate of adjusted mortality among institutionalised individuals, the peak incidence was delayed by approximately three weeks. Having dementia was shown to be a risk factor for death, and, unlike the non-institutionalised group, neither obesity nor age were shown to be significantly associated with the risk of death among the institutionalised. These differential characteristics should be able to guide the actions to be taken by the health administration in the event of a similar infectious situation among institutionalised elderly people.

Medical vulnerability of individuals with Down syndrome to severe COVID-19-data from the Trisomy 21 Research Society and the UK ISARIC4C survey.

BACKGROUND: Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. METHODS: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. FINDINGS: The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p < 0.01), whereas altered consciousness/confusion were more frequent (p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. INTERPRETATION: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. FUNDING: Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.

Clinical Characterization of Patients With COVID-19 in Primary Care in Catalonia: Retrospective Observational Study.

BACKGROUND: The country of Spain has one of the highest incidences of COVID-19, with more than 1,000,000 cases as of the end of October 2020. Patients with a history of chronic conditions, obesity, and cancer are at greater risk from COVID-19; moreover, concerns surrounding the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin type II receptor blockers (ARBs) and its relationship to COVID-19 susceptibility have increased since the beginning of the pandemic. OBJECTIVE: The objectives of this study were to compare the characteristics of patients diagnosed with COVID-19 to those of patients without COVID-19 in primary care; to determine the risk factors associated with the outcome of mortality; and to determine the potential influence of certain medications, such as ACEIs and ARBs, on the mortality of patients with COVID-19. METHODS: An observational retrospective study of patients diagnosed with COVID-19 in the Catalan Central Region of Spain between March 1 and August 17, 2020, was conducted. The data were obtained from the Primary Care Services Information Technologies System of the Catalan Institute of Health in Barcelona, Spain. RESULTS: The study population included 348,596 patients (aged >15 years) registered in the Primary Care Services Information Technologies System of the Catalan Central Region. The mean age of the patients was 49.53 years (SD 19.42), and 31.17% of the patients were aged ≥60 years. 175,484/348,596 patients (50.34%) were women. A total of 23,844/348,596 patients (6.84%) in the population studied were diagnosed with COVID-19 during the study period, and the most common clinical conditions of these patients were hypertension (5267 patients, 22.1%) and obesity (5181 patients, 21.7%). Overall, 2680/348,596 patients in the study population (0.77%) died during the study period. The number of deaths among patients without COVID-19 was 1825/324,752 (0.56%; mean age 80.6 years, SD 13.3), while among patients diagnosed with COVID-19, the number of deaths was 855/23,844 (3.58%; mean age 83.0 years, SD 10.80) with an OR of 6.58 (95% CI 6.06-7.15). CONCLUSIONS: We observed that women were more likely to contract COVID-19 than men. In addition, our study did not show that hypertension, obesity, or being treated with ACEIs or ARBs was linked to an increase in mortality in patients with COVID-19. Age is the main factor associated with mortality in patients infected with SARS-CoV-2.