Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study

BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None

Modeling methane fluxes in wetlands with gas-transporting plants. 3. Plot scale.

A process model based on kinetic principles was developed for methane fluxes from wetlands with gas-transporting plants and a fluctuating water table. Water dynamics are modeled with the 1-D Richards equation. For temperature a standard diffusion equation is used. The depth-dependent dynamics of methane, oxygen, molecular nitrogen, carbon dioxide, soil carbon, electron acceptors in oxidized and in reduced form are affected by transport processes and kinetic processes. Modeled transport processes are convection and diffusion in the soil matrix, ebullition, and plant-mediated gas transport. Modeled kinetic processes are carbon mineralization, aerobic respiration, methane production, methane oxidation, electron acceptor reduction, and electron acceptor reoxidation. Concentration gradients around gas-transporting roots in water-saturated soil are accounted for by the models from the two previous papers, ensuring an explicit connection between process knowledge at the kinetic level (millimeter scale) and methane fluxes at the plot scale. We applied the model to a fen, and without any fitting, simulated methane fluxes are within 1 order of magnitude of measured methane fluxes. The seasonal variations however, are much weaker in the simulations compared to the measurements. Simulated methane fluxes are sensitive to several uncertain parameters such as the distribution over depth of carbon mineralization, the total pool size of reduced and oxidized electron acceptors, and the root-shoot ratio. Because of the process-based character of the model it is probable that these sensitivities are present in reality as well, which explains why the measured variability is usually very high. Interestingly, heterogeneities within a rooted soil layer seem to be less important than heterogeneities between different soil layers. This is due to the strong influence of the interaction between water table and profile scale processes on the oxygen input to the system and hence on net methane production. Other existing process models are discussed and compared with the presented model