COVID-19: Development of a robust mathematical model and simulation package with consideration for ageing population and time delay for control action and resusceptibility

The current global health emergency triggered by the pandemic COVID-19 is one of the greatest challenges mankind face in this generation. Computational simulations have played an important role to predict the development of the current pandemic. Such simulations enable early indications on the future projections of the pandemic and is useful to estimate the efficiency of control action in the battle against the SARS-CoV-2 virus. The SEIR model is a well-known method used in computational simulations of infectious viral diseases and it has been widely used to model other epidemics such as Ebola, SARS, MERS, and influenza A. This paper presents a modified SEIRS model with additional exit conditions in the form of death rates and resusceptibility, where we can tune the exit conditions in the model to extend prediction on the current projections of the pandemic into three possible outcomes; death, recovery, and recovery with a possibility of resusceptibility. The model also considers specific information such as ageing factor of the population, time delay on the development of the pandemic due to control action measures, as well as resusceptibility with temporal immune response. Owing to huge variations in clinical symptoms exhibited by COVID-19, the proposed model aims to reflect better on the current scenario and case data reported, such that the spread of the disease and the efficiency of the control action taken can be better understood. The model is verified using two case studies for verification and prediction studies, based on the real-world data in South Korea and Northern Ireland, respectively.Comment: 14 pages, 9 figures, To appear in Physica D: Nonlinear Phenomena (2020

The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active

Induction of neutralizing antibody response against four dengue viruses in mice by intramuscular electroporation of tetravalent DNA vaccines.

DNA vaccine against dengue is an interesting strategy for a prime/boost approach. This study evaluated neutralizing antibody (NAb) induction of a dengue tetravalent DNA (TDNA) vaccine candidate administered by intramuscular-electroporation (IM-EP) and the benefit of homologous TDNA boosting in mice. Consensus humanized pre-membrane (prM) and envelope (E) of each serotypes, based on isolates from year 1962-2003, were separately cloned into a pCMVkan expression vector. ICR mice, five-six per group were immunized for three times (2-week interval) with TDNA at 100 µg (group I; 25 µg/monovalent) or 10 µg (group II; 2.5 µg/monovalent). In group I, mice received an additional TDNA boosting 13 weeks later. Plaque reduction neutralization tests (PRNT) were performed at 4 weeks post-last immunization. Both 100 µg and 10 µg doses of TDNA induced high NAb levels against all DENV serotypes. The median PRNT50 titers were comparable among four serotypes of DENV after TDNA immunization. Median PRNT50 titers ranged 240-320 in 100 µg and 160-240 in 10 µg groups (p = ns). A time course study of the 100 µg dose of TDNA showed detectable NAb at 2 weeks after the second injection. The NAb peaked at 4 weeks after the third injection then declined over time but remained detectable up to 13 weeks. An additional homologous TDNA boosting significantly enhanced the level of NAb from the nadir for at least ten-fold (p<0.05). Of interest, we have found that the use of more recent dengue viral strain for both vaccine immunogen design and neutralization assays is critical to avoid a mismatching outcome. In summary, this TDNA vaccine candidate induced good neutralizing antibody responses in mice; and the DNA/DNA prime/boost strategy is promising and warranted further evaluation in non-human primates