New Coronavirus News from 24 Sep 2022

Forecasting admissions in psychiatric hospitals before and during Covid-19: a retrospective study with routine data | Scientific Reports [Nature.com, 24 Sep 2022]

Authored by J. Wolff, A. Klimke, M. Marschollek & T. Kacprowski

Abstract
The COVID-19 pandemic has strong effects on most health care systems. Forecasting of admissions can help for the efficient organisation of hospital care. We aimed to forecast the number of admissions to psychiatric hospitals before and during the COVID-19 pandemic and we compared the performance of machine learning models and time series models. This would eventually allow to support timely resource allocation for optimal treatment of patients. We used admission data from 9 psychiatric hospitals in Germany between 2017 and 2020. We compared machine learning models with time series models in weekly, monthly and yearly forecasting before and during the COVID-19 pandemic. A total of 90,686 admissions were analysed. The models explained up to 90% of variance in hospital admissions in 2019 and 75% in 2020 with the effects of the COVID-19 pandemic. The best models substantially outperformed a one-step seasonal naïve forecast (seasonal mean absolute scaled error (sMASE) 2019: 0.59, 2020: 0.76). The best model in 2019 was a machine learning model (elastic net, mean absolute error (MAE): 7.25). The best model in 2020 was a time series model (exponential smoothing state space model with Box-Cox transformation, ARMA errors and trend and seasonal components, MAE: 10.44). Models forecasting admissions one week in advance did not perform better than monthly and yearly models in 2019 but they did in 2020. The most important features for the machine learning models were calendrical variables. Model performance did not vary much between different modelling approaches before the COVID-19 pandemic and established forecasts were substantially better than one-step seasonal naïve forecasts. However, weekly time series models adjusted quicker to the COVID-19 related shock effects. In practice, multiple individual forecast horizons could be used simultaneously, such as a yearly model to achieve early forecasts for a long planning period and weekly models to adjust quicker to sudden changes.

New Coronavirus News from 2 Sep 2022

Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants [iScience, 2 Sep 2022]

Authored by Xing J, Shankar R, Ko M, Zhang K, Zhang S, Drelich A, Paithankar S, Chekalin E, Chua MS, Rajasekaran S, Kent Tseng CT, Zheng M, Kim S, Chen B

Abstract
The molecular manifestations of host cells responding to SARS-CoV-2 and its evolving variants of infection are vastly different across the studied models and conditions, imposing challenges for host-based antiviral drug discovery. Based on the postulation that antiviral drugs tend to reverse the global host gene expression induced by viral infection, we retrospectively evaluated hundreds of signatures derived from 1,700 published host transcriptomic profiles of SARS/MERS/SARS-CoV-2 infection using an iterative data-driven approach. A few of these signatures could be reversed by known anti-SARS-CoV-2 inhibitors, suggesting the potential of extrapolating the biology for new variant research. We discovered IMD-0354 as a promising candidate to reverse the signatures globally with nanomolar IC50 against SARS-CoV-2 and its five variants. IMD-0354 stimulated type I interferon antiviral response, inhibited viral entry, and down-regulated hijacked proteins. This study demonstrates that the conserved coronavirus signatures and the transcriptomic reversal approach that leverages polypharmacological effects could guide new variant therapeutic discovery.

New Coronavirus News from 29 Sep 2022

Repurposing existing drugs to fight new COVID-19 variants [MSUToday, 29 Sep 2022]

By: Emilie Lorditch

MSU researchers are using big data and AI to identify current drugs that could be applied to treat new COVID-19 variants

Finding new ways to treat the novel coronavirus and its ever-changing variants has been a challenge for researchers, especially when the traditional drug development and discovery process can take years. A Michigan State University researcher and his team are taking a hi-tech approach to determine whether drugs already on the market can pull double duty in treating new COVID variants.

“The COVID-19 virus is a challenge because it continues to evolve,” said Bin Chen, an associate professor in the College of Human Medicine. “By using artificial intelligence and really large data sets, we can repurpose old drugs for new uses.”

Chen built an international team of researchers with expertise on topics ranging from biology to computer science to tackle this challenge. First, Chen and his team turned to publicly available databases to mine for the unique coronavirus gene expression signatures from 1,700 host transcriptomic profiles that came from patient tissues, cell cultures and mouse models.
These signatures revealed the biology shared by COVID-19 and its variants.

With the virus’s signature and knowing which genes need to be suppressed and which genes need to be activated, the team was able to use a computer program to screen a drug library consisting of FDA-approved or investigational drugs to find candidates that could correct the expression of signature genes and further inhibit the coronavirus from replicating. Chen and his team discovered one novel candidate, IMD-0354, a drug that passed phase I clinical trials for the treatment of atopic dermatitis. A group in Korea later observed that it was 90-fold more effective against six COVID-19 variants than remdesivir, the first drug approved to treat COVID-19. The team further found that IMD-0354 inhibited the virus from copying itself by boosting the immune response pathways in the host cells. Based on the information learned, the researchers studied a prodrug of IMD-0354 called IMD-1041. A prodrug is an inactive substance that is metabolized within the body to create an active drug.

“IMD-1041 is even more promising as it is orally available and has been investigated for chronic obstructive pulmonary disease, a group of lung diseases that block airflow and make it difficult to breathe,” Chen said. “Because the structure of IMD-1041 is undisclosed, we are developing a new artificial intelligence platform to design novel compounds that hopefully could be tested and evaluated in more advanced animal models.”

The research was published in the journal iScience.

This project was led by two senior postdoctoral scholars in the Chen lab: Jing Xing, who recently became a young investigator at the Chinese Academy of Sciences, and Rama Shankar, with the support from researchers from Institut Pasteur Korea, Shanghai Institute of Materia Medica, University of Texas Medical Branch, Spectrum Health in Grand Rapids and Stanford University.