A prediction method for influenza during COVID-19 in Shanxi Province, China: LSTM-SARIMA hybrid model based on Singular Spectrum Analysis (preprint)

To handle the difficulties of modeling and prediction caused by the abnormal influenza sequence during COVID-19, this study established a hybrid prediction model of Long-Short Term Memory neural network (LSTM) and seasonal autoregressive integrated moving average (SARIMA) based on Singular spectrum analysis (SSA), which provided an effective scientific basis for the high-precision prediction of influenza in Shanxi Province during the COVID-19. Seasonal-trend decomposition using Loess (STL) was adopted to analyze the season characteristics of the ratio of weekly influenza-like illness (ILI) patients in Shanxi Province, China, from the 14th week in 2010 to the 13th week in 2021. The SARIMA model, the LSTM model and the LSTM-SARIMA hybrid model based on SSA were established to predict the influenza in Shanxi Province during the COVID-19. Mean Absolute Error (MAE) and Mean Absolute Percentage Error (MAPE) were used to evaluate the performance of the models. Affected by the COVID-19, the influenza time sequence in Shanxi Province has been complicated since the beginning of 2020, with the peak incidence much lower than before. Compared with those of the SARIMA model, the MAE and MAPE of the LSTM-SARIMA hybrid model based on SSA decreased by 28.9 and 32.2%, respectively, in fitting performance; in terms of prediction performances, the MAE and MAPE decreased by 52.5 and 52.1%, respectively. Compared with those of the LSTM model, the MAE and MAPE of the LSTM-SARIMA hybrid model based on SSA decreased by 26.2 and 27.5%, respectively, in fitting performance; in terms of prediction performances, the MAE and MAPE decreased by 35.0 and 35.3%, respectively. The fitting and prediction performances of the LSTM-SARIMA hybrid model based on SSA were better than those of the SARIMA and the LSTM models. Generally speaking, we can apply the LSTM-SARIMA hybrid model based on SSA to the prediction of influenza during the COVID-19, and offer a leg-up for public policy.

The COVID-19 Healthcare Personnel Study (CHPS): Overview, Methods and Preliminary Report (preprint)

Introduction. The COVID-19 Healthcare Personnel Study (CHPS) was designed to assess and mitigate adverse short and long-term physical and mental health impacts of the COVID-19 pandemic on New York's health care workforce. Here we report selected baseline results. Methods. Online survey of New York State physicians, nurse practitioners and physician assistants registered with the New York State Department of Health. Survey-weighted descriptive results were analyzed using frequencies, proportions, and means, with 95% confidence intervals. Odds ratios were calculated for association using survey-weighted logistic regression. Results. Approximately 51.5% (95% CI 49.1, 54.0) of the survey-weighted respondents reported having worked directly or in close physical contact with COVID-19 patients. Of those tested for COVID-19, 27.3% (95% CI 22.5, 32.2) were positive. Having symptoms consistent with COVID-19 was associated with reporting a subsequent positive COVID-19 test (OR=14.0, 95% CI 5.7, 34.7). Over half of the respondents, (57.6%) reported a negative impact of the COVID-19 efforts on their mental health. Respondents who indicated that they were redeployed or required to do different functions than usual in response to COVID-19 were more likely to report negative mental health impacts (OR=1.3, 95% CI 1.1, 1.6). Conclusions. At the height of the COVID-19 pandemic in New York State in Spring 2020, more than half of physicians, nurse practitioners and physician assistants included in this study responded to the crisis, often at a cost to their physical and mental health and disruption to their lives.

Brilacidin, a COVID-19 Drug Candidate, Exhibits Potent In Vitro Antiviral Activity Against SARS-CoV-2 (preprint)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than one million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin-a de novo designed synthetic small molecule that captures the biological properties of HDPs-on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is primarily a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin has demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 and thus supports brilacidin as a promising COVID-19 drug candidate. Highlights: Brilacidin potently inhibits SARS-CoV-2 in an ACE2 positive human lung cell line. Brilacidin achieved a high Selectivity Index of 426 (CC50=241{micro}M/IC50=0.565{micro}M). Brilacidin's main mechanism appears to disrupt viral integrity and impact viral entry. Brilacidin and remdesivir exhibit excellent synergistic activity against SARS-CoV-2. Significance Statement: SARS-CoV-2, the emergent novel coronavirus, has led to the current global COVID-19 pandemic, characterized by extreme contagiousness and high mortality rates. There is an urgent need for effective therapeutic strategies to safely and effectively treat SARS-CoV-2 infection. We demonstrate that brilacidin, a synthetic small molecule with peptide-like properties, is capable of exerting potent in vitro antiviral activity against SARS-CoV-2, both as a standalone treatment and in combination with remdesivir, which is currently the only FDA-approved drug for the treatment of COVID-19.

Amino acid transporter B0AT1 influence on ADAM17 interactions with SARS-CoV-2 receptor ACE2 putatively expressed in intestine, kidney, and cardiomyocytes (preprint)

SARS-CoV-2 exhibits significant experimental and clinical gastrointestinal, renal, and cardiac muscle tropisms responsible for local tissue-specific and systemic pathophysiology capriciously occurring in about half of COVID-19 patients. The underlying COVID-19 mechanisms engaged by these extra-pulmonary organ systems are largely unknown. We approached this knowledge gap by recognizing that neutral amino acid transporter B0AT1 (alternately called NBB, B, B0 in the literature) is a common denominator expressed nearly exclusively by three particular cell types: intestinal epithelia, renal proximal tubule epithelium, and cardiomyocytes. B0AT1 provides uptake of glutamine and tryptophan. The gut is the main depot expressing over 90% of the body's entire pool of SARS-CoV-2 receptor angiotensin converting enzyme-2 (ACE2) and B0AT1. Recent cryo-EM studies established that ACE2 forms a thermodynamically favored dimer-of-heterodimers complex with B0AT1 assembled in the form of a dimer of two ACE2:B0AT1 heterodimers anchored in plasma membranes. Prior epithelial cell studies demonstrated ACE2 chaperone trafficking of B0AT1. This contrasts with monomeric expression of ACE2 in lung pneumocytes, in which B0AT1 is undetectable. The cell types in question also express a disintegrin and metalloproteinase-17 (ADAM17) known to cleave and shed the ectodomain of monomeric ACE2 from the cell surface, thereby relinquishing protection against unchecked renin-angiotensin-system (RAS) events of COVID 19. The present study employed molecular docking modeling to examine the interplaying assemblage of ACE2, ADAM17 and B0AT1. We report that in the monomer form of ACE2, neck region residues R652-N718 provide unimpeded access to ADAM17 active site pocket, but notably R708 and S709 remained >10-15 [A] distant. In contrast, interference of ADAM17 docking to ACE2 in a dimer-of-heterodimers arrangement was directly correlated with the presence of a neighboring B0AT1 subunit complexed to the partnering ACE2 subunit of the 2ACE2:2B0AT1 dimer of heterodimers, representing the expression pattern putatively exclusive to intestinal, renal and cardiomyocyte cell types. The monomer and dimer-of-heterodimers docking models were not influenced by the presence of SARS-CoV-2 receptor binding domain (RBD) complexed to ACE2. The results collectively provide the underpinnings for understanding the role of B0AT1 involvement in COVID-19 and the role of ADAM17 steering ACE2 events in intestinal and renal epithelial cells and cardiomyocytes, with implications useful for consideration in pandemic public hygiene policy and drug development.