How to Prepare for the Next Pandemic -- Investigation of Correlation Between Food Prices and COVID-19 From Global and Local Perspectives (preprint)

The coronavirus disease (COVID-19) has caused enormous disruptions to not only the United States, but also the global economy. Due to the pandemic, issues in the supply chain and concerns about food shortage drove up the food prices. According to the U.S. Bureau of Labor Statistics, the prices for food increased 4.1% and 3.7% over the year ended in August 2020 and August 2021, respectively, while the amount of annual increase in the food prices prior to the COVID-19 pandemic is less than 2.0%. Previous studies show that such kinds of exogenous disasters, including the 2011 Tohoku Earthquake, 9/11 terrorist attacks, and major infectious diseases, and the resulted unusual food prices often led to subsequent changes in people's consumption behaviors. We hypothesize that the COVID-19 pandemic causes food price changes and the price changes alter people's grocery shopping behaviors as well. To thoroughly explore this, we formulate our analysis from two different perspectives, by collecting data both globally, from China, Japan, United Kingdom, and United States, and locally, from different groups of people inside the US. In particular, we analyze the trends between food prices and COVID-19 as well as between food prices and spending, aiming to find out their correlations and the lessons for preparing the next pandemic.

Genome-wide characterization of SARS-CoV-2 cytopathogenic proteins in the search of antiviral targets (preprint)

Therapeutic inhibition of critical viral functions is important for curtailing coronavirus disease-2019 (COVID-19). We sought to identify antiviral targets through genome-wide characterization of SARS-CoV-2 proteins that are crucial for viral pathogenesis and that cause harmful cytopathic effects. All twenty-nine viral proteins were tested in a fission yeast cell-based system using inducible gene expression. Twelve proteins including eight non-structural proteins (NSP1, NSP3, NSP4, NSP5, NSP6, NSP13, NSP14 and NSP15) and four accessory proteins (ORF3a, ORF6, ORF7a and ORF7b) were identified that altered cellular proliferation and integrity, and induced cell death. Cell death correlated with the activation of cellular oxidative stress. Of the twelve proteins, ORF3a was chosen for further study in mammalian cells. In human pulmonary and kidney epithelial cells, ORF3a induced cellular oxidative stress associated with apoptosis and necrosis, and caused activation of pro-inflammatory response with production of the cytokines TNF-alpha, IL-6, and IFN-beta1, possibly through the activation of NF-kappa B. To further characterize the mechanism, we tested a natural ORF3a Beta variant, Q57H, and a mutant with deletion of the highly conserved residue, deltaG188. Compared to wild type ORF3a, the delataG188 variant yielded more robust activation of cellular oxidative stress, cell death, and innate immune response. Since cellular oxidative stress and inflammation contribute to cell death and tissue damage linked to the severity of COVID-19, our findings suggest that ORF3a is a promising, novel therapeutic target against COVID-19.

Tetracycline as an inhibitor to the coronavirus SARS-CoV-2 (preprint)

The coronavirus SARS-CoV-2 remains an extant threat against public health on a global scale. Cell infection begins when the spike protein of SARS-CoV-2 binds with the cell receptor, angiotensin-converting enzyme 2 (ACE2). Here, we address the role of Tetracycline as an inhibitor for the receptor-binding domain (RBD) of the spike protein. Targeted molecular investigation show that Tetracycline binds more favorably to the RBD (-9.40 kcal/mol) compared to Chloroquine (-6.31 kcal/mol) or Doxycycline (-8.08 kcal/mol) and inhibits attachment to ACE2 to a greater degree (binding efficiency of 2.98 $\frac{\text{kcal}}{\text{mol}\cdot \text{nm}^2}$ for Tetracycline-RBD, 5.59 $\frac{\text{kcal}}{\text{mol}\cdot \text{nm}^2}$ for Chloroquine-RBD, 5.16 $\frac{\text{kcal}}{\text{mol}\cdot \text{nm}^2}$ for Doxycycline-RBD). Stronger Tetracycline inhibition is verified with nonequilibrium PMF calculations, for which the Tetracycline-RBD complex exhibits the lowest free energy profile along the dissociation pathway from ACE2. Tetracycline appears to target viral residues that are usually involved in significant hydrogen bonding with ACE2; this inhibition of cellular infection complements the anti-inflammatory and cytokine suppressing capability of Tetracycline, and may further reduce the duration of ICU stays and mechanical ventilation induced by the coronavirus SARS-CoV-2.

Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19 (preprint)

A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, the molecular and cellular mechanisms by which the virus causes lethal immunopathology are poorly understood. Here, we utilize multi-omics single-cell analysis to probe dynamic immune responses in patients with stable or progressive manifestations of COVID-19, and assess the effects of tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling of gene expression and cell lineage protein markers reveals a prominent type-1 interferon response across all immune cells, especially in progressive patients. An anti-inflammatory innate immune response and a pre-exhaustion phenotype in activated T cells are hallmarks of progressive disease. Skewed T cell receptor repertoires in CD8 T cells and uniquely enriched V(D)J sequences are also identified in COVID-19 patients. B cell repertoire and somatic hypermutation analysis are consistent with a primary immune response, with possible contribution from memory B cells. Our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19, which may contribute to delayed virus clearance and has implications for therapeutic intervention.

A Clinical Multi-center Study of Pregnant Women with COVID-19 in Hubei, China (preprint)

Background: Coronavirus disease 2019 (COVID-19) has rapidly spread to more than 200 countries. Thus far, reports regarding multi-center data from throughout gestation in women with COVID-19 and newborn outcomes are scarce.Methods: We retrospectively reviewed data from 92 pregnant women with COVID-19 (PW-COVID-19) and their 78 newborns from 27 hospitals in 12 regions of Hubei, China. The demographic, epidemiological, clinical, laboratory, and therapeutic data and pregnancy, perinatal, and neonatal outcomes were analyzed. Follow-up was censored until April 7, 2020.Findings: Median maternal age was 31.0 years (IQR 28·0-33·0), with nine patients in the first trimester, five in the second trimester, and 78 in the third trimester. None of the patients died, and most (92·4%) recovered and were discharged. Seventy-five deliveries (including three sets of twins) comprised 66 cesarean sections and nine vaginal deliveries, with 21 preterm and 57 full-term infants. Seventeen live births had radiological findings of pulmonary infection. One newborn tested positive for SARS-CoV-2 nucleic acid, and three newborns were viral antibody-positive: two IgG (+) and IgM (-), and one IgG (+) and IgM (+). The median suspected duration of virus exposure was 7 days (IQR 0 to 27).Interpretation: Compared to the pregnant women with other viral infections, such as SARS, MERS, and Zika virus infection, PW-COVID-19 had similar manifestations and relatively better outcomes. The termination time and delivery mode in PW-COVID-19 should be evaluated based on both the maternal and fetal situations. The possibility of maternal-to-fetal transmission of SARS-CoV-2 requires further investigation.Authors Shujie Liao and Renjie Wang contributed equally to this work.