Results: There were 636,282 new cases and 28,325 deaths of COVID-19 in the USA from March 1 to April 15, 2020, with a crude mortality of 4.45%. The daily new cases peaked at 35,098 cases on April 10, 2020 and the daily deaths peaked at 2,494 on April 15, 2020. The search interest of COVID, "COVID pneumonia" and "COVID heart" were correlated with COVID-19 daily incidence, with 12 or 14 days of delay (Pearson's r = 0.978, 0.978 and 0.979, respectively) and deaths with 19 days of delay (Pearson's r = 0.963, 0.958 and 0.970, respectively). The 7-day follow-up with prospectively collected data showed no significant correlations of the observed data with the predicted daily new cases or daily deaths, using search interest of COVID, COVID heart, and COVID pneumonia.

The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22−/− mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22−/− mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22−/− compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22−/− brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22−/− mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.

Parkinson’s disease (PD) is mainly managed by pharmacological therapy (e.g., Benserazide and dopamine agonists). However, prolonged use of these drugs would gradually diminish their dopaminergic effect. Gut dysbiosis was observed in some patients with PD, suggesting close association between the gut microbiome and PD. Probiotics modulate the host’s gut microbiota beneficially. A 3-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the beneficial effect of probiotic co-administration in patients with PD. Eighty-two PD patients were recruited and randomly divided into probiotic [n = 48; Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8), Benserazide, dopamine agonists] and placebo (n = 34; placebo, Benserazide, dopamine agonists) groups. Finally, 45 and 29 patients from Probio-M8 and placebo groups provided complete fecal and serum samples for further omics analysis, respectively. The results showed that Probio-M8 co-administration conferred added benefits by improving sleep quality, alleviating anxiety, and gastrointestinal symptoms. Metagenomic analysis showed that, after the intervention, there were significantly more species-level genome bins (SGBs) of Bifidobacterium animalis, Ruminococcaceae, and Lachnospira, while less Lactobacillus fermentum and Klebsiella oxytoca in Probio-M8 group (P < 0.05). Interestingly, Lactobacillus fermentum correlated positively with the scores of UPDRS-III, HAMA, HAMD-17, and negatively with MMSE. Klebsiella oxytoca correlated negatively with feces hardness. Moreover, co-administering Probio-M8 increased SGBs involved in tryptophan degradation, gamma-aminobutyric acid, short-chain fatty acids, and secondary bile acid biosynthesis, as well as serum acetic acid and dopamine levels (P < 0.05). Taken together, Probio-M8 synergized with the conventional regimen and strengthened the clinical efficacy in managing PD, accompanied by modifications of the host’s gut microbiome, gut microbial metabolic potential, and serum metabolites.

Infections with West Nile virus (WNV) are typically asymptomatic, but some patients experience severe neurological disease and even death. Over 1500 fatalities have resulted from the more than 37,000 WNV cases in the USA between 1999 and 2012. While it is clear that age is a significant risk factor, markers of immune status associated with susceptibility to severe infections are incompletely defined. We have taken advantage of stable characteristics of individual status to profile immune markers from a stratified cohort of healthy subjects with a history of asymptomatic or severe infection with WNV. We characterized individual variations in antibody and serum cytokine levels and genome-wide transcriptional profiles of peripheral blood cells (PBMCs). While antibody levels were not significantly different between cohorts, we found that subjects with a history of severe infection had significantly lower levels of serum IL-4, and that these changes in IL-4 levels were associated with altered gene expression patterns in PBMCs. In addition, we identified a signature of 105 genes that displayed altered expression levels when comparing subjects with a history of asymptomatic or severe infection. These results suggest that systems-level analysis of immune system status can be used to identify factors relevant for susceptibility to severe infections, and specifically point to an important contribution for IL-4 in resistance to WNV infection.