Phospholipid remodeling and its derivatives are associated with COVID-19 severity.

BACKGROUND: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. OBJECTIVE: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. METHODS: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. RESULTS: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. CONCLUSION: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.

Phospholipid remodeling and its derivatives are associated with the severity of COVID-19

Graphical Background Timely medical interventions in severe cases of COVID-19 and better understanding of the pathogenesis are essential for reducing the mortality, but early classification of severe cases and its progression is challenging. Objective To investigate the levels of circulating phospholipid metabolites and their relationship with the severity of COVID-19 and the potential role of phospholipids in the progression of the disease. Methods In this study, we performed non-targeted lipidomic analysis of plasma samples (n=150) collected from COVID-19 patients (N=46) with three levels of severity, healthy individuals and subjects with metabolic diseases. Results Results showed that phospholipid metabolism was significantly altered in COVID-19 patients. A panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with the severity of COVID-19, in which 16 phospholipid ratios were shown to distinguish severe patients from mild cases and healthy controls, and 9 of which were at variance with those in subjects with metabolic diseases. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC16:1 and (PE18:1/22:6)/LPE18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC16:1 and LPE18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC16:1 and LPE18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. Conclusion These results demonstrate significant Lands cycle remodeling in patients with severe COVID-19, and suggest the potential utility of selective phospholipids with functional consequences in evaluating COVID-19 severity and its pathogenesis. Phospholipid ratio correlated with the severity of COVID-19, and the biological functions of phospholipid derivatives may be associated with exacerbation of the disease

Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids.

Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.

Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients.

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.

Equipment-free, gold nanoparticle based semiquantitative assay of SARS-CoV-2-S1RBD IgG from fingertip blood: A practical strategy for on-site measurement of COVID-19 antibodies.

COVID-19 remains as a major threat to human society. A reliable, sensitive, rapid, and low requirement assay for serum neutralizing antibodies is needed as a pandemic management tool for estimation of revaccination time and implementation of "immune passport". Using gold nanoparticle (AuNR) as an immunosensor, we have established a semi-quantitative, instrument-free assay for measuring antibody level against SRAS-CoV-2 spike1 (S1) receptor binding domain (RBD) from fingertip blood samples. The testing results by the developed method correlated well with those obtained from conventional ELISA assay, indicating reliable quantitation could be achieved without use of plate reader. A declined of immunoglobulin G (IgG) antibody associated with vaccination time was observed, which agreed well with the data from other reports. The developed method provides a potentially complementary strategy for on-site measurement of COVID-19 antibodies.

Investigation of PM2.5 pollution during COVID-19 pandemic in Guangzhou, China.

The COVID-19 pandemic has raised awareness about various environmental issues, including PM2.5 pollution. Here, PM2.5 pollution during the COVID-19 lockdown was traced and analyzed to clarify the sources and factors influencing PM2.5 in Guangzhou, with an emphasis on heavy pollution. The lockdown led to large reductions in industrial and traffic emissions, which significantly reduced PM2.5 concentrations in Guangzhou. Interestingly, the trend of PM2.5 concentrations was not consistent with traffic and industrial emissions, as minimum concentrations were observed in the fourth period (3/01-3/31, 22.45 µg/m3) of the lockdown. However, the concentrations of other gaseous pollutants, e.g., SO2, NO2 and CO, were correlated with industrial and traffic emissions, and the lowest values were noticed in the second period (1/24-2/03) of the lockdown. Meteorological correlation analysis revealed that the decreased PM2.5 concentrations during COVID-19 can be mainly attributed to decreased industrial and traffic emissions rather than meteorological conditions. When meteorological factors were included in the PM2.5 composition and backward trajectory analyses, we found that long-distance transportation and secondary pollution offset the reduction of primary emissions in the second and third stages of the pandemic. Notably, industrial PM2.5 emissions from western, southern and southeastern Guangzhou play an important role in the formation of heavy pollution events. Our results not only verify the importance of controlling traffic and industrial emissions, but also provide targets for further improvements in PM2.5 pollution.

Influence of COVID-19 lockdown on the variation of organic aerosols: Insight into its molecular composition and oxidative potential.

To prevent the transmission of the novel coronavirus disease 2019 (COVID-19), China adopted nationwide lockdown measures on January 25, 2020, leading to an evident diminution in the observed air pollutants. To investigate the influence of the lockdown on atmospheric chemistry, the specific molecular composition, oxidative potential of organic aerosols (OAs) in PM2.5 were studied using a high-resolution orbitrap mass spectrometry at a typical coal-combustion city, Linfen, in the North China Plain (NCP). The major air pollutants including PM2.5, PM10, SO2, NO2, and CO were observed to be diminished by 28.6-45.4%, while O3 was augmented by 52.5% during the lockdown compared to those before the lockdown. A significant decrease of oxygen-containing (CHO) compounds (24.7%) associated with anthropogenic acids was observed during the lockdown, implying a reduction in fossil fuel combustion. The coal-burning related sulfur-containing organosulfates (CHOS-) and nitrooxy-sulfates (CHONS-) have also shown attenuated in both their relative abundances and anthropogenic/biogenic ratios. Amine/amide-like CHON + components have decreased by 27.6%, while nitro/nitrooxy-containing CHON- compounds have only decreased by 7.1%. Multi-source nitrogen-containing (CHN) compounds have shown a moderate elimination of 24.0%, while the identified high-condensed azaarenes have fallen from 17.7% to 14.7%, implying a potential reduction in the health risk of OAs during quarantine. The measurement of OAs' oxidative potential through dithiothreitol (DTT) assay has confirmed that as it had dropped from 0.88 nmol min-1 m-3 to 0.80 nmol min-1 m-3. High correlations were observed between the abundance of OA subgroups with the concentration of PM2.5 after the execution of the lockdown, suggesting a potential elevation in the contribution of organic components to the total PM2.5 level. Our study provides insightful compositional and health-related information in the variation of OAs during the lockdown period and attests to the validity of joint-control strategy in controlling the level and health risks of numerous atmospheric pollutants.

Release of tens of thousands of microfibers from discarded face masks under simulated environmental conditions.

While mechanical abrasion by water and sediment is a primary and critical step in weathering process, the upsurge of discarded face masks will undoubtedly become a potential source of micro-/nanofibers owing to the spread of novel coronavirus (COVID-19) pneumonia. However, effects of mechanical abrasion on discarded face masks have neither been seriously addressed nor understood. Therefore, we conducted a simulated experiment to explore abundance, size distribution and morphology of microfibers released from common, surgical and face filtering piece (FFP) masks after mechanical abrasion. Technologies such as Fourier transform infrared spectrometry, fluorescence microscopy, scanning electron microscopy, and confocal laser scanning microscopy were used. Results showed that the abundance of released microfibers followed order of surgical > common > FFP in both water and sediment environments, and the maximum abundance reached 272 ± 12.49 items per square centimeter of mask (items·cm-2) after sediment abrasion. Taking surgical mask for further investigation, the length of released fiber was observed to vary from 47.78 µm to 3.93 mm, and 72.41-89.58% of the total number of released microfibers fell in the range of 0.1-1 mm. However, microfibers with a very small length (1-100 µm) can occupy 0.09-13.59% of the total number of released fibers in sediment environment. The roughness of fiber surface after sediment abrasion was successively increased. Furthermore, the morphology analysis showed significant changes with countless cracks and many prominent protrusions on fiber surface after sediment abrasion. The cracks and protrusions may further accelerate mask decomposition, thereby potentially resulting in the adsorption of other contaminants and the release of self-containing chemicals. This study provides a valuable database of microfibers released from discarded face masks at the primary but critical stage, and further contributes knowledge on environmental impact of discarded personal protective equipment due to COVID-19.

Mass Spectrometry-based Proteomics and Glycoproteomics in COVID-19 Biomarkers Identification: A Mini-review.

The first corona-pandemic, coronavirus disease 2019 (COVID-19) caused a huge health crisis and incalculable damage worldwide. Knowledge of how to cure the disease is urgently needed. Emerging immune escaping mutants of the virus suggested that it may be potentially persistent in human society as a regular health threat as the flu virus. Therefore, it is imperative to identify appropriate biomarkers to indicate pathological and physiological states, and more importantly, clinic outcomes. Proteins are the performers of life functions, and their abundance and modification status can directly reflect the immune status. Protein glycosylation serves a great impact in modulating protein function. The use of both unmodified and glycosylated proteins as biomarkers has also been proved feasible in the studies of SARS, Zika virus, influenza, etc. In recent years, mass spectrometry-based glycoproteomics, as well as proteomics approaches, advanced significantly due to the evolution of mass spectrometry. We focus on the current development of the mass spectrometry-based strategy for COVID-19 biomarkers' investigation. Potential application of glycoproteomics approaches and challenges in biomarkers identification are also discussed.

Intertidal Zone Effects on Occurrence, Fate and Potential Risks of Microplastics with Perspectives under COVID-19 Pandemic

Micro-(nano-)plastics have become emerging contaminants worldwide in recent years. However, there has not been a critical review on their fate and potential risk in intertidal zones with different geological conditions. Thus, this review provides a comprehensive analysis of the roles of intertidal zones in accumulation or transportation of microplastics, involving convergence, migration, plastiglomerate, and ingestion effects. It is found that microplastics (MPs) are likely to be stranded in mudflats but be transported across the sandy beaches according to their intrinsic and external conditions. Meanwhile, MPs could also form the contamination of plastiglomerate and act as vectors for contaminants, even pathogens, in rocky and biological beaches. Thus, MPs together with nanoplastics (NPs) could potentially threaten the ecosystems of the intertidal zone by their ingestion and translocation. In view of the upsurge of personal protective equipment (PPE) during COVID-19, the occurrence of discarded PPE in the intertidal zones has also been summarized and discussed. Despite that the amount of discarded PPE is relatively smaller than other MPs, the pollution caused by these wastes could increase the possibility for pathogen-attached MPs becoming the source for spreading disease among wildlife and humans. It will be of vital importance for understanding the roles of intertidal zone in influencing the fate and ecotoxicity of the MPs. Moreover, the in-depth discussion on fate of the PPE in each kinds of intertidal zones can be conducive to drawing more attentions on plastic concerns in COVID-19 pandemic and achieving environmental sustainability.

Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV-infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-ß expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-ß expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-ß induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.

Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.