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

Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.

BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028). INTERPRETATION: Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies. FUNDING: Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos.

The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. METHODS: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. FINDINGS: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. INTERPRETATION: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. FUNDING: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.

COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study.

BACKGROUND: COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose. METHODS: VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28-49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data. FINDINGS: Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11-0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31-0·87]; p=0·012), and thiopurine (0·69 [0·51-0·95]; p=0·021), but not with ustekinumab (0·64 [0·39-1·06]; p=0·083), or vedolizumab (0·84 [0·54-1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22-2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80-0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021). INTERPRETATION: A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors. FUNDING: Pfizer.

Mental Health and Psychological Responses During the Coronavirus Disease 2019 Epidemic: A Comparison Between Wuhan and Other Areas in China.

OBJECTIVE: This study aimed to compare the mental health and psychological responses in Wuhan, a severely affected area, and other areas of China during the coronavirus disease 2019 (COVID-19) epidemic. METHODS: This cross-sectional study was conducted on February 10-20, 2020. A set of online questionnaires was used to measure mental health and responses. A total of 1397 participants from Wuhan (age, 36.4 ± 10.7 years; male, 36.1%) and 2794 age- and sex-matched participants from other areas of China (age, 35.9 ± 9.9 years; male, 39.0%) were recruited. RESULTS: Compared with their counterparts, participants from Wuhan had a significantly higher prevalence of any mental health problems (46.6% versus 32.2%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.65-2.17), anxiety (15.2% versus 6.2%; adjusted OR = 2.65, 95% CI = 2.14-3.29), depression (18.3% versus 9.7%; adjusted OR = 2.11, 95% CI = 1.74-2.54), suicidal ideation (10.5% versus 7.1%; adjusted OR = 1.60, 95% CI = 1.28-2.02), and insomnia (38.6% versus 27.6%; adjusted OR = 1.70, 95% CI = 1.48-1.96). Participants from Wuhan had a slightly higher rate of help-seeking behavior (7.1% versus 4.2%; adjusted OR = 1.76, 95% CI = 1.12-2.77) but similar rate of treatment (3.5% versus 2.7%; adjusted OR = 1.23, 95% CI = 0.68-2.24) for mental problems than did their counterparts. In addition, compared with their counterparts, participants from Wuhan gave higher proportions of responses regarding "fearful" (52% versus 36%, p < .001), "discrimination against COVID-19 cases" (64% versus 58%, p = .006), "strictly comply with preventive behaviors" (98.7% versus 96%, p = .003), and "fewer living and medical supplies" (<2 weeks: 62% versus 57%, p = .015). CONCLUSIONS: The COVID-19 epidemic has raised enormous challenges regarding public mental health and psychological responses, especially in the highly affected Wuhan area. The present findings provide important information for developing appropriate strategies for the prevention and management of mental health problems during COVID-19 and other epidemics.

Exploring the Potential Pharmacological Mechanism of Hesperidin and Glucosyl Hesperidin against COVID-19 Based on Bioinformatics Analyses and Antiviral Assays.

The development of anti-COVID-19 drugs has become the top priority since the outbreak of the epidemic, and Traditional Chinese medicine plays an important role in reducing mortality. Here, hesperidin and its glycosylation product, glucosyl hesperidin were selected to determine their antiviral activity against SARS-CoV-2 due to their structural specificity as reported. To be specific, their binding ability with ACE2, M, S, RBD and N proteins were verified with both in silico and wet lab methods, i.e., molecular docking and binding affinity tests, including biolayer interferometry assay (BLI) and isothermal titration calorimetry assay (ITC). Moreover, systematic pharmacological analysis was conducted to reveal their pharmacological mechanism in treating COVID-19. Finally, their antiviral activity against SARS-CoV-2 was determined in vitro in a biosafety level 3 (BSL3) laboratory. The results demonstrated their outstanding binding affinity with ACE2, M, S and RBD proteins, while showed barely unobserved binding with N protein, indicating their key roles in influencing the invasion and early replication phase of SARS-CoV-2. In addition, both hesperidin and glucosyl hesperidin were shown to have a great impact on immune, inflammation and virus infection induced by COVID-19 according to the systematic pharmacological analysis. Moreover, the IC50s of hesperidin and glucosyl hesperidin against SARS-CoV-2 were further determined (51.5 [Formula: see text]M and 5.5 mM, respectively) with cell-based in vitro assay, suggesting their great anti-SARS-CoV-2 activity. All in all, present research was the first to verify the binding ability of hesperidin and glucosyl hesperidin with SARS-CoV-2 proteins with both in silico and wet-lab methods and proposed the possibility of applying hesperidin and glucosyl hesperidin to treat COVID-19.

A survey of mental health status of obstetric nurses during the novel coronavirus pneumonia pandemic.

ABSTRACT: To investigate the mental health status of obstetric nurses and its influencing factors during the novel coronavirus epidemic period, so as to provide theoretical reference for hospital decision-makers and managers.From February 25 to March 20, 2020, we conducted a cross-sectional survey through online questionnaire, and selected obstetric nurses from Jilin and Heilongjiang Provinces as the research objects by convenience sampling.Three hundred eighteen valid questionnaires were collected; the results of Symptom Checklist 90 showed that the scores of "obsessive-compulsive", "depression", "anxiety", "hostility", "phobia", and "psychosis" were higher than the Chinese norm (P < .01). There were 107 people whose total score of Symptom Checklist 90 was more than 160, and 83 people whose number of positive items was more than 43. Logistic regression results showed that married, temporary employment, lack of support and communication from family and relatives, onerous task, and unbearable responsibility were independent risk factors for mental disorder.There is a great psychological burden for obstetric nurses during the epidemic period. Decision makers should focus on necessary psychological intervention for those that are married, temporarily employed, and those lacking family supports including communication. At the same time, managers should distribute tasks reasonably to avoid psychological burdens caused by overwork.

COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study.

BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations. INTERPRETATION: For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised. FUNDING: Pfizer.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Advanced applications of mass spectrometry imaging technology in quality control and safety assessments of traditional Chinese medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCMs) have made great contributions to the prevention and treatment of human diseases in China, and especially in cases of COVID-19. However, due to quality problems, the lack of standards, and the diversity of dosage forms, adverse reactions to TCMs often occur. Moreover, the composition of TCMs makes them extremely challenging to extract and isolate, complicating studies of toxicity mechanisms. AIM OF THE REVIEW: The aim of this paper is therefore to summarize the advanced applications of mass spectrometry imaging (MSI) technology in the quality control, safety evaluations, and determination of toxicity mechanisms of TCMs. MATERIALS AND METHODS: Relevant studies from the literature have been collected from scientific databases, such as "PubMed", "Scifinder", "Elsevier", "Google Scholar" using the keywords "MSI", "traditional Chinese medicines", "quality control", "metabolomics", and "mechanism". RESULTS: MSI is a new analytical imaging technology that can detect and image the metabolic changes of multiple components of TCMs in plants and animals in a high throughput manner. Compared to other chemical analysis methods, such as liquid chromatography-mass spectrometry (LC-MS), this method does not require the complex extraction and separation of TCMs, and is fast, has high sensitivity, is label-free, and can be performed in high-throughput. Combined with chemometrics methods, MSI can be quickly and easily used for quality screening of TCMs. In addition, this technology can be used to further focus on potential biomarkers and explore the therapeutic/toxic mechanisms of TCMs. CONCLUSIONS: As a new type of analysis method, MSI has unique advantages to metabolic analysis, quality control, and mechanisms of action explorations of TCMs, and contributes to the establishment of quality standards to explore the safety and toxicology of TCMs.

Rapid Detection of Anti-SARS-CoV-2 Antibody Using a Selenium Nanoparticle-Based Lateral Flow Immunoassay.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is highly transmissible. Early and rapid testing is necessary to effectively prevent and control the outbreak. Detection of SARS-CoV-2 antibodies with lateral flow immunoassay can achieve this goal. In this study, SARS-CoV-2 nucleoprotein (NP) was expressed and purified. We used the selenium nanoparticle as the labeling probe coupled with the NP to prepare an antibody (IgM and IgG) detection kit. The detection limit, cross reaction, sensitivity and specificity of the kit is verified. Separate detection of IgM and IgG, such as in this assay, was performed in order to reduce mutual interference and improve the accuracy of the test results.The final purity of NP was 91.83%. Selenium nanoparticle and NP successfully combined with stable effect. The LOD of the kit was 20 ng/mL for anti-NP IgG and 60 ng/mL for anti-NP IgM, respectively. The kit does not cross reaction with RF. The sensitivity of the kit was 94.74% and the specificity was 96.23%. The assay kit does not require any special device for reading the results and the readout is a simple color change that can be evaluated with the naked eye. This kit is suitable for rapid and real-time detection of the SARS-CoV-2 antibody IgG and IgM.

Application of Traditional Chinese Medicine and Systems Pharmacology in Drug Prevention and Treatment against COVID-19.

A novel coronavirus named SARS-CoV-2 is causing the severe acute pneumonia (COVID-19) and rapid spread nationally and internationally, resulting in a major global health emergency. Chinese governments and scientists have implemented a series of rigorous measures and scientific research to prevent and control the SARS-CoV-2 infection. However, there is still no specific antiviral drug or vaccine against SARS-CoV-2. It has been proven that traditional Chinese medicine (TCM) exerts an important role in the prevention and treatment of the COVID-19 caused by SARS-CoV-2 during the outbreak. Although the therapeutic effects of these TCM formulas are attractive, the molecular mechanism of action has not been fully elucidated. An emerging strategy of systems pharmacology has been proposed to be a promising method to interpret drug action in complex biological systems and quickly screen out the bioactive compounds from TCM to treat treatment of COVID-19 caused by SARS-CoV-2. Therefore, in this study, the epidemiology, TCM therapy, and the systems pharmacology-based method for TCM are reviewed for COVID-19 to provide a perspective for the prevention and treatment of SARS-CoV-2 infection. Further efforts should be made to reduce disease burden and improve the ability to design antiviral drugs and vaccines, which will benefit the health care system, economic development and even social stability.

Serum levels of the IgA isotype switch factor TGF-ß1 are elevated in patients with COVID-19.

We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-ß1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-ß1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2-specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-ß1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-ß1 may play a key role in COVID-19.

Multiplexed analysis of circulating IgA antibodies for SARS-CoV-2 and common respiratory pathogens in COVID-19 patients.

Previous studies have revealed a diagnostic role of pathogen-specific IgA in respiratory infections. However, co-detection of serum specific IgA for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common respiratory pathogens remains largely unexplored. This study utilizes a protein microarray technology for simultaneous and quantitative measurements of specific IgAs for eight different respiratory pathogens including adenovirus, respiratory syncytial virus, influenza virus type A, influenza virus type B, parainfluenza virus, mycoplasma pneumoniae, chlamydia pneumoniae, and SARS-CoV-2 in serum sample of patients with coronavirus disease 2019 (COVID-19). A total of 42 patients with COVID-19 were included and categorized into severe cases (20 cases) and nonsevere cases (22 cases). The results showed that co-detection rate of specific-IgA for SARS-CoV-2 with at least one pathogen were significantly higher in severe cases than that of nonsevere cases (72.2% vs. 46.2%, p = .014). Our study indicates that co-detection of IgA antibodies for respiratory pathogens might provide diagnostic value for the clinics and also be informative for risk stratification and disease management in patients with COVID-19.

Auxiliary Diagnosis for COVID-19 with Deep Transfer Learning.

To assist physicians identify COVID-19 and its manifestations through the automatic COVID-19 recognition and classification in chest CT images with deep transfer learning. In this retrospective study, the used chest CT image dataset covered 422 subjects, including 72 confirmed COVID-19 subjects (260 studies, 30,171 images), 252 other pneumonia subjects (252 studies, 26,534 images) that contained 158 viral pneumonia subjects and 94 pulmonary tuberculosis subjects, and 98 normal subjects (98 studies, 29,838 images). In the experiment, subjects were split into training (70%), validation (15%) and testing (15%) sets. We utilized the convolutional blocks of ResNets pretrained on the public social image collections and modified the top fully connected layer to suit our task (the COVID-19 recognition). In addition, we tested the proposed method on a finegrained classification task; that is, the images of COVID-19 were further split into 3 main manifestations (ground-glass opacity with 12,924 images, consolidation with 7418 images and fibrotic streaks with 7338 images). Similarly, the data partitioning strategy of 70%-15%-15% was adopted. The best performance obtained by the pretrained ResNet50 model is 94.87% sensitivity, 88.46% specificity, 91.21% accuracy for COVID-19 versus all other groups, and an overall accuracy of 89.01% for the three-category classification in the testing set. Consistent performance was observed from the COVID-19 manifestation classification task on images basis, where the best overall accuracy of 94.08% and AUC of 0.993 were obtained by the pretrained ResNet18 (P < 0.05). All the proposed models have achieved much satisfying performance and were thus very promising in both the practical application and statistics. Transfer learning is worth for exploring to be applied in recognition and classification of COVID-19 on CT images with limited training data. It not only achieved higher sensitivity (COVID-19 vs the rest) but also took far less time than radiologists, which is expected to give the auxiliary diagnosis and reduce the workload for the radiologists.