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1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1970343

ABSTRACT

Background Asthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear. Methods COVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects. Results The strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188;and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p<0.05). Moreover, the level of NAbs in COVID-19 survivors was positively correlated with the percentage of Treg and cTfh2 cells (r=0.5037, p=0.002;and r=0.4846, p=0.0141), and negatively correlated with the percentage of Th1 and Th17 cells (r=-0.5701, p=0.0003;and r=-0.3656, p=0.0308), the ratio of Th1/Th2, Th17/Treg, and cTfh1/cTfh2 cell (r=-0.5356, r=-0.5947, r=-0.4485;all p<0.05). The decay rate of NAbs in the COVID-19 survivors with asthma was not significantly different from that of those without asthma at 16-month follow-up. Conclusion The level of SARS-CoV-2-specific NAbs in COVID-19 survivors with asthma was higher than that of those without asthma at 8-month follow-up. The SARS-CoV-2-specific T cell immunity was associated with blood eosinophils and Treg percentages. The SARS-CoV-2-specific humoral immunity was closely associated with cTfh2/cTfh1 imbalance and Treg/Th17 ratio. According to the findings, asthmatic patients in COVID-19 convalescent period may benefit from an enhanced specific humoral immunity, which associates with skewed Th2/Th1 and Treg/Th17 immune.

2.
Int J Behav Med ; 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1920134

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted many people's meaning in life and health behaviors. This study aimed to verify the relationship among meaning in life (MIL), epidemic risk perception, health locus of control (HLC), and preventive health behaviors among older adults after the COVID-19 outbreak was declared a pandemic. METHOD: In this longitudinal study, 164 participants aged 55 years and above completed the following measures at time 1 (February 19, 2021) and one month later at time 2 (March 19, 2021): Meaning in Life in the Epidemic Questionnaire, Epidemic Risk Perception Questionnaire, Multidimensional Health Locus of Control Scale, and Health Behaviors Before and After the Epidemic Survey. Hayes' SPSS Process Macro was used to analyze the mediating effect of epidemic risk perception (model 4) and the moderating role of powerful others HLC in the mediation model (model 14). RESULTS: The results showed that after controlling for gender, age, education level, and health behaviors at the baseline, risk perception had a significant mediating effect on the relationship between MIL and preventive health behaviors (ß = .02, SE = .01, 95% CI [.00, .04]). In addition, powerful others HLC had a moderating effect on the second half of the mediating effect (ß = .02, p = .02, 95% CI [.00, .03]). Specifically, compared to the older adults with low powerful others HLC, the risk perception of older adults with high powerful others HLC increased preventive health behaviors. CONCLUSION: Practitioners should adequately cultivate older adults' risk awareness and reinforce the importance of advice from doctors and professionals, thereby effectively enhancing the preventive health behaviors of older adults in China during the COVID-19 pandemic.

3.
Front Microbiol ; 13: 735363, 2022.
Article in English | MEDLINE | ID: covidwho-1809432

ABSTRACT

Objective: We aimed to evaluate the performance of nanopore amplicon sequencing detection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples. Method: We carried out a single-center, prospective cohort study in a Wuhan hospital and collected a total of 86 clinical samples, including 54 pharyngeal swabs, 31 sputum samples, and 1 fecal sample, from 86 patients with coronavirus disease 2019 (COVID-19) from Feb 20 to May 15, 2020. We performed parallel detection with nanopore-based genome amplification and sequencing (NAS) on the Oxford Nanopore Technologies (ONT) minION platform and routine reverse transcription quantitative polymerase chain reaction (RT-qPCR). In addition, 27 negative control samples were detected using the two methods. The sensitivity and specificity of NAS were evaluated and compared with those of RT-qPCR. Results: The viral read number and reference genome coverage were both significantly different between the two groups of samples, and the latter was a better indicator for SARS-CoV-2 detection. Based on the reference genome coverage, NAS revealed both high sensitivity (96.5%) and specificity (100%) compared with RT-qPCR (80.2 and 96.3%, respectively), although the samples had been stored for half a year before the detection. The total time cost was less than 15 h, which was acceptable compared with that of RT-qPCR (∼2.5 h). In addition, the reference genome coverage of the viral reads was in line with the cycle threshold value of RT-qPCR, indicating that this number could also be used as an indicator of the viral load in a sample. The viral load in sputum might be related to the severity of the infection, particularly in patients within 4 weeks after onset of clinical manifestations, which could be used to evaluate the infection. Conclusion: Our results showed the high sensitivity and specificity of the NAS method for SARS-CoV-2 detection compared with RT-qPCR. The sequencing results were also used as an indicator of the viral load to display the viral dynamics during infection. This study proved the wide application prospect of nanopore sequencing detection for SARS-CoV-2 and may more knowledge about the clinical characteristics of COVID-19.

4.
Front Microbiol ; 13: 782421, 2022.
Article in English | MEDLINE | ID: covidwho-1742229

ABSTRACT

While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2-3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.

5.
Front Immunol ; 13: 796682, 2022.
Article in English | MEDLINE | ID: covidwho-1731771

ABSTRACT

In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Hepatitis A Virus Cellular Receptor 2/immunology , Natural Killer T-Cells/immunology , SARS-CoV-2/immunology , Humans , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-4/immunology , Signal Transduction/immunology
6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321361

ABSTRACT

Background: Since December 2019, coronavirus disease 2019 (COVID-19), as an infectious disease with cytokine storm, has become an emerging global challenge. To assess the duration of SARS-COV-2 viral shedding and associated risk factors in COVID-19 patients. Methods: : COVID-19 patients with interleukin (IL)-1b, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α cytokines data consecutively admitted to Tongji Hospital from January 27, 2020 through February 5, 2020 were enrolled and been followed up until March 24, 2020. We utilized Kaplan-Meier method and Cox proportional hazards regression analysis to assess the duration of viral shedding and risk factors affecting virus clearance. Results: : 246 inpatients with laboratory confirmed COVID-19 were enrolled. The median duration of viral shedding was 24 days, ranging from 6 to 63 days. Age, severity of COVID-19, albumin, lactate dehydrogenase (LDH), D-dimer, ferritin and sIL-2R were associated with duration of viral shedding. Administration of lopinavir-ritonavir, arbidol, oseltamivir and intravenous immunoglobulin did not shorten viral shedding time. Multivariate cox regression analysis revealed that sIL-2R, LDH and severity of COVID-19 were independent factors associated with duration of viral shedding. At stratified analysis, the viral shedding time was positively correlated with age, sIL-2R and LDH in non-corticosteroid subgroup, while negatively correlated with lymphocyte count in corticosteroid group. Conclusions: : The present study demonstrated that elevated sIL-2R, increased LDH and severe status were related to prolongation of viral shedding in COVID-19 inpatients. Further research is urgent to investigate the mechanism of immune reaction involved in the virus clearance process and aim to the optimal antiviral therapy.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325009

ABSTRACT

Face-to-face speech data collection has been next to impossible globally due to COVID-19 restrictions. To address this problem, simultaneous recordings of three repetitions of the cardinal vowels were made using a Zoom H6 Handy Recorder with external microphone (henceforth H6) and compared with two alternatives accessible to potential participants at home: the Zoom meeting application (henceforth Zoom) and two lossless mobile phone applications (Awesome Voice Recorder, and Recorder;henceforth Phone). F0 was tracked accurately by all devices;however, for formant analysis (F1, F2, F3) Phone performed better than Zoom, i.e. more similarly to H6. Zoom recordings also exhibited unexpected drops in intensity. The results suggest that lossless format phone recordings present a viable option for at least some phonetic studies.

8.
Nat Biomed Eng ; 6(3): 276-285, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671563

ABSTRACT

The detection of samples at ultralow concentrations (one to ten copies in 100 µl) in biofluids is hampered by the orders-of-magnitude higher amounts of 'background' biomolecules. Here we report a molecular system, immobilized on a liquid-gated graphene field-effect transistor and consisting of an aptamer probe bound to a flexible single-stranded DNA cantilever linked to a self-assembled stiff tetrahedral double-stranded DNA structure, for the rapid and ultrasensitive electromechanical detection (down to one to two copies in 100 µl) of unamplified nucleic acids in biofluids, and also of ions, small molecules and proteins, as we show for Hg2+, adenosine 5'-triphosphate and thrombin. We implemented an electromechanical biosensor for the detection of SARS-CoV-2 into an integrated and portable prototype device, and show that it detected SARS-CoV-2 RNA in less than four minutes in all nasopharyngeal samples from 33 patients with COVID-19 (with cycle threshold values of 24.9-41.3) and in none of the 54 COVID-19-negative controls, without the need for RNA extraction or nucleic acid amplification.


Subject(s)
COVID-19 , Graphite , COVID-19/diagnosis , Humans , Ions , RNA, Viral/genetics , SARS-CoV-2/genetics
9.
Front Immunol ; 12: 780804, 2021.
Article in English | MEDLINE | ID: covidwho-1648493

ABSTRACT

Objectives: Currently, cardiovascular risk associated with COVID-19 has been brought to people's attention, but the mechanism is not clear. The aim of this study is to elucidate the mechanisms based on multiple omics data. Methodology: Weighted gene co-expression network analysis (WGCNA) was used to identify key pathways. Combination analysis with aneurysm and atherosclerosis related pathways, hypoxia induced factor-1 (HIF-1) signaling were identified as key pathways of the increased cardiovascular risk associated with COVID-19. ScMLnet algorithm based on scRNA-seq was used to explore the regulation of HIF-1 pathway by intercellular communication. Proteomic analysis was used to detect the regulatory mechanisms between IL18 and HIF-1 signaling pathway. Pseudo time locus analysis was used to study the regulation of HIF1 signaling pathway in macrophages and vascular smooth muscle cells (VSMC) phenotypic transformation. The Virtual Inference of protein-activity by Enriched Regulon (VIPER) analysis was used to study the activity of regulatory proteins. Epigenetic analysis based on methylation revealed epigenetic changes in PBMC after SARS-CoV-2 infection. Potential therapeutic compounds were explored by using Cmap algorithm. Results: HIF-1 signaling pathway is a common key pathway for aneurysms, atherosclerosis and SARS-CoV-2 infection. Intercellular communication analysis showed that macrophage-derived interleukin-18 (IL-18) activates the HIF-1 signaling pathway through IL18R1. Proteomic analysis showed that IL18/IL18R1 promote NF-κB entry into the nucleus, and activated the HIF-1 signaling pathway. Macrophage-derived IL18 promoted the M1 polarization of macrophages and the syntactic phenotype transformation of VSMCs. MAP2K1 mediates the functional regulation of HIF-1 signaling pathway in various cell types. Epigenetic changes in PBMC after COVID-19 infection are characterized by activation of the type I interferon pathway. MEK inhibitors are the promising compounds for the treatment of HIF-1 overactivation. Conclusions: The IL18/IL18R1/HIF1A axis is expected to be an therapeutic target for cardiovascular protection after SARS-CoV-2 infection. MEK inhibitors may be an choice for cardiovascular protection after SARS-COV-2 infection.


Subject(s)
Aneurysm/etiology , Aneurysm/metabolism , Atherosclerosis/etiology , Atherosclerosis/metabolism , COVID-19/blood , COVID-19/complications , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Interleukin-18 Receptor alpha Subunit/metabolism , Interleukin-18/metabolism , SARS-CoV-2 , Signal Transduction , Aneurysm/pathology , Atherosclerosis/pathology , COVID-19/virology , Case-Control Studies , Cells, Cultured , Epigenesis, Genetic , Humans , Interferon Type I/metabolism , Leukocytes, Mononuclear/metabolism , Macrophages/metabolism , Myocytes, Smooth Muscle/metabolism , NF-kappa B/metabolism , Proteomics/methods , RNA-Seq/methods , Risk Factors , Single-Cell Analysis/methods
10.
Nano Lett ; 21(22): 9450-9457, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1500414

ABSTRACT

Direct SARS-CoV-2 nucleic acid testing with fast speed and high frequency is crucial for controlling the COVID-19 pandemic. Here, direct testing of SARS-CoV-2 nucleic acid is realized by field-effect transistors (FETs) with an electro-enrichable liquid gate (LG) anchored by tetrahedral DNA nanostructures (TDNs). The applied gate bias electrostatically preconcentrates nucleic acids, while the liquid gate with TDNs provides efficient analyte recognition and signal transduction. The average diagnosis time is ∼80 s, and the limit of detection approaches 1-2 copies in 100 µL of clinical samples without nucleic acid extraction and amplification. As such, TDN-LG FETs solve the dilemma of COVID-19 testing on mass scale that diagnosis accuracy and speed undergo trade-off. In addition, TDN-LG FETs achieve unamplified 10-in-1 pooled nucleic acid testing for the first time, and the results are consistent with PCR. Thus, this technology promises on-site and wide population COVID-19 screening and ensures safe world-reopening.


Subject(s)
COVID-19 , Nanostructures , Nucleic Acids , COVID-19 Testing , DNA/genetics , Humans , Pandemics , SARS-CoV-2 , Sensitivity and Specificity
11.
Blood ; 136(Supplement 1):38-38, 2020.
Article in English | PMC | ID: covidwho-1339061

ABSTRACT

Background:The prevalence of deep vein thrombosis in hospitalized patients with COVID-19 is higher and is associated with adverse outcomes. However, the treatment options received by patients with different classifications are different, and previous studies have not discussed the differences in specific coagulation parameters between patients with mild, severe, and critically ill COVID-19.Aim:To investigate the change in coagulation function and the incidence of low limb venous thromboembolic events in mild/severe/critically ill patients with COVID-19.Methods:A retrospective analysis of coagulation parameters and lower extremity venous ultrasound examination results in 77 patients with laboratory-confirmed COVID-19 admitted to the first affiliated hospital of Harbin Medical University. We discussed the occurrence of vascular complications in patients with normal, severe and critically ill patients Rate and explore the nature of such vascular events. The anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis and patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Approval was obtained from the local institutional review board and all procedures were performed in accordance with the Declaration of Helsinki.Results:The incidence of low limb venous thromboembolic events in COVID-19 patients included in the study was 28.6% (22/77). A total of 22 cases with deep vein thrombosis, 13 of whom with multiple thrombosis events, and 9 cases with independent distal deep vein thrombosis. There were 0 cases, 8 cases (17.4%) and 14 cases (87.5%) of patients with deep vein thrombosis occurred in mild, severe and critically ill patients, respectively. There were 4 cases (50%) and 9 cases (64.29%) of severe and critically ill patients with multiple deep vein thrombosis events, respectively. There was no difference in age and gender between patients with lower extremity venous thrombosis and those without. The mortality rate of patients with thrombotic events has an upward trend;the mortality rate of patients with thrombosis is 18.18%, and the mortality rate of patients without thrombosis is 3.64%. Compared with mild patients, white blood cell counts, neutrophil percentage, fibrinogen, IL-6, IL-10 serum levels are higher in severe and critically ill patients. The patients whose ultrasonography reported thrombosis mostly showed a dynamic increase and/or a significant increase in D-dimer. The patients whose ultrasonography reported no thrombosis showed mildly elevated D-dimer or within the normal range.Conclusions:The development of massive venous thrombotic events, as observed in our study cohort, suggests the possibility of COVID-19 associated hypercoagulability and endothelial activation and/or dysfunction in affected individuals.Figure

12.
Aging Dis ; 12(3): 691-704, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1315004

ABSTRACT

The coronavirus disease 2019 (COVID-19) has spread rapidly as a pandemic around the world. In addition to severe acute respiratory syndrome, more and more studies have focused on the complication of COVID-19, especially ischemic stroke. Here, we propose several pathophysiological processes and possible mechanisms underlying ischemic stroke after COVID-19 for early prevention and better treatment of COVID-19-related stroke.

13.
Sci Rep ; 11(1): 13854, 2021 07 05.
Article in English | MEDLINE | ID: covidwho-1297314

ABSTRACT

To describe the long-term health outcomes of patients with COVID-19 and investigate the potential risk factors. Clinical data during hospitalization and at a mean (SD) day of 249 (15) days after discharge from 40 survivors with confirmed COVID-19 (including 25 severe cases) were collected and analyzed retrospectively. At follow-up, severe cases had higher incidences of persistent symptoms, DLCO impairment, and higher abnormal CT score as compared with mild cases. CT score at follow-up was positively correlated with age, LDH level, cumulative days of oxygen treatment, total dosage of glucocorticoids used, and CT peak score during hospitalization. DLCO% at follow-up was negatively correlated with cumulative days of oxygen treatment during hospitalization. DLCO/VA% at follow-up was positively correlated with BMI, and TNF-α level. Among the three groups categorized as survivors with normal DLCO, abnormal DLCO but normal DLCO/VA, and abnormal DLCO and DLCO/VA, survivors with abnormal DLCO and DLCO/VA had the lowest serum IL-2R, IL-8, and TNF-α level, while the survivors with abnormal DLCO but normal DLCO/VA had the highest levels of inflammatory cytokines during hospitalization. Altogether, COVID-19 had a greater long-term impact on the lung physiology of severe cases. The long-term radiological abnormality maybe relate to old age and the severity of COVID-19. Either absent or excess of inflammation during COVID-19 course would lead to the impairment of pulmonary diffusion function.


Subject(s)
COVID-19/epidemiology , Lung/virology , Respiration Disorders/virology , SARS-CoV-2/pathogenicity , Survivors , Adult , Aged , Follow-Up Studies , Humans , Lung/physiopathology , Male , Middle Aged , Respiration Disorders/physiopathology , Respiratory Physiological Phenomena , Retrospective Studies , Survivors/statistics & numerical data
14.
J Acoust Soc Am ; 149(6): 3910, 2021 06.
Article in English | MEDLINE | ID: covidwho-1276870

ABSTRACT

Face-to-face speech data collection has been next to impossible globally as a result of the COVID-19 restrictions. To address this problem, simultaneous recordings of three repetitions of the cardinal vowels were made using a Zoom H6 Handy Recorder with an external microphone (henceforth, H6) and compared with two alternatives accessible to potential participants at home: the Zoom meeting application (henceforth, Zoom) and two lossless mobile phone applications (Awesome Voice Recorder, and Recorder; henceforth, Phone). F0 was tracked accurately by all of the devices; however, for formant analysis (F1, F2, F3), Phone performed better than Zoom, i.e., more similarly to H6, although the data extraction method (VoiceSauce, Praat) also resulted in differences. In addition, Zoom recordings exhibited unexpected drops in intensity. The results suggest that lossless format phone recordings present a viable option for at least some phonetic studies.


Subject(s)
COVID-19 , Speech , Acoustics , Humans , Phonetics , SARS-CoV-2 , Speech Acoustics
15.
The Asia-Pacific Education Researcher ; 2021.
Article in English | PMC | ID: covidwho-1244634
16.
Chin J Nat Med ; 19(4): 305-320, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1193536

ABSTRACT

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.


Subject(s)
Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Administration, Oral , Alkaloids/analysis , Animals , COVID-19 , Chromatography, High Pressure Liquid , Flavonoids/analysis , Mice , SARS-CoV-2 , Saponins/analysis , Triterpenes/analysis
17.
Natl Sci Rev ; 7(6): 1003-1011, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-820587

ABSTRACT

A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19). We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China. To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients. Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals. Seventeen cytokines were linked to 2019-nCoV loads. Fifteen cytokines, namely M-CSF, IL-10, IFN-α2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-γ, IL-1α, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics. Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections. These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease. Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized.

18.
J Allergy Clin Immunol ; 146(3): 542, 2020 09.
Article in English | MEDLINE | ID: covidwho-806592
19.
J Allergy Clin Immunol ; 146(2): 335-336, 2020 08.
Article in English | MEDLINE | ID: covidwho-739890
20.
J Med Virol ; 92(11): 2684-2692, 2020 11.
Article in English | MEDLINE | ID: covidwho-526739

ABSTRACT

BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID-19) has turned into a public health emergency of international concern. Epidemiological research has shown that sex is associated with the severity of COVID-19, but the underlying mechanism of sex predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID-19. METHODS: In this retrospective study, we enrolled 548 COVID-19 inpatients from Tongji Hospital from 26 January to 5 February 2020, and followed up to 3 March 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. The Cox proportional hazard regression model was applied to identify the gendered effect on mortality of COVID-19 after adjusting for age, comorbidity, and smoking history. The multiple linear regression method was used to explore the influence of sex on inflammation reaction. RESULTS: Males had higher mortality than females did (22.2% vs 10.4%), with an hazard ratio of 1.923 (95% confidence interval, 1.181-3.130); elder age and comorbidity were significantly associated with decease of COVID-19 patients. Excess inflammation reaction was related to severity of COVID-19. Male patients had greater inflammation reaction, with higher levels of interleukin 10, tumor necrosis factor-α, lactose dehydrogenase, ferritin, and hyper-sensitive C-reactive protein, but a lower lymphocyte count than females adjusted by age and comorbidity. CONCLUSIONS: Sex, age, and comorbidity are critical risk factors for mortality of COVID-19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males, especially elder males, to develop a cytokine storm, causing potential acute respiratory distressed syndrome, multiple organ failure and decease.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Cytokine Release Syndrome/immunology , Inflammation/virology , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , China/epidemiology , Comorbidity , Cytokine Release Syndrome/virology , Female , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Inflammation/epidemiology , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Severity of Illness Index , Sex Factors , Young Adult
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