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1.
Frontiers in cellular and infection microbiology ; 12, 2022.
Article in English | EuropePMC | ID: covidwho-1989772

##### ABSTRACT

The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.

2.
Hum Vaccin Immunother ; : 2090176, 2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1956538

##### ABSTRACT

Patients with rheumatic diseases (RD) are considered to be a high-risk population for infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The effectiveness of inactivated COVID-19 vaccinations (ICVs) was described as more effective than 95%. Despite this, no data on the immunogenicity and safety of the ICV in Han race stable RD patients in China. In this study, we sought to assess the safety and immunogenicity of the ICVs in RD patients in South China. A total of 80 adult stable RD patients were recruited. Following 14-35 days of immunization, cheiluminescence immunoassays (CLIA) were utilized to detect antibodies titers. An investigation into the relative parameters on the immunogenicity response to vaccination was carried out using logistic regression analysis. Compared to the HC group, the positive response of IgG and Nab in RD patients were lower than those in healthy control (HC) (P = .040 and P < .0001, respectively) after two doses of ICV were inoculated. The use of methotrexate (P = .016) and prednisolone (P = .018), and the level of red blood cell distribution width-C (RDW-C) (P = .035) and C-reactive protein (P = .015) were independently associated with lower rises in the magnitude of COVID-19 vaccine antibodies. No vaccine-related serious adverse reactions were observed in either group. After receiving two doses of ICVs, the production of protective antibodies in stable RD patients treated with immunosuppressive agents may decrease. It was discovered that ICVs were safe and well tolerated by RD patients.

What is the context?There are currently no accessible data on the efficacy and safety of inactivated COVID-19 vaccinations in South China RD patients who are receiving immunosuppressive medications.What is new?Inactivated COVID-19 vaccinations were immunogenic in stable RD patients in our investigation. No significant adverse reactions to the vaccination were seen in either group. No disease flares were observed in our study.What is the impact?Inactivated COVID-19 vaccinations are immunogenic and safe in stable RD patients in China, according to the findings of this study. The use of methotrexate or prednisolone, the RDW-C level, and the CRP level may all have an effect on the development of protective antibodies following vaccination.

3.
Zool Res ; 43(2): 147-149, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1912573

##### Subject(s)
Genome , Genomics , Primates , Animals , Evolution, Molecular , Primates/genetics
4.
Zhongguo Zhen Jiu ; 42(6): 634-8, 2022 Jun 12.
Article in Chinese | MEDLINE | ID: covidwho-1903928

##### ABSTRACT

OBJECTIVE: To observe the clinical effect of acupuncture on coronavirus disease 2019 (COVID-19) based on the conventional treatment. METHODS: A total of 35 patients with COVID-19 of mild or ordinary type were involved (3 cases dropped off). Acupuncture was applied on the basis of western medicine and Chinese materia medica treatment. Dazhui (GV 14), Fengchi (GB 20), Kongzui (LU 6), Hegu (LI 4), etc. were selected as the main acupoints, the supplementary acupoints and the reinforcing and reducing manipulations were selected according to syndrome differentiation. Acupuncture treatment was given once a day, 5 times a week. On day 3 and day 7 of acupuncture, relief condition of the main symptoms was observed. Before acupuncture and on day 3 and day 7 of acupuncture, efficacy evaluation scale of TCM on COVID-19 (efficacy evaluation scale) score was recorded. The effects of different intervention time of acupuncture on patients' hospitalization time were compared, the understanding of acupuncture treatment of patients discharged from hospital was recorded, the clinical efficacy and safety of acupuncture treatment were evaluated. RESULTS: On day 3 and day 7 of acupuncture, the symptoms of lung system and non lung system were both relieved; the scores of efficacy evaluation scale were both decreased compared before acupuncture (P<0.05), and the efficacy evaluation scale score of day 7 of acupuncture were lower than day 3 of acupuncture (P<0.05). The average hospitalization time of patients received early acupuncture was shorter than late acupuncture (P<0.05). The total effective rate was 84.4% (27/32) on day 7 of acupuncture, which was higher than 34.4% (11/32) on day 3 of acupuncture (P<0.05). During the acupuncture treatment, there were neither adverse reactions in patients nor occupational exposures in doctors. The patients generally believed that acupuncture could promote the recovery of COVID-19 and recommended acupuncture treatment. CONCLUSION: On the basis of the conventional treatment, acupuncture can effectively relieve the clinical symptoms in patients with COVID-19, early intervention of acupuncture can accelerate the recovery process. Acupuncture has good safety, clinical compliance and recognition of patients.

##### Subject(s)
Acupuncture Therapy , COVID-19 , Acupuncture Points , COVID-19/therapy , Combined Modality Therapy , Humans , Treatment Outcome
5.
ACS Appl Bio Mater ; 5(7): 3329-3337, 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1900418

##### ABSTRACT

Thousands of breakthrough infections are confirmed after intramuscular (i.m.) injection of the approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two major factors might contribute to breakthrough infections. One is the emergence of mutant variants of SARS-CoV-2, and the other is that i.m. injection has an inefficient ability to activate mucosal immunity in the upper respiratory tract. Here, we devised a dual-chambered nanocarrier that can codeliver the adjuvant CBLB502 with prefusion-spike (pre-S) onto a ferritin nanoparticle. This vaccine enabled enhanced systemic and local mucosal immunity in the upper and lower respiratory tract. Further, codelivery of CBLB502 with pre-S induced a Th1/Th2-balanced immunoglobulin G response. Moreover, the codelivery nanoparticle showed a Th1-biased cellular immune response as the release of splenic INF-Î³ was significantly heightened while the level of IL-4 was elevated to a moderate extent. In general, the developed dual-chambered nanoparticle can trigger multifaceted immune responses and shows great potential for mucosal vaccine development.

##### Subject(s)
COVID-19 , Nanoparticle Drug Delivery System , Peptides , Spike Glycoprotein, Coronavirus , Antibodies, Viral , COVID-19 Vaccines/immunology , Ferritins , Humans , Immunity, Mucosal , Peptides/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/immunology
6.
Entropy (Basel) ; 24(5)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1875520

##### ABSTRACT

The accurate prediction of gross box-office markets is of great benefit for investment and management in the movie industry. In this work, we propose a machine learning-based method for predicting the movie box-office revenue of a country based on the empirical comparisons of eight methods with diverse combinations of economic factors. Specifically, we achieved a prediction performance of the relative root mean squared error of 0.056 in the US and of 0.183 in China for the two case studies of movie markets in time-series forecasting experiments from 2013 to 2016. We concluded that the support-vector-machine-based method using gross domestic product reached the best prediction performance and satisfies the easily available information of economic factors. The computational experiments and comparison studies provided evidence for the effectiveness and advantages of our proposed prediction strategy. In the validation process of the predicted total box-office markets in 2017, the error rates were 0.044 in the US and 0.066 in China. In the consecutive predictions of nationwide box-office markets in 2018 and 2019, the mean relative absolute percentage errors achieved were 0.041 and 0.035 in the US and China, respectively. The precise predictions, both in the training and validation data, demonstrate the efficiency and versatility of our proposed method.

7.
J Clin Invest ; 132(10)2022 05 16.
Article in English | MEDLINE | ID: covidwho-1846632

##### ABSTRACT

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

##### Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Middle Aged , SARS-CoV-2 , T-Lymphocytes , Young Adult
8.
Environ Pollut ; 305: 119308, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1796874

##### ABSTRACT

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases.

##### Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/analysis , Air Pollution/analysis , Biomarkers/analysis , Humans , Particulate Matter/analysis , Young Adult
9.
Education and information technologies ; : 1-24, 2022.
Article in English | EuropePMC | ID: covidwho-1728296

##### ABSTRACT

The MOOCs (Massive Open Online Courses) forum carries rich discussion data that contains multi-level cognition-related behavior patterns, which brings the potential for an in-depth investigation into the development trend of the group and individual cognitive presence in discourse interaction. This paper describes a study conducted in the context of an introductory astronomy course on the Chinese MOOCs platform, examining the relationship between discussion pacings (i.e., instructor-paced or learner-paced discussion), cognitive presence, and learning achievements. Using content analysis, lag sequential analysis, logistic regression, and grouped regression approaches, the study analysed the online discussion data collected from the Astronomy Talk course involving 2603 participants who contributed 24,018 posts. The findings of the study demonstrated the significant cognitive sequential patterns, and revealed the significant differences in the distribution of cognitive presence with different discussion pacings and learning achievement groups, respectively. Moreover, we found that the high-achieving learners were mostly in the exploration, integration, and resolution phase, and learner-paced discussion had a greater moderating effect on the relationship between cognitive presence and learning achievements. Based on the findings and discussion, suggestions for improving the learners’ cognitive presence and learning achievements in the MOOC environment are discussed.

10.
Front Res Metr Anal ; 6: 706164, 2021.
Article in English | MEDLINE | ID: covidwho-1715082

##### ABSTRACT

Under the background of coronavirus disease 2019 (COVID-19), online health information seeking has become one of the most important information needs of the public and even the only channel for health information seeking in this special period. A review of the research on online health information-seeking behavior will help give full play to the previous academic research, further emphasize the necessity of online health information-seeking research, and promote the development of research in this field. This study firstly presents the research overview of online health information-seeking behavior by using the informetric method. Secondly, an overview is carried out from the perspective of online health information platforms, groups, quality, satisfaction, etc., to explore the influencing factors and their relationships in the process of online health information seeking. On this basis, the existing behavioral models are integrated and sorted out to build a new behavioral theoretical model in line with the current online health information seeking.

11.
Front Med (Lausanne) ; 9: 829273, 2022.
Article in English | MEDLINE | ID: covidwho-1715010

##### ABSTRACT

Detection of serum-specific SARS-CoV-2 antibody has become a complementary means for the identification of coronavirus disease 2019 (COVID-19). As we already know, the neutralizing antibody titers in patients with COVID-19 decrease during the course of time after convalescence, whereas the duration of antibody responses in the convalescent patients has not been defined clearly. In the current study, we collected 148 serum samples from 37 confirmed COVID-19 cases with different disease severities. The neutralizing antibodies (Nabs), IgM and IgG against COVID-19 were determined by CLIA Microparticle and microneutralization assay, respectively. The time duration of serum titers of SARS-CoV-2 antibodies were recorded. Our results indicate that IgG (94.44%) and Nabs (89.19%) can be detected at low levels within 190-266 days of disease onset. The findings can advance knowledge regarding the antibody detection results for COVID-19 patients and provide a method for evaluating the immune response after vaccination.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315720

##### ABSTRACT

The outbreak of COVID-19 caused by SARS-CoV-2 has rapidly spread worldwide and has caused over 1,400,000 infections and 80,000 deaths. There are currently no drugs or vaccines with proven efficacy for its prevention and little knowledge was known about the pathogenicity mechanism of SARS-CoV-2 infection. Previous studies showed both virus and host-derived MicroRNAs (miRNAs) played crucial roles in the pathology of virus infection. In this study, we use computational approaches to scan the SARS-CoV-2 genome for putative miRNAs and predict the virus miRNA targets on virus and human genome as well as the host miRNAs targets on virus genome. Furthermore, we explore miRNAs involved dysregulation caused by the virus infection. Our results implicated that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Impressively, we found hsa-miR-4661-3p was predicted to target the S gene of SARS-CoV-2, and a virus-encoded miRNA MR147-3p could enhance the expression of TMPRSS2 with the function of strengthening SARS-CoV-2 infection in the gut. The study may provide important clues for the mechisms of pathogenesis of SARS-CoV-2.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315716

##### ABSTRACT

Due to the Covid-19 pandemic, more than 500 US-based colleges and universities went "test-optional" for admissions and promised that they would not penalize applicants for not submitting test scores, part of a longer trend to rethink the role of testing in college admissions. However, it remains unclear how (and whether) a college can simultaneously use test scores for those who submit them, while not penalizing those who do not--and what that promise even means. We formalize these questions, and study how a college can overcome two challenges with optional testing: $\textit{strategic applicants}$ (when those with low test scores can pretend to not have taken the test), and $\textit{informational gaps}$ (it has more information on those who submit a test score than those who do not). We find that colleges can indeed do so, if and only if they are able to use information on who has test access and are willing to randomize admissions.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315284

##### ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic has caused tremendous amount of deaths and a devastating impact on the economic development all over the world. Thus, it is paramount to control its further transmission, for which purpose it is necessary to find the mechanism of its transmission process and evaluate the effect of different control strategies. To deal with these issues, we describe the transmission of COVID-19 as an explosive Markov process with four parameters. The state transitions of the proposed Markov process can clearly disclose the terrible explosion and complex heterogeneity of COVID-19. Based on this, we further propose a simulation approach with heterogeneous infections. Experimentations show that our approach can closely track the real transmission process of COVID-19, disclose its transmission mechanism, and forecast the transmission under different non-drug intervention strategies. More importantly, our approach can helpfully develop effective strategies for controlling COVID-19 and appropriately compare their control effect in different countries/cities.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324806

##### ABSTRACT

Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients get more attention. Here we report a cohort study on the follow up of 182 recovered patients under medical isolation observation. There are 20 (10.99 %) patients out of the 182 were detected SARS-CoV-2 RNA turned positive, but none of them shows any clinical symptomatic recurrence indicating that COVID-19 has a good prognosis. Females and young patients aged under 15 have higher re-positive rate than the average, and none of the severe patients turned re-positive. Notably, most of the re-positive cases turn negative in the followed tests, suggesting that the importance of dynamic surveillance of SARS-CoV-2 RNA for infectivity assessment.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322246

##### ABSTRACT

Background: Currently, coronavirus disease 2019 (COVID-19) has spread worldwide and become a global health concern. Here, we report a familial cluster of COVID-19 infection in a northern Chinese region and share our local experience. Methods A familial cluster of six patients infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) was included for analysis. The demographic data, clinical features, laboratory examinations, and epidemiological characteristics of enrolled cases were collected and analyzed. Results Two family members (Cases 1 and 2) had Hubei exposure history and were admitted to the hospital with a confirmed diagnosis of COVID-19;eight familial members who had contact with them during the incubation period were isolated in a hospital. Finally, the condition of four members (Cases 3, 4, 5, and 6) was as follows. Case 3 had negative SARS-CoV-2 RT-PCR results but was suspected to have COVID-19 because of radiographic abnormalities. Cases 4 and 5 developed COVID-19. Due to positive SARS-CoV-2 RT-PCR results, Case 6 was considered an asymptomatic carrier. In addition, four close contacts did not have evidence of SARS-CoV-2 infection. Conclusions Our findings suggest that COVID-19 has infectivity during the incubation period and preventive quarantine is effective for controlling an outbreak of COVID-19 infection.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318905

##### ABSTRACT

Objective: To analyze the dynamic of total, IgA, IgM and IgG antibody of the confirmed COVID-19 patients during convalescent phases to understand the kinetics of antibody response among recovered patients. Methods: From March 4 to April 29, 2020, a total of 143 recovered COVID-19 patients with clear date of illness onset available were enrolled in this study. Nasopharyngeal and anal swabs were collected for SARS-CoV-2 RNA testing. Blood samples were collected for antibodies testing. Results: A total of 275 blood samples up to 96 days after illness onset were collected from 143 recovered patients. High titers of total and IgG antibodies continued to persist for over 3 months, with 100% and 99.3% patients remaining positive for total and IgG antibody. IgM antibody declined rapidly with a median time to seronegative at 67 (95%CI: 59, 75) days after illness onset. Around 25% patients were seronegative for IgA antibody at month 3 after illness onset. No statistical significance difference was founded in the antibody kinetics between patients with and without re-detectable positive RT-PCR results during in convalescent phases. Conclusion: Similar high antibody titers of total and IgG antibody continued to persist for over 3 months among recovered COVID-19 patients with and without re-detectable positive RT-PCR results.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315259

##### ABSTRACT

Background: During the fight against coronavirus disease 2019 (COVID-19) in China, Qingfei Paidu decoction (QFPDD) has been widely applied to treat COVID-19 patients. Retrospective studies showed that QFPDD could improve clinical outcomes of COVID-19. Thus, it is necessary and interesting to explore the action mode of QFPDD for further application and development. Methods: Sprague-Dawley (SD) rats were randomly divided into two groups, QFPDD (n=9) and control (n=10) groups. They were parallelly treated for 12 days with QFPDD and warm distilled water, respectively. At the endpoint, the microRNA (miRNA or miR) profiles in serum were detected to identify differently expressed miRNAs (DEMs). Then, the action mode of QFPDD were explored via review of potential roles of DEMs and functional enrichment analysis of their targets (e.g., GO enrichment and KEGG pathway analysis), especially focusing on the aspects of immunity, inflammation, virus infection and pulmonary fibrosis. Core genes were identified based on KEGG pathway analysis. Metabolomics were detected in serum and significantly changed metabolites (SCMs), especially the metabolic substrates and products of enzyme of core gene were identified as biomarkers to validate the regulation of DEMs to enzyme activity of core gene through metabolomic analysis and linear correlation analysis between SCMs and DEMs. Results: 23 DEMs were identified in the serum between QFPDD and control groups, with 1636 predicted genes. Reported evidence has showed that both the DEMs and their target genes involve regulation of immunity, inflammation, virus infection and pulmonary fibrosis. Phospholipase C, gamma 1 (Plcg1) was identified as a core gene and predicted to be upregulated attributed to downregulation of novel-89-mature. The levels of three SCMs, PC(P-18:1(11Z)/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:5(4Z,7Z,10Z,13Z,16Z)/P-18:0) and PC(16:1(9Z)/16:1(9Z)), which were the metabolic substrates of phospholipase C, were significantly reduced in QFPDD group, in addition, PC(P-18:1(11Z)/22:5(4Z,7Z,10Z,13Z,16Z)) and PC(22:5(4Z,7Z,10Z,13Z,16Z)/P-18:0) presented positively linear correlation with the expression level of novel-89-mature. The level of phosphorylcholine, a product of PCs metabolized by phospholipase C, was significantly elevated in QFPDD group. Conclusion: QFPDD can induce modification of miRNAs profile, and subsequently multi-regulate the immunity, inflammation, virus infection and pulmonary fibrosis in vivo, playing an important role for the positive outcomes of COVID-19 patients treated by QFPDD in China.

19.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315184

##### ABSTRACT

Background: Numerous epidemiological studies showed close relationships of outdoor air pollution with increased risk of cancer, infection, and cardiopulmonary diseases. However, a very limited number of studies investigate the potential biomarkers of the co-exposures of particle matters (PM) and bioaerosols, especially under current circumstances of the Coronavirus disease 2019 (COVID-19) pandemic. In the present study, we aimed to identify metabolic candidate biomarkers that are associated with co-exposure to PM and bioaerosols.Methods: We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites of 92 samples from young healthy individuals collected at three different time points with exposure to clean, polluted ambient, and purified air , followed by a cycling test after air re-pollution and re-purification with two additional time points. Subsequently, we compared metabolomic profiles in between two-time points via an integrated analysis, plus KEGG enriched pathway and time series analysis.Findings: We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure, respectively. The results from KEGG data and time series analysis indicated significantly enriched pathways and dynamic alterations of metabolomic profiles, respectively. 16-Dehydroprogesterone and 4-Hydroxyphenylethanol in urine might be used as biomarkers for diagnosis of PM- or bioaerosol-relevant diseases.Interpretation: The present studies revealed dynamic alterations in urinary metabolites of young healthy humans with the cycling of the clean and polluted air environment. Our findings help to investigate detrimental health effects of airborne PM and bioaerosols in a real-time manner and improve clinically diagnostic tools for PM- and bioaerosol-related diseases.Funding Information: This work was financially supported by the National Natural Science Foundation of China [NSFC Grant no. 81673958, 82074262, and 81828010];CAMS Innovation Fund for Medical Sciences [CIFMS 2016-I2M-3-013];The Drug Innovation Major Project of China [2018ZX09711001-007-002].Declaration of Interests: The authors declare no conflicts of interest in this work.Ethics Approval Statement: Our study was approved by the Ethical Committee of Guang'anmen Hospital. All recruited subjects provided written informed consent.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312698

##### ABSTRACT

Background: No specific therapeutic agents or vaccines are available for the treatment of Coronavirus disease 2019 (Covid-19) yet. In this study, we aimed to assess the efficacy of high dose ulinastatin for patients with Covid-19. Methods: Twelve patients hospitalized with confirmed SARS-CoV-2 infection were treated with high dose of ulinastatin beyond standard care. The changes of clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. Results: A total of 10 patients with severe Covid-19 and 2 patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0 ± 11.9 years, ranging from 48 to 87 years. Nine of 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12), and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70 ± 77.70 mg/L). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP decreased significantly and returned to normal in 83.3% of patients (10/12;mean, 6.87 ± 6.63 mg/L) on the seventh day after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not need further oxygen therapy seven days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. No obvious adverse events were observed. Conclusions: Our preliminary data revealed that high dose of ulinastatin treatment was safe and showed a potential beneficial effect for patients with Covid-19.