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2.
Biomed Environ Sci ; 34(12): 984-991, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1608702

ABSTRACT

Objective: Early triage of patients with coronavirus disease 2019 (COVID-19) is pivotal in managing the disease. However, studies on the clinical risk score system of the risk factors for the development of severe disease are limited. Hence, we conducted a clinical risk score system for severe illness, which might optimize appropriate treatment strategies. Methods: We conducted a retrospective, single-center study at the JinYinTan Hospital from January 24, 2020 to March 31, 2020. We evaluated the demographic, clinical, and laboratory data and performed a 10-fold cross-validation to split the data into a training set and validation set. We then screened the prognostic factors for severe illness using the least absolute shrinkage and selection operator (LASSO) and logistic regression, and finally conducted a risk score to estimate the probability of severe illness in the training set. Data from the validation set were used to validate the score. Results: A total of 295 patients were included. From 49 potential risk factors, 3 variables were measured as the risk score: neutrophil to lymphocyte ratio ( OR, 1.27; 95% CI, 1.15-1.39), albumin ( OR, 0.76; 95% CI, 0.70-0.83), and chest computed tomography abnormalities ( OR, 2.01; 95% CI, 1.41-2.86) and the AUC of the validation cohort was 0.822 (95% CI, 0.7667-0.8776). Conclusion: This report may help define the potential of developing severe illness in patients with COVID-19 at an early stage, which might be related to the neutrophil to lymphocyte ratio, albumin, and chest computed tomography abnormalities.


Subject(s)
COVID-19/diagnosis , Risk Assessment , Aged , Female , Humans , Male , Middle Aged , Nomograms , Retrospective Studies , Severity of Illness Index
3.
Life (Basel) ; 11(12)2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1572550

ABSTRACT

The SARS-CoV-2 virus is deadly, contagious, can cause COVID-19 disease, and endangers public health and safety. The development of SARS-CoV-2 inactivation technology is crucial and imminent in current pandemic period. Neutron radiation is usually used to sterilize viruses because neutron radiation is 10 times more effective than gamma-rays in inactivating viruses. In this work we established a closed SARS-CoV-2 inactivation container model by the Monte Carlo method and simulated the inactivation performance by using several different neutrons sources. To study the effects of inactivation container factors, including the reflector thickness, the type of the reflector material, the SARS-CoV-2 layer area and the distance from the radiation source on the energy deposition of a single neutron particle in SARS-CoV-2 sample, we simulated the neutron energy deposition on a SARS-CoV-2 sample. The simulation results indicate that the saturated thicknesses of reflector materials for graphite, water and paraffin are approximately 30 cm, 15 cm, and 10 cm, respectively, and the energy deposition (radiation dose) becomes larger when the SARS-CoV-2 layer area is smaller and the SARS-CoV-2 layer is placed closer to the neutron source. The calculated single-neutron energy deposition on 10 × 10 cm2 SARS-CoV-2 layer is about 3.0059 × 10-4 MeV/g with graphite as the reflection layer, when the 14 MeV neutron source intensity is 1012 n/s and the SARS-CoV-2 layer is 5 cm away from the neutron source. If the lethal dose of SARS-CoV-2 is assumed as the IAEA recommended reference dose, 25 kGy, the SARS-CoV-2 could be decontaminated in about 87 min, and the sterilization time could be less than 52 s if the 14 MeV neutron intensity is increased to 1014 n/s.

4.
Phytomedicine ; 95: 153874, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1560696

ABSTRACT

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) pose a huge threat to human public health, no specific treatment is available. Jinzhen granule (JZ) is a traditional eight ingredients-Chinese medicine with prominent efficacy for treating viral-induced diseases. However, little is known about the antiviral effect and mechanism of JZ against SARS-CoV-2 and HCoV-229E. PURPOSE: This study aimed to reveal the antiviral effects of JZ against SARS-CoV-2 and HCoV-229E, and to further explore the underlying mechanisms regulating the host immune response. METHODS: The chromatographic separation of JZ was performed using a Shimadzu analytical high-performance liquid chromatograph with UV detection and Alltech ELSD 2000ES. We conducted cytopathic effect (CPE) and plaque reduction assays to evaluate the antiviral effect of JZ. A lethal human angiotensin converting enzyme 2 (hACE2) transgenic mouse model of SARS-CoV-2 was established to determine the protective effect of JZ on mortality and lung virus titers. Real-time quantitative PCR assays were used to analyze the expression of proinflammatory cytokines in vitro and in vivo. Western blotting was further performed to determine the activities on regulating the nuclear factor kappa B (NF-κB)/MAPK pathway. Finally, mitochondrial membrane potential assays, flow cytometry analysis and western blotting were used to assess the anti-apoptotic potency toward HCoV-229E infection. RESULTS: The results showed that 13 chemical components were identified and five peaks were determined and quantitated (gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92 mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g). We found that JZ exerted inhibitory potency against SARS-CoV-2 and HCoV-229E in vitro by using CPE and plaque reduction assays, and it was further found that JZ protected mice infected by SARS-CoV-2 from death and inhibited lung virus titers. JZ also significantly decreased the induction of inflammatory cytokines (IL-1α, IL-6, CCL-5 and MIP-1ß), similar to the observed in vitro effect. Moreover, JZ suppressed the release of inflammatory cytokines in vitro and it decreased the protein expression of p-p38 MAPK, p-JNK, p-NF-κB p65 and p-IκBα induced by HCoV-229E and increased the expression of IκBα. Notably, JZ significantly protected HCoV-229E-infected Huh-7 cells from mitochondrial damage and decreased apoptotic cells. The activation of the mitochondria-mediated apoptotic pathway was inhibited by JZ, as shown by the reduced expression of cleaved caspase-9, caspase-3 and p-PARP. CONCLUSIONS: In conclusion, JZ (gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92 mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g) exhibited antiviral activities against SARS-CoV-2 and HCoV-229E by regulating the NF-κB/MAPK pathway and the mitochondria-mediated apoptotic pathway. These findings demonstrated the efficacy of JZ against CoVs and suggested JZ treatment as a novel clinical therapeutic strategy for COVID-19.


Subject(s)
Antiviral Agents , Coronavirus 229E, Human , Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19 , Coronavirus 229E, Human/drug effects , Humans , MAP Kinase Signaling System , Mice , NF-kappa B
5.
Adv Sci (Weinh) ; 8(23): e2102593, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1559092

ABSTRACT

Fast and accurate identification of microbial pathogens is critical for the proper treatment of infections. Traditional culture-based diagnosis in clinics is increasingly supplemented by metagenomic next-generation-sequencing (mNGS). Here, RNA/cDNA-targeted sequencing (meta-transcriptomics using NGS (mtNGS)) is established to reduce the host nucleotide percentage in clinic samples and by combining with Oxford Nanopore Technology (ONT) platforms (meta-transcriptomics using third-generation sequencing, mtTGS) to improve the sequencing time. It shows that mtNGS improves the ratio of microbial reads, facilitates bacterial identification using multiple-strategies, and discovers fungi, viruses, and antibiotic resistance genes, and displaying agreement with clinical findings. Furthermore, longer reads in mtTGS lead to additional improvement in pathogen identification and also accelerate the clinical diagnosis. Additionally, primary tests utilizing direct-RNA sequencing and targeted sequencing of ONT show that ONT displays important potential but must be further developed. This study presents the potential of RNA-targeted pathogen identification in clinical samples, especially when combined with the newest developments in ONT.

6.
Phytomedicine ; 95: 153868, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1556410

ABSTRACT

BACKGROUND: Huashibaidu Formula (HSBD) for the COVID-19 treatment has been supported by the China's Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia. However, it is not clear whether HSBD can improve blood oxygen saturation and when it should be used with conventional therapies. PURPOSE: To access the effect of HSBD combined with conventional treatment on blood oxygen saturation of COVID-19 patients. METHODS: A single-center retrospective cohort study was conducted to collect the confirmed severe COVID-19 patients' information, treated by the National Traditional Chinese Medicine Medical Team at the Jinyintan hospital between January 24 and March 31, 2020. According to whether HSBD was used during hospitalization, participants were separated into the conventional treatment group and the HSBD group (HSBD and conventional treatment). The primary observation indicators included the time for relieving blood oxygen saturation and the improvement ratio of blood oxygen saturation in each group. RESULTS: Of 111 patients with severe COVID-19, 53.2% (59/111) received HSBD, and 46.8% (52/111) only received conventional treatment, respectively. No statistically significant difference was found in image, clinical symptoms, and past medical history between the two groups (p > 0.05). Notably, the median time for relieving blood oxygen saturation in the conventional treatment group was 11 days (IQR, 8-14.25), while that in the HSBD group was only 6 days (IQR, 3.25-10.75), which was significantly shortened by 4.09 days (95%CI, 2.07-6.13; p= 0.0001), compared with the conventional treatment group. After repeated measurement design analysis, the main effect within times (p< 0.001) and the main effect were significantly different under the oxygen saturation dimension between two groups (p= 0.004). However, time and group interaction were observed no significant difference (p= 0.094). After 14 days of treatment, the improvement ratio of the HSBD group over the conventional treatment group was 1.20 (95%CI, 0.89-1.61). CONCLUSION: For severe COVID-19 patients, the HSBD has a tendency to shorten the time for relieving blood oxygen saturation. After taking a course of HSBD, the effect can be more obvious.


Subject(s)
COVID-19 , COVID-19/drug therapy , Humans , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
7.
Preprint in English | Other preprints | ID: ppcovidwho-296386

ABSTRACT

Neutrophils are rapidly recruited from the peripheral blood to the inflammatory site to initiate inflammatory response against pathogenic infections. The process to recruit neutrophils must be properly regulated since the abnormal accumulation of neutrophils can cause organ damage and dysfunction. The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a common cause of respiratory failure that is characterized by the infiltration of neutrophils and epithelial integrity disruption. Indeed, recent studies suggest a pathogenic role of neutrophils in the clinic severity of the coronavirus disease 2019 (COVID-19) ARDS. The chemokine CXCL1, which is rapidly induced by inflammatory stimuli, plays a key role in neutrophil influx during lung inflammation. The molecular basis of Cxcl1 induction is not fully understood. Here we report that TET1, a member of the ten eleven translocation (TET) methylcytosine dioxygenase protein family, displays a striking specificity in the regulation of gene expression in macrophages. RNA sequencing (RNA-seq) analysis showed that Tet1 disruption significantly altered the expression of only 48 genes that include Cxcl1 and several other genes known to be important for cell migration and trafficking in bone marrow derived macrophages (BMDMs) in response to LPS stimulation. TET1 regulates the induction of Cxcl1 by facilitating the DNA demethylation of the Cxcl1 promoter. In Tet1 −/− mice, the induction of Cxcl1 was suppressed, resulting in defective neutrophil recruitment to the lung during LPS-induced acute lung injury. Our results identify a novel epigenetic mechanism that selectively controls Cxcl1 induction and neutrophil recruitment during acute lung injury. Key Points TET1 has a striking specificity in macrophage gene regulation and controls Cxcl1 induction by inflammatory stimuli via DNA demethylation Neutrophil recruitment is defective in Tet1 deficient mice during acute lung injury

8.
Signal Transduct Target Ther ; 6(1): 414, 2021 Dec 06.
Article in English | MEDLINE | ID: covidwho-1556321

ABSTRACT

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

9.
Clin Exp Med ; 2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1479486

ABSTRACT

The optimal timing of glucocorticoid treatment for coronavirus disease 2019 (COVID-19) pneumonia is uncertain. We evaluated the clinical outcomes of methylprednisolone therapy (MPT) for patients with a high-risk common type (HRCT) COVID-19 pneumonia. We conducted a multicenter retrospective cohort study in Northeast China. A comparison was performed between the standard treatment (SDT) group and the SDT + MPT group to determine the efficacy of methylprednisolone in treating HRCT COVID-19 pneumonia. We collected the medical records of 403 patients with HRCT COVID-19 pneumonia (127 in the SDT + MPT group and 276 in the SDT group). None of the patients had received mechanical ventilation or died. Furthermore, there were no side effects associated with MPT. Patients in the SDT + MPT group treated with methylprednisolone received an intravenous injection for a median interval of five days (interquartile range of 3 to 7 days). The trends in lymphocyte count, C-reactive protein, interleukin 6, lactic acid dehydrogenase, respiratory rate, SpO2, PaO2, D-dimer and body temperature were similar between the SDT + MPT and SDT groups. The results for the SDT + MPT group seemed to improve faster than those for the SDT group; however, the results were not statistically significant. Clinical outcomes revealed that the average hospitalized days and the rate of progression to severe type COVID-19 pneumonia in both the SDT + MPT group and the SDT group were 14.56 ± 0.57 days versus 16.55 ± 0.3 days (p = 0.0009) and 21.26% (27/127) versus 32.4% (89/276) (p = 0.0247), respectively. The 16-day nucleic acid negative rate was higher in the SDT + MPT group than in the SDT group, 81.73% (104/127) versus 65.27% (180/276) (p = 0.0006). MPT effectively prevents patients with HRCT COVID-19 pneumonia from progressing to the severe stage.

10.
Int J Gen Med ; 14: 6647-6659, 2021.
Article in English | MEDLINE | ID: covidwho-1470715

ABSTRACT

Introduction: The current COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2 is a quickly developing global health crisis, yet the mechanisms of pathogenesis in COVID-19 are not fully understood. Methods: The RNA sequencing data of SARS-CoV-2-infected cells was obtained from the Gene Expression Omnibus (GEO). The differentially expressed mRNAs (DEmRNAs), long non-coding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) were identified by edgeR, and the SARS-CoV-2-associated competing endogenous RNA (ceRNA) network was constructed based on the prediction of bioinformatic databases. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted with the SARS-CoV-2-related DEmRNAs, and the protein-protein interaction network was also built basing on STRING database. The ROC analysis was performed for assessing the diagnostic efficiency of hub genes. Results: The results indicated that SARS-CoV-2-related DEmRNAs were associated with the interferon signaling pathway and other antiviral processes, such as IFNL3, IFNL1 and CH25H. Our analysis suggested that lncRNA NEAT1 might regulate the host immune response through two miRNAs, hsa-miR-374-5p and hsa-miR-155-5p, which control the expression of SOCS1, IL6, IL1B, CSF1R, CD274, TLR6, and TNF. Additionally, IFI6, HRASLS2, IGFBP4 and PTN may be potential targets based on an analysis comparing the transcriptional responses of SARS-CoV-2 infection with that of other respiratory viruses. Discussion: The unique ceRNA network identified potential non-coding RNAs and their possible targets as well as a new perspective to understand the molecular mechanisms of the host immune response to SARS-CoV-2. This study may also aid in the development of innovative diagnostic and therapeutic strategies.

11.
Front Med (Lausanne) ; 8: 696976, 2021.
Article in English | MEDLINE | ID: covidwho-1450816

ABSTRACT

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

12.
Science ; 373(6559):1142-1146, 2021.
Article in English | Academic Search Complete | ID: covidwho-1391207

ABSTRACT

Coronavirus 3′-to-5′ exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10–nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle. ExoN also recognizes and excises nucleotide analog inhibitors incorporated into the nascent RNA, undermining the effectiveness of nucleotide analog–based antivirals. Here we present cryo–electron microscopy structures of both wild-type and mutant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp10-nsp14 in complex with an RNA substrate bearing a 3′-end mismatch at resolutions ranging from 2.5 to 3.9 angstroms. The structures reveal the molecular determinants of ExoN substrate specificity and offer insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. Our findings provide guidance for rational design of improved anticoronavirus therapies. [ABSTRACT FROM AUTHOR] Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

13.
Front Med (Lausanne) ; 8: 684864, 2021.
Article in English | MEDLINE | ID: covidwho-1337651

ABSTRACT

Background: COVID-19 is a global pandemic. The prevention of SARS-CoV-2 infection and the rehabilitation of survivors are currently the most urgent tasks. However, after patients with COVID-19 are discharged from the hospital, how long the antibodies persist, whether the lung lesions can be completely absorbed, and whether cardiopulmonary abnormalities exist remain unclear. Methods: A total of 56 COVID-19 survivors were followed up for 12 months, with examinations including serum virus-specific antibodies, chest CT, and cardiopulmonary exercise testing. Results: The IgG titer of the COVID-19 survivors decreased gradually, especially in the first 6 months after discharge. At 6 and 12 months after discharge, the IgG titer decreased by 68.9 and 86.0%, respectively. The IgG titer in patients with severe disease was higher than that in patients with non-severe disease at each time point, but the difference did not reach statistical significance. Among the patients, 11.8% were IgG negative up to 12 months after discharge. Chest CT scans showed that at 3 and 10 months after discharge, the lung opacity had decreased by 91.9 and 95.5%, respectively, as compared with that at admission. 10 months after discharge, 12.5% of the patients had an opacity percentage >1%, and 18.8% of patients had pulmonary fibrosis (38.5% in the severe group and 5.3% in the non-severe group, P < 0.001). Cardiopulmonary exercise testing showed that 22.9% of patients had FEV1/FVC%Pred <92%, 17.1% of patients had FEV1%Pred <80%, 20.0% of patients had a VO2 AT <14 mlO2/kg/min, and 22.9% of patients had a VE/VCO2 slope >30%. Conclusions: IgG antibodies in most patients with COVID-19 can last for at least 12 months after discharge. The IgG titers decreased significantly in the first 6 months and remained stable in the following 6 months. The lung lesions of most patients with COVID-19 can be absorbed without sequelae, and a few patients in severe condition are more likely to develop pulmonary fibrosis. Approximately one-fifth of the patients had cardiopulmonary dysfunction 6 months after discharge.

15.
Pharmacol Res ; 161: 105290, 2020 11.
Article in English | MEDLINE | ID: covidwho-1318948

ABSTRACT

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Adult , Aged , Aged, 80 and over , China , Cohort Studies , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged , Time-to-Treatment , Treatment Outcome , Young Adult
16.
Pharmacol Res ; 158: 104850, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318927

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host's immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-κB p65, p-IκBα and p-p38 MAPK, while increasing the expression of IκBα. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-κB/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.


Subject(s)
Betacoronavirus/drug effects , Complex Mixtures/pharmacology , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Signal Transduction/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19 , Cell Proliferation/drug effects , Cells, Cultured , Chlorocebus aethiops , Coronavirus Infections/virology , Humans , Inflammation Mediators/metabolism , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Virion/drug effects
17.
J Ethnopharmacol ; 279: 114367, 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1281457

ABSTRACT

BACKGROUND: Although the rapid emergence of coronavirus disease 2019 (COVID-19) poses a considerable threat to global public health, no specific treatment is available for COVID-19. ReDuNing injection (RDN) is a traditional Chinese medicine known to exert antibacterial, antiviral, antipyretic, and anti-inflammatory effects. In addition, RDN has been recommended in the diagnosis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pneumonia by the National Health Council and the National Administration of Chinese Medicine. However, there is no information regarding its efficacy against COVID-19. AIM OF STUDY: This study was designed to determine the clinical efficacy of RDN in patients with COVID-19 and characterize its antiviral activity against SARS-CoV-2 in vitro. MATERIALS AND METHODS: A total of 50 adults with COVID-19 were included in this study, and the primary endpoint was recovery from clinical symptoms following 14 days of treatment. General improvements were defined as the disappearance of the major symptoms of infection including fever, fatigue, and cough. The secondary endpoints included the proportion of patients who achieved clinical symptom amelioration on days 7 and 10, time to clinical recovery, time to a negative nucleic acid test result, duration of hospitalization, and time to defervescence. Plaque reduction and cytopathic effect assays were also performed in vitro, and reverse-transcription quantitative PCR was performed to evaluate the expression of inflammatory cytokines (TNF-α, IP-10, MCP-1, IL-6, IFN-α, IFN-γ, IL-2 and CCL-5) during SARS-CoV-2 infection. RESULTS: The RDN group exhibited a shorter median time for the resolution of clinical symptoms (120 vs. 220 h, P < 0.0001), less time to a negative PCR test result (215 vs. 310 h, P = 0.0017), shorter hospitalization (14.8 vs. 18.5 days, P = 0.0002), and lower timeframe for defervescence (24.5 vs. 75 h, P = 0.0001) than the control group. In addition, time to improved imaging was also shorter in the RDN group than in the control group (6 vs.8.9 days, P = 0.0273); symptom resolution rates were higher in the RDN group than in the control group at 7 (96.30% vs. 39.13%, P < 0.0001) and 10 days (96.30% vs. 56.52%, P = 0.0008). No allergic reactions or anaphylactic responses were reported in this trial. RDN markedly inhibited SARS-CoV-2 proliferation and viral plaque formation in vitro. In addition, RDN significantly reduced inflammatory cytokine production in infected cells. CONCLUSIONS: RDN relieves clinical symptoms in patients with COVID-19 and reduces SARS-CoV-2 infection by regulating inflammatory cytokine-related disorders, suggestion that this medication might be a safe and effective treatment for COVID-19.


Subject(s)
COVID-19 , Cytokines/analysis , Drugs, Chinese Herbal , SARS-CoV-2 , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Nucleic Acid Testing/methods , Cell Line , China/epidemiology , Cytotoxicity Tests, Immunologic/methods , Drug Monitoring/methods , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Symptom Assessment/methods , Treatment Outcome
19.
Radiology ; 299(2): E230-E240, 2021 05.
Article in English | MEDLINE | ID: covidwho-1203991

ABSTRACT

Background It is unknown if there are cardiac abnormalities in persons who have recovered from coronavirus disease 2019 (COVID-19) without cardiac symptoms or in those who have normal biomarkers and normal electrocardiograms. Purpose To evaluate cardiac involvement in participants who had recovered from COVID-19 without clinical evidence of cardiac involvement by using cardiac MRI. Materials and Methods This prospective observational cohort study included 40 participants who had recovered from COVID-19 with moderate (n = 24) or severe (n = 16) pneumonia and who had no cardiovascular medical history, were without cardiac symptoms, had normal electrocardiograms, had normal serologic cardiac enzyme levels, and had been discharged for more than 90 days between May and September 2020. Demographic characteristics were recorded, serum cardiac enzyme levels were measured, and cardiac MRI was performed. Cardiac function, native T1, extracellular volume fraction (ECV), and two-dimensional (2D) strain were quantitatively evaluated and compared with values in control subjects (n = 25). Comparisons among the three groups were performed by using one-way analysis of variance with Bonferroni-corrected post hoc comparisons (for normal distribution) or Kruskal-Wallis tests with post hoc pairwise comparisons (for nonnormal distribution). Results Forty participants (mean age, 54 years ± 12 [standard deviation]; 24 men) were enrolled; participants had a mean time between admission and cardiac MRI of 158 days ± 18 and between discharge and cardiac MRI examination of 124 days ± 17. There were no left or right ventricular size or functional differences between participants who had recovered from COVID-19 and healthy control subjects. Only one (3%) participant had positive late gadolinium enhancement located at the mid inferior wall. Global ECV values were elevated in participants who had recovered from COVID-19 with moderate or severe pneumonia compared with those in healthy control subjects (median ECV, 29.7% vs 31.4% vs 25.0%, respectively; interquartile range, 28.0%-32.9% vs 29.3%-34.0% vs 23.7%-26.0%, respectively; P < .001 for both). The 2D global left ventricular longitudinal strain was reduced in both groups of participants (moderate COVID-19 group, -12.5% [interquartile range, -15.5% to -10.7%]; severe COVID-19 group, -12.5% [interquartile range, -15.4% to -8.7%]) compared with the healthy control group (-15.4% [interquartile range, -17.6% to -14.6%]) (P = .002 and P = .001, respectively). Conclusion Cardiac MRI myocardial tissue and strain imaging parameters suggest that a proportion of participants who had recovered from COVID-19 had subclinical myocardial abnormalities detectable months after recovery. © RSNA, 2021 Online supplemental material is available for this article.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Heart Diseases/etiology , Heart Diseases/physiopathology , Magnetic Resonance Imaging/methods , SARS-CoV-2 , China , Cohort Studies , Female , Heart/diagnostic imaging , Heart/physiopathology , Heart Diseases/diagnostic imaging , Humans , Male , Middle Aged , Prospective Studies
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