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1.
Health Science Reports ; 5(3):e572, 2022.
Article in English | Wiley | ID: covidwho-1782603

ABSTRACT

Background We compared the temporal changes of immunoglobulin M (IgM), IgG, and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (N), spike 1 subunit (S1), and receptor-binding domain (RBD), and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) to understand the humoral immunity in COVID-19 patients for developing drugs and vaccines for COVID-19. Methods A total of five confirmed COVID-19 cases in Nissan Tamagawa Hospital in early August 2020 were recruited in this study. Using a fully automated chemiluminescence immunoassay analyzer, we measured the levels of IgG, IgA, and IgM against SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2 in COVID-19 patients' sera acquired multiple times in individuals from 0 to 76 days after symptom onset. Results IgG levels against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA increasing before IgG and IgM in some cases. The NAb levels were more than cut-off value in 4/5 COVID-19 patients some of whose antibodies against RBD did not exceed the cut-off value in the early stage. Furthermore, NAb levels against SARS-CoV-2 increased and kept above cut-off value more than around 70 days after symptom onset in all cases. Conclusion Our findings indicate COVID-19 patients should be examined for IgG, IgA, and IgM against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 to analyze the diversity of patients' immune mechanisms.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332294

ABSTRACT

The papain-like protease (PL pro ) in coronavirus is one of key cysteine proteases responsible for the proteolytic processing of viral polyproteins, and plays an important role in dysregulation of host immune response. PL pro is a promising therapeutic target with a major challenge in inhibitor design due to the restricted S1/S2 sites for two consecutive glycine of substrates. Here we reported the discovery of two activators of the SARS-CoV-2 PL pro from a biochemical screening, and the identification of the unique residue, C270, as an allosteric and covalent regulation site for the activators. This site was also specifically modified by glutathione oxidized, resulting in the S-glutathionylation and activation of the protease. Furthermore, one compound was found to allosterically inhibit the protease by covalent binding to this crucial site. Together, these results elucidated an unrevealed molecular mechanism for allosteric modulation of the protease’s activity, and provided a new strategy for discovery of allosteric inhibitors of the SARS-CoV-2 PL pro .

3.
NPJ Climate and Atmospheric Science ; 5(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1764207

ABSTRACT

With improving PM2.5 air quality, the tropospheric ozone (O3) has become the top issue of China’s air pollution control. Here, we combine comprehensive observational data analysis with models to unveil the contributions of different processes and precursors to the change of O3 during COVID-19 lockdown in the Yangtze River Delta (YRD), one of the most urbanized megacity regions of eastern China. Despite a 44 to 47% reduction in volatile organic compounds (VOCs) and nitrogen oxides (NOx) emissions, maximum daily 8-h average (MDA8) ozone concentrations increase from 28 ppbv in pre-lockdown to 43 ppbv in lockdown period. We reproduce this transition with the WRF-Chem model, which shows that ~80% of the increase in MDA8 is due to meteorological factors (seasonal variation and radiation), and ~20% is due to emission reduction. We find that daytime photochemistry does not lead to an increase but rather a decrease of daytime O3 production during the lockdown. However, the reduced O3 production is overwhelmed by the weakened nitric oxide (NO) titration resulting in a net increase of O3 concentration. Although the emission reduction increases O3 concentration, it leads to a decrease in the Ox (O3 + NO2) concentration, suggesting reduced atmospheric oxidation capacity on a regional scale. The dominant effect of NO titration demonstrates the importance of prioritizing VOCs reduction, especially from solvent usage and the petrochemical industry with high emission ratios of VOCs/NOx.

4.
Emerg Microbes Infect ; : 1-32, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1764465

ABSTRACT

AbstractAnalysis of large-scale gene expression post vaccination can provide an overview of immune responses. We used transcriptional approaches to comprehensively analyze the innate immune response signatures elicited by protein subunit (PS) vaccine ZF2001 and a mRNA vaccine named RRV. A fine-grained time-dependent dissection of large-scale gene expression post immunization revealed that ZF001 induced MHC class II-related genes, including cd74 and H2-Aa, more expeditiously than RRV. Notably, RRV induced MHC class I-related genes like Tap1/2, B2m and H2-D1/K1. At day 21 post immunization, the titers of binding and neutralization antibody (NAb) induced by both vaccines were comparable, which were accordant with the expression level of genes essential to BCR/TCR signaling transduction and B/T cells activation at day 7. However, compared to ZF2001, the early responses of RRV were more robust, including activation of pattern recognition receptors (PRRs), expression of genes involved in RNA degradation and transcription inhibition, which are directly related to anti-viral signal. This pattern also coincided with the induction of cytokines by RRV. Generally, the transcriptomic patterns of two very different vaccines mapped here provide a framework for establishing correlates between induction of genes and protection, which can be tailored for evoking specific and potent immune responses against SARS-CoV-2.

5.
Research (Wash D C) ; 2022: 9802969, 2022.
Article in English | MEDLINE | ID: covidwho-1761681

ABSTRACT

Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed. Multiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism. Here, we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase (also known as nonstructural protein 12 (NSP12)) of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants, including omicron and IHU. Mechanistically, heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer. A mild daily heat treatment maintains low levels of both wild-type and P323L mutant of NSP12, suggesting clinical potential. Collectively, this novel mechanism, heat-induced NSP12 degradation, suggests a prospective heat-based intervention against SARS-CoV-2.

6.
Int J Environ Res Public Health ; 19(6)2022 03 17.
Article in English | MEDLINE | ID: covidwho-1760592

ABSTRACT

Digital mental health services (DMHSs) have great potential for mitigating the mental health burden related to COVID-19, but public accessibility (ease of acquiring services when needed) to DMHSs during the pandemic is largely unknown. Accessibility to DMHSs was tracked longitudinally among a nationwide sample of 18,804 adults in China from before to one year after COVID-19 outbreak. Unconditional and conditional latent growth curve models and latent growth mixture models were fitted to explore the overall growth trend, influencing factors, and latent trajectory classes of accessibility to DMHSs throughout COVID-19. Generalized estimating equation models and generalized linear mixed models were employed to explore the association between accessibility to DMHSs and long-term mental health symptoms. We found that people generally reported increased difficulty in accessing DMHSs from before to one year after COVID-19 outbreak. Males, youngsters, individuals with low socioeconomic status, and individuals greatly affected by COVID-19 reported greater difficulty in accessing DMHSs. Four DMHS accessibility trajectory classes were identified: "lowest-great increase" (6.3%), "moderate low-slight increase" (44.4%), "moderate high-slight decrease" (18.1%) and "highest-great decrease" (31.2%). Trajectory classes reporting greater difficulty in accessing DMHSs were at higher risk for long-term mental symptoms. In conclusion, an overall increase in difficulty in accessing DMHSs is observed throughout COVID-19, and heterogeneity exists in DMHS accessibility trajectories. Our results suggest that easy access to DMHSs should be consistently facilitated. Moreover, access gaps should be reduced across demographic groups, and target populations for service allocation should alter as the pandemic evolves.


Subject(s)
COVID-19 , Mental Disorders , Mental Health Services , Adult , COVID-19/epidemiology , Health Services Accessibility , Humans , Male , Mental Disorders/epidemiology , Mental Health
7.
J Virol ; 96(4): e0160021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1759291

ABSTRACT

A comprehensive study of the B cell response against SARS-CoV-2 could be significant for understanding the immune response and developing therapeutical antibodies and vaccines. To define the dynamics and characteristics of the antibody repertoire following SARS-CoV-2 infection, we analyzed the mRNA transcripts of immunoglobulin heavy chain (IgH) repertoires of 24 peripheral blood samples collected between 3 and 111 days after symptom onset from 10 COVID-19 patients. Massive clonal expansion of naive B cells with limited somatic hypermutation (SHM) was observed in the second week after symptom onset. The proportion of low-SHM IgG clones strongly correlated with spike-specific IgG antibody titers, highlighting the significant activation of naive B cells in response to a novel virus infection. The antibody isotype switching landscape showed a transient IgA surge in the first week after symptom onset, followed by a sustained IgG elevation that lasted for at least 3 months. SARS-CoV-2 infection elicited poly-germ line reactive antibody responses. Interestingly, 17 different IGHV germ line genes recombined with IGHJ6 showed significant clonal expansion. By comparing the IgH repertoires that we sequenced with the 774 reported SARS-CoV-2-reactive monoclonal antibodies (MAbs), 13 shared spike-specific IgH clusters were found. These shared spike-specific IgH clusters are derived from the same lineage of several recently published neutralizing MAbs, including CC12.1, CC12.3, C102, REGN10977, and 4A8. Furthermore, identical spike-specific IgH sequences were found in different COVID-19 patients, suggesting a highly convergent antibody response to SARS-CoV-2. Our analysis based on sequencing antibody repertoires from different individuals revealed key signatures of the systemic B cell response induced by SARS-CoV-2 infection. IMPORTANCE Although the canonical delineation of serum antibody responses following SARS-CoV-2 infection has been well established, the dynamics of antibody repertoire at the mRNA transcriptional level has not been well understood, especially the correlation between serum antibody titers and the antibody mRNA transcripts. In this study, we analyzed the IgH transcripts and characterized the B cell clonal expansion and differentiation, isotype switching, and somatic hypermutation in COVID-19 patients. This study provided insights at the repertoire level for the B cell response after SARS-CoV-2 infection.


Subject(s)
Antibodies, Neutralizing/genetics , Antibodies, Viral/genetics , B-Lymphocytes/immunology , COVID-19/genetics , Immunoglobulin G/genetics , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Humans , Immunoglobulin G/immunology , Receptors, Antigen, B-Cell/immunology
8.
Gene ; 2022.
Article in English | EuropePMC | ID: covidwho-1755706

ABSTRACT

Both feline coronavirus (FCoV) and SARS-CoV-2 are coronaviruses that infect cats and humans, respectively. However, cats have been shown to be susceptible to SARS-CoV-2, and FCoV also had been shown to infect human. To elucidate the relationship between FCoV and SARS-CoV-2, we highlight the main characteristics of the genome, the receptor usage, and the correlation of the receptor-binding domain (RBD) of spike proteins in FCoV and SARS-CoV-2. It is demonstrated that FCoV and SARS-CoV-2 are closely related to the main characteristics of the genome, receptor usage, and RBD of spike proteins with similar furin cleavage sites. In particular, the affinity of the conserved feline angiotensin-converting enzyme 2 (fACE2) receptor to the RBD of SARS-CoV-2 suggests that cats are susceptible to SARS-CoV-2. In addition, cross-species of coronaviruses between cats and humans or other domesticated animals are also discussed. This review sheds light on cats as potential intermediate hosts for SARS-CoV-2 transmission, and cross-species transmission or zoonotic infection of FCoV and SARS-CoV-2 between cats and humans was identified.

9.
Front Cell Infect Microbiol ; 12: 807332, 2022.
Article in English | MEDLINE | ID: covidwho-1753361

ABSTRACT

In the early stage of coronavirus disease 2019 (COVID-19), most cases are identified as mild or moderate illnesses. Approximately 20% of hospitalised patients become severe or critical at the middle or late stage of the disease. The predictors and risk factors for prognosis in those with mild or moderate disease remain to be determined. Of 694 patients with COVID-19, 231 patients with mild or moderate disease, who were hospitalised at 10 hospitals in Wenzhou and nearby counties in China, were enrolled in this retrospective study from 17 January to 20 March 2020. The outcomes of these patients included progression from mild/moderate illness to severe or critical conditions. Among the 231 patients, 49 (21.2%) had a poor prognosis in the hospital. Multivariate logistic regression analysis showed that higher inflammation/coagulopathy/immunology responsive index (ICIRI=[c-reactive protein × fibrinogen × D-dimer]/CD8 T cell count) on admission (OR=345.151, 95% CI=23.014-5176.318) was associated with increased odds ratios for poor prognosis. The area under the receiver operating characteristic curve for ICIRI predicting severe and critical condition progression was 0.65 (95% CI=0.519-0.782) and 0.80 (95% CI=0.647-0.954), with cut-off values of 870.83 and 535.44, respectively. Conversely, age, sex, comorbidity, neutrophil/lymphocyte ratio, CD8 T cell count, and c-reactive protein, fibrinogen, and D-dimer levels alone at admission were not good predictors of poor prognosis in patients with mild or moderate COVID-19. At admission, a novel index, ICIRI, tends to be the most promising predictor of COVID-19 progression from mild or moderate illness to severe or critical conditions.


Subject(s)
Blood Coagulation Disorders/virology , COVID-19 , Inflammation/virology , C-Reactive Protein , CD8-Positive T-Lymphocytes/immunology , COVID-19/complications , COVID-19/diagnosis , COVID-19/immunology , Fibrin Fibrinogen Degradation Products , Fibrinogen , Humans , ROC Curve , Retrospective Studies
10.
Viruses ; 14(4):655, 2022.
Article in English | MDPI | ID: covidwho-1753696

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by infection of SARS-CoV-2 and its variants has posed serious threats to global public health, thus calling for the development of potent and broad-spectrum antivirals. We previously designed and developed a peptide-based pan-coronavirus (CoV) fusion inhibitor, EK1, which is effective against all human CoVs (HCoV) tested by targeting the HCoV S protein HR1 domain. However, its relatively short half-life may limit its clinical use. Therefore, we designed, constructed, and expressed a recombinant protein, FL-EK1, which consists of a modified fibronectin type III domain (FN3) with albumin-binding capacity, a flexible linker, and EK1. As with EK1, we found that FL-EK1 could also effectively inhibit infection of SARS-CoV-2 and its variants, as well as HCoV-OC43. Furthermore, it protected mice from infection by the SARS-CoV-2 Delta variant and HCoV-OC43. Importantly, the half-life of FL-EK1 (30 h) is about 15.7-fold longer than that of EK1 (1.8 h). These results suggest that FL-EK1 is a promising candidate for the development of a pan-CoV fusion inhibitor-based long-acting antiviral drug for preventing and treating infection by current and future SARS-CoV-2 variants, as well as other HCoVs.

11.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330371

ABSTRACT

Population antibody response is believed to be important in selection of new variant viruses. We identified that SARS-CoV-2 infections elicit a population immune response mediated by a lineage of VH1-69 germline antibodies. The representative antibody R1-32 targets a novel semi-cryptic epitope defining a new class of RBD targeting antibodies. Binding to this non-ACE2 competing epitope leading to spike destruction impairing virus entry. Based on epitope location, neutralization mechanism and analysis of antibody binding to spike variants we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of this population antibody response. These substitutions, including L452R found in the Delta variant, disrupt interaction mediated by the VH1-69 specific hydrophobic HCDR2 to impair antibody-antigen association allowing variants to escape. Lacking 452/490 substitutions, the Omicron variant is sensitive to this class of antibodies. Our results provide new insights into SARS-CoV-2 variant genesis and immune evasion.

12.
Chin Med Sci J ; 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1732612

ABSTRACT

Mother-to-child transmission (MTCT) of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries. In 2007, WHO launched the global elimination of MTCT (EMTCT) of syphilis. Given the high burden of congenital syphilis, China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis. The congenital syphilis incidence rate per 100 000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019. However, due to the global pandemic of COVID-19, the current measures for eliminating MTCT of syphilis are great challenged. In this article, we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years, point out that we have made remarkable achievements due to the national health policy support and strong leadership of the government. In the context of COVID-19 pandemics, strengthening emergency response to the regional outbreaks of COVID-19 and adopting safe, rapid, early and high-quality clinical care to ensure that 100% of pregnant women receive prenatal syphilis testing services, ensuring the availability of Benzathine penicillin for the treatment, and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are key measures to determine the effect of MTCT of syphilis. Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.

13.
Viruses ; 14(3)2022 03 06.
Article in English | MEDLINE | ID: covidwho-1732247

ABSTRACT

Our previous studies have shown that cholesterol-conjugated, peptide-based pan-coronavirus (CoV) fusion inhibitors can potently inhibit human CoV infection. However, only palmitic acid (C16)-based lipopeptide drugs have been tested clinically, suggesting that the development of C16-based lipopeptide drugs is feasible. Here, we designed and synthesized a C16-modified pan-CoV fusion inhibitor, EK1-C16, and found that it potently inhibited infection by SARS-CoV-2 and its variants of concern (VOCs), including Omicron, and other human CoVs and bat SARS-related CoVs (SARSr-CoVs). These results suggest that EK1-C16 could be further developed for clinical use to prevent and treat infection by the currently circulating MERS-CoV, SARS-CoV-2 and its VOCs, as well as any future emerging or re-emerging coronaviruses.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , COVID-19/drug therapy , Humans , Lipopeptides/pharmacology , Palmitic Acid/pharmacology , SARS-CoV-2
14.
J Clin Ultrasound ; 50(3): 375-382, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1729146

ABSTRACT

BACKGROUND: This study aimed to find the correlation between severe computed tomography (CT) lung scores and nasopharyngeal viral load (Ct value) in the severity of COVID-19 disease progression. METHOD: In this study, 37 patients diagnosed with COVID-19 were categorized into severely ill and not severely ill samples. Their Ct values, epidemiological data, lung CT, and laboratory test results were collected three times, respectively, on the first day of their hospital admission, 3-5 days thereafter, and prior to hospital discharge. Among the 37 patients, 8 progressed from not severely ill to severely ill; we also paid attention and observed changes in clinical parameters of COVID-19 patients who entered our city from other cities (imported cases) and the infected local residents who contacted these imported patients (non-imported cases). RESULTS: Among the 37 patients, the Ct values and lung severity scores (LSSs) were similar in imported and non-imported cases (F = 0.59 and 2.56; p = 0.45 and 0.12, respectively) but the proportion of severely ill imported patients was significantly higher compared with non-imported patients (F = 7.77; p = 0.01). Additionally, 21.6% of patients' illness worsened; lymphocyte counts and Ct values were significantly lowered, and C-reactive protein and LSS significantly increased during COVID-19 disease progression. Furthermore, LSS negatively correlated with lymphocyte and mononuclear cell counts, as well as Ct values (Pearson's rank = -0.763, -0.824, and -0.588; p = 0.028, 0.012, and 0.003, respectively). CONCLUSION: In the severity of COVID-19 disease progression, nasopharyngeal viral load and lung CT severity were closely related, and LSS negatively correlated with lymphocyte and mononuclear cell counts, as well as Ct values.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Lung/diagnostic imaging , Retrospective Studies , Tomography, X-Ray Computed , Viral Load
15.
BMC Health Serv Res ; 22(1): 284, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1724482

ABSTRACT

BACKGROUND: The present study aimed 1) to examine the effects of epidemic-related job stressors, perceived social support and organizational support on the burnout and well-being of Chinese healthcare workers in the period of COVID-19 regular epidemic prevention and control and 2) to investigate the moderating effects of social support and organizational support on the relationship between job stressors and burnout and well-being within the theoretical framework of the Job Demands-Resources (JD-R) model. METHODS: A sample of healthcare workers (N = 3477) from 22 hospitals in Beijing, China participated in the cross-sectional investigation in October 2020 and reported epidemic-related job stressors, perceived social support, organizational support, burnout, anxiety and depression symptoms. RESULTS: 1) Medical doctors, females, people aged from 30 to 50, and those who worked in the second line during the pandemic reported higher scores of psychological symptoms and burnout in the period of regular epidemic prevention and control; 2) Epidemic-related job stressors positively predicted burnout, anxiety, and depression among healthcare workers; 3) Perceived social support and organizational support were negatively related to reported burnout, anxiety and depression symptoms; 4) Social support reduced the adverse effects of epidemic-related job stressors on anxiety and depression but enhanced the association between stressors and burnout; 5) Organizational support mitigated the adverse effects of epidemic-related job stressors on depression. CONCLUSION: The results shed light on preventing burnout and enhancing the psychological well-being of healthcare workers under epidemic prevention and control measures by reducing epidemic-related job stressors and strengthening personal and organizational support systems.


Subject(s)
Burnout, Professional , COVID-19 , Aged , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Burnout, Psychological , COVID-19/epidemiology , Cross-Sectional Studies , Female , Health Personnel/psychology , Humans , Job Satisfaction , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
16.
Evid Based Complement Alternat Med ; 2022: 3051797, 2022.
Article in English | MEDLINE | ID: covidwho-1714456

ABSTRACT

Background: This study discusses the anti-inflammatory mechanism of Yiqi Huayu Jiedu decoction (YQHYJD) and studies the intervening effect of YQHYJD on the inflammatory cytokines in acute respiratory distress syndrome (ARDS) rats by inhibiting the TLR4/NLRP3 signal pathway. The aim of the probe is to provide evidence to support the identification of therapeutic targets in Chinese medicine treatment, which broadens the alternatives for the treatment of ARDS. Method: A lipopolysaccharide (LPS)-induced ARDS model group is established on rats by tail vein injection. A medicine group is established on ARDS rats by prophylactic administration using YQHYJD. Materials are collected, and tests are conducted according to experimental processes. Result: The rats in the medicine group gained weight compared with those in the ARDS model group. Pathological sections from the medicine group indicated improved condition in terms of pulmonary and interstitial edema in the lung tissues of rats compared with that from the ARDS model group. The percentage of neutrophil of the medicine group was significantly brought down compared with that of the ARDS model group (P < 0.001). Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in the level of inflammatory cytokines. It was observed that the levels of IL-1ß and IL-18 in serum of the medicine group significantly decreased (P < 0.001 and P < 0.01), the contents of TLR4 and NLRP3 in bronchoalveolar lavage fluid (BALF) of the medicine group decreased, and the contents of TLR4 and NLRP3 in lung tissue homogenate of the medicine group significantly decreased (P < 0.05, P < 0.001, P < 0.01, and P < 0.05). In further mass spectrum identification of the proteins from the same animal groups, it was observed that the expressions of inflammatory proteins TNFRSF1, LBP, and NOS2 of the medicine group were reduced. The differences were statistically significant. Conclusions: The pharmacological action of YQHYJD's anti-inflammatory mechanism is closely associated with the regulation of inflammatory cytokines TLR4, NLRP3, IL-1ß, IL-18, TNFRSF1, LBP, and NOS2 on the TLR4/NLRP3 signal pathway.

18.
International Review of Economics & Finance ; 2022.
Article in English | ScienceDirect | ID: covidwho-1702149

ABSTRACT

We use a susceptible-infective-removed (SIR) model to examine the impacts of different isolation measures to combat the COVID-19 pandemic. The model predicts that strong isolation measures in the early stage of the pandemic can not only delay the time for the number of infections and deaths to reach the peak but also greatly reduce the cumulative number of infections and deaths. We verify the model predictions by using the simulation and the data of the COVID-19 cases. The results are independent of the joint distribution of the fatality rate and the initial number of active cases.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325418

ABSTRACT

Object: A recently developing pneumonia called COVID-19 which caused by SARS-CoV-2 has quickly spread across the world. Lymphopenia and a proinflammatory cytokine storm frequently happened in severe COVID-19 patients. But no specific immunomodulate therapy on COVID-19 had been reported. In this retrospect case control study, we observed the potential therapeutic effect of recombinant human interleukin-2 (rIL-2) on severe COVID-19 patients in a hospital in Wuhan, China. Methods: : Fifty nine severe cases with COVID-19 admitted in hospital from January 29, 2020 to February 29, 2020 were included in this study. Twenty patients received a one-week to 10 days subcutaneous injection of the recombinant human interleulin-2 1 million IU per day other than regular treatment were classified as rIL-2 group. Twenty from thirty nine patients with regular treatment without intervention of rIL-2 were matched as the control group. Clinical characteristic such as age, gender, symptoms, signs, laboratory data and comorbidities were paired in these two groups. Changes of lymphocytes counts, IL-6 and C- reactive protein (CRP) before and after rIL-2 treatment and differences between rIL-2 group and non-rIL-2 group were analyzed. Results: : There were a clearly visible increasing in lymphocyte counts and a decreasing in CRP level in non rIL-2 group and rIL-2 group. The difference of the change of lymphocyte counts were significant in rIL-2 group and non-rIL-2 group (p<0.01). Though CRP decreased more in rIL-2 group, it did not show a significant difference between the two groups (p>0.05). Conclusion: RIL-2 might be a prospective adjuvant therapy for severe COVID-19 patients by increasing lymphocytes number.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325408

ABSTRACT

Background: Since December 2019, 2019-nCoV has emerged in Wuhan, China, the fast pace of transmission is wreaking global public health crisis. Country’s reaction speed is critical for the control of public health emergency (PHE), especially in the early stage of an outbreak. Compared with SARS pandemic, whether has the efficiency of initial public health emergency response to COVID-19 in mainland China been improved? And whether is there still existing vulnerabilities in current PHE system? Studies on this topic are relatively few. We tried to find the answers, evidences and alternatives. Methods: : We conducted a retrospective comparative study. The speed of hospital reporting, pathogen identification and government decision-making between SARS and COVID-19 were compared by selecting 5 critical events from initial public health emergency response timeline. Besides, combining with the two pandemics' progress curves, we discussed the characteristics of their peak time. Results: : (1) SARS completed the entire initial public health emergency response in 127 days, and COVID-19 completed in 44 days. Response speed has been shorted nearly by 3 times. (2) Both the first SARS and COVID-19 cases were reported in 19 days. It doesn't appear that hospital reporting speed becomes faster. (3) The accumulated time completing pathogen identification were 118 days for SARS and 31 days for COVID-19. The speed has been improved by more than 3 times. (4) 9 days after the completion of pathogen identification, national government made emergency policies for SARS while the interval between pathogen identification and national government's decision-making for COVID-19 was 13 days. (5) The peak time of SARS came about 80 days later than that of COVID-19. But both the two pandemics' peak occurred about 20 days after the national government's decision-making, and then the curves went down dramatically. Conclusions: : The speed of initial public health emergency response to pandemic has been improved due to faster identification. However, some deficiencies and challenges in early alert and authorities' decision-making still remain. Therefore, Chinese government should put more stress on improving hospital's sensitivity to new emerging infectious diseases and timeliness of government's decision-making.

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