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1.
International journal of biological sciences ; 18(2):889-900, 2022.
Article in English | EuropePMC | ID: covidwho-1610605

ABSTRACT

Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.

3.
Int J Chron Obstruct Pulmon Dis ; 16: 3337-3346, 2021.
Article in English | MEDLINE | ID: covidwho-1581602

ABSTRACT

Background: SARS-CoV-2 tends to cause more severe disease in patients with COPD once they are infected. We aimed to investigate the rates of influenza, pneumococcal and COVID-19 vaccination uptake in patients with COPD and to determine whether the COVID-19 pandemic and widespread vaccination against COVID-19 had any impact on the intention to accept influenza vaccines in these patients. Methods: We conducted a multi-center and cross-sectional survey in seven tertiary hospitals in Beijing and consecutively recruited outpatients with COPD from June 1st to July 30th, 2021. The survey included patient's clinical characteristics, uptake of influenza, pneumococcal and COVID-19 vaccination, vaccine knowledge, attitude towards vaccines, and the change of intention to receive influenza vaccination after COVID-19 epidemic and COVID-19 vaccination in Beijing. Results: A total of 264 patients were enrolled. The rate of COVID-19 vaccination during the study period was 39.0%. The rates of influenza vaccination in the past season and pneumococcal vaccination in the past year were 22.7% and 5.7%, respectively. Of the patients who had not received COVID-19 vaccination (n = 161), only 16.2% reported that COVID-19 vaccination was recommended by clinicians, while 23.5% had no knowledge regarding COVID-19 vaccination. About 51.1% of the patients reported that their intention to receive influenza vaccination was influenced by the COVID-19 pandemic. COVID-19 vaccination was independently associated with a positive change in intention to receive influenza vaccination. Conclusion: The coverage rate of COVID-19 vaccination among patients with COPD in Beijing was 39.0%, and that of influenza and pneumococcal vaccination was very low. The COVID-19 pandemic and the COVID-19 vaccination campaign showed a significant, positive impact on patients with COPD in terms of influenza vaccination. Improving awareness of the effectiveness and safety of vaccines among both healthcare professionals and patients could increase vaccination coverage in patients with COPD.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Pulmonary Disease, Chronic Obstructive , COVID-19 Vaccines , Cross-Sectional Studies , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Intention , Pandemics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2 , Vaccination
4.
Aging (Albany NY) ; 13(20): 23459-23470, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1498163

ABSTRACT

BACKGROUND: Since April 2021, the SARS-CoV-2 (B.1.167) Delta variant has been rampant worldwide. Recently, this variant has spread in Guangzhou, China. Our objective was to characterize the clinical features and risk factors of severe cases of the Delta variant in Guangzhou. METHODS: A total of 144 patients with the Delta variant were enrolled, and the data between the severe and non-severe groups were compared. Logistic regression methods and Cox multivariate regression analysis were used to investigate the risk factors of severe cases. RESULTS: The severity of the Delta variant was 11.1%. Each 1-year increase in age (OR, 1.089; 95% CI, 1.035-1.147; P = 0.001) and each 1-µmol/L increase in total bilirubin (OR, 1.198; 95% CI, 1.021-1.406; P = 0.039) were risk factors for severe cases. Moreover, the risk of progression to severe cases increased 13.444-fold and 3.922-fold when the age was greater than 58.5 years (HR, 13.444; 95% CI, 2.989-60.480; P = 0.001) or the total bilirubin level was greater than 7.23 µmol/L (HR, 3.922; 95% CI, 1.260-12.207; P = 0.018), respectively. CONCLUSION: Older age and elevated total bilirubin were independent risk factors for severe cases of the Delta variant in Guangzhou, especially if the age was greater than 58.5 years or the total bilirubin level was greater than 7.23 µmol/L.


Subject(s)
COVID-19/therapy , SARS-CoV-2/isolation & purification , Adult , COVID-19/diagnosis , COVID-19/mortality , COVID-19/prevention & control , COVID-19 Vaccines , Cardiovascular Diseases/epidemiology , China/epidemiology , Comorbidity , Cough/etiology , Diabetes Mellitus, Type 2/epidemiology , Female , Fever/etiology , Hospital Mortality , Humans , Hypertension/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2/genetics , Severity of Illness Index
5.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5117-5122, 2021 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1485611

ABSTRACT

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.


Subject(s)
COVID-19/therapy , China , Evidence-Based Medicine , Humans , Medicine, Chinese Traditional , Practice Guidelines as Topic , SARS-CoV-2
6.
J Virol ; 2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1232341

ABSTRACT

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine.IMPORTANCEEffective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

7.
Bull World Health Organ ; 99(5): 374-380, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1218472

ABSTRACT

A surge in the number of international arrivals awaiting coronavirus disease 2019 (COVID-19) screening overwhelmed health-care workers and depleted medical resources in designated hospitals in Beijing, China in March 2020. The People's Government of Beijing Municipality therefore issued a policy which required the mandatory transfer of all asymptomatic passengers arriving from a foreign country to designated quarantine hotels, and the transfer of passengers with fever or respiratory symptoms to designated hospitals. Xiaotangshan Designated Hospital, a severe acute respiratory syndrome hospital in 2003, was rapidly renovated and put into operation with the main tasks of screening and isolating symptomatic international arrivals at Beijing Capital International Airport, providing basic medical care for mild to moderate COVID-19-positive cases, and rapidly referring severe to critical COVID-19-positive cases to higher-level hospitals. During the month-long period of its operation, 2171 passengers were screened and 53 were confirmed as having COVID-19 (six severe to critical). We describe how the use of Xiaotangshan Designated Hospital in this way enabled the efficient grouping and assessment of passengers arriving from a foreign country, the provision of optimal patient care without compromising public safety and the prioritization of critically ill patients requiring life-saving treatment. The designated hospital is a successful example of the World Health Organization's recommendation to renovate existing medical infrastructures to improve the COVID-19 response capacity. The flexible design of Xiaotangshan Designated Hospital means that it can be repurposed and reopened at any time to respond to the changing pandemic conditions.


Subject(s)
Airports , COVID-19/epidemiology , COVID-19/prevention & control , Hospitals, Special/organization & administration , Mass Screening/organization & administration , China/epidemiology , Humans , Internationality , Pandemics , SARS-CoV-2 , Severity of Illness Index
8.
Int Immunopharmacol ; 97: 107685, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1188659

ABSTRACT

BACKGROUND: The 2019 Coronavirus (COVID-19) pandemic poses a huge threat internationally; however, the role of the host immune system in the pathogenesis of COVID-19 is not well understood. METHODS: Cytokine and chemokine levels and characterisation of immune cell subsets from 20 COVID-19 cases after hospital admission (17 critically ill and 3 severe patients) and 16 convalescent patients were determined using a multiplex immunoassay and flow cytometry, respectively. RESULTS: IP-10, MCP-1, MIG, IL-6, and IL-10 levels were significantly higher in acute severe/critically ill patients with COVID-19, whereas were normal in patients who had reached convalescence. CD8 T cells in severe and critically ill COVID-19 patients expressed high levels of cytotoxic granules (granzyme B and perforin)and was hyperactivated as evidenced by the high proportions of CD38. Furthermore, the cytotoxic potential of natural killer (NK) cells, and the frequencies of myeloid dendritic cells and plasmacytoid dendritic cells was reduced in patients with severe and critical COVID-19; however, these dysregulations were found to be restored in convalescent phases. CONCLUSION: Thus, elicitation of the hyperactive cytokine-mediated inflammatory response, dysregulation of CD8 T and NK cells, and deficiency of host myeloid and plasmacytoid DCs, may contribute to COVID-19 pathogenesis and provide insights into potential therapeutic targets and strategies.


Subject(s)
COVID-19/blood , COVID-19/immunology , Convalescence , Inflammation/etiology , ADP-ribosyl Cyclase 1/blood , Acute Disease , Adult , Aged , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/enzymology , CD8-Positive T-Lymphocytes/immunology , Chemokine CCL2/blood , Chemokine CXCL10/blood , Chemokine CXCL9/blood , Critical Illness , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Dendritic Cells/immunology , Female , Granzymes/metabolism , Humans , Interleukin-10/blood , Interleukin-6/blood , Killer Cells, Natural/enzymology , Killer Cells, Natural/immunology , Male , Membrane Glycoproteins/blood , Middle Aged , Perforin/metabolism
9.
J Virol ; 2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1127541

ABSTRACT

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine.IMPORTANCEEffective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

10.
Nat Commun ; 12(1): 1346, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1111984

ABSTRACT

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/pathogenicity , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Blotting, Western , COVID-19/therapy , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular/physiology , Immunization, Passive , Immunohistochemistry , Macaca mulatta , Mice , Mice, Inbred BALB C , Microscopy, Electron , SARS-CoV-2/immunology
12.
Clin Lab ; 66(11)2020 Nov 01.
Article in English | MEDLINE | ID: covidwho-922947

ABSTRACT

BACKGROUND: To investigate the clinical value of multi-index combined detection in the diagnosis of new coronavirus disease 2019 (COVID-19). METHODS: A total of 63 laboratory confirmed patients treated in our hospital were selected as the COVID-19 group, including 28 severe patients and 35 non-severe patients. Another 50 healthy subjects undergoing physical examination simultaneously were selected as the healthy group. Here we performed a study on the laboratory characteristics and explored their efficacy for diagnosis of the disease. RESULTS: Compared with healthy people, the abnormal indicators of patients with COVID-19 are low levels of lymphocytes (LYM), red blood cells (RBC), hemoglobin (HGB), platelets (PLT), total protein (TP), and albumin (ALB), and high levels of monocytes (MON), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and C-reactive protein (CRP). The level of MON and CRP in severe patients were significantly increased compared with non-severe pneumonia patients, and indicators such as LYM and ALB were significantly reduced (p < 0.05). The sensitivity and specificity of the combined detection of LYM, MON, RBC, HGB, PLT, TP, ALB, AST, GGT, and CRP was 97.7% and 91.7%, which was higher than the single item (p < 0.05). The sensitivity and specificity of combined detection of LYM, MON, ALB, and CRP to predict the severity of COVID-19 were 96.4% and 73.0%, which were higher than those of separate detections (p < 0.05). CONCLUSIONS: The index of LYM, MON, RBC, HGB, PLT, TP, ALB, AST, GGT, and CRP can be used for the diagnosis of new COVID-19, and the indicators of LYM, MON, ALB, and CRP may be predictors of severe pneumonia. The combined detection of the laboratory indexes can diagnose COVID-19 and predict the severity more effectively and accurately.


Subject(s)
Biomarkers/blood , Clinical Laboratory Techniques , Coronavirus Infections/blood , Pneumonia, Viral/blood , Adult , Aged , COVID-19 , COVID-19 Testing , Case-Control Studies , Coronavirus Infections/diagnosis , Female , Humans , Lymphocyte Count , Male , Middle Aged , Pandemics
13.
Int J Chron Obstruct Pulmon Dis ; 15: 2487-2494, 2020.
Article in English | MEDLINE | ID: covidwho-874299

ABSTRACT

Background: Social distancing and restriction measures during the COVID-19 epidemic may have impacts on medication availability and healthcare utilization for COPD patients, and thereby affect standard disease management. We aimed to investigate the change of respiratory symptoms, pharmacological treatment and healthcare utilization of COPD patients during the epidemic in Beijing, China. Methods: We conducted a single-center, cross-sectional survey performed at Peking University Third Hospital and recruited patients with COPD who were interviewed by phone call. Clinical data, including respiratory symptoms, pharmacological treatment, management and healthcare access before and during the COVID-19 epidemic from January 25 to April 25, 2020, were collected. Results: A total of 153 patients were enrolled for analysis. Before the epidemic, 81.7% (125/153) had long-term maintenance medication and ICS/LABA (60.8%) and LAMA (57.5%) were most commonly used. During the epidemic, 75.2% (115/153) maintained their pharmacological treatment and 6.5% (10/153) had to reduce or stop taking medications, with a slight decrease of patients taking ICS/LABA (53.6%) and LAMA (56.9%). Most of the patients [76.5% (117/153)] had a low symptom burden, with a CAT score <10 during the epidemic. Of 153 patients, 45 (29.4%) patients reported worsening of respiratory symptoms but only 15.6% (7/45) sought medical care in hospitals, while the remaining expressed concerns about cross-infection in the hospital (55.5%, 25/45) or had mild symptoms which were managed by themselves (28.8%, 13/45). Conclusion: During the COVID-19 epidemic in Beijing, most of our COPD patients maintained their long-term pharmacological treatment and had mild-to-moderate symptoms. Approximately, 30.0% of the patients experienced worsening of respiratory symptoms, but most of them did not seek medical care in the hospital due to concerns about cross-infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Health Services Accessibility , Patient Acceptance of Health Care , Pneumonia, Viral/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy , Aged , Aged, 80 and over , Beijing , COVID-19 , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pandemics , Pulmonary Disease, Chronic Obstructive/complications , SARS-CoV-2 , Self-Management
15.
J Clin Biochem Nutr ; 67(2): 126-130, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-696117

ABSTRACT

Severe patients of the coronavirus disease 2019 (COVID-19) may progress rapidly to critical stage. This study aimed to identify factors useful for predicting the progress. 33 severe COVID-19 patients at the intensive care unit were included in this study. During treatment, 13 patients deteriorated and required further treatment for supporting organ function. The remaining 20 patients alleviated and were transferred to the general wards. The multivariate COX regression analyses showed that hypoproteinemia was an independent risk factor associated with deterioration of severe patients (HR, 0.763; 95% CI, 0.596 to 0.978; p = 0.033). The restricted cubic spline indicated that when HR = 1, the corresponding value of albumin is 29.6 g/L. We used the cutoff of 29.6 g/L to divide these patients. Kaplan-Meier curves showed that the survival rate of the high-albumin group was higher than that of the low-albumin group. Therefore, hypoalbuminemia may be an independent risk factor to evaluate poor prognosis of severely patients with COVID-19, especially when albumin levels were below 29.6 g/L.

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