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1.
Atmos Environ (1994) ; 268: 118848, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1509577

ABSTRACT

The role of meteorological conditions has long been recognized in modulating regional air quality. The impact of near-surface turbulence, nevertheless, remains poorly understood. To curb the spread of COVID-19, a variety of lockdown measures were implemented, providing us an unprecedented opportunity to examine the joint impact of emission control and meteorology on regional air quality. Here we examined the variations of planetary boundary layer (PBL) height, PM2.5 concentrations, turbulence kinetic energy (TKE), vertical wind shear, and their associations in Chengdu, Sichuan province in Southwest China between January 13 and February 24, 2020, by synergistically using micro pulse lidar, ground-level meteorological and PM2.5 measurements, as well as ultrasonic anemometer observations. During the study period, Sichuan basin was primarily regulated by the straight west wind, with an averaged wind speed of 2-3 m/s at 850 hPa, indicative of a relatively stable atmospheric dispersion condition. TKE was positively correlated with PBL height but negatively correlated with PM2.5. The PM2.5 concentration varied dramatically during pre- and post-lockdown periods but remained near constant at a relatively low level during the lockdown period. Meanwhile, the negative correlation between TKE and PM2.5 was much stronger during the lockdown and post-lockdown periods, when aerosol emissions were significantly reduced. Moreover, the correlation between TKE and PM2.5 exhibited large diurnal variability, with the strongest correlation observed during the daytime when solar radiation and turbulent mixing generally reached their peaks. Overall, the observational results in Chengdu underscore the non-negligible impact of turbulence on regional PM2.5 concentrations, which could help better understand the variation of regional air pollution events.

2.
Signal Transduct Target Ther ; 6(1): 347, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1437669

ABSTRACT

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/pharmacology , Basigin/antagonists & inhibitors , Basigin/metabolism , COVID-19/drug therapy , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , COVID-19/genetics , Chlorocebus aethiops , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/metabolism , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
3.
Diabetes Res Clin Pract ; 178: 108977, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1322066

ABSTRACT

AIM: COVID-19 has spread globally with heavy impact on most countries and our therapeutic strategies in COVID-19 patients with diabetes are still limited. Recently, some new information was added to this field. We performed this updated meta-analysis to reveal the underlying effect of metformin on COVID-19 patients with diabetes. METHODS: We searched the PubMed, Embase and CNKI (China National Knowledge Infrastructure) databases for all articles. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the effect of metformin on COVID-19 patients with diabetes. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. RESULTS: We collected 17 studies including 20,719 COVID-19 patients with diabetes. Our results found that metformin was associated with significantly decreased mortality and severity in COVID-19 patients with diabetes (OR = 0.64, 95% CI = 0.51-0.79 for mortality, and OR = 0.81, 95% CI = 0.66-0.99 for severity). CONCLUSIONS: Our meta-analysis indicated that following metformin treatment might benefit the patients with T2DM, both the mortality and severity. However, patients with severe COVID-19 should be monitored closely for the development of lactic acidosis, acidosis, and decreased kidney function.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Metformin , COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use
4.
Signal Transduct Target Ther ; 6(1): 194, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232064

ABSTRACT

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , COVID-19/metabolism , Lung/metabolism , SARS-CoV-2/metabolism , Adolescent , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , COVID-19/pathology , Double-Blind Method , Female , Humans , Lung/pathology , Lung/virology , Male , Middle Aged
5.
Signal Transduct Target Ther ; 5(1): 283, 2020 12 04.
Article in English | MEDLINE | ID: covidwho-957563

ABSTRACT

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.


Subject(s)
Basigin/genetics , COVID-19/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Basigin/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Host-Pathogen Interactions/immunology , Humans , Lung/immunology , Lung/pathology , Lung/virology , Mice , Pandemics , Protein Binding/immunology , Protein Domains/genetics , Protein Domains/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Virus Internalization
6.
BMC Public Health ; 20(1): 1292, 2020 Aug 26.
Article in English | MEDLINE | ID: covidwho-730208

ABSTRACT

BACKGROUND: The COVID-19 pandemic has become a great threat to public health, which has greatly impacted the study and life of undergraduate students in China. This study aims to perform a survey of their knowledge, attitude and practice (KAP) associated with COVID-19. METHODS: A cross-sectional survey was designed to gather information regarding the COVID-19 related KAP among undergraduates during the home isolation in the outbreak. Subjects were recruited from 10 universities in Shaanxi Province, China. Enrollees voluntarily submitted their answers to a pre-designed questionnaire online. RESULTS: A total of 872 subjects (female, 534; male, 338) were enrolled with ages from 17 to 25 years old. This cohort included 430 medical and 442 non-medical students, 580 freshmen and 292 higher school year students. There were 453 from public schools and 442 from private school, residing in 28 regions and provinces at the time of study. Results showed that appropriate knowledge was acquired by 82.34% subjects; the levels were significantly higher in undergraduates from public universities and medical majors than those from private schools and non-medical majors (p<0.05). 73.81% subjects reported positive attitudes; females showed significantly higher levels of positive attitudes than males (p<0.05). Proactive practice was found in 87.94% subjects. Using a common scoring method, the overall scores for Knowledge, Attitude and Practice were 4.12 ± 0.749 (range: 0 ~ 5), 8.54 ± 1.201 (range: 0 ~ 10), and 8.91 ± 1.431 (range: 0 ~ 10), respectively. There was a positive correlation between attitude and practice (r = 0.319, p < 0.05) in the whole study group. Total KAP score was 21.57 ± 2.291 (range: 0 ~ 25), which was significantly different between gender groups and major groups. CONCLUSIONS: Most undergraduates acquired necessary knowledge, positive attitude and proactive practice in response to COVID-19 outbreak; but their KAP scores significantly varied by gender, major and school types.


Subject(s)
Coronavirus Infections/prevention & control , Health Knowledge, Attitudes, Practice , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Students/psychology , Adolescent , Adult , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Pneumonia, Viral/epidemiology , Students/statistics & numerical data , Surveys and Questionnaires , Universities , Young Adult
7.
Complement Ther Med ; 52: 102473, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-591555

ABSTRACT

OBJECTIVE: Presentation of a case illustrating the benefits of traditional Chinese medicine (TCM) for treatment of Coronavirus disease 2019 (COVID-19) in critically ill patients. CLINICAL FEATURES AND OUTCOME: A 58-year-old woman presented with cough, fever, dizziness, chest tightness, polypnea and poor appetite. She was admitted to Guizhou Provincial People's hospital, and diagnosed with critically ill type of COVID-19 in February 2020. According to the patient's symptoms and signs, the TCM syndrome differentiation was qi deficiency, dampness-stasis and toxin accumulation. Then she received the combined therapy of a modified Chinese herbal formula and Western medicine. During a twelve-day period of treatment, her respiratory distress and appetite quickly improved. Abnormal laboratory indicators were resumed in time and lung lesions in CT scan largely absorbed. No side effects associated with this Chinese herbal formula were found. Before discharge, two consecutive nasopharyngeal swabs were shown to be negative for severe acute respiratory coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Our case report suggests that collaborative treatments with traditional Chinese medicine prove beneficial in the management of COVID-19 in critically ill patients. In order to give optimal care for this COVID-19 crisis for the whole world, Chinese medicine practitioners and Western medical doctors should work together in frontline.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Pneumonia, Viral/drug therapy , Betacoronavirus , COVID-19 , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Illness , Drug Combinations , Female , Humans , Indoles/therapeutic use , Lopinavir/therapeutic use , Methylprednisolone/therapeutic use , Middle Aged , Moxifloxacin/therapeutic use , Noninvasive Ventilation , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Qi , Ritonavir/therapeutic use , SARS-CoV-2
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