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1.
Ann Vasc Surg ; 2021 Oct 10.
Article in English | MEDLINE | ID: covidwho-1458689

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

2.
Front Immunol ; 12: 677025, 2021.
Article in English | MEDLINE | ID: covidwho-1403470

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global crisis; however, our current understanding of the host immune response to SARS-CoV-2 infection remains limited. Herein, we performed RNA sequencing using peripheral blood from acute and convalescent patients and interrogated the dynamic changes of adaptive immune response to SARS-CoV-2 infection over time. Our results revealed numerous alterations in these cohorts in terms of gene expression profiles and the features of immune repertoire. Moreover, a machine learning method was developed and resulted in the identification of five independent biomarkers and a collection of biomarkers that could accurately differentiate and predict the development of COVID-19. Interestingly, the increased expression of one of these biomarkers, UCHL1, a molecule related to nervous system damage, was associated with the clustering of severe symptoms. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T-cell and B-cell responses to SARS-CoV-2 infection, with B-cell response plateaued in the acute phase and declined thereafter, whereas T-cell response can be maintained for up to 6 months post-infection onset and T-cell clonality was positively correlated with the serum level of anti-SARS-CoV-2 IgG. Together, the significantly altered genes or biomarkers, as well as the abnormally high levels of B-cell response in acute infection, may contribute to the pathogenesis of COVID-19 through mediating inflammation and immune responses, whereas prolonged T-cell response in the convalescents might help these patients in preventing reinfection. Thus, our findings could provide insight into the underlying molecular mechanism of host immune response to COVID-19 and facilitate the development of novel therapeutic strategies and effective vaccines.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Leukocytes, Mononuclear/chemistry , Transcriptome , Adult , Aged , Antibodies, Viral/blood , B-Lymphocytes/immunology , Biomarkers/blood , COVID-19/blood , COVID-19/virology , China , Cohort Studies , Female , Humans , Leukocytes, Mononuclear/immunology , Machine Learning , Male , Middle Aged , SARS-CoV-2/physiology , Sequence Analysis, RNA , T-Lymphocytes/immunology , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/immunology
4.
Nat Prod Res ; 34(16): 2249-2254, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1343564

ABSTRACT

The enhanced osteoblast differentiation is beneficial to the prevention of osteoporosis. In this study, a homogeneous polysaccharide (LRP-S2A) with the potential of promoting osteoblast differentiation was obtained from the fruits of Lycium ruthenicum, a traditional herb for treatment of postmenopausal metabolic disorders. Structural identification indicated that LRP-S2A, with a relative molecular weight of 2.65 × 106 Da and an uronic acid content of 41.8%, contained Rha, Ara, Gal, Glc and GlcA in a molar ratio of 1.00 : 2.07 : 0.57 : 2.59 : 4.33 and was composed of a backbone consisting of 6-O-Me-α-(1→4)-D-GlcpA, 2-O-acetyl-α-(1→4)-D-Glcp, α-(1→2,4)-L-Rhap, ß-(1→3)-D-Galp andα-(1→3,5)-L-Araf, and some branches consisting of 6-O-Me-α-(1→4)-D-GlcpA and terminal α-L-Araf. These results suggested that LRP-S2A with the potential of promoting osteoblast differentiation was a new acidic polysaccharide.


Subject(s)
Cell Differentiation/drug effects , Lycium/chemistry , Osteoblasts/cytology , Polysaccharides/chemistry , Animals , Cells, Cultured , Fruit/chemistry , Humans , Molecular Weight , Polysaccharides/pharmacology , Uronic Acids/analysis
5.
Mol Syst Biol ; 17(8): e10239, 2021 08.
Article in English | MEDLINE | ID: covidwho-1335457

ABSTRACT

Understanding the mechanism of SARS-CoV-2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID-19. These were deduced from the gene expression signature of SARS-CoV-2-infected A549 cells screened against Connectivity Map and prioritized by network proximity analysis with respect to disease modules in the viral-host interactome. We also identified immuno-modulating compounds aiming at suppressing hyperinflammatory responses in severe COVID-19 patients, based on the transcriptome of ACE2-overexpressing A549 cells. Experiments with Vero-E6 cells infected by SARS-CoV-2, as well as independent syncytia formation assays for probing ACE2/SARS-CoV-2 spike protein-mediated cell fusion using HEK293T and Calu-3 cells, showed that several predicted compounds had inhibitory activities. Among them, salmeterol, rottlerin, and mTOR inhibitors exhibited antiviral activities in Vero-E6 cells; imipramine, linsitinib, hexylresorcinol, ezetimibe, and brompheniramine impaired viral entry. These novel findings provide new paths for broadening the repertoire of compounds pursued as therapeutics against COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Evaluation, Preclinical/methods , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , COVID-19/genetics , COVID-19/virology , Chlorocebus aethiops , Drug Repositioning , HEK293 Cells , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/physiology , Humans , Imidazoles/pharmacology , Pyrazines/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Salmeterol Xinafoate/pharmacology , Vero Cells
6.
Sport in Society: Cultures, Commerce, Media, Politics ; 23(11):1841-1860, 2020.
Article in English | CAB Abstracts | ID: covidwho-1319115

ABSTRACT

Previous research has overlooked the influence of non-mega sport events on local residents' perceptions of quality of life and their attitude toward the hosting of events;in particular, there is a major research void in understanding residents' opinions in Chinese cities that are making escalated efforts in staging small to medium size sport events. This study examined the relationships among the perceived impacts of sport event, quality of life, and event support of local residents at a marathon event in China. Findings revealed that perceived psychological and social impacts by local residents were found to be positively predictive of their quality of life and event support, perceived economic impact had no significant influence, perceived environmental impact was significant in facilitating residents' quality of life although it was not influential of their support for the event directly. Implications are discussed furtherly.

7.
Clin Invest Med ; 44(2): E48-54, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1278876

ABSTRACT

PURPOSE: The aim of the study was to describe the use of masks among health care personnel (HCP) exposed to index cases of coronavirus disease 2019 (COVID-19), and to evaluate any association with infection rate. METHODS: We did a retrospective, observational study of HCP at Zhongnan Hospital of Wuhan University for the management of COVID-19 (before person-to-person transmission was official confirmed, no additional protection was provided). A questionnaire was given to all staff listed on the roster in the clinical regions providing care for index patients with COVID-19. All participants were surveyed regarding hand-washing and use of surgical masks and gloves and were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were analysed (Student's t test and Pearson χ2 test) for an association between infection and use of personal protective equipment. RESULTS: Exposure of a total of 299 non-infected and 30 infected staff was confirmed. None of the 149 staff who reported use of all three preventative measures (hand-washing and use of gloves and masks) became infect-ed. In contrast, all 30 of the staff who became infected had omitted at least one of the measures. Fewer staff who wore surgical masks (P=0.000003) became infected compared with those who did not. Infections rates were significantly lower in HCP from the internal medicine departments, as these personnel generally wore masks. CONCLUSION: An association was found between SARS-CoV-2 infection of HCP and the non-use of masks when working with index cases in clinical settings. We recommend that all HCP follow the strict instructions for prevention and treatment of nosocomial infection during intimate contact with COVID-19, especially staff from surgical departments.


Subject(s)
COVID-19/prevention & control , Masks , Occupational Exposure/prevention & control , Personal Protective Equipment , Physicians , SARS-CoV-2 , Adult , COVID-19/transmission , China , Delivery of Health Care , Female , Gloves, Surgical , Hand Disinfection , Health Personnel , Humans , Male , Middle Aged , Retrospective Studies
8.
Microbiol Spectr ; 9(1): e0016921, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1270881

ABSTRACT

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. Here, we determined the crystal structure of the N terminus (amino acids [aa] 11 to 125) of SARS-CoV-2 Nsp1 at a 1.25-Å resolution. Further functional assays showed that the N terminus of SARS-CoVs Nsp1 alone loses the ability to colocalize with ribosomes and inhibit protein translation. The C terminus of Nsp1 can colocalize with ribosomes, but its protein translation inhibition ability is significantly weakened. Interestingly, fusing the C terminus of Nsp1 with enhanced green fluorescent protein (EGFP) or other proteins in place of its N terminus restored the protein translation inhibitory ability to a level equivalent to that of full-length Nsp1. Thus, our results suggest that the N terminus of Nsp1 is able to stabilize the binding of the Nsp1 C terminus to ribosomes and act as a nonspecific barrier to block the mRNA channel, thus abrogating host mRNA translation.


Subject(s)
SARS-CoV-2/genetics , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , COVID-19 , Crystallography, X-Ray , HEK293 Cells , Humans , Protein Biosynthesis , Protein Conformation , Protein Domains , RNA, Messenger , Sequence Analysis, Protein , Viral Nonstructural Proteins/metabolism
9.
J Chem Inf Model ; 60(12): 5735-5745, 2020 12 28.
Article in English | MEDLINE | ID: covidwho-1065777

ABSTRACT

The emergence of the new coronavirus (nCoV-19) has impacted human health on a global scale, while the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under the current adverse situation, we employ virtual screening tools in searching for drugs and natural products which have been already deposited in DrugBank in an attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Additionally, we have built an interactive online platform (https://shennongproject.ai/) for browsing these results with the visual display of a small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory work, it may serve not only as the assessment tool for the new drug discovery but also an educational web site for the public.


Subject(s)
Antiviral Agents/chemistry , COVID-19/drug therapy , Drug Evaluation, Preclinical/methods , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/pharmacology , Computer Simulation , Databases, Pharmaceutical , Drug Design , Humans , Molecular Docking Simulation , Protein Conformation , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Software , Viral Proteins/metabolism
10.
Infect Dis Ther ; 10(1): 483-494, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1061212

ABSTRACT

INTRODUCTION: Since December 2019, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic in China and worldwide. New drugs for the treatment of COVID-19 are in urgent need. Considering the long development time for new drugs, the identification of promising inhibitors from FDA-approved drugs is an imperative and valuable strategy. Recent studies have shown that the S1 and S2 subunits of the spike protein of SARS-CoV-2 utilize human angiotensin-converting enzyme 2 (hACE2) as the receptor to infect human cells. METHODS: We combined molecular docking and surface plasmon resonance (SPR) to identify potential inhibitors for ACE2 from available commercial medicines. We also designed coronavirus pseudoparticles that contain the spike protein assembled onto green fluorescent protein or luciferase reporter gene-carrying vesicular stomatitis virus core particles. RESULTS: We found that thymoquinone, a phytochemical compound obtained from the plant Nigella sativa, is a potential drug candidate. SPR analysis confirmed the binding of thymoquinone to ACE2. We found that thymoquinone can inhibit SARS-CoV-2, SARS-CoV, and NL63 pseudoparticles infecting HEK293-ACE2 cells, with half-maximal inhibitory concentrations of 4.999, 7.598, and 6.019 µM, respectively. The SARS-CoV-2 pseudoparticle inhibition had half-maximal cytotoxic concentration of 35.100 µM and selection index = 7.020. CONCLUSION: Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.

11.
Front Med (Lausanne) ; 7: 597967, 2020.
Article in English | MEDLINE | ID: covidwho-1058424

ABSTRACT

Objectives: This work aims to study the gastrointestinal (GI) symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and the susceptibility factors of the stomach for SARS-CoV-2. Materials and Methods: We investigated the SARS-CoV-2 susceptibility by analyzing the expression distribution of viral entry-associated genes, ACE2 and TMPRSS2, in single-cell RNA sequencing data derived from 12 gastric mucosa samples. We also analyzed the epidemiological, demographic, clinical, and laboratory data of 420 cases with SARS-CoV-2-caused coronavirus disease 2019 (COVID-19). Results: ACE2 and TMPRSS2 are specifically expressed in enterocytes which are mainly from gastric mucosa samples with Helicobacter pylori (H. pylori) infection history and intestinal metaplasia (IM). A total of 420 patients were surveyed, of which 62 were with and 358 were without GI symptoms. There is a significant difference in average hospital stay (p < 0.001) and cost (p < 0.001) between the two groups. Among 23 hospitalized patients including seven with upper GI symptoms and 16 with lower GI symptoms, six (85.7%) and five (31.3%) had H. pylori infection history, respectively (p = 0.03). Of 18 hospitalized patients with initial upper GI symptoms, none of the eight patients with mucosal protective agent therapy (e.g., sucralfate suspension gel, hydrotalcite tablets) had diarrhea subsequently, whereas six out of 10 patients without mucosal protective agent therapy had diarrhea subsequently (p = 0.01). Conclusion: IM and H. pylori infection history may be susceptibility factors of SARS-CoV-2, and the mucosal protective agent may be useful for the blockade of SARS-CoV-2 transmission from the stomach to the intestine.

13.
Preprint | CAplus | ID: ppcovidwho-4917

ABSTRACT

A review on digital publishing platform for science-tech periodicals under major public emergency in relation to social responsibility and mission.

14.
Expert Rev Gastroenterol Hepatol ; 15(6): 657-664, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-990446

ABSTRACT

INTRODUCTION: Appendectomy remains the gold standard for treating uncomplicated and complicated appendicitis. However, the vermiform appendix may play a significant role in the immune system (secondary immune function) and maintain a reservoir of the normal microbiome for the human body. The aim of this study was to summarize the long-term effects after appendectomy and discuss whether appendectomy is suitable for all appendicitis patients. AREAS COVERED: A comprehensive and unbiased literature search was performed in PubMed. The terms 'appendix,' 'appendicitis,' 'appendectomy,' and 'endoscopic retrograde appendicitis therapy' were searched in the title and/or abstract. This review summarizes the long-term effects of appendectomy on some diseases in humans and describes three methods including appendectomy, medical treatment, and an 'organ-sparing' technique, named endoscopic retrograde appendicitis therapy (ERAT) to treat appendicitis. EXPERT OPINION: Appendectomy remains the first-line therapy for appendicitis. The patient's problem is appendix, not appendicitis. If we treat appendicitis, the problem should be resolved. During COVID-19, an initial antibiotic treatment of mild appendicitis represents a promising strategy. For patients who are worried about the long-term adverse effect after appendectomy and have a strong desire to preserve the appendix and are aware of the risk of appendicitis recurrence, medical treatment, or ERAT could be proposed.


Subject(s)
Appendectomy/adverse effects , Appendicitis/surgery , COVID-19/prevention & control , Postoperative Complications/epidemiology , Anti-Bacterial Agents/therapeutic use , Appendicitis/drug therapy , Appendicitis/etiology , COVID-19/epidemiology , COVID-19/transmission , Endoscopy , Humans , Patient Selection
15.
Curr Med Res Opin ; 37(2): 219-224, 2021 02.
Article in English | MEDLINE | ID: covidwho-942189

ABSTRACT

PURPOSE: To describe the radiological features of coronavirus disease 19 (COVID-19) and to explore the significant signs that indicate severity of disease. MATERIALS AND METHODS: We collected data retrospectively of 180 cases of COVID-19, from 15 January 2020 to 31 March 2020, from both the Wuhan Zhongnan and Beijing Ditan Hospitals, including 103 cases of mild and 77 cases of severe pneumonia. All patients had their first chest computed tomography scan within five days of symptom onset. The dandelion sign was defined by a focal ground glass opacity (GGO) with a central thickening of the airway wall, and the focal crazy paving sign was defined by a focal GGO with thickening of the interlobular septa. RESULTS: Consolidation presented in only 4.9% (5/103) of the mild pneumonia cases, which was significantly lower than that in severe pneumonia cases (70.1% 54/77), p < .001). Multifocal distribution and pure GGOs were observed more frequently in severe cases of pneumonia (p < .05). The dandelion sign was present in 86.4% (89/103) of the mild pneumonia cases, significantly more frequent than those with severe pneumonia (13.0% [10/77], p < .001). The focal crazy paving sign presented in 65.0% (67/103) of the mild pneumonia cases and was significantly more frequent than in severe cases (23.4% [18/77], p < .001). The hospital stay duration of the mild pneumonia group (13.6 ± 7.2 days) was significantly shorter than the severe pneumonia group (26.6 ± 11.7 days, p < .001). CONCLUSIONS: Consolidation, pure GGO and multifocal distribution on a CT scan were associated with severe COVID-19. The dandelion and focal crazy paving signs indicate mild COVID-19.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Adult , Aged , COVID-19/physiopathology , Coronavirus , Coronavirus Infections , Female , Humans , Length of Stay , Male , Middle Aged , Pneumonia , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed/methods
16.
BMC Cardiovasc Disord ; 20(1): 479, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-917918

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic. Studies showed COVID-19 affected not only the lung but also other organs. In this study, we aimed to explore the cardiac damage in patients with COVID-19. METHODS: We collected data of 100 patients diagnosed as severe type of COVID-19 from February 8 to April 10, 2020, including demographics, illness history, physical examination, laboratory test, and treatment. In-hospital mortality were observed. Cardiac damage was defined as plasma hypersensitive troponin I (hsTnI) over 34.2 pg/ml and/or N-terminal-pro brain natriuretic peptide (NTproBNP) above 450 pg/ml at the age < 50, above 900 pg/ml at the age < 75, or above 1800 pg/ml at the age ≥ 75. RESULTS: The median age of the patients was 62.0 years old. 69 (69.0%) had comorbidities, mainly presenting hypertension, diabetes, and cardiovascular disease. Fever (69 [69.0%]), cough (63 [63.0%]), chest distress (13 [13.0%]), and fatigue (12 [12.0%]) were the common initial symptoms. Cardiac damage occurred in 25 patients. In the subgroups, hsTnI was significantly higher in elder patients (≥ 60 years) than in the young (median [IQR], 5.2 [2.2-12.8] vs. 1.9 [1.9-6.2], p = 0.018) and was higher in men than in women (4.2 [1.9-12.8] vs. 2.9 [1.9-7.4], p = 0.018). The prevalence of increased NTproBNP was significantly higher in men than in women (32.1% vs. 9.1%, p = 0.006), but was similar between the elder and young patients (20.0% vs. 25.0%, p = 0.554). After multivariable analysis, male and hypertension were the risk factors of cardiac damage. The mortality was 4.0%. CONCLUSIONS: Cardiac damage exists in patients with the severe type of COVID-19, especially in male patients with hypertension. Clinicians should pay more attention to cardiac damage.


Subject(s)
Coronavirus Infections/complications , Heart Diseases/etiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Pneumonia, Viral/complications , Age Factors , Aged , Biomarkers/blood , COVID-19 , China , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Heart Diseases/diagnosis , Heart Diseases/mortality , Hospital Mortality , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Sex Factors , Troponin I/blood
17.
Sci Rep ; 10(1): 17718, 2020 10 19.
Article in English | MEDLINE | ID: covidwho-880700

ABSTRACT

COVID-19 has been widely spreading. We aimed to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n = 37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison (HC). Compared with PA patients, PP patients had much improved laboratory findings. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. Persistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.


Subject(s)
B-Lymphocytes/cytology , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , T-Lymphocytes/cytology , Adult , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Betacoronavirus/isolation & purification , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , COVID-19 , Case-Control Studies , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Killer Cells, Natural/cytology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
18.
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Article in English | MEDLINE | ID: covidwho-824547

ABSTRACT

BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , Betacoronavirus , COVID-19 , China , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Negative Results , Pandemics , SARS-CoV-2
19.
Preprint | SSRN | ID: ppcovidwho-900

ABSTRACT

Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent

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