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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324430

ABSTRACT

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319507

ABSTRACT

As a result of the global epidemic of coronavirus disease 2019 (COVID-19), many European countries and regions have been strongly affected. The case fatality rate (CFR) is the most important index to evaluate the hazards associated with an epidemic situation. We aimed to present a method to calculate the instant CFR and to evaluate and compare the instant CFR of COVID-19 in the four European countries that have been most impacted: Italy, Spain, France and Germany. The daily COVID-19 case data from January 30, 2020, to July 9, 2020 in Italy, Spain, France and Germany were collected from WHO reports. Death time was calculated as the difference between the peak dates of the number of daily confirmed cases and the number of deaths in each of the four countries. The estimated dates of diagnosis of the declared deaths were a death time prior to the dates of death. The instant fatality rate of COVID-19 was calculated as the ratio of the number of cumulative deaths to the number of cumulative confirmed cases;these deaths and confirmed cases occurred on the same estimated dates of diagnosis. As of July 9, 2020, the COVID-19 death time was 6, 4, 6 and 12 days in Italy, Spain, France and Germany, respectively. The instant CFR of COVID-19 was 14.4%~27.6%, 2.2%~14.7%, 8.2%~25.0% and 2.0%~10.5% in Italy, Spain, France and Germany, respectively. The average CFR of COVID-19 was highest in France (16.7%) and lowest in Germany (5.0%). Since late April 2020, the CFR has stabilized at approximately 15%, 20% and 5% in Italy, France and Germany, respectively. Since early June, 2020, the CFR in Spain has stabilized at approximately 11%. We have established a more accurate way to calculate the CFR that may provide a basis for the prevention and control of infectious diseases.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308295

ABSTRACT

Background: An epidemic of COVID-19 outbroke in Wuhan, China, since December 2019. The ordinary medical services were hindered. However, the emergency cases, including aneurysmal subarachnoid hemorrhage (aSAH), still required timely intervention. Thus, it provoked challenges to the routine management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China. Methods: : Demographic, clinical, and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and several detailed protocols. Neurological outcomes were evaluated by the modified Rankin Scale (mRS). Results: : A total of 127 aSAH referred to our emergency department, and 42 (33.1%) underwent craniotomy clipping between January 20, 2020, and March 25, 2020. The incidence of preoperative hospitalized adverse events, and the perioperative outcomes were similar (-0.1, 95% CI -1.0 to 0.8, P =0.779) to the retrospective period last year (2019.01-2019.03). After the propensity score matching (PSM), there were still no statistical differences in prognostic parameters between the two groups. 8 (19.0%) of the 42 individuals were initially screened as preliminary undetermined COVID-19 cases, in which 2 of them underwent craniotomy clipping in the negative pressure operating room (OR). The prognosis of patients with varied COVID-19 screening results was similar (F(2, 39)=0.393, P =0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission, and all showed negative. The false-negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (-0.3, 95% CI -1.4 to 0.9, P =0.653). Conclusions: : Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307717

ABSTRACT

The worst-hit area of coronavirus disease 2019 (COVID-19) in China was Wuhan City and its affiliated Hubei Province, where the outbreak has been well controlled. The case fatality rate (CFR) is the most direct indicator to evaluate the hazards of an infectious disease. However, most reported CFR on COVID-19 represent a large deviation from reality. We aimed to establish a more accurate way to estimate the CFR of COVID-19 in Wuhan and Hubei and compare it to the reality. The daily case notification data of COVID-19 from December 8, 2019, to May 1, 2020, in Wuhan and Hubei were collected from the bulletin of the Chinese authorities. The instant CFR of COVID-19 was calculated from the numbers of deaths and the number of cured cases, the two numbers occurred on the same estimated diagnosis dates. The instant CFR of COVID-19 was 1.3%-9.4% in Wuhan and 1.2%-7.4% in Hubei from January 1 to May 1, 2020. It has stabilized at 7.69% in Wuhan and 6.62% in Hubei since early April. The cure rate was between 90.1% and 98.8% and finally stabilized at 92.3% in Wuhan and stabilized at 93.5% in Hubei. The mortality rates were 34.5/100 000 in Wuhan and 7.61/100 000 in Hubei. In conclusion, this approach reveals a way to accurately calculate the CFR, which may provide a basis for the prevention and control of infectious diseases.

5.
Nat Commun ; 12(1): 502, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-1387327

ABSTRACT

The multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80-90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein's central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical properties of the resulting condensates. In cells, N forms condensates that recruit the stress granule protein G3BP1, highlighting a potential role for N in G3BP1 sequestration and stress granule inhibition. The SARS-CoV-2 membrane (M) protein independently induces N protein phase separation, and three-component mixtures of N + M + RNA form condensates with mutually exclusive compartments containing N + M or N + RNA, including annular structures in which the M protein coats the outside of an N + RNA condensate. These findings support a model in which phase separation of the SARS-CoV-2 N protein contributes both to suppression of the G3BP1-dependent host immune response and to packaging genomic RNA during virion assembly.


Subject(s)
COVID-19/virology , Coronavirus Nucleocapsid Proteins/metabolism , RNA, Viral/metabolism , SARS-CoV-2/metabolism , Viral Matrix Proteins/metabolism , COVID-19/genetics , COVID-19/metabolism , Cell Membrane/virology , Coronavirus Nucleocapsid Proteins/chemistry , Coronavirus Nucleocapsid Proteins/genetics , DNA Helicases/genetics , DNA Helicases/metabolism , Humans , Phosphoproteins/chemistry , Phosphoproteins/genetics , Phosphoproteins/metabolism , Poly-ADP-Ribose Binding Proteins/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , Protein Binding , Protein Domains , RNA Helicases/genetics , RNA Helicases/metabolism , RNA Recognition Motif Proteins/genetics , RNA Recognition Motif Proteins/metabolism , RNA, Viral/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/genetics
6.
Chin Neurosurg J ; 6(1): 38, 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-992580

ABSTRACT

BACKGROUND: An epidemic of COVID-19 broke out in Wuhan, China, since December 2019. The ordinary medical services were hindered. However, the emergency cases, including aneurysmal subarachnoid hemorrhage (aSAH), still required timely intervention. Thus, it provoked challenges to the routine management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China. METHODS: Demographic, clinical, and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and several detailed protocols. Neurological outcomes were evaluated by the modified Rankin Scale (mRS). RESULTS: A total of 127 aSAH were referred to our emergency department, and 42 (33.1%) underwent craniotomy clipping between January 20, 2020, and March 25, 2020. The incidence of preoperative hospitalized adverse events and the perioperative outcomes were similar (- 0.1, 95% CI - 1.0 to 0.8, P = 0.779) to the retrospective period last year (January 2019-March 2019). After the propensity score matching (PSM), there were still no statistical differences in prognostic parameters between the two groups. Eight (19.0%) of the 42 individuals were initially screened as preliminary undetermined COVID-19 cases, in which 2 of them underwent craniotomy clipping in the negative pressure operating room (OR). The prognosis of patients with varied COVID-19 screening results was similar (F(2, 39) = 0.393, P = 0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission, and all showed negative. The false-negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (- 0.3, 95% CI - 1.4 to 0.9, P = 0.653). CONCLUSIONS: Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.

7.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-711

ABSTRACT

Background: The outbreak of the coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the worldwide COVID-19 cases are increasing

8.
Nurs Open ; 8(1): 147-155, 2021 01.
Article in English | MEDLINE | ID: covidwho-754766

ABSTRACT

Aim: To investigate the psychological status of medical staff with medical device-related nasal and facial pressure ulcers (MDR PUs) during the outbreak of COVID-19, analyse the correlation between their psychological status and personality traits, so as to provide a reference for personalized psychological support. Design: A total of 207 medical staff who were treating the COVID-19 epidemic from Hunan and Hubei provinces were enrolled in this analytic questionnaire-based study. Methods: We used these measures: Eysenck Personality Questionnaire Short Scale (EPQ-RSC), Social Appearance Anxiety Scale (SAAS), Positive and Negative Affect Scale (PANAS) and demographic information forms online. Results: Medical staff wearing protective equipment are particularly susceptible to nasal and facial MDR PUs, which is increasing their social appearance anxiety; neuroticism is significantly related to social appearance anxiety and negative emotion. We should pay more attention to their psychological state, cultivate good personality characteristics and reduce negative emotions, and thereby alleviate their MDR PUs-related appearance anxiety.


Subject(s)
Anxiety/psychology , Facial Injuries/psychology , Health Personnel/psychology , Personal Protective Equipment/adverse effects , Pressure Ulcer/psychology , Adult , Body Image/psychology , COVID-19/psychology , COVID-19/therapy , Case-Control Studies , Cross-Sectional Studies , Facial Injuries/etiology , Female , Humans , Male , Middle Aged , Pandemics , Personality Tests , Pressure Ulcer/etiology , SARS-CoV-2
9.
Clin Infect Dis ; 71(15): 853-857, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-719207

ABSTRACT

In December 2019, the coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and now has spread in many countries. Pregnant women are a population susceptible to COVID-19 and are more likely to have complications and even progress to severe illness. We report a case of neonatal COVID-19 in China with pharyngeal swabs testing positive by real-time reverse-transcription polymerase chain reaction assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pregnancy Complications, Infectious/diagnostic imaging , Pregnancy Complications, Infectious/virology , Adult , Betacoronavirus/pathogenicity , COVID-19 , China , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/virology , Infectious Disease Transmission, Vertical , Pandemics , Pregnancy , SARS-CoV-2
10.
Biomed Pharmacother ; 129: 110281, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-608227

ABSTRACT

Qingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/pharmacology , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 , Computer Simulation , Coronavirus Infections/virology , Drugs, Chinese Herbal/administration & dosage , Humans , Lethal Dose 50 , Molecular Docking Simulation , Pandemics , Pneumonia, Viral/virology
11.
Int J Infect Dis ; 97: 1-6, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-601411

ABSTRACT

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China. METHODS: A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. RESULTS: In China, the instant CFR of COVID-19 was 3.8-14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1±2.9%, while the CFR was 1.0±0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9±2.9% in China, and stabilized at 94.3%, while it was 99.0±0.4% in China except Hubei Province. CONCLUSIONS: The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Pneumonia, Viral/mortality , COVID-19 , China/epidemiology , Disease Outbreaks , Humans , Pandemics , SARS-CoV-2
12.
J Clin Invest ; 130(5): 2620-2629, 2020 05 01.
Article in English | MEDLINE | ID: covidwho-98087

ABSTRACT

BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokines/blood , Cytokines/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , T-Lymphocytes/immunology , Adult , Aged , COVID-19 , Cell Count , China , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Female , Gene Expression Profiling , Gene Expression Regulation/immunology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Retrospective Studies , Severity of Illness Index
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