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2.
J Med Virol ; 2020 Jul 09.
Article in English | MEDLINE | ID: covidwho-636704

ABSTRACT

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.

3.
Aging (Albany NY) ; 12(13): 12468-12478, 2020 07 03.
Article in English | MEDLINE | ID: covidwho-634334

ABSTRACT

OBJECTIVE: This study aimed to assess the disease conditions of patients with inflammatory bowel disease (IBD) in Hubei Province during the outbreak of Coronavirus Disease 2019 (COVID-19) by questionnaire online and guide their self-management during this epidemic. RESULTS: A total of 102 eligible questionnaires were included. No patient we surveyed reported a diagnosis of COVID-19. Our result showed that 67.86% of patients with ulcerative colitis (UC) and 80.43% of patients with Crohn's disease (CD) were in remission, 85.29%of patients had a good quality of life. Part of the patients (21.57%) reported their disease conditions worsening. The reduction in physical exercise was a risk factor for worsening conditions (OR=17.593, p=0.009). Some patients reported an alteration of medication regimens during the epidemic. CONCLUSIONS: The epidemic of COVID-19 might have a certain impact on many aspects of Hubei IBD patients within four weeks after the traffic control. Doctors could utilize the results from our questionnaire to guide IBD patients' self-management. METHODS: A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the 6-point Mayo Score, the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within four weeks of traffic control after the outbreak, it also included questions about patients' self-reported disease conditions and their epidemiological features of COVID-19.


Subject(s)
Coronavirus Infections , Inflammatory Bowel Diseases , Pandemics , Pneumonia, Viral , Self-Management/methods , Surveys and Questionnaires , Adolescent , Adult , Aged , Betacoronavirus , China/epidemiology , Coronavirus Infections/epidemiology , Disease Outbreaks , Female , Humans , Inflammatory Bowel Diseases/epidemiology , Male , Middle Aged , Pneumonia, Viral/epidemiology , Quarantine , Young Adult
4.
Clin Chim Acta ; 510: 47-53, 2020 Jul 06.
Article in English | MEDLINE | ID: covidwho-633898

ABSTRACT

BACKGROUND: The novel SARS-CoV-2 caused a large number of infections and deaths worldwide. Thus, new ideas for an appropriated assessment of patients' condition and clinical treatment are of utmost importance. Therefore, in this study, the laboratory parameters of patients with coronavirus disease 2019 (COVID-19) were evaluated to identify the correlation between cytokine expression and other laboratory parameters. METHODS: A retrospective and single-center study was performed in Wuhan, involving 83 severe or critical COVID-19 patients admitted to the intensive care unit (ICU). Laboratory parameters in ICU patients with laboratory-confirmed infection of SARS-CoV2 were collected. The association between parameters was assessed by Spearman's rank correlation. RESULTS: Patients' median age was 66 years (IQR, 57-73), and 55 (66%) were men. Among the 83 patients, 61 (73%) had 1 or more coexisting medical condition. The median concentration of IL-2R, IL-6, IL8, IL10, and TNFα were above the normal range, without IL-1ß. A significant negative correlation between IL-6 and platelet count was discovered (r2 = -0.448, P < 0.001) as well as a significant correlation between IL-6 and other platelet parameters. Finally, a correlation between multiple cytokines and coagulation indicators was found, pro-inflammatory factors were found to be more associated to coagulation parameters, with the highest correlation between IL-6 and the International normalized ratio (INR) (r2 = 0.444, P < 0.001). CONCLUSIONS: Our results suggested that cytokines play an important role in the pathogenesis of COVID-19. In addition, IL-6 seems more relevant in the evaluation of the condition of COVID-19 patients.

5.
F1000Res ; 9: 129, 2020.
Article in English | MEDLINE | ID: covidwho-627045

ABSTRACT

We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL pro) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart.  With the 3CL pro molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache.  The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.


Subject(s)
Benzimidazoles/pharmacology , Betacoronavirus/drug effects , Carbamates/pharmacology , Coronavirus Infections , Cysteine Endopeptidases/chemistry , Fluorenes/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Pandemics , Pneumonia, Viral , Viral Nonstructural Proteins/chemistry , Coronavirus Infections/drug therapy , Drug Repositioning , Humans , Pneumonia, Viral/drug therapy
6.
Front. Pediatr. ; (8)20200605.
Article in English | ELSEVIER | ID: covidwho-615555

ABSTRACT

COVID-19, an emerging infectious disease, has quickly spread all over the world. All human populations are susceptible to this disease. Here we present two pediatric COVID-19 cases, both of whom exhibited negative SARS-CoV-2 nucleic acid tests upon nasopharyngeal swab and were initially diagnosed with influenza A infection. COVID-19 was later confirmed in both patients by serum antibodies of SARS-CoV-2 and nucleic acid test on stool samples. Because children are susceptible to many respiratory pathogens, especially influenza, we concluded that children can be coinfected with multiple pathogens, and more attention should be paid to the exploration of SARS-CoV-2 during the pandemic of COVID-19. This report shows the possibility of misdiagnosis or missed diagnosis of children with COVID-19. We suggest that highly suspected pediatric COVID-19 cases with negative nucleic acid tests on nasopharyngeal swabs should be further checked by performing a nucleic acid test on stool samples and testing serum for antibodies against SARS-CoV-2.

7.
Front. Cell Dev. Biol. ; (8)20200522.
Article in English | ELSEVIER | ID: covidwho-612660

ABSTRACT

Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.

8.
Plants ; 6(9): 1-12, 20200601.
Article in English | ELSEVIER | ID: covidwho-609035

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease-2019 (COVID-19), is a pandemic disease that has been declared as modern history’s gravest health emergency worldwide. Until now, no precise treatment modality has been developed. The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. Furthermore, the gas chromatography-mass spectrometry (GC–MS) analysis displayed 22 compounds in geranium oil and 9 compounds in lemon oil. Citronellol, geraniol, and neryl acetate were the major compounds of geranium oil and limonene that represented major compound of lemon oil. Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells. The results suggest that geranium and lemon essential oils and their derivative compounds are valuable natural anti-viral agents that may contribute to the prevention of the invasion of SARS-CoV-2/COVID-19 into the human body.

9.
Cell Res ; 30(8): 678-692, 2020 08.
Article in English | MEDLINE | ID: covidwho-599672

ABSTRACT

A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC50 values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors. A complex crystal structure of SARS-CoV-2 Mpro with GC-376, determined at 2.15 Å resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.

10.
Pediatr Infect Dis J ; 39(7): e87-e90, 2020 07.
Article in English | MEDLINE | ID: covidwho-590916

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is becoming a global threat. However, our understanding of the clinical characteristics and treatment of critically ill pediatric patients and their ability of transmitting the coronavirus that causes COVID-19 still remains inadequate because only a handful pediatric cases of COVID-19 have been reported. METHODS: Epidemiology, clinical characteristics, treatment, laboratory data and follow-up information and the treatment of critically ill infant were recorded. RESULTS: The infant had life-threatening clinical features including high fever, septic shock, recurrent apnea, petechiae and acute kidney injury and persistent declined CD3+, CD4+ and CD8+ T cells. The duration of nasopharyngeal virus shedding lasted for 49 days even with the administration of lopinavir/ritonavir for 8 days. The CD3+, CD4+ and CD8+ T cells was partially recovered 68 days post onset of the disease. Accumulating of effector memory CD4+ T cells (CD4+TEM) was observed among T-cell compartment. The nucleic acid tests and serum antibody for the severe acute respiratory syndrome coronavirus 2 of the infant's mother who kept intimate contact with the infant were negative despite no strict personal protection. CONCLUSIONS: The persistent reduction of CD4+ and CD8+ T cells was the typical feature of critically ill infant with COVID-19. CD4+ and CD8+ T cells might play a key role in aggravating COVID-19 and predicts a more critical course in children. The prolonged nasopharyngeal virus shedding was related with the severity of respiratory injury. The transmission of SARS-CoV-2 from infant (even very critical cases) to adult might be unlikely.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Betacoronavirus/isolation & purification , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Coronavirus Infections/virology , Critical Illness , Humans , Infant , Lopinavir/therapeutic use , Lymphocyte Count , Male , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Ritonavir/therapeutic use , Virus Shedding/immunology
11.
Pharmacol Res ; 159: 105008, 2020 Jun 09.
Article in English | MEDLINE | ID: covidwho-591422
15.
Arthritis Rheumatol ; 2020 Jun 30.
Article in English | MEDLINE | ID: covidwho-621296

ABSTRACT

OBJECTIVES: Coagulopathy is one of the characteristics of critically ill patients with Coronavirus Disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, but their role in COVID-19 remains unclear. We aimed to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 critically ill and 13 non-critically ill patients with COVID-19 were tested for anti-cardiolipin (aCL) and anti-ß2-glycoprotein 1 (aß2GP1) (IgG, IgM, and IgA) and IgG aß2GP1-D1 by the chemiluminescence assay (CIA) and IgM and IgG anti-phosphatidylserine/prothrombin (aPS/PT) by ELISA. RESULTS: aPLs were detected in 47.0% of critically ill patients (31/66), but not in patients with non-critical conditions. IgA aß2GP1 was the most common aPL, present in 28.8% (19/66) critically ill patients, followed by IgA aCL (25.8%,17/66) and IgG aß2GP1 (18.2%,12/66). For multiple aPLs, IgA aß2GP1+IgA aCL was the most common type (22.7%, 15/66), followed by IgA aß2GP1+IgA aCL+ IgG aß2GP1 (15.2%, 10/66). aPLs emerge around 35-39 days post-disease onset. Dynamic analysis of aPLs revealed 4 patterns based on persistence or transient appearance of the aPLs. Patients with multiple aPLs displayed significantly higher incidence of cerebral infarction (p=0.023). CONCLUSIONS: aPLs were common in critically ill patients. Multiple medium or high levels aPLs may help identify patients at risk of developing cerebral infarction. aPLs may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of "COVID-19-induced-APS-like-syndrome". Long-term follow-up on COVID-19 patients positive for aPLs would be of great importance.

16.
J Infect Dis ; 222(3): 367-371, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-436918

ABSTRACT

The viral RNA shedding time (VST) for severe acute respiratory syndrome coronavirus 2 has not been well characterized. Clinical data were collected and compared between patients with short and long VSTs (in the lower and upper quartiles, respectively). The probability of recurrent positive reverse-transcription polymerase chain reaction results decreased sharply to 4.8% after 3 consecutive negative results. A series of ≥3 consecutive negative results was suitable as a criterion for the end of viral RNA shedding. The VST for shedding from the respiratory tract was significantly shorter in patients with normal B-cell counts on admission than in those with decreased B-cell counts (median [interquartile range], 11 [9-13] vs 16 [12-20] days, respectively; P = .001).


Subject(s)
B-Lymphocytes/physiology , Betacoronavirus/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Respiratory System/virology , Virus Shedding , Betacoronavirus/immunology , Case-Control Studies , China , Cytokines/metabolism , Female , Humans , Logistic Models , Lymphocyte Count , Male , Middle Aged , Pandemics , Proportional Hazards Models , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , Retrospective Studies , Risk Factors , Time Factors
17.
Emerg Microbes Infect ; 9(1): 1175-1179, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-361278

ABSTRACT

Different primers/probes sets have been developed all over the world for the nucleic acid detection of SARS-CoV-2 by quantitative real time polymerase chain reaction (qRT-PCR) as a standard method. In our recent study, we explored the feasibility of droplet digital PCR (ddPCR) for clinical SARS-CoV-2 nucleic acid detection compared with qRT-PCR using the same primer/probe sets issued by Chinese Center for Disease Control and Prevention (CDC) targeting viral ORF1ab or N gene, which showed that ddPCR could largely minimize the false negatives reports resulted by qRT-PCR [Suo T, Liu X, Feng J, et al. ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens. medRxiv [Internet]. 2020;2020.02.29.20029439. Available from: https://medrxiv.org/content/early/2020/03/06/2020.02.29.20029439.abstract]. Here, we further stringently compared the performance of qRT-PCR and ddPCR for 8 primer/probe sets with the same clinical samples and conditions. Results showed that none of 8 primer/probe sets used in qRT-PCR could significantly distinguish true negatives and positives with low viral load (10-4 dilution). Moreover, false positive reports of qRT-PCR with UCDC-N1, N2 and CCDC-N primers/probes sets were observed. In contrast, ddPCR showed significantly better performance in general for low viral load samples compared to qRT-PCR. Remarkably, the background readouts of ddPCR are relatively lower, which could efficiently reduce the production of false positive reports.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Multiplex Polymerase Chain Reaction , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction , DNA Primers , DNA Probes , Humans , Multiplex Polymerase Chain Reaction/methods , Pandemics , Real-Time Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/standards , Sensitivity and Specificity , Viral Load
19.
Emerg Microbes Infect ; 9(1): 1259-1268, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-342833

ABSTRACT

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , False Negative Reactions , Humans , Limit of Detection , Pandemics , RNA, Viral/genetics , Viral Load/methods
20.
Ann Rheum Dis ; 79(8): 1007-1013, 2020 08.
Article in English | MEDLINE | ID: covidwho-342666

ABSTRACT

OBJECTIVE: The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice. METHODS: This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020. RESULTS: Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage. CONCLUSIONS: Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered. TRIAL REGISTRATION NUMBER: ChiCTR2000030795.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Rheumatic Diseases/virology , Adult , Aged , China , Coronavirus Infections/pathology , Coronavirus Infections/virology , Diarrhea/virology , Fatigue/virology , Female , Fever/virology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Respiratory Insufficiency/virology , Retrospective Studies , Symptom Flare Up
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