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3.
EClinicalMedicine ; 2020.
Article | WHO COVID | ID: covidwho-689222

ABSTRACT

BackgroundThe outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health New and effective intervention strategies are urgently needed to combat the disease

4.
EClinicalMedicine ; 2020.
Article | WHO COVID | ID: covidwho-684336

ABSTRACT

Background The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health New and effective intervention strategies are urgently needed to combat the disease Methods We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol Patients were assigned in a 1:2 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2, every 48 h for three consecutive dosages, in addition to standard treatment (experimental group), or standard treatment alone (control group) The end point was the time to discharge from the hospital This study is registered with chictr org cn, ChiCTR2000030262 Findings A total of thirty-three eligible COVID-19 patients were enrolled from February 1, 2020 to April 6, 2020, eleven were assigned to the IFN-κ plus TFF2 group, and twenty-two to the control group Safety and efficacy were evaluated for both groups No treatment-associated severe adverse effects (SAE) were observed in the group treated with aerosol inhalation of IFN-κ plus TFF2, and no significant differences in the safety evaluations were observed between experimental and control groups CT imaging was performed in all patients with the median improvement time of 5 0 days (IQR 3 0–9 0) in the experimental group versus 8 5 days (IQR 3 0–17 0) in the control group (p<0 05) In addition, the experimental group had a significant shorten median time in cough relief (4 5 days [IQR 2 0–7 0]) than the control group did (10 0 days [IQR 6 0–21 0])(p<0 005), in viral RNA reversion of 6 0 days (IQR 2 0–13 0) in the experimental group vs 9 5 days (IQR 3 0–23 0) in the control group (p < 0 05), and in the median hospitalization stays of 12 0 days (IQR 7 0–20 0) in the experimental group vs 15 0 days (IQR 10 0–25 0) in the control group (p<0 001), respectively Interpretation Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization These data support to explore a scale-up trial with IFN-κ plus TFF2 Funding National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission

5.
Research square ; 2020.
Article | WHO COVID | ID: covidwho-669637

ABSTRACT

Studies of novel coronavirus disease (COVID-19) have reported varying estimates of epidemiological parameters such as serial intervals and reproduction numbers By compiling a unique line-list database of transmission pairs in mainland China, we demonstrated that serial intervals of COVID-19 have shortened substantially from a mean of 7 8 days to 2 6 days within a month This change is driven by enhanced non-pharmaceutical interventions, in particular case isolation We also demonstrated that using real-time estimation of serial intervals allowing for variation over time would provide more accurate estimates of reproduction numbers, than by using conventional definition of fixed serial interval distributions These findings are essential to improve the assessment of transmission dynamics, forecasting future incidence, and estimating the impact of control measures

6.
Science ; 369(6499): 77-81, 2020 07 03.
Article in English | MEDLINE | ID: covidwho-667322

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/immunology , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , Betacoronavirus/isolation & purification , Chlorocebus aethiops , Coronavirus Infections/immunology , Coronavirus Infections/virology , Dose-Response Relationship, Immunologic , Female , Immunogenicity, Vaccine , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Pilot Projects , Pneumonia, Viral/virology , Rats , Rats, Wistar , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vero Cells , Viral Load , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Viral Vaccines/immunology
7.
Open Access (OA) Online-First Publ. Res. Pap. COVID-19 ; 2020.
Article | WHO COVID | ID: covidwho-660710

ABSTRACT

A review Acupuncture has played important role in infection disease pandemic This review provided guiding opinions on acupuncture intervention for the new coronavirus pneumonia (second edition)

8.
mBio ; 11(4)2020 07 21.
Article in English | MEDLINE | ID: covidwho-660818

ABSTRACT

To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness in vitro than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans.IMPORTANCE During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.

9.
Science ; 2020 Jul 21.
Article in English | MEDLINE | ID: covidwho-658227

ABSTRACT

Studies of novel coronavirus disease (COVID-19) have reported varying estimates of epidemiological parameters including serial interval distributions, i.e., the time between illness onset in successive cases in a transmission chain, and reproduction numbers. By compiling a line-list database of transmission pairs in mainland China, we show that mean serial intervals of COVID-19 have shortened substantially from 7.8 days to 2.6 days within a month (January 9 to February 13, 2020). This change is driven by enhanced non-pharmaceutical interventions, in particular case isolation. We also show that using real-time estimation of serial intervals allowing for variation over time, provides more accurate estimates of reproduction numbers than using conventionally fixed serial interval distributions. These findings could improve assessment of transmission dynamics, forecasting future incidence, and estimating the impact of control measures.

10.
mSphere ; 5(4)2020 07 08.
Article in English | MEDLINE | ID: covidwho-639765

ABSTRACT

Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential.


Subject(s)
Henipavirus Infections , Nipah Virus/pathogenicity , Animals , Betacoronavirus/pathogenicity , Congresses as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Henipavirus Infections/diagnosis , Henipavirus Infections/prevention & control , Henipavirus Infections/therapy , Humans , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Zoonoses/epidemiology
11.
Clin Immunol ; 218: 108524, 2020 Jul 11.
Article in English | MEDLINE | ID: covidwho-639598

ABSTRACT

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation.

12.
Open Forum Infect. Dis. ; 5(7)20200501.
Article in English | ELSEVIER | ID: covidwho-623975

ABSTRACT

Background. There is currently a lack of nonspecific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. Methods. A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) in China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. Results. Our nomogram predicted probabilities of COVID-19 with an area under the receiver operating characteristic curve of 0.913 (95% confidence interval [CI], 0.883-0.937), greater than that of the lymphocyte:monocyte ratio (0.849; 95% CI, 0.812-0.880; P = .0007), lymphocyte percentage (0.808; 95% CI, 0.768-0.843; P < .0001), monocyte count (0.780; 95% CI, 0.739-0.817; P < .0001), or age (0.656; 95% CI, 0.610-0.699; P < .0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. Conclusions. We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.

13.
Environ Pollut ; 266(Pt 1): 115161, 2020 Jul 02.
Article in English | MEDLINE | ID: covidwho-627126

ABSTRACT

As the number of Coronavirus Disease (2019) (COVID-19) cases increase globally, countries are taking more aggressive preventive measures against this pandemic. Transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) include droplet and contact transmissions. There are also evidence of transmission through aerosol generating procedures (AGP) in specific circumstances and settings. Institutionalized populations without mobility and living in close proximity with unavoidable contact are especially vulnerable to higher risks of COVID-19 infection, such as the elderly in nursing homes, children in orphanages, and inmates in prisons. In these places, higher prevention and control measures are needed. In this study, we proposed prevention and control strategies for these facilities and provided practical guidance for general measures, health management, personal protection measures, and prevention measures in nursing homes, orphanages, and prisons, respectively.

14.
Virus Res ; 286: 198073, 2020 Jun 24.
Article in English | MEDLINE | ID: covidwho-613450

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. Up to now, numerous medicines have been applied or approved for the prevention and control of the virus infection. However, the efficiency of each medicine or combination is completely different or still unknown. In this review, we discuss the types, characteristics, antiviral mechanisms, and shortcomings of recommended candidate medicines for SARS-CoV-2 infection, as well as perspectives of the drugs for the disease treatment, which may provide a theoretical basis for drug screening and application.

15.
Nature ; 582(7811): 289-293, 2020 06.
Article in English | MEDLINE | ID: covidwho-608904

ABSTRACT

A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019-2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)1-4. Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (Mpro) of SARS-CoV-2: Mpro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-25,6. We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of Mpro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds-including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds-as inhibitors of Mpro. Six of these compounds inhibited Mpro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 µM. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.


Subject(s)
Betacoronavirus/chemistry , Cysteine Endopeptidases/chemistry , Drug Discovery/methods , Models, Molecular , Protease Inhibitors/chemistry , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Cells, Cultured/virology , Coronavirus Infections/enzymology , Coronavirus Infections/virology , Drug Design , Drug Evaluation, Preclinical , Humans , Pandemics , Pneumonia, Viral/enzymology , Pneumonia, Viral/virology , Protease Inhibitors/pharmacology , Protein Structure, Tertiary
16.
Clin Infect Dis ; 2020 Jun 18.
Article in English | MEDLINE | ID: covidwho-603806

ABSTRACT

BACKGROUND: Knowledge on the epidemiological features and transmission patterns of COVID-19 is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics. METHODS: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1,407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9,120 COVID-19 confirmed cases reported during January 15 - February 29, 2020. Statistical model fittings were used to identify the super-spreaders and estimate serial interval distributions. Age and gender-stratified hazard of infection were estimated for household versus non-household transmissions. RESULTS: There were 34 primary cases identified as super-spreaders, with 5 super-spreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% CrI: 4.4, 5.5) and 5.2 (95% CrI: 4.9, 5.7) days for household transmissions and 5.2 (95% CrI: 4.6, 5.8) and 5.3 (95% CrI: 4.9, 5.7) days for non-household transmissions, respectively. Hazard of being infected outside of households is higher for age between 18 and 64 years, whereas hazard of being infected within households is higher for young and old people. CONCLUSIONS: Non-negligible frequency of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced non-pharmaceutical interventions to mitigate this pandemic.

18.
Emerg Microbes Infect ; 9(1): 1497-1505, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-595010

ABSTRACT

In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , SARS Virus/immunology , Serologic Tests/methods , Severe Acute Respiratory Syndrome/diagnosis , Antibodies, Viral/blood , Betacoronavirus/isolation & purification , Cross Reactions , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay/methods , HEK293 Cells , Humans , Immunoprecipitation , Nucleocapsid Proteins/immunology , Pandemics , Protein Domains/immunology , SARS Virus/isolation & purification , Spike Glycoprotein, Coronavirus/immunology
19.
Emerg Infect Dis ; 26(9)2020 Jun 09.
Article in English | MEDLINE | ID: covidwho-591915

ABSTRACT

Cities across China implemented stringent social distancing measures in early 2020 to curb coronavirus disease outbreaks. We estimated the speed with which these measures contained transmission in cities. A 1-day delay in implementing social distancing resulted in a containment delay of 2.41 (95% CI 0.97-3.86) days.

20.
J Med Virol ; 2020 May 29.
Article in English | MEDLINE | ID: covidwho-436660

ABSTRACT

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID-19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with SARS-CoV-2, including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest CT. All laboratory examination were measured within first 24 hours after admission, and chest CT were performed before admission. 56 (65.9%) patients had a history of exposure to Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID-2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (p=0.003) and coronary heart disease (p=0.017). All severe and critical patients infected with SARS-CoV-2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (p<0.001). Severe and critical patients showed higher WBC count (p=0.006), NEU count (p=0.001), NEU% (p=0.002), PCT (p=0.011), CRP (p=0.003), PT (p=0.035), D-dimer (p=0.025), AST (p=0.006), and lower LYM count (p=0.019), LYM% (p=0.001), ALB (p<0.001). Logistic regression analysis showed NEU count is a independent risk factor for deterioration, with the threshold of 6.5×109 ·L-1 . We concluded that the laboratory independent risk factor for the progression of COVID-19 pneumonia is NEU count. In addition, COVID-19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease. This article is protected by copyright. All rights reserved.

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