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1.
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

2.
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

3.
Med ; 2020.
Article | WHO COVID | ID: covidwho-664427

ABSTRACT

Summary Background The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown Methods Genome wide screening was used to establish intra-viral and viral-host interactomes Quantitative proteomics was used to investigate peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19 Findings We elucidated 286 host proteins targeted by SARS-CoV-2 and more than 350 host proteins that are significantly perturbed in COVID-19 derived PBMCs This signature in severe COVID-19 PBMCs reveals significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as downregulation of proteins mediating T cell receptor signaling From the interactome, we further identified that non-structural protein 10 interacts with NF-kappa-B-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients Conclusions Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit for therapeutic intervention

4.
Emerg Microbes Infect ; 9(1): 1537-1545, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-611841

ABSTRACT

Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Follow-Up Studies , Health Status Indicators , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Retrospective Studies , Time Factors , Treatment Outcome , Virus Shedding , Young Adult
5.
Biosci Trends ; 14(3): 161-167, 2020 Jul 17.
Article in English | MEDLINE | ID: covidwho-593589

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a serious public health threat to the whole world, and the number of infected is still rising dramatically at this moment. Several studies have confirmed that cytokine storms play a critical role in causing a case to worsen from mild to severe or critical. The current treatment for cytokine storms is limited, so the international medical community is focusing on a specific and effective remedy. Jaktinib hydrochloride is a broad spectrum JAK inhibitor. It can inhibit cytokine-induced immune activation by multiple mechanisms and also slow viral proliferation by inhibiting AAK1 without causing unacceptable toxicity. Jaktinib hydrochloride has great potential for the treatment of patients with coronavirus disease 2019 (COVID-19).


Subject(s)
Coronavirus Infections/drug therapy , Janus Kinase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Betacoronavirus , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Cytokines/metabolism , Humans , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology
6.
Cell Death Dis ; 11(6): 438, 2020 06 08.
Article in English | MEDLINE | ID: covidwho-591593

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Since its first report in December 2019, despite great efforts made in almost every country worldwide, this disease continues to spread globally, especially in most parts of Europe, Iran, and the United States. Here, we update the recent understanding in clinical characteristics, diagnosis strategies, as well as clinical management of COVID-19 in China as compared to Italy, with the purpose to integrate the China experience with the global efforts to outline references for prevention, basic research, treatment as well as final control of the disease. Being the first two countries we feel appropriate to evaluate the evolution of the disease as well as the early result of the treatment, in order to offer a different baseline to other countries. It is also interesting to compare two countries, with a very significant difference in population, where the morbidity and mortality has been so different, and unrelated to the size of the country.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adolescent , Adult , Aged , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , Asymptomatic Diseases , Child , Child, Preschool , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Female , Humans , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Italy/epidemiology , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Young Adult
7.
Theranostics ; 10(12): 5613-5622, 2020.
Article in English | MEDLINE | ID: covidwho-203318

ABSTRACT

Rationale: Some patients with coronavirus disease 2019 (COVID-19) rapidly develop respiratory failure or even die, underscoring the need for early identification of patients at elevated risk of severe illness. This study aims to quantify pneumonia lesions by computed tomography (CT) in the early days to predict progression to severe illness in a cohort of COVID-19 patients. Methods: This retrospective cohort study included confirmed COVID-19 patients. Three quantitative CT features of pneumonia lesions were automatically calculated using artificial intelligence algorithms, representing the percentages of ground-glass opacity volume (PGV), semi-consolidation volume (PSV), and consolidation volume (PCV) in both lungs. CT features, acute physiology and chronic health evaluation II (APACHE-II) score, neutrophil-to-lymphocyte ratio (NLR), and d-dimer, on day 0 (hospital admission) and day 4, were collected to predict the occurrence of severe illness within a 28-day follow-up using both logistic regression and Cox proportional hazard models. Results: We included 134 patients, of whom 19 (14.2%) developed any severe illness. CT features on day 0 and day 4, as well as their changes from day 0 to day 4, showed predictive capability. Changes in CT features from day 0 to day 4 performed the best in the prediction (area under the receiver operating characteristic curve = 0.93, 95% confidence interval [CI] 0.87~0.99; C-index=0.88, 95% CI 0.81~0.95). The hazard ratios of PGV and PCV were 1.39 (95% CI 1.05~1.84, P=0.023) and 1.67 (95% CI 1.17~2.38, P=0.005), respectively. CT features, adjusted for age and gender, on day 4 and in terms of changes from day 0 to day 4 outperformed APACHE-II, NLR, and d-dimer. Conclusions: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.


Subject(s)
Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Lung/pathology , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , Adult , Aged , Algorithms , Artificial Intelligence , Betacoronavirus , China , Disease Progression , Female , Humans , Image Processing, Computer-Assisted , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Prognosis , Retrospective Studies , Tomography, X-Ray Computed
8.
J Infect ; 80(5): e1-e6, 2020 05.
Article in English | MEDLINE | ID: covidwho-7451

ABSTRACT

BACKGROUND: Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. METHODS: In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. RESULTS: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. CONCLUSIONS: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.


Subject(s)
Coronavirus Infections/pathology , Disease Progression , Pneumonia, Viral/pathology , Adult , Betacoronavirus , China , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Female , Fever/etiology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prognosis , Retrospective Studies , Time Factors , Tomography, X-Ray Computed
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