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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309728

ABSTRACT

Purpose: Persistent negative results (at least 3 times) of reverse transcription–polymerase chain reaction (RT-PCR) from pharyngeal swabs are not rare in coronavirus disease 2019 (COVID-19) patients, but their characteristics have not yet been well studied. Methods: PCR confirmed, serum antibody confirmed with persistent negative PCR results, and clinically diagnosed patients hospitalized in two medical centers during February and March 2020 were included. Differences in clinical, imaging and laboratory characteristics as well as factors affecting their prognosis were analyzed. Results: There were 114 PCR confirmed, 17 serology confirmed and 21 clinically diagnosed patients included. Time from onset of disease to the first PCR and admission were similar among the groups. Compared with PCR-confirmed patients, serology-confirmed patients were older and likely to have hypertension, vomiting, or symptoms of chest pain and dyspnea. Regarding imaging manifestations, serology-confirmed patients were more prone to pleural effusion. In addition, higher levels of C-reactive protein, neutrophil-to-lymphocyte ratio, total bilirubin, D-dimer, fibrinogen, troponin, interleukin-6 and IL-8 were also found. Although with similar mortality, serology confirmed patients were more likely to have disease progression. High levels of D-dimer and IL-6 were possibly the underlying factors leading to their worse prognosis. On the other hand, clinically diagnosed patients were more similar to PCR-confirmed patients. Conclusion: Serology confirmed COVID-19 patients with at least three negative PCR results had different clinical characteristics and were likely to have disease progression, possibly due to more severe hypercoagulation status and cytokine storm.

2.
BMJ ; 369: m1849, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1495142

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Treatment Outcome
3.
Front Pharmacol ; 11: 560209, 2020.
Article in English | MEDLINE | ID: covidwho-843841

ABSTRACT

OBJECTIVE: Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan City, China, coronavirus disease 2019 (COVID-19) has become a global pandemic. However, no special therapeutic drugs have been identified for COVID-19. The aim of this study was to search for drugs to effectively treat COVID-19. MATERIALS AND METHODS: We conducted a retrospective cohort study with a total of 162 adult inpatients (≥18 years old) from Ruijin Hospital (Shanghai, China) and Tongji Hospital (Wuhan, China) between January 27, 2020, and March 10, 2020. The enrolled COVID-19 patients were first divided into the Lianhuaqingwen (LHQW) monotherapy group and the LHQW + Arbidol combination therapy group. Then, these two groups were further classified into moderate and severe groups according to the clinical classification of COVID-19. RESULTS: The early combined usage of LHQW and Arbidol can significantly accelerate the recovery of patients with moderate COVID-19 by reducing the time to conversion to nucleic acid negativity, the time to chest CT improvement, and the length of hospital stay. However, no benefit was observed in severe COVID-19 patients treated with the combination of LHQW + Arbidol. In this study, both Arbidol and LHQW were well tolerated without serious drug-associated adverse events. CONCLUSION: The early combined usage of LHQW and Arbidol may accelerate recovery and improve the prognosis of patients with moderate COVID-19.

4.
Clinical eHealth ; 3:7-15, 2020.
Article in English | PMC | ID: covidwho-822402

ABSTRACT

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

5.
EMBO Rep ; : e50308-e50308, 2020.
Article in English | MEDLINE | ID: covidwho-662381

ABSTRACT

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-ß induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy.

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