第一轮入围论文100篇
(编号246)
Background
There have been many studies about coronavirus disease 2019 (COVID-19), but the clinical significance of quantitative serum severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific IgM and IgG levels of COVID-19 patients have not been exhaustively analyzed. We aimed to investigate the time profiles of these IgM/IgG levels in COVID-19 patients and their correlations with clinical features.
Methods
A multicenter clinical study was conducted from February 20 to March 5 2020. It involved 179 COVID-19 patients (108 males and 71 females) from five hospitals in Huangshi in Hubei Province, China. To detect SARS-CoV-2-specific IgM/IgG, quantitative antibody assays (two-step indirect immunoassays with direct chemiluminescence technology) based on the nucleocapsid protein (NP) and spike protein 1 (S1) were used. For normally distributed data, means were compared using the t-test, χ2-test, or exact probability method. For categorical data, medians were compared using Mann–Whitney U test.
Results
The median age was 57 (44–69) years (58 [38–69] for males and 57 [49–68] for females). The median duration of positive nucleic acid test was 22.32 (17.34–27.43) days. The mortality rate was relatively low (3/179, 1.68%). Serum SARS-CoV-2-specific IgG was detected around week 1 after illness onset, gradually increased until peaking in weeks 4 and 5, and then declined. Serum IgM peaked in weeks 2 and 3, then gradually declined and returned to its normal range by week 7 in all patients. Notably, children had milder respiratory symptoms with lower SARS-CoV-2-specific IgM/IgG levels. The duration of positive nucleic acid test in the chronic obstructive pulmonary disease (COPD) group was 30.36 (18.99–34.76) days, which was significantly longer than that in the non-COPD group (21.52 [16.75–26.51] days; P = 0.025). The peak serum SARS-CoV-2-specific IgG was significantly positively correlated with the duration of positive nucleic acid test. The incidence rate of severe and critical cases in the IgMhi group (using the median IgM level of 29.95 AU/mL as the cutoff for grouping) was about 38.0% (19/50), which was twice as much as that in the IgMlo group (18.4%; 9/49). The patients with positive chest imaging and lymphocytopenia (<1 × 109/L) had a higher SARS-CoV-2-specific IgM level.
Conclusions
Quantitative SARS-CoV-2-specific IgM and IgG levels are helpful for the diagnosis, severity classification, and management of COVID-19 patients, and they should be monitored in each stage of this disease.
(编号247)
Background
Novel coronavirus disease 2019 (COVID-19) is an ongoing global pandemic with high mortality. Although several studies have reported different risk factors for mortality in patients based on traditional analytics, few studies have used artificial intelligence (AI) algorithms. This study investigated prognostic factors for COVID-19 patients using AI methods.
Methods
COVID-19 patients who were admitted in Wuhan Infectious Diseases Hospital from December 29, 2019 to March 2, 2020 were included. The whole cohort was randomly divided into training and testing sets at a 6:4 ratio. Demographic and clinical data were analyzed to identify predictors of mortality using least absolute shrinkage and selection operator (LASSO) regression and LASSO-based artificial neural network (ANN) models. The predictive performance of the models was evaluated using receiver operating characteristic (ROC) curve analysis.
Results
A total of 1145 patients (610 male, 53.3%) were included in the study. Of the 1145 patients, 704 were assigned to the training set and 441 were assigned to the testing set. The median age of the patients was 57 years (range: 47–66 years). Severity of illness, age, platelet count, leukocyte count, prealbumin, C-reactive protein (CRP), total bilirubin, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were identified as independent prognostic factors for mortality. Incorporating these nine factors into the LASSO regression model yielded a correct classification rate of 0.98, with area under the ROC curve (AUC) values of 0.980 and 0.990 in the training and testing cohorts, respectively. Incorporating the same factors into the LASSO-based ANN model yielded a correct classification rate of 0.990, with an AUC of 0.980 in both the training and testing cohorts.
Conclusions
Both the LASSO regression and LASSO-based ANN model accurately predicted the clinical outcome of patients with COVID-19. Severity of illness, age, platelet count, leukocyte count, prealbumin, CRP, total bilirubin, APACHE II score, and SOFA score were identified as prognostic factors for mortality in patients with COVID-19.
(编号256)
Background: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an
inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.
Methods: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy
Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0
and 14, of either KCONVAC (5 or 10 mg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either
KCONVAC (at 5 or 10 mg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial,
the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the
administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody
seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.
Results: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-mg vaccine (n = 24), 10-mg vaccine (n = 24), or
placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-mg vaccine (n = 100 for 0/14 or 0/28
regimens), 10-mg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and
seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-mg vaccine, or placebo, respectively. In the phase 2
trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-mg vaccine, or placebo,
respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were
reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody
responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.
Conclusions: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These
results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.
Trial Registration: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?
proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
(编号257)
No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 107 cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO2/FiO2 ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSC infusion associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC MSC transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSC infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long term treatment outcomes in patients with serious COVID-19.
(编号258)
Background:
Interferon kappa (IFN-κ) is a type I interferon (IFN-I) that inhibits virus replication by evoking interferon-stimulated genes (ISGs). However, as an evolutionarily ancient interferon, IFN-κ may function differently from the later emerged interferon-α and β.
Methods:
Conventional molecular biology methods were used to determine the localization of IFN-κ and its structure and function. In addition, we employed RT-PCR, western blot, and RNA-Seq technologies to characterize the ISGs expression profile and antiviral activities exerted by IFN-κ or IFN-α2.
Results:
Human IFN-κ exists in two forms upon ectopic expression, one located on the cell membrane and the other secreted outside the cells. The membrane-anchored IFN-κ showed the ability to induce ISGs and curtail RNA virus replication, whereas the secreted IFN-κ failed to do so. Structural analyses indicated that 1-27aa at the N-terminus was the signal peptide, and 28-37aa was predicted as the transmembrane region. However, our data demonstrated that both of them were not associated with membrane localization of IFN-κ; the former influenced the expression and secretion of IFN-κ, and the latter had an impact on the induction of ISGs. In addition, prokaryotic purified soluble mature human IFN-κ was also capable of inducing ISGs and inhibiting RNA virus replication. Importantly, human IFN-κ induced a faster ISG response but with a lower intensity and a shorter half-life than the response of IFN-α2. In contrast, IFN-α2 started to function later but was stronger and more durable than IFN-κ.
Conclusions:
Human IFN-κ-induced ISG response and inhibited respiratory RNA virus replication dependent on cell-to-cell interactions. In addition, compared with IFN-α2, IFN-κ exerted effects more rapidly in the early phase, with less intensity and a shorter half-life. Therefore, IFN-κ may constitute the first line of IFN-I against respiratory virus infections.
(编号289)
Objective: Adult-onset Still’s disease (AOSD) is a rare but clinically well-known polygenic systemic autoinflammatory disease. In this
review, we aim to present frontiers in the pathogenesis, clinical features, diagnosis, biomarkers, disease course, prognosis, and
treatment in AOSD.
Data sources: We retrieved information from the PubMed database up to July 2019, using various search terms and relevant words,
including AOSD and Still’s disease.
Study selection: We included data from peer-reviewed journals. Both basic and clinical studies were selected.
Results: Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of
macrophages and neutrophils followed by a cytokine storm. Diagnosis and prognosis evaluation of AOSD is still challenging;
therefore, there is an urgent need to identify better biomarkers. Biologic agents, including interleukin (IL)-1b, IL-6, and tumor
necrosis factor-a antagonists in the treatment of AOSD, have good prospect.
Conclusion: This review highlights the advances in pathogenesis, potential biomarkers, disease course, and treatment in AOSD.
(编号297)
Objective: Coronavirus disease 2019 (COVID-19) is a global public health crisis. There are no specific antiviral agents for the treatment of SARS-CoV-2. Information regarding the effect of Abidol on in-hospital mortality is scarce. The present study aimed to evaluate the treatment effect of Abidol for patients with COVID-19 before and after propensity score matching (PSM).
Methods: This retrospective cohort study analyzed 1019 patients with confirmed COVID-19 in China from December 22, 2019 to March 13, 2020. Patients were divided to Abidol (200mg, tid, 5–7 days, n=788, 77.3%) and No-Abidol (n=231, 22.7%) groups. The
primary outcome was the mortality during hospitalization.
Results: Among 1019 COVID-19 patients, the age was (60.4±14.5) years. Abidol-treated patients, compared with No-Abidol treated patients, had a shorter duration from onset of symptoms to admission, less frequent renal dysfunction, lower white blood cell counts (lymphocytes <0.8) and erythrocyte sending rate, lower interleukin-6, higher platelet counts and plasma IgG and oxygen saturation, and less frequent myocardial injury. The mortality during hospitalization before PSM was 17.9% in Abidol group and 34.6% in No-Abidol (hazard ratio (HR) = 2.610, 95% confident interval (CI): 1.980–3.440), all seen in severe and critical patients. After PSM, the in-hospital death was 13.6% in Abidol and 28.6% in No-Abidol group (HR=2.728, 95% CI: 1.598–4.659).
Conclusions: Abidol-treatment results in less in-hospital death for severe and critical patients with COVID-19. Further randomized study is warranted to confirm the findings from this study.
