NSUN2-mediated M5c methylation of IRF3 mRNA negatively regulates type I interferon responses during various viral infections.

5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-ß production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the antiviral innate response is more dramatically enhanced in Nsun2+/- mice than in Nsun2+/+ mice. The highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation enhanced cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), or Zika virus (ZIKV) resulted in a reduction of endogenous NSUN2 levels. Especially, SARS-CoV-2 infection (WT strain and BA.1 omicron variant) also decreased endogenous levels of NSUN2 in COVID-19 patients and K18-hACE2 KI mice, further increasing type I interferon and downstream ISGs. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease during SARS-CoV-2 and various viral infections to boost antiviral responses for effective elimination of viruses.

Impact Factors of COVID-19 Vaccination Hesitancy in patients after lung cancer surgery: an outpatients-based cross-sectional study (preprint)

Background The safety and efficacy of several vaccine candidates have been tested and found to be effective and safe against COVID-19. But, little is known about the actual level of people with lung cancer willing to accept a COVID-19 vaccine and the impact factors that affect acceptability. The survey aimed to determine the prevalence of vaccine hesitancy in lung cancer patients after surgery and characterize underlying factors contributing to reluctance.Methods An clinical survey was inducted from May 1, 2021, to August 20, 2021. Eligible participants were 18 years or older, were diagnosed with lung cancer, and received lung cancer surgery, including lobectomy, sublobectomy, and pneumonectomy. Data were collected on a self-administered questionnaire from 294 lung cancer patients after surgery.Results Among the final included 281 participants, 54.1% were female, and 93.6% were of Han ethnicity. 48.0% were in pathologic stage I, 36.3% in stage II, 10.3% in stage III, and 5.3% in stage IV. The vaccination hesitancy/refusal rate was 41.6%. In multivariable regression analysis, age over 60 years old, low educational level, duration of cancer (< 1 year), subjective health status, current cancer treatments use, presence of postoperative pain, and report of the items “ever hesitated or refused to get a vaccination,” “get negative information about getting the COVID-19 vaccine”, “worried about vaccine adverse reactions,” and “worried about the COVID vaccine interferes with cancer treatments” were independently associated with hesitant of the COVID-19 vaccine.Conclusions Vaccine hesitancy is common among lung cancer patients after surgery, related mainly to health status and concerns about side effects, worsens cancer prognosis, and interferes with cancer treatments. These results suggest that vaccination programs may need tailoring to specific populations’ hesitancy.

T cell responses to adenoviral vectors expressing the SARS-CoV-2 nucleoprotein.

SARS-CoV-2 vaccines aim to protect against COVID-19 through neutralizing antibodies against the viral spike protein. Mutations within the spike's receptor-binding domain may eventually reduce vaccine efficacy, necessitating periodic updates. Vaccine-induced immunity could be broadened by adding T cell-inducing antigens such as SARS-CoV-2's nucleoprotein (N). Here we describe two replication-defective chimpanzee adenovirus (AdC) vectors from different serotypes expressing SARS-CoV-2 N either in its wild-type form or fused into herpes simplex virus glycoprotein D (gD), an inhibitor of an early T cell checkpoint. The vaccines induce potent and sustained CD8+ T cell responses that are broadened upon inclusion of gD. Depending on the vaccine regimen booster immunizations increase magnitude and breadth of T cell responses. Epitopes that are recognized by the vaccine-induced T cells are highly conserved among global SARS-CoV-2 isolates indicating that addition of N to COVID-19 vaccines may lessen the risk of loss of vaccine-induced protection due to variants.

Effect of internet-delivered cognitive behavioral therapy on insomnia in convalescent patients with COVID-19: Protocol for a systematic review and meta-analysis.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has made a serious public health threat worldwide. Recent evidence has indicated that COVID-19 patients in convalescence frequently experience insomnia, which reduces their quality of life and causes unknown risks. The positive effect of cognitive behavior on insomnia has been well addressed in previous studies. Given the high infectivity and epidemicity of COVID-19, Internet-delivered intervention may be safer than face-to-face treatment. However, whether Internet-delivered cognitive behavioral therapy can effectively improve the insomnia of COVID-19 patients in convalescence has not been completely determined yet. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of Internet-delivered cognitive behavioral therapy on insomnia in COVID-19 patients in convalescence, with the aim to confer some guidance for its clinical application. METHODS AND ANALYSIS: This systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). Two researchers will retrieve the relevant literature on Internet-delivered cognitive behavioral therapy for insomnia in convalescent patients with COVID-19 in PubMed, Web of Science, Embase, MEDLINE, Cochrane Library, Clinical Trials gov, Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) from inception to 11th of December. In addition, we will review the relevant trials and references of the included literature and manually searched the grey literature. The two researchers will independently extracted data and information and evaluated the quality of the included literature. The Review Manager software (version 5.3) and Stata software (version 14.0) will be used for data analysis. The mean difference or the standardized mean difference of 95% CI will be used to calculate continuous variables to synthesize the data. In addition, I2 and Cochrane will be used for heterogeneity assessment. TRIAL REGISTRATION: PROSPERO registration number CRD42021271278.

Pneumonia scoring systems for severe COVID-19: which one is better.

PURPOSE: To investigate the predictive significance of different pneumonia scoring systems in clinical severity and mortality risk of patients with severe novel coronavirus pneumonia. MATERIALS AND METHODS: A total of 53 cases of severe novel coronavirus pneumonia were confirmed. The APACHE II, MuLBSTA and CURB-65 scores of different treatment methods were calculated, and the predictive power of each score on clinical respiratory support treatment and mortality risk was compared. RESULTS: The APACHE II score showed the largest area under ROC curve in both noninvasive and invasive respiratory support treatment assessments, which is significantly different from that of CURB-65. Further, the MuLBSTA score had the largest area under ROC curve in terms of death risk assessment, which is also significantly different from that of CURB-65; however, no difference was noted with the APACHE II score. CONCLUSION: For patients with COVID, the APACHE II score is an effective predictor of the disease severity and mortality risk. Further, the MuLBSTA score is a good predictor only in terms of mortality risk.

Myocardial Injury on Admission as a Risk in Critically Ill COVID-19 Patients: A Retrospective in-ICU Study.

OBJECTIVE: The aim of this study was to investigate the incidence, clinical presentation, cardiovascular (CV) complications, and mortality risk of myocardial injury on admission in critically ill intensive care unit (ICU) inpatients with COVID-19. DESIGN: A single-center, retrospective, observational study. SETTING: A newly built ICU in Tongji hospital (Sino-French new city campus), Huazhong University of Science and Technology, Wuhan, China. PARTICIPANTS: Seventy-seven critical COVID-19 patients. INTERVENTIONS: Patients were divided into a myocardial injury group and nonmyocardial injury group according to the on-admission levels of high-sensitivity cardiac troponin I. MEASUREMENTS AND MAIN RESULTS: Demographic data, clinical characteristics, laboratory tests, treatment, and clinical outcome were evaluated, stratified by the presence of myocardial injury on admission. Compared with nonmyocardial injury patients, patients with myocardial injury were older (68.4 ± 10.1 v 62.1 ± 13.5 years; p = 0.02), had higher prevalence of underlying CV disease (34.1% v 11.1%; p = 0.02), and in-ICU CV complications (41.5% v 13.9%; p = 0.008), higher Acute Physiology and Chronic Health Evaluation II scores (20.3 ± 7.3 v 14.4 ± 7.4; p = 0.001), and Sequential Organ Failure Assessment scores (7, interquartile range (IQR) 5-10 v 5, IQR 3-6; p < 0.001). Myocardial injury on admission increased the risk of 28-day mortality (hazard ratio [HR], 2.200; 95% confidence interval [CI] 1.29 to 3.74; p = 0.004). Age ≥75 years was another risk factor for mortality (HR, 2.882; 95% CI 1.51-5.50; p = 0.002). CONCLUSION: Critically ill patients with COVID-19 had a high risk of CV complications. Myocardial injury on admission may be a common comorbidity and is associated with severity and a high risk of mortality in this population.

Benevolent Creativity Buffers Anxiety Aroused by Mortality Salience: Terror Management in COVID-19 Pandemic.

With the outbreak of the COVID-19 crisis, the public keeps getting epidemic-related information on the media. News reports on the increasing number of fatalities have exposed individuals to death, which causes negative emotional experiences such as tension, anxiety, and fear. This study aimed to investigate whether creativity could serve as an anxiety-buffer when mortality is salient. Based on previous findings, the present study utilized type of creative task and personal search for meaning as moderators. In Study 1, a 2 (mortality salience: absent, present) × 2 (type of creative task: benevolent, malevolent) between-subject design was utilized, and 168 subjects were randomly assigned to four experimental conditions. In Study 2, 221 subjects were recruited. The experimental procedure was similar to Study 1, except that the priming paradigm of mortality was changed and search for meaning was included as an additional moderating variable. State anxiety was measured as the dependent variable in both studies. Results of Study 1 showed that, while the benevolent creative task could buffer anxiety in the mortality salience condition, the malevolent creative task did not have the same effect. Furthermore, there was a significant interaction between mortality salience, type of creative task, and search for meaning in life on anxiety. In Study 2, the buffering function of benevolent creativity was more intense for participants with a higher level of search for meaning. Together, these findings reveal the influence of different types of creative tasks on individual anxiety levels under death priming conditions and the moderating effect of search for meaning in this relationship. Further, they suggest the need to focus on the role of creativity in terror management.

Clinical characteristics and survival analysis in critical and non-critical patients with COVID-19 in Wuhan, China: a single-center retrospective case control study.

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.

Correlation between cytokines and coagulation-related parameters in patients with coronavirus disease 2019 admitted to ICU.

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.

Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19.

BACKGROUND: The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. OBJECTIVE: To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. STUDY DESIGN: This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. RESULTS: Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. CONCLUSION: The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.