Risk factors for severe COVID-19 infection and the impact of COVID-19 infection on disease progression among patients with AAV (preprint)

Objective To identify risk factors for COVID-19 infection and investigate the impact of COVID-19 infection on chronic kidney disease (CKD) progression and vasculitis flare in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods This cohort study retrospectively analyzed the prevalence and severity of COVID-19 infection in 276 patients with AAV who were followed up. Logistic regression was employed to estimate the risk of COVID-19 infection as well as CKD progression and vasculitis flare upon COVID-19 infection.Results During the 6-month observation period, 213 (77.2%) of 276 patients had a diagnosis of COVID-19 infection. Of these 213 patients, 49 (23.0%) had a COVID-19-related inpatient admission, including 17 patients who died of COVID-19 infection. AAV patients with severe COVID-19 infection were more likely to be male (OR 1.921 [95% CI 1.020–3.619], P = 0.043), suffered from worse kidney function (serum creatinine [Scr], OR 1.901 [95% CI 1.345–2.687], P < 0.001), had higher C-reactive protein (CRP) (OR 1.054 [95% CI 1.010–1.101], P = 0.017) and less likely to have evidence of initial vaccination (OR 0.469 [95% CI 0.231–0.951], P = 0.036), and Scr and COVID-19 vaccination were proven to be significantly associated with severe COVID-19 infection even after multivariable adjustment. Severe COVID-19 infection was significantly associated with subsequent CKD progression (OR 7.929 [95% CI 2.030-30.961], P = 0.003) and vasculitis flare (OR 11.842 [95% CI 1.048-133.835], P = 0.046) among patients with AAV.Conclusion AAV patients who were male, and with worse kidney function were more susceptible to severe COVID-19 infection, which subsequently increased the risk of CKD progression and vasculitis flare.

Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern (preprint)

SARS-CoV-2 variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22995 and 28866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.

Operation mode selection of offshore wind power PPP project: A case in China (preprint)

As the world economy recovers from the coronavirus pandemic, we used coal in large quantities to fuel economic growth. The issue of excessive carbon emissions is once again causing concern. In this context, how to cope with the risks faced by offshore wind power projects and choose the most favorable PPP project operation mode has become a hot research issue in the dual-carbon background. This study identifies risk factors for offshore wind power PPP projects and constructs an analytical hierarchical process consistent with a triangular ambiguity number for empowerment. The VIKOR hesitancy fuzzy multi-attribute method based on prospect theory is used for the terminal decision and comparative analysis. We have constructed a model of operational mode selection for PPP projects for offshore wind power generation and verified its practicality and scientificity through empirical calculations. This paper discusses and points out the rational progress model of future offshore wind power project PPP model and based on this maximizes the venture of offshore wind power PPP project. The above studies are expected to provide a useful reference for the reasonable burden of offshore wind PPP projects and the development of current energy sources in a low-carbon context.

Association between the infection probability of COVID-19 and ventilation rates: An update for SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the current coronavirus disease 2019 (COVID-19) pandemic, is evolving. Thus, the risk of airborne transmission in confined spaces may be higher, and corresponding precautions should be re-appraised. Here, we obtained the quantum generation rate (q) value of three SARS-CoV-2 variants (Alpha, Delta, and Omicron) for the Wells-Riley equation with a reproductive number-based fitted approach and estimated the association between the infection probability and ventilation rates. The q value was 89–165 h−1 for Alpha variant, 312–935 h−1 for Delta variant, and 725–2,345 h−1 for Omicron variant. The ventilation rates increased to ensure an infection probability of less than 1%, and were 8,000–14,000 m3 h−1, 26,000–80,000 m3 h−1, and 64,000–250,000 m3 h−1 per infector for the Alpha, Delta, and Omicron variants, respectively. If the infector and susceptible person wore N95 masks, the required ventilation rates decreased to about 1/100 of the values required without masks, which can be achieved in most typical scenarios. An air purifier was ineffective for reducing transmission when used in scenarios without masks. Preventing prolonged exposure time in confined spaces remains critical in reducing the risk of airborne transmission for highly contagious SARS-CoV-2 variants.

Perceived social support and professional identity in nursing students during the COVID-19 pandemic era: The mediating effects of self-efficacy and the moderating role of anxiety (preprint)

Background Health professionals, including nurses, experienced heavy workloads and significant physical and mental health challenges during the coronavirus disease (COVID) 19 pandemic, which may affect career choices for those considering nursing and for nursing students. The COVID-19 pandemic is not only a period of risk, but also an occasion to redeploy the PI of nursing students. However, the relationship between PSS, SE, PI and anxiety remains unclear. This study aims to explore whether perceived social support (PSS) has an indirect effect on professional identity (PI) through mediation of self-efficacy (SE) and whether the anxiety can moderate the relationship between perceived social support and self-efficacy in nursing students during their internship period.Methods An observational, national cross-sectional study was conducted following the STROBE guidelines. An online questionnaire was completed by 2,457 nursing students from 24 provinces in China during their internship during September to October 2021. Measures included Chinese translations of the Professional Identity Questionnaire for Nursing Students, the Perceived Social Support Scale, the General Self-Efficacy Scale, the 7-item Generalized Anxiety disorder scale.Results Both PSS (r = 0.46, p < 0.001) and SE (r = 0.51, p < 0.001) were positively correlated with PI. The indirect effect of PSS on PI through SE was positive (β = 0.348, p < 0.001), with an effect of 72.7%. The results of the moderating effect analysis showed that anxiety attenuated the effect of PSS on SE. Moderation models indicated that anxiety has a weak negative moderating effect on the effect of PSS on SE (β = − 0.0308, p < 0.05).Conclusions A better PSS and higher scores in SE were associated with PI in nursing students, and a better PSS had an indirect effect on the PI of nursing students through SE. Anxiety played a negative moderating role in the relationship between PSS and SE.

A bibliometrics analysis and visualization of autism spectrum disorder

Background The prevalence of autism spectrum disorder (ASD) increased rapidly in the last 20 years. Although related research has developed rapidly, little is known about its etiology, diagnostic marker, or drug treatment, which forces researchers to review and summarize its development process and look for the future development direction. Methods We used bibliometrics to analyze papers of ASD in the Web of Science from 1998 to 2021, to draw the network of authors, institutions, countries, and keywords in the ASD field, and visualize the results. Results A total of 40,597 papers were included with a continually increasing trend. It turns out that the research on ASD is mainly concentrated in universities. The United States has the largest number of ASD studies, followed by England and Canada. The quality of papers related to ASD is generally high, which shows that ASD research has become a hot spot of scientific research. The keywords of ASD etiology and diagnostic markers can be classified into at least 7 aspects. The detection of keywords shows that ASD research is mostly based on its subtypes, takes children as the study population, focuses on neurodevelopmental imaging or genetics, and pays attention to individual differences. And ASD research has changed greatly under the impact of Corona Virus Disease 2019 in the past 2 years. Conclusion We consider the future development direction should be based on the improvement of case identification, accurate clinical phenotype, large-scale cohort study, the discovery of ASD etiology and diagnostic markers, drug randomized controlled trials, and telehealth.

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020

Background The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China. Method From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes. Result A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world. Conclusions The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

N-Acetylcysteine Treatment Accelerates Patient-Reported Outcomes Improvement in Patients With COVID-19 A Prospective Study (preprint)

Background: Since its outbreak in late December 2019, the coronavirus disease 2019 (COVID-19) has culminated in a global pandemic, and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continued to mutate, with increasing rates of transmission and pathogenicity, having a serious worldwide impact. This study aims to assess the benefits of the health-related quality of life of using N-acetylcysteine(NAC).Methods: In this prospective observational research, 63 confirmed COVID-19 patients who were treated between the ends of January and March 2020 were divided into patients treated with NAC-treatment (32 cases) and non-NAC-treatment groups (31 cases). Patients were followed up at discharge and at 1, 3, and 6 months after discharge. The clinical treatment effects of the two groups were compared, and the St. George’s Respiratory Questionnaire (SGRQ) evaluated patient-reported outcomes.Results: There were strong correlations between SGRQ component scores (0.728, 0.749, 0.850; P < 0.001 for all items) as well as between each SGRQ component score and the total patient score (0.822, 0.958, 0.957; P < 0.001 for all items). In the univariate analysis, the change differences of one month after discharge compared with discharge between two groups patients were statistically significant in the impacts and total scores (753.000, P < 0.001; 644.000, P = 0.042); the change differences of three months after discharge compared with discharge were also significant in the activity, impacts, and total scores (660.500, P = 0.022; 800.000, P < 0.001; 707.000, P = 0.004). In the multivariate analysis, the factors that have statistically significant influence on the unit value of SGRQ total score difference (UVDSGRQ) is NAC treatment (β = 1.954, P < 0.001), disease severity (β = 3.179, P < 0.001), follow-up duration (β = -0.232, P = 0.001), as well as NAC treatment and follow-up duration interaction item (β = -0.436, P = 0.004).Conclusion: Our study shows as the follow-up time increases, the SGRQ total scores of patients treated with NAC decreases significantly faster than those who were treated without NAC. In the treatment of COVID-19 patients, increasing the use of NAC has clinical significance.

The natural gas consumption and mortality nexus: A mediation analysis

Boosting natural gas consumption can contribute to a healthy China. To examine the link between natural gas consumption and mortality, this study utilizes a balanced panel dataset including 30 Chinese provinces from 2001 to 2019. The fully modified ordinary least squares (FMOLS) method is employed to reveal the long-term cointegration, and the Dumitrescu and Hurlin (D-H) test is further applied to explore the causal relations. Moreover, this study estimates the mediation effects of particulate matter (PM 2.5) emissions on mortality. The empirical results indicate that climbing natural gas consumption can effectively reduce the mortality rate. At the national level, a 1% increase in natural gas consumption leads to a 0.02% decrease in the mortality rate. In addition, the causality analysis uncovers the existence of significant regional heterogeneity. An increase in natural gas consumption will exert a stronger impact in curbing mortality in high gross domestic product (High-GDP) or high natural gas consumption (High-NG) regions. In addition to directly affecting mortality, natural gas consumption also has an indirect impact through the mediation effects of PM 2.5 emissions. Finally, implications for policy and practice are put forward for the Chinese government pertaining to build a healthy China and advance the natural gas industry. • The nexus between natural gas consumption and mortality in China is investigated for 2001–2019. • Natural gas consumption negatively affects mortality rates. • Bidirectional causality link between natural gas consumption and mortality rate is detected. • Natural gas consumption not only directly affects mortality but also indirectly affect mortality by influencing PM 2.5 emissions. [ FROM AUTHOR] Copyright of Energy is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Rational development of a combined mRNA vaccine against COVID-19 and influenza (preprint)

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

Identification of RPSA as a Potential Biomarker in Bronchoalveolar Lavage Fluid for Acute Respiratory Distress Syndrome (preprint)

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition leading to severe pulmonary injuries, and proteomic analysis of bronchoalveolar lavage fluid (BALF) might elucidate potential biomarkers for diagnosis and targets for treatment of ARDS. Methods: Through iTRAQ analysis, we investigated paired BALF samples from three ARDS patients in the acute and recovery phases. The proteins sharing the same expression patterns between the two ARDS phases among different patients were determined as co-upregulated and co-downregulated proteins (CUDPs), and differentially expressed proteins (DEPs), whose fold change > 1.2 and P value < 0.05, were selected from CUDPs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to determine the enriched functions and pathways of the CUDPs. Protein-protein interaction (PPI) network was generated at STRING database, and hub genes were identified by the Cytoscape software. A549 cells were treated by lipopolysaccharide (LPS) to simulate alveolar epithelial cells in ARDS. Results: We identified 374 CUDPs and 53 DEPs. The GO analysis indicated that the most significantly enriched function was neutrophil mediated immunity response, and the KEGG analysis revealed that the 374 CUDPs were most significantly enriched in Coronavirus disease COVID-19 interaction. RPSA was discovered as the most top hub gene among DEPs, and was downregulated at protein levels during ARDS recovery. Moreover, we further confirmed that both RNA and protein level of RPSA increased upon inflammatory stimulation in vitro. Conclusion: Our results proposed RPSA as a candidate for biomarker and therapeutic target of ARDS.

A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection (preprint)

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

Influence of the First-wave COVID-19 Pandemic on Emergency Acute Coronary Syndrome: a Multicenter Retrospective Study From a Non-epicenter Region (preprint)

Background: The COVID-19 pandemic presented severe challenges to emergency practice of acute coronary syndrome (ACS). However, poor evidence was shown on ACS in a non-hot-spot region. We sought to clarify the influence of the first-wave COVID-19 pandemic on emergency ACS from a non-epicenter region. Methods: : This retrospective multicenter study was conducted in emergency ACS patients during the pandemic (from 2020-01-23 to 2020-03-29) and the ones during the same period in 2019. Clinical characteristics, timeline parameters and treatment strategies were compared between different groups. Association of the pandemic with non-invasive therapy was further assessed. Results: : Compared with 2019, ACS had a drop in admission (267 cases vs. 475 cases) and invasive therapy (140 cases vs. 318 cases). Also, process delays were detected including the period from symptom onset to first medical contact (S-to-FMC, 5h vs. 2.5h), the period from FMC to electrocardiogram (ECG) completed (8min vs. 4min) and the period from FMC to dual antiplatelet therapy (FMC-to-DAPT, 25min vs. 19min). Primary percutaneous coronary intervention (PPCI) decreased by 54.9% in STEMI and early invasive therapy decreased by 59.2% in NSTE-ACS. The proportion of invasive therapy in NSTE-ACS decreased more than in STEMI (16.9% vs. 10.1%) with longer process delay. The pandemic was associated with increased non-PPCI in STEMI (OR=1.707, 95%CI 1.082-2.692, P=0.021) and elevated medication in NSTE-ACS (OR=2.029, 95%CI 1.268-3.247, P=0.003), respectively. Conclusion: Even in a non-epicenter region, the first-wave COVID-19 pandemic caused a significant reduction of invasive therapy and evident process delays in emergency ACS.

Clinicopathological and Immunological Features of Patients With New Onset Kidney Disease After Inactivated SARS-CoV-2 Vaccination: An Observational Cohort Study (preprint)

Background: The onset of various kidney diseases have been reported after COVID-19 vaccination. However, detailed clinical and pathological examination of kidney injury in patients receiving inactivated vaccines are lacking.Methods: We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021. We obtained samples of blood, urine, and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observation were described. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein and Nucleoprotein were stained using immune-fluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay.Findings: The study group included 17 patients, including immune complex mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-GBM nephritis, acute tubulointerstitial nephritis, and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and 10 (58.82%) after the second dose. We found no definitive evidence of SARS-CoV-2 Spike protein or Nucleoprotein deposition in the kidney biopsy samples. Serological markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients.Interpretation: We observed various kidney diseases following inactivated SARS-CoV-2 vaccine administration. Our findings provide an evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of inactivated SARS-CoV-2 vaccine renal safety.Funding: This study was funded by National Natural Science Foundation of China (91742205, 82170711, 81800636, 82070733, 81625004), Clinical Medicine Plus X—Young Scholars Project of Peking University (PKU2021LCXQ017), the Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046), Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), and Beijing Young Scientist Program (BJJWZYJH01201910001006).Declaration of Interest: The authors declare no competing interests.Ethical Approval: This study was approved by the institutional review board of Peking University First Hospital (2021-352) and the Committee on Human Subject Research and Ethics of Yunnan University (CHSRE2021020). Written Informed Consent Form was obtained from each participant.

Renal dysfunction and prognosis of COVID-19 patients: a hospital-based retrospective cohort study (preprint)

Introduction: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains unclear.Materials and methods: This prospective case-cohort study analyzed 154 COVID-19 patients from the Second People’s Hospital of Fuyang City in Anhui Province. Clinical and demographic information were collected. Renal function was evaluated and its prognosis was followed up. Results: Of 154 hospitalized patients with COVID-19, 125 were common and 29 were severe patients. On admission, 16 (10.4%) patients were with renal dysfunction. Serum creatinine and cystatin C were increased, eGFR was decreased in severe patients compared with those in common patients. Renal dysfunction was more common in severe patients. By multivariate logistic regression, male, higher age and hypertension were three importantly independent risk factors of renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in two weeks after discharge. Conclusion: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in two weeks after discharge.

Clinical Features and Risk Factors for Secondary Infection in Critically Ill Patients With COVID-19 (preprint)

Background: To analyze the clinical features and the possible risk factors of secondary infection, and explore their impact on prognosis of COVID-19. Methods: A total of 165 severe and critical hospitalized patients diagnosed with COVID-19 were included. The clinical characteristics, laboratory tests, imaging data, secondary infections and outcomes were analyzed. Results: The mean age of total patients was (57.3±15.2) years, of which 111 were males (67.3%). 108 cases were with basic diseases (65.5%), and 1 death (0.6%). The secondary infection rate in critical patients was significantly higher than in severe patients (P <0.05). The secondary infections were mainly lung infections. The pathogens were principally Burkholderia multivorans, Stenotrophomonas maltophilia, Acinetobacter baumannii and Klebsiella pneumoniae. The recovery rate of 28 days in the infected group was significantly lower than that in the non-infected group (p < 0.001).The utilization rate and usage time of invasive ventilator, and deep vein catheterization, catheter indwelling and ECMO were the risk factors for the secondary infected patients.Conclusion: Secondary infection is an extremely common complication in critically ill patients and a trigger point for exacerbation of the disease. An effective control on the secondary infection will do good to the prognosis of COVID-19 patients.

Impaired cellular immunity to SARS-CoV-2 in severe COVID-19 patients (preprint)

The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, the basis of which remains largely unclear. Currently, though convalescent individuals have been shown with both cellular and humoral immune responses, there is very limited understanding on the immune responses, especially adaptive immune responses, in patients with severe COVID-19. Here, we examined 10 blood samples from COVID-19 patients with acute respiratory distress syndrome (ARDS). The majority of them (70%) mounted SARS-CoV-2-specific humoral immunity with production of neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, accompanied with decreased IFN{gamma} expression in CD4+ T cells in peripheral blood from severe patients. Most notably, we failed in detecting SARS-CoV-2-specific IFN{gamma} production by peripheral blood lymphocytes from these patients. Our work thus indicates that COVID-19 patients with severe symptoms are associated with defective cellular immunity, which not only provides insights on understanding the pathogenesis of COVID-19, but also has implications in developing an effective vaccine to SARS-CoV-2.

Myocardial Injury at Early Stage and Its Association with Death Risk of Patients with COVID-19: A Hospital-Based Prospective Case-Cohort Study (preprint)

Background: There are growing evidence demonstrating that coronavirus disease 2019 (COVID-19) is companied by acute myocardial injury. However, the association of SARS-CoV-2-induced myocardial injury with death risk of COVID-19 is unclear.Methods: This prospective case-cohort study analyzed 355 COVID-19 patients from two hospitals in different regions. Clinical and demographic information were collected. Myocardial injury was evaluated and its prognosis was followed up. Results: Of 355 hospitalized patients with COVID-19, 213 were mild, 90 severe and 52 critically ill patients. On admission, 220 (62.0%) patients were with myocardial injury. Myocardial injury was more popular in critically ill patients. Using multivariate logistic regression, male, older age and comorbidity with hypertension were three crucial independent risk factors predicting myocardial injury of COVID-19 patients. Among 220 COVID-19 patients with myocardial injury, 33 (15.0%) died on mean 10.9 day after hospitalization. Mortality was increased among COVID-19 patients with myocardial injury (15.0% vs 1.74%, RR=8.625, P<0.001). Follow-up study observed that at least one myocardial index of 21.3% patients remained abnormal 14 days after discharge. Conclusion: Myocardial injury at early stage elevates mortality of COVID-19 patients. Male elderly patients with hypertension are more vulnerable to myocardial injury. SARS-CoV-2-induced myocardial injury has not completely recovered 14 days after discharge.