Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines.

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

Associated factors of burnout among Chinese vaccination staff during COVID-19 epidemic: A cross-sectional study.

Objective: During the COVID-19 epidemic, vaccination staff had three main aspects of work: routine vaccination for children and adults, COVID-19 vaccination and COVID-19 prevention and control. All these works significantly increased the workload of vaccination staff. This study aimed to investigate the prevalence and influencing factors of burnout among vaccination staff in Hangzhou, China. Methods: A total of 501 vaccination staff from 201 community/township healthcare centers in Hangzhou were recruited using a cross-sectional survey through WeChat social platform. The Maslach Burnout Inventory-General Scale (MBI-GS) was used to assess the level of burnout. Descriptive statistics were made on the characteristics of participants. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors of burnout. Univariate analysis and multiple linear regression were used to determine the relative predictors of exhaustive emotion, cynicism, and personal accomplishment. Results: During the COVID-19 pandemic, 20.8% of the vaccination staff experienced burnout. Educational level above undergraduate education level, medium professional title, and more working time in COVID-19 vaccination work reported a higher degree of job burnout. The vaccination staff was experiencing a high degree of exhaustive emotion, cynicism, and low personal accomplishment. Professional title, working place, and working time for COVID-19 vaccination were associated with exhaustive emotion and cynicism. Professional title and participation time for COVID-19 prevention and control were associated with personal accomplishment. Conclusions: Our findings suggest that the prevalence rate of burnout is high among vaccination staff during the COVID-19 pandemic, especially with a low level of personal accomplishment. Psychological intervention for vaccination staff is urgently needed.

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

BACKGROUND: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies. METHODS: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, acalabrutinib, or both, were orally administered zanubrutinib 160 mg twice daily or 320 mg once daily per investigator. The primary endpoint was recurrence and change in severity of ibrutinib or acalabrutinib intolerance events based on investigator-assessed adverse events. Secondary endpoints were investigator-assessed overall response rate; duration of response; disease control rate; and progression-free survival. Analyses included all patients who received any dose of the study drug. This study is registered with ClinicalTrials.gov, NCT04116437. FINDINGS: Between Oct 14, 2019, and Sept 8, 2021, 67 patients (36 [54%] men and 31 [46%] women) who were intolerant of ibrutinib (n=57; cohort 1) or of acalabrutinib or acalabrutinib and ibrutinib (n=10; cohort 2) were enrolled. 63 (94%) patients were White, one (2%) had multiple ethnicities, and three (5%) had unreported or unknown ethnicity. Most intolerance events (81 [70%] of 115 for ibrutinib; 15 [83%] of 18 for acalabrutinib) did not recur with zanubrutinib. Of the recurring events, seven (21%) of 34 ibrutinib intolerance events and two (67%) of three acalabrutinib intolerance events recurred at the same severity with zanubrutinib; 27 (79%) ibrutinib intolerance events and one (33%) acalabrutinib intolerance event recurred at a lower severity with zanubrutinib. No events recurred at higher severity. No grade 4 intolerance events recurred. 64 (96%) of 67 patients had one or more adverse events with zanubrutinib; the most common adverse events were contusion (in 15 [22%] of 67 patients), fatigue (14 [21%]), myalgia (ten [15%]), arthralgia (nine [13%]), and diarrhoea (nine [13%]). Atrial fibrillation occurred in three (4%) patients (all grade 2). Eight (12%) of 67 patients had serious adverse events (anaemia, atrial fibrillation, bronchitis, COVID-19, COVID-19 pneumonia, febrile neutropenia, salmonella gastroenteritis, transfusion reaction, trigeminal nerve disorder, and urinary tract infection). No treatment-related deaths occurred. The median follow-up time was 12·0 months (IQR 8·2-15·6). Among the 64 efficacy-evaluable patients, disease control rate was 93·8% (60; 95% CI 84·8-98·3) and overall response rate was 64·1% (41; 95% CI 51·1-75·7). The median duration of response was not reached; the 12-month event-free duration of response rate was 95·0% (95% CI 69·5-99·3). Similarly, median progression-free survival was not reached; 18-month progression-free survival was 83·8% (95% CI 62·6-93·6). INTERPRETATION: Patients intolerant of previous BTK inhibitors have limited treatment options. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib. FUNDING: BeiGene.

Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

Early detection of rumors based on source tweet-word graph attention networks.

The massively and rapidly spreading disinformation on social network platforms poses a serious threat to public safety and social governance. Therefore, early and accurate detection of rumors in social networks is of vital importance before they spread on a large scale. Considering the small-world property of social networks, the source tweet-word graph is decomposed from the global graph of rumors, and a rumor detection method based on graph attention network of source tweet-word graph is proposed to fully learn the structure of rumor propagation and the deep representation of text contents. Specifically, the proposed model can adequately capture the contextual semantic association representation of source tweets during the propagation and extract semantic features. For the data sparseness of the early stage of information dissemination, text attention mechanism based on opinion similarity can aggregate and capture more tweet propagation structure features to help improve the efficiency of early detection of rumors. Through the analysis of the experimental results on real public datasets, the rumor detection performance of the proposed method is better than that of other baseline methods. Especially in the early rumor detection tasks, the proposed method can detect rumors with an accuracy of nearly 90% in the early stage of information dissemination. And it still has good robustness with noise interference.

An investigation on trust in AI-enabled collaboration: Application of AI-Driven chatbot in accommodation-based sharing economy.

Several measures taken to control the spread of the COVID-19 pandemic have severely disrupted the accommodation sharing sector. This study attempts to find solutions to aid the recovery of the accommodation sharing sector via team efforts. Accordingly, we focus on the integration of artificial intelligence (AI) and collaboration. Despite the significant developments in AI technologies, there exists no research considering the application of AI in team collaboration. Utilizing the design science research method and collaboration engineering, we developed an AI-driven prototype system, AI-Driven, for collaboration process recommendation. Qualitative results show that the newly developed tool for collaboration process recommendation has achieved satisfactory performance. Furthermore, we investigated the antecedents and outcomes of trust in the AI-driven collaboration context. From a practical perspective, we propose several solutions to the challenges looming over the accommodation sharing sector according to collaboration deliverables. Furthermore, a system prototype was developed to facilitate collaboration process recommendation and provide procedural guidance.

Phenonizer: A Fine-Grained Phenotypic Named Entity Recognizer for Chinese Clinical Texts.

Biomedical named entity recognition (BioNER) from clinical texts is a fundamental task for clinical data analysis due to the availability of large volume of electronic medical record data, which are mostly in free text format, in real-world clinical settings. Clinical text data incorporates significant phenotypic medical entities (e.g., symptoms, diseases, and laboratory indexes), which could be used for profiling the clinical characteristics of patients in specific disease conditions (e.g., Coronavirus Disease 2019 (COVID-19)). However, general BioNER approaches mostly rely on coarse-grained annotations of phenotypic entities in benchmark text dataset. Owing to the numerous negation expressions of phenotypic entities (e.g., "no fever," "no cough," and "no hypertension") in clinical texts, this could not feed the subsequent data analysis process with well-prepared structured clinical data. In this paper, we developed Human-machine Cooperative Phenotypic Spectrum Annotation System (http://www.tcmai.org/login, HCPSAS) and constructed a fine-grained Chinese clinical corpus. Thereafter, we proposed a phenotypic named entity recognizer: Phenonizer, which utilized BERT to capture character-level global contextual representation, extracted local contextual features combined with bidirectional long short-term memory, and finally obtained the optimal label sequences through conditional random field. The results on COVID-19 dataset show that Phenonizer outperforms those methods based on Word2Vec with an F1-score of 0.896. By comparing character embeddings from different data, it is found that character embeddings trained by clinical corpora can improve F-score by 0.0103. In addition, we evaluated Phenonizer on two kinds of granular datasets and proved that fine-grained dataset can boost methods' F1-score slightly by about 0.005. Furthermore, the fine-grained dataset enables methods to distinguish between negated symptoms and presented symptoms. Finally, we tested the generalization performance of Phenonizer, achieving a superior F1-score of 0.8389. In summary, together with fine-grained annotated benchmark dataset, Phenonizer proposes a feasible approach to effectively extract symptom information from Chinese clinical texts with acceptable performance.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Assessing social support impact on depression, anxiety, and stress among undergraduate students in Shaanxi province during the COVID-19 pandemic of China.

Following the 2019 coronavirus disease (COVID-19) outbreak in China, undergraduate students may experience psychological changes. During emergency circumstances, social support is an important factor influencing the mental health condition among undergraduate students in Shaanxi province. This study aims to find the factors associated with mental health symptoms of depression, anxiety, and stress among undergraduate students in Shaanxi province during the COVID-19 pandemic in China. A cross-sectional study was conducted from Feb 23 to Mar 7, 2020. A total of 1278 undergraduate students from the universities located in Shaanxi province participated in this study. The mental health symptoms were measured by 12-item Perceived Social Support Scale (PSSS) and Depression Anxiety Stress Scale (DASS-21) instruments. This survey showed that females receive more social support compared to males (t = -5.046, P<0.001); males have higher-level depression symptoms (t = 5.624, P<0.001); males have higher-level anxiety symptoms (t = 6.332, P<0.001), males have higher-level stress symptoms (t = 5.58, P<0.001). This study also found participants who have low social support was negatively correlated with mental health symptoms. In Conclusion, Males and low social support were associated with having the higher level of depression, anxiety, and stress symptoms among undergraduate students in Shaanxi province during the COVID-19 pandemic in China. Therefore, it is suggested that people should supply more social support for undergraduate students in Shaanxi province during COVID-19 pandemic.

Impact of chemotherapy on lymphocytes and serological memory in recovered COVID-19 patients with acute leukemia.

Chemotherapy is the major method of treatment for acute leukemia to date, while intensive chemotherapy may impair immunity. We previously reported that leukemia patients were more susceptible to COVID-19 than the overall population. However, for COVID-19 recovered patients with leukemia, the impacts of intensive chemotherapy on the immune memory of COVID-19 are unknown. This study characterized the changes in immune cells and SARS-CoV-2 antibodies in acute leukemia patients, who underwent chemotherapy after recovering from COVID-19. The study enrolled three groups of individuals. One group was a total of three acute leukemia patients, who recovered well from COVID-19 before the last cycle of chemotherapy. The other two groups were six COVID-19 recovered healthy people, and six normal uninfected healthy people, respectively. Levels of B cells, T cells, and NK cells in peripheral blood were analyzed by multiparameter flow cytometry. Besides, the SARS-CoV-2 antibodies were monitored. The results showed that B cells were severely decreased after chemotherapy, especially memory B cells. Most of the T cells and NK cells showed only minor changes after chemotherapy, except for γδ T cells. The serum levels of SARS-CoV-2 antibodies were not significantly affected after chemotherapy in two leukemia patients. However, interestingly, one leukemia patient's SARS-CoV-2 IgM showed dramatically increase, suggesting possible loss of serological memory after chemotherapy. These findings raised the concern for the stability of immune memory against SARS-CoV-2 during chemotherapy and the choice of anti-leukemia treatment in the COVID-19 pandemic.

Clinical characteristics, therapeutic management, and prognostic factors of adult COVID-19 inpatients with hematological malignancies.

Patients with hematological malignancies with immunodeficiency are at high risk for SARS-CoV-2 infection. We retrospective summarized clinical characteristics of coronavirus disease 2019 (COVID-19) inpatients with hematological malignancies, shared treatment experiences, and analysis prognostic factors. Fourteen patients were enrolled. The median duration of viral shedding was 27.5 days in survivors. The median duration of time to death was 13 days in non-survivors. Non-survivors tend to present lower neutrophil count, more imaging finding of bilateral diffuse patch opacities, more undergoing intensive chemotherapy or immunosuppression. Laboratory and image findings were atypical and diverse. COVID-19 inpatients undergoing intensive chemotherapy or immunosuppression might have increased risk of death. The diagnostic value of specific antibody detection is limited. Therefore, adult COVID-19 inpatients with hematological malignancies present atypical, severe symptoms, decreased virus clearance ability, abnormal antibody response and poor outcome. During the epidemic, the pros and cons need to be carefully weighed while selecting the treatment methods.

Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

As of March 24, 2020, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for 379,661 infection cases with 16,428 deaths globally, and the number is still increasing rapidly. Herein, we present four critically ill patients with SARS-CoV-2 infection who received supportive care and convalescent plasma. Although all four patients (including a pregnant woman) recovered from SARS-CoV-2 infection eventually, randomized trials are needed to eliminate the effect of other treatments and investigate the safety and efficacy of convalescent plasma therapy.

No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019.

OBJECTIVE: To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle. DESIGN: Observational, cross-sectional study. SETTING: Tertiary referral center. PATIENT(S): Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. RESULT(S): Six patients (19%) demonstrated scrotal discomfort suggestive of viral orchitis around the time of COVID-19 confirmation. Severe acute respiratory syndrome-CoV-2 was not detected in semen after a median of 31 days (interquartile range, 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. CONCLUSION(S): Severe acute respiratory syndrome-CoV-2 was not detected in the semen of patients recovering from COVID-19 1 month after COVID-19 diagnosis. Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.

Clinical and immunological features of severe and moderate coronavirus disease 2019.

BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

Identification of Kidney Transplant Recipients with Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) is a novel and lethal infectious disease, posing a threat to global health security. The number of cases has increased rapidly, but no data concerning kidney transplant (KTx) recipients infected with COVID-19 are available. To present the epidemiological, clinical, and therapeutic characteristics of KTx recipients infected with COVID-19, we report on a case series of five patients who were confirmed as having COVID-19 through nucleic acid testing (NAT) from January 1, 2020 to February 28, 2020. The most common symptoms on admission to hospital were fever (five patients, 100%), cough (five patients, 100%), myalgia or fatigue (three patients, 60%), and sputum production (three patients, 60%); serum creatinine or urea nitrogen levels were slightly higher than those before symptom onset. Four patients received a reduced dose of maintenance immunosuppressive therapy during hospitalization. As of March 4, 2020 NAT was negative for COVID-19 in three patients twice in succession, and their computed tomography scans showed improved images. Although greater patient numbers and long-term follow-up data are needed, our series demonstrates that mild COVID-19 infection in KTx recipients can be managed using symptomatic support therapy combined with adjusted maintenance immunosuppressive therapy.