ACE2 mimetic antibody potently neutralizes all SARS-CoV-2 variants and fully protects in XBB.1.5 challenged monkeys (preprint)

The rapid evolution of SARS-CoV-2 to variants with improved transmission efficiency and reduced sensitivity to vaccine-induced humoral immunity has abolished the protective effect of licensed therapeutic human monoclonal antibodies (mAbs). To fill this unmet medical need and protect vulnerable patient populations, we isolated the P4J15 mAb from a previously infected, vaccinated donor, with <20 ng/ml neutralizing activity against all Omicron variants including the latest XBB.2.3 and EG.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ~93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. Although SARS-CoV-2 mutants escaping neutralization by P4J15 were selected in vitro, these displayed lower infectivity, poor binding to ACE2, and the corresponding "escape" mutations are accordingly rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, we show that P4J15 confers complete prophylactic protection. We conclude that the P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug.

Anxiety, depression, and related factors in hemodialysis patients during the lockdown period of COVID- 19 in China: a multicenter study.

The outbreak of coronavirus disease 2019 (COVID-19) made a huge impact on hemodialysis (HD) patients. The aim of the study was to survey the anxiety, depression and related factors of HD patients during the lockdown and to explore the factors that affect their anxiety and depression. From February 1 to 15, 2020, an online survey was conducted in HD patients; the survey collected information on demographic data, epidemic perception, travel status and Zung's Self-rating Anxiety Scale (SAS) and Zung's Self-rating Depression Scale (SDS). The original SAS and SDS data from 96 HD patients gathered between May and August 2018 were retained as data for the control group. A total of 506 HD patients were recruited, and the prevalence of anxiety and depression was 22.33% and 45.45%, respectively. They had significantly higher SAS and SDS scores than the HD patients before the epidemic (p < 0.01; p < 0.05). It was found that self-threat perception, trouble related to transportation and skipping dialysis sessions were factors related to anxiety in HD patients during the lockdown (p ˂ 0.05). Education level, trouble related to transportation and the awareness of the seriousness of the epidemic were factors related to depression (p ˂ 0.05). During the COVID-19 lockdown period, HD patients reported higher levels of psychological distress than HD patients before the pandemic. Psychological support and transport policies should be provided to them.

Epidemiological survey of an epidemic of COVID-19 due to occupational exposure in Qinghai, 2021

Objective: To analyze the epidemiological characteristics of an epidemic of coronavirus disease 2019 (COVID-19) caused by occupational exposure in Xining, Qinghai province, from October 17 to November 2, 2021 and provide evidence for the prevention and control of COVID-19 epidemic. Methods: In accordance with the requirements of the COVID-19 prevention and control protocol (eighth edition), epidemiological survey and field response were conducted and throat swabs were collected from the confirmed cases and close contacts. Real time-PCR(RT-PCR) was used to detect severe acute respiratory syndrome coronavirus (SARS-CoV-2) nucleic acid. Gene sequencing was performed for the throat swabs of partial confirmed cases by high throughput sequencing. Results: A total of 11 COVID-19 cases were reported in this epidemic, including 3 cases in a family and 8 cases in medical staff. Nine cases were women, 2 cases were men. The cases in epidemic had 3 generations. The average incubation period was 3.18 day. The infection was mainly occurred in working place. The risk factors included sharing telephone, computer and other office equipment. The initial symptoms were cough (10 cases, 90.97%). Unstandardized taking off protective suit in field epidemiological survey and inappropriate design of waterproof boot cover were the main risk factors for the occupational exposure. The SARS-CoV-2 detected belonged to VOC/Delta variant. Conclusion: This epidemic was caused by occupational exposure. It is suggested to strengthen the field supervision and guide of the wearing of protective suits, improve the design of waterproof boot cover and reduce the contacts of field workers with others.

[Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm].

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale–Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic.

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale-Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Posttraumatic stress disorder symptoms among Chinese college students following the COVID-19 outbreak.

Objective: This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms in college students 1 month after the lockdown of Wuhan to identify possible risk factors for PTSD symptoms in a cross-sectional study. Methods: Out of 10,502 who responded, 9,274 students impacted by the COVID-19 pandemic were included in our study. PTSD symptoms was evaluated by the Impact of Event Scale-revised (IES-R). Anxiety/depression symptoms were evaluated by the Kessler Psychological Distress Scale (K10). Personality traits, coping style, and social support were assessed by the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). Logistic regression analysis was utilized to further explore risk factors for PTSD symptoms. Results: More than 1 month after the COVID-19 outbreak, 13.1% of college students developed PTSD symptoms, indicating that COVID-19 associated stressful experiences were connected with PTSD symptoms. After the COVID-19 outbreak, subjects with symptomatologic PTSD symptoms were more likely to experience strained relationships with their family, to have close contact with COVID-19 patients and to drop out of college. The logistic regression model demonstrated the association factors of PTSD symptoms. Neuroticism, psychoticism and an avoidant coping style were associated with increased risk for PTSD symptoms, while an active coping style was protective against PTSD symptoms during this pandemic. Conclusion: The results showed that PTSD symptoms was prevalent in Chinese college students 1 month after the COVID-19 outbreak. Effective psychological support work should be carried out accordingly.

Anxiety prevalence and its association with physical activity in patients with non-communicable diseases during COVID-19 lockdown: a cross-sectional study in Shanghai, China.

BACKGROUND: Quarantine due to the COVID-19 pandemic may have created great psychological stress among vulnerable populations. We aimed to investigate the prevalence of anxiety and explore the association between physical activities (PA) and anxiety risk in people with non-communicable diseases during the period of COVID-19 lockdown. METHODS: We conducted a cross-sectional telephone survey from February 25 to April 20, 2020, the period of COVID-19 lockdown in Shanghai. Up to 8000 patients with type 2 diabetes and/or hypertension were selected using multi-stage cluster random sampling. PA level was measured based on the International Physical Activity Questionnaire using Metabolic Equivalent for Task scores, while symptoms of anxiety were assessed by the 7-item Generalized Anxiety Disorder scale. Multiple logistic regression analyses were performed to evaluate the associations of type and level of PA with the risk of anxiety. RESULTS: Of a total 4877 eligible patients, 2602 (53.4%) reported with anxiety, and 2463 (50.5%), 123 (2.5%) and 16 (0.3%) reported with mild, moderate, and severe anxiety. The prevalence of anxiety was higher in the females, the elders, non-smokers, non-drinkers, and patients with diabetes, and the associations of anxiety with sex, age, smoking, drinking and diagnosis of diabetes were significant. A significant negative association was observed for housework activities (OR 0.53, 95%CI: [0.45, 0.63], p < 0.001) and trip activities (OR 0.55, 95%CI: [0.48, 0.63], p < 0.001) with anxiety, but no significant was found for exercise activities (OR 1.06, 95%CI: [0.94, 1.20], p = 0.321). Compared with patients with a low PA level, those with a moderate (OR 0.53, 95%CI: [0.44, 0.64], p < 0.001) or a high PA level (OR 0.51, 95%CI: [0.43, 0.51], p < 0.001) had a lower prevalence of anxiety. CONCLUSION: This study demonstrates a higher prevalence of anxiety in patients with hypertension, diabetes, or both during the COVID-19 lockdown. The negative associations of housework and trip activities with anxiety highlight the potential benefit of PA among patients with non-communicable diseases.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

Sputum deposition classification for mechanically ventilated patients using LSTM method based on airflow signals.

A novel sputum deposition classification method for mechanically ventilated patients based on the long-short-term memory network (LSTM) method was proposed in this study. A wireless ventilation airflow signals collection system was designed and used in this study. The ventilation airflow signals were collected wirelessly and used for sputum deposition classification. Two hundred sixty data groups from 15 patients in the intensive care unit were compiled and analyzed. A two-layer LSTM framework and 11 features extracted from the airflow signals were used for the model training. The cross-validations were adopted to test the classification performance. The sensitivity, specificity, precision, accuracy, F1 score, and G score were calculated. The proposed method has an accuracy of 84.7 ± 4.1% for sputum and non-sputum deposition classification. Moreover, compared with other classifiers (logistic regression, random forest, naive Bayes, support vector machine, and K-nearest neighbor), the proposed LSTM method is superior. In addition, the other advantages of using ventilation airflow signals for classification are its convenience and low complexity. Intelligent devices such as phones, laptops, or ventilators can be used for data processing and reminding medical staff to perform sputum suction. The proposed method could significantly reduce the workload of medical staff and increase the automation and efficiency of medical care, especially during the COVID-19 pandemic.

Preparation of the RIPK3 Polyclonal Antibody and Its Application in Immunoassays of Nephropathogenic Infectious Bronchitis Virus-Infected Chickens.

Receptor interacting protein kinase 3 (RIPK3) is a vital serine/threonine kinase in regulating the programmed destruction of infected cells to defend against RNA viruses. Although the role of RIPK3 in viruses in mice is well characterized, it remains unclear where in nephropathogenic infectious bronchitis virus (NIBV) in chickens. Here, we use a self-prepared polyclonal antibody to clarify the abundance of RIPK3 in tissues and define the contributions of RIPK3 in tissue damage caused by NIBV infection in chickens. Western blot analyses showed that RIPK3 polyclonal antibody can specifically recognize RIPK3 in the vital tissues of Hy-Line brown chicks and RIPK3 protein is abundantly expressed in the liver and kidney. Moreover, NIBV significantly upregulated the expression levels of RIPK3 in the trachea and kidney of chicks in a time-dependent manner. In addition, the activation of necroptosis in response to NIBV infection was demonstrated by the coimmunoprecipitation (CoIP) experiments through RIPK3 in the necrosome, which phosphorylates its downstream mixed-spectrum kinase structural domain-like protein (MLKL). Our findings offered preliminary insights into the key role of RIPK3 protein in studying the underlying mechanism of organ failure caused by NIBV infection.

A New Precise High Flow Oxygen Therapy System Based on Sliding Mode Control Strategy

In recent years, precise high flow oxygen therapy as a new type of oxygen therapy machine has gradually attracted people’s attention and has been widely used in hospital emergency and clinical treatment of respiratory diseases;especially in recent years, severe coronavirus disease (COVID-19) has played an important role in the treatment of patients. This paper presents a new type of precise high flow oxygen therapy machine with electromagnetic pneumatic flow valve as the core control element. A sliding mode control strategy based on the system is proposed to realize the accurate control of oxygen concentration and output flow of oxygen therapy mixture. The physical equipment of the precision high flow system is established, and its working performance is verified through the test platform. The optimization design goal of the precision high flow equipment is achieved.

Prevalence of Dementia in China in 2015: A Nationwide Community-Based Study.

Objective: This study aims to estimate the prevalence of dementia and Alzheimer's disease (AD) and associated risk factors among the general Chinese population. Methods: We carried out a nationwide study including 24,117 participants aged 60 years and older in China using a multistage clustered sampling. Dementia and AD were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. Face-to-face interviews were administered by the trained interviewers to obtain information on demographics, lifestyle factors, and previous diseases. Results: The overall weighted prevalence of dementia was 4.22% (95%CI 2.27-6.17%) for people aged 60 years and older, was higher in women than in men and increased with age. Daily tea drinking and daily exercises were the protective factors for both dementia and AD. Engaging in social and intellectual activities was significantly associated with a lower risk of dementia and AD. Conclusions: A large number of population with dementia posed a significant challenge to China where the population is rapidly aging. The increase of public awareness, building more care facilities, and training dementia specialists and professional caregivers are all urgently needed and should be the future priorities of dementia care in China.

SARS-CoV-2 Omicron potently neutralized by a novel antibody with unique Spike binding properties (preprint)

The SARS-CoV-2 Omicron variant exhibits very high levels of transmission, pronounced resistance to authorized therapeutic human monoclonal antibodies and reduced sensitivity to vaccine-induced immunity. Here we describe P2G3, a human monoclonal antibody (mAb) isolated from a previously infected and vaccinated donor, which displays picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other current variants, and is thus markedly more potent than all authorized or clinically advanced anti-SARS-CoV-2 mAbs. Structural characterization of P2G3 Fab in complex with the Omicron Spike demonstrates unique binding properties to both down and up spike trimer conformations at an epitope that partially overlaps with the receptor-binding domain (RBD), yet is distinct from those bound by all other characterized mAbs. This distinct epitope and angle of attack allows P2G3 to overcome all the Omicron mutations abolishing or impairing neutralization by other anti-SARS-COV-2 mAbs, and P2G3 accordingly confers complete prophylactic protection in the SARS-CoV-2 Omicron monkey challenge model. Finally, although we could isolate in vitro SARS-CoV2 mutants escaping neutralization by P2G3 or by P5C3, a previously described broadly active Class 1 mAb, we found these viruses to be lowly infectious and their key mutations extremely rare in the wild, and we could demonstrate that P2G3/P5C3 efficiently cross-neutralized one another's escapees. We conclude that this combination of mAbs has great prospects in both the prophylactic and therapeutic settings to protect from Omicron and other VOCs.

Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission, and vaccine resistance.

The appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has caused panic responses around the world because of its high transmission rate and number of mutations. This review summarizes the highly mutated regions, the essential infectivity, transmission, vaccine breakthrough and antibody resistance of the Omicron variant of SARS-CoV-2. The Omicron is highly transmissible and is spreading faster than any previous variant, but may cause less severe symptoms than previous variants. The Omicron is able to escape the immune system's defenses and coronavirus disease 2019 vaccines are less effective against the Omicron variant. Early careful preventive steps including vaccination will always be key for the suppression of the Omicron variant.

Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.

Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity.

Ivermectin does not protect against SARS-CoV-2 infection in the Syrian hamster model (preprint)

Ivermectin, an FDA-approved antiparasitic drug, has been reported to have in vitro activity against SARS-CoV-2. An increasing off-label use of Ivermectin for COVID-19 has been reported. We here assessed the effect of Ivermectin in Syrian hamsters infected with the SARS-CoV-2 Beta (B.1.351) variant. Infected animals received a clinically relevant dose of Ivermectin (0.4 mg/kg subcutaneously dosed) once daily for four consecutive days after which the effect was quantified. Ivermectin monotherapy did not reduce lung viral load and even significantly worsened the SARS-CoV-2-induced lung pathology. Additionally, it did not potentiate the activity of Molnupiravir (Lagevrio) when combined with this drug. This study contributes to the growing body of evidence that Ivermectin does not result in a beneficial effect in the treatment of COVID-19. These findings are important given the increasing, dangerous off-label use of Ivermectin for the treatment of COVID-19.

Knowledge, Attitude, and Perceived Barriers of Newly Graduated Registered Nurses Undergoing Standardized Training in Intensive Care Unit Toward Early Mobilization of Mechanically Ventilated Patients: A Qualitative Study in Shanghai

Aim: To explore the knowledge and attitudes of newly graduated registered nurses, who have undergone standardized training in the intensive care unit, about the early mobilization of mechanically ventilated patients and identify perceived barriers to the application of early mobilization. Background: Early mobilization of mechanically ventilated patients has been gradually gaining attention, and its safety and effectiveness have also been verified. Nurses in intensive care units are the implementers of early mobilization, and the quality of their care is closely related to patient prognosis. However, the knowledge and attitude of newly graduated registered nurses undergoing standardized training, in intensive care units, on the early mobilization of mechanically ventilated patients and the obstacles they face in clinical implementation are still unclear. Methods: This qualitative study utilized the phenomenological method to explore the experiences of 15 newly graduated registered nurses undergoing standardized training in intensive care units in a 3rd hospital in Shanghai, China. Semi-structured face-to-face interviews were conducted in June 2020. The Colaizzi seven-step framework was used for data analysis. Findings: A total of 15 new nurses comprised the final sample after data saturation. Three main themes emerged from the analysis and seven subthemes: perceived importance, low implementation rate, and perceived barriers. Conclusions: Newly graduated registered nurses undergoing standardized training in intensive care units have a high level of awareness of the importance of early mobilization of mechanically ventilated patients and are willing to implement it. However, there is a lack of relevant knowledge and other obstacles that restrict clinical implementation. Early mobilization should be included in the standardized training of new nurses in intensive care units.