Nitrogen-rich based conjugated microporous polymers for highly efficient adsorption and removal of COVID-19 antiviral drug chloroquine phosphate from environmental waters

Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel CN bond linked conjugated microporous polymers (CMPs) (BPT–DMB–CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent CN bond linked in the internal framework of BPT–DMB–CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich NH bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g−1), BPT–DMB–CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g−1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT–DMB–CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π − π, C  H···π interactions and size-matching effect in the CQP adsorption system on BPT–DMB–CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT–DMB–CMP. BPT–DMB–CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8%, even in the serum of uremic patients, HCSs could remove 94.75% and 98.33% of parathyroid hormone (PTH) and β2-microglobulin (β2-MG) efficiently within 5-10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment.

Depressive symptoms and gender differences in older adults in Hong Kong during the COVID-19 pandemic: a network analysis approach.

Background: The 2019 novel coronavirus disease (COVID-19) outbreak had a detrimental impact on the mental health of older adults. This study evaluated the central symptoms and their associations in the network of depressive symptoms and compared the network structure differences between male and female older adults in Hong Kong. Methods: Altogether, 3,946 older adults participated in this study. We evaluated the centrality indicators for network robustness using stability and accuracy tests, and examined the potential differences between the structure and connectivity of depression networks in male and female older adults. Results: The overall prevalence of depressive symptoms was 43.7% (95% CI=40.6-46.7%) in males, and 54.8% (95% CI=53.1-56.5%) in females (P<0.05). Sad Mood, Guilt, Motor problems and Lack of Energy were influential symptoms in the network model. Gender differences were found in the network global strength, especially in the following edges: Sad Mood--Guilt, Concentration--Guilt, Anhedonia--Motor, Lack of Energy--Suicide, Appetite--Suicide and Concentration--Suicide. Conclusions: Central symptoms in the depressive symptom network among male and female older adults may be prioritized in the treatment and prevention of depression during the pandemic.

Functional metal-organic framework as high-performance adsorbent for selective enrichment of pharmaceutical contaminants in aqueous samples

Facile and sensitive analysis methods for pharmaceutical contaminants in aqueous environment are of vital importance for water safety, especially when large amounts of anti-viral drugs are being used, discharged and accumulated. In this work, we used functional metal-organic framework (MOF) as high-performance adsorbent for selective enrichment of such pharmaceutical contaminants in aqueous samples. The MOF was synthesized via a new synthesis method previously developed by our group and immobilized on paper membrane to be used in solid-phase extraction (SPE) device. Different metal ions were anchored by MOF to screen out the adsorbent with the best affinity. The targets were a potential anti-COVID-19 drug favipiravir, and its structural and functional analogues (ingredients or intermediates, other anti-viral drugs). To deeply understand the adsorption mechanisms, quantum calculation and computational fluid dynamics (CFD) simulation were both applied. The experimental and in-silico results together demonstrated that the as-prepared MOF adsorbent possessed high affinity and fast dynamics. The established SPE-based liquid chromatography (LC) method worked well in the range of 10-1000 ng/mL, with only 3 mg of adsorbent per device and 5 mL sample needed, and no mass spectrometer (MS) included, which was very efficient compared to commercial adsorbents. The results met the current detection needs in the application scenario, and inspirable for later design of well-behaved adsorbents.

Broadly neutralizing antibodies target the coronavirus fusion peptide (preprint)

The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.

Workplace violence against frontline clinicians in emergency departments during the COVID-19 pandemic.

BACKGROUND: Frontline clinicians working in emergency departments (ED) were at disportionate risk of workplace violence (WPV). We investigated the prevalence of WPV and its relationship with quality of life (QOL) in this group of health professionals in China during the COVID-19 pandemic. METHODS: A cross-sectional, online study was conducted. The nine-item Workplace Violence Scale measured WPV. RESULTS: A total of 1,103 ED clinicians participated in this study. The overall prevalence of WPV against ED clinicians was 29.2% (95% CI [26.5%-31.9%]). Having family/friends/colleagues infected with COVID-19 (Odds Ratio (OR) = 1.82, P = 0.01), current smoking (OR = 2.98, P < 0.01) and severity of anxiety symptoms (OR = 1.08, P < 0.01) were independently and positively associated with WPV, while working in emergency intensive care units (OR = 0.45, P < 0.01) was negatively associated with WPV. After controlling for covariates, clinicians experiencing WPV had a lower global QOL compared to those without (F(1, 1103) = 10.9,P < 0.01). CONCLUSIONS: Prevalence of workplace violence against ED clinicians was common in China during the COVID-19 pandemic. Due to the negative impact of WPV on QOL and quality of care, timely preventive measures should be undertaken for ED clinicians.

How Chinese Herbal Medicine Prevents Epidemics: From Ancient Pestilences to COVID-19 Pandemic.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for effective control and prevention. Chinese medicine (CM) has developed systematic theories and approaches for infectious disease prevention over 2000 years. Here, we review and analyze Chinese herbal medicines (CHM) used in infectious disease prevention from ancient pestilences to modern epidemics and pandemics to share cumulative preventive medical experience. A total of 829 formulas, including 329 herbs from 189 ancient books, 131 formulas with 152 herbs, and 13 Chinese patent medicines (CPM) from 30 official Chinese prevention programs used in ancient epidemics, SARS, influenza and COVID-19 prevention, were reviewed and analyzed. Preventive CHM mainly has four functions and can be taken orally or applied externally. CHM that kill pathogens (Realgar [Xionghuang], Cyrtomium Fortunei J. Sm[Guanzhong]) were commonly used externally for disinfection in ancient prevention while CHM tonifying Qi (Astragali Radix [Huangq], Glycyrrhizae Radix et Rhizoma [Gancao]) are used for modern prevention. Taking CHM that expel pathogens (Realgar [Xionghuang], Lonicerae Japonicae Flos[Jinyinhua]) and CHM eliminating dampness (Atractylodis Rhizoma [Cangzhu], Pogostemonis Herba[Guanghuoxiang]) have been commonly used from ancient times to COVID-19. Damp toxins are a common characteristic of infectious diseases such as SARS and COVID-19. Thus, taking CHM expelling damp toxins and tonifying Qi are the main methods for SARS and COVID-19 prevention. CHM with different approaches have been widely used in infectious disease prevention from ancient times to the present. Multiple CM prevention methods may provide new perspectives for future pandemics.

Ultrapotent bispecific antibodies neutralize emerging SARS-CoV-2 variants (preprint)

The emergence of SARS-CoV-2 variants that threaten the efficacy of existing vaccines and therapeutic antibodies underscores the urgent need for new antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells of COVID-19 patients. The three most potent antibodies targeted distinct regions of the RBD, and all three neutralized the SARS-CoV-2 variants B.1.1.7 and B.1.351. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the ACE2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five ultrapotent bispecific antibodies that inhibit authentic SARS-CoV-2 infection at concentrations of <1 ng/mL. Through a novel mode of action three bispecific antibodies cross-linked adjacent spike proteins using dual NTD/RBD specificities. One bispecific antibody was >100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, six of nine bispecific antibodies neutralized B.1.1.7, B.1.351 and the wild-type virus with comparable potency, despite partial or complete loss of activity of at least one parent monoclonal antibody against B.1.351. Furthermore, a bispecific antibody that neutralized B.1.351 protected against SARS-CoV-2 expressing the crucial E484K mutation in the hamster model. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.

Workplace Violence Among Frontline Clinicians in Emergency Departments Amidst the COVID-19 Pandemic (preprint)

Background: Frontline clinicians working in the emergency department (ED) were at disportionate risk of workplace violence (WPV). This study investigated the prevalence of WPV and its association on quality of life (QOL) among this population in China during the COVID-19 pandemic.Results: The overall prevalence of WPV was 29.2% (95%CI: 26.5%-31.9%). Multiple logistic regression analysis revealed that having family/friends/colleagues infected with COVID-19 (OR=1.81, P=0.01), current smoking status (OR=3.24, P<0.01) and severity of anxiety symptoms (OR=1.13, P<0.01) were positively associated with WPV.  Working in inpatient ED units (OR=0.45, P<0.01) was negatively associated with WPV. After controlling for covariates, clinicians experiencing WPV had a lower overall QOL compared to those without (F (1, 1103) =14.2, P<0.01).Conclusions: Prevalence of workplace violence was common among ED clinicians in China during the COVID-19 pandemic. Considering the negative impact of WPV on QOL and care quality, timely preventive measures should be undertaken for ED clinicians.

The Effect of the Physical Fitness and Breathing Training Program in COVID-19 patients in Wuhan, China: prospective study (preprint)

Background Corona Virus Disease 2019 (COVID-19) has adverse effects on patients’ respiratory system. Therefore the pulmonary rehabilitation is particularly necessary for COVID-19 patients. A recent qualitative study indicated that patients perceived the impact of fatigue on their daily lives to be a key factor in decreasing their quality of life. This study aimed to investigate the knowledge and needs of physical fitness and breathing training, and to explore the impact of physical fitness and breathing training on COVID-19 patients. Methods From Feb 16, 2020 to Apr 6, 2020, a self-designed questionnaire was used to investigate the knowledge and needs of physical fitness and breathing training in COVID-19 inpatients. And then the participants received an intervention about physical fitness and breathing training which lasted 2 weeks. The 9-item Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) was used to measure COVID-19 related fatigue before and after the intervention. Findings According to a 5-point Likert scale, the 133 COVID-19 patients had only an "not really" and "uncertain" knowledge of physical fitness and breathing training (2.47±1.17). 86.98% of the patients expected to receive guidance of physical fitness and breathing training through video teaching. Differences were observed in fatigue, General fatigue component (15.0(8.0) vs. 19.0(10.0), P<0.01); Functional ability component (4.0 (3.0) vs. 7.0(4.0), P<0.01); Psychological component (6.0(5.0) vs.7.0 (5.0), P<0.01), after the intervention, Moderate degree (36.09% vs. 28.57%) alleviated to mild degree (51.12% vs. 66.91%). SpO2-% 86 ((75, 89) vs. 92(89, 98), P<0.001), and Oxygen flow-L/min (2(0,4) vs. 8(3,9), P<0.001). In our study, 130 healthcare professionals took part in this program. None of the participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARSCoV- 2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%).Interpretation COVID-19 patients had insufficient knowledge of physical fitness and breathing training for pulmonary rehabilitation. Patients should be guided to receive training, which can be benefit for patients.

Analysis of similarities and differences between coronavirus disease 2019 and severe acute respiratory syndrome

Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are epidemic, contagious, sudden, and publicly harmful diseases. The whole-genome nucleotide identity of the pathogens causing the two diseases reached 79.5%. The mechanism and treatment of COVID-19 are still under investigation. Combining the experiences of SARS prevention and treatment in 2003, and the case data and literature of COVID-19, the similarities and differences between the two diseases in terms of causes, susceptible people, characteristics, dialectical mode, and treatment were analyzed. The two diseases are both plagues in terms of Chinese medicine. The cause of SARS was 'heat poison,' and its pathogenesis was 'heat poison, stasis, and qi and yin deficiency.' Therefore the treatment regimen was mainly to clear away heat, detoxicate, and expel evil. While the cause of COVID-19 was 'wet poison,' and its pathogenesis was 'wet, poison, heat, stasis, close, syncope, and yang collapse.' Hence the basic treatment strategy was to declare lung and remove dampness. Treatment of COVID-19 was clearing away evil qi as soon as possible, with the basic treatment regimen, which was declaring lung, removing dampness, and dispelling the evil. Combined with Traditional Chinese medicine's (TCM's) understanding and experience in SARS prevention and treatment, and Chinese clinical cured cases, we try to provide strategies for people all over the world to understand and respond to COVID-19, through the analysis and comparison. To improve COVID-19 prevention and treatment regimen and give full play to the advantages of TCM.

Prevalence of depression and its impact on quality of life among frontline nurses in emergency departments during the COVID-19 outbreak.

BACKGROUND: Frontline medical staff exposed to the novel coronavirus disease (COVID-19) could be psychologically and mentally exhausted. This study examined the prevalence of depressive symptoms (depression hereafter) and their correlates and the association between depression and quality of life (QOL) in Emergency Department (ED) nurses during the COVID-19 pandemic in China. METHODS: This national, cross-sectional online survey was conducted between March 15 and March 20, 2020 in China. Depression and QOL were measured using the 9-item Patient Health Questionnaire, and the World Health Organization Quality of Life Questionnaire-Brief Version, respectively. RESULTS: The overall prevalence of depression in 1103 ED nurses was 43.61% (95% CI=40.68-46.54%). Multiple logistic regression analysis revealed that working in tertiary hospitals (OR=1.647, P=0.009), direct patient care of COVID-19 patients (OR=1.421, P=0.018), and current smokers (OR=3.843, P<0.001) were significantly associated with depression. After controlling for covariates, nurses with depression had an overall lower QOL compared to those without (F(1,1103)=423.83, P<0.001). CONCLUSION: Depression was common among ED nurses during the COVID-19 pandemic. Considering the negative impact of depression on quality of patient care and nurses' QOL, a heightened awareness of, and early treatment for depression for frontline ED nurses should be provided.

A Single-Center Retrospective and Descriptive Study of Hepatobiliary and Pancreatic Surgical Oncology during the COVID-19 Epidemic (preprint)

Objective: In the battle against COVID-19, most medical resources in China have been directed to infected patients in Wuhan. Thus, patients with hepatobiliary pancreatic tumors who are not suffering from COVID-19 are often not given timely and effective anti-cancer treatments. In this study, we aimed to describe clinical characteristics, treatment, and outcomes of patients with hepatobiliary and pancreatic oncology from our department, which retained normal working during the COVID-19 epidemic. We also sought to formulate a set of standardized hospitalization and treatment processes.Methods: A retrospective and descriptive study was conducted involving patients hospitalized from February 1, 2020, to February 29, 2020 (Return to work after the Spring Festival), at our Department of Hepatobiliary and Pancreatic Surgical Oncology. Results: The study included 92 patients from 12 provinces in the north of China who underwent surgical resection at our Department of Hepatobiliary and Pancreatic Surgical Oncology during the COVID-19 epidemic. Robotic surgery was performed on 82% (75/92) of patients, while the rest underwent laparoscopic (2/92) and open surgery (15/92). Eighty-six patients had malignant tumor, and six had emergency benign diseases. Only five patients had severe pancreatic fistula, and three had biliary fistula after operation. Conclusions: The standardized hospitalization and treatment processes described in this study could prevent cross-infection of patients and still ensure timely treatment of patients with hepatobiliary and pancreatic cancers. These study findings will guide the management of surgical oncology departments and treatment of patients with hepatobiliary and pancreatic oncology during serious epidemics.

Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients (preprint)

Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NF{kappa}B, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

Analysis of early chest high resolution CT images of novel coronavirus pneumonia / 中华放射学杂志

Objective@#To investigate the first chest HRCT imaging manifestations infected with novel coronavirus pneumonia (NCP).@*Method@#A retrospective analysis of the first chest HRCT images of 106 patients with NCP clinically diagnosed in our hospital from January 3 to 25, 2020. Lesion distribution, morphology and surrounding involvement were analyzed.@*Result@#Lesions were found in the first lung HRCT of 106 patients, with unilateral lung distribution in 11 cases (10.4%), bilateral lung distribution in 95 cases (89.6%), and peripheral distribution of lung in 65 cases (61.3%). 41 cases (38.7%) were distributed at the same time; 8 cases (7.5%) were 1 lesion, 5 cases (4.7%) were 2 lesions, 93 cases (87.8%) were multiple lesions, and 12 cases were nodular lesions (11.3%). 94 cases of ground-glass lesions (88.7%), 7 cases of cord-like lesions (6.6%), 15 cases (14.2%) of coexisting lesions of two or more forms; 10 cases (9.4%) involving one lung lobe There were 96 cases (90.6%) involving two or more lung lobes; 24 cases (22.6%) with enlarged mediastinal lymph nodes (19 cases over 60 years old, accounting for 79.2%); 3 cases with pleural effusion (2.8 %), 1 case had pericardial effusion (0.9%), and 2 cases had pleural involvement / thickening (1.9%). Patients over 60 years of age mostly present with multiple lesions, multiple morphology, peripheral and central distribution of lungs, involving multiple lung lobes, and enlarged mediastinal lymph nodes.@*Conclusions@#Lung lesions of NCP patients can be detected for the first time by chest HRCT, which is the preferred imaging method. Thoracic HRCT scans play an important role in the early diagnosis of new coronavirus (NCP). .