Nervous system manifestations related to COVID-19 and their possible mechanisms.

In December 2019, the novel coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection broke. With the gradual deepening understanding of SARS-CoV-2 and COVID-19, researchers and clinicians noticed that this disease is closely related to the nervous system and has complex effects on the central nervous system (CNS) and peripheral nervous system (PNS). In this review, we summarize the effects and mechanisms of SARS-CoV-2 on the nervous system, including the pathways of invasion, direct and indirect effects, and associated neuropsychiatric diseases, to deepen our knowledge and understanding of the relationship between COVID-19 and the nervous system.

Efficacy and Safety of a Booster Vaccination with Two Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: Results of a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial in Abu Dhabi.

IMPORTANCE: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. OBJECTIVE: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. DESIGN: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. SETTING: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. PARTICIPANTS: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. INTERVENTIONS: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5µg and 4µg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. RESULTS: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2-13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2-11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9-63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2-87.8%) for WIV04 and 86.3% (95% CI, 79.6-91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). CONCLUSIONS AND RELEVANCE: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT04510207).

Parental Attitudes Towards Vaccination Against COVID-19 in China During Pandemic.

Purpose: The Chinese government has authorized the emergency use of an inactivated vaccine for COVID-19 in children and adolescents aged 3 to 17 years. This study aimed to investigate parents' attitudes towards vaccinating their children against COVID-19 and influencing factors. Patients and Methods: Through an online questionnaire survey, we collected self-reported children's demographic characteristics, physical conditions and parents' attitudes towards COVID-19 vaccination for children. The parents in the unwilling group received online consultation about the benefits and risks of COVID-19 vaccine and were asked to complete the questionnaire again. Results: A total of 868 participants were recruited from July 2021 to August 2021 in Nanjing, China. Overall, 76.0% of parents were willing to accept vaccination for children. Parents' willingness increased with children's age (P=0.018) and height (P=0.034), but decreased if the children fell sick within previous one month (P=0.030). Most of the unwilling parents gave a higher score to the risk of vaccination (53.76 VS 40.18). Unsafety (63.8%) and unfamiliarity (24.0%) were their major concerns. After consultation with a health worker, 24% of the unwilling parents turned willing. Conclusion: Children's age and recent physical condition are related to parents' attitudes towards vaccination for children against COVID-19. The major concerns of parents are unsafety and unfamiliarity. Parents view health workers as a reliable source of vaccine information. A successful consultation with health workers to understand the benefits and risks of vaccination can increase parents' willingness. This study provides insight into parents' attitudes towards vaccination for children against COVID-19 in China and related influencing factors. Our findings could be referenced in establishing policies for vaccinating children against COVID-19 in China.

Proteomic Analysis of Human Milk Reveals Nutritional and Immune Benefits in the Colostrum from Mothers with COVID-19.

Despite the well-known benefits of breastfeeding and the World Health Organization's breastfeeding recommendations for COVID-19 infected mothers, whether these mothers should be encouraged to breastfeed is under debate due to concern about the risk of virus transmission and lack of evidence of breastmilk's protective effects against the virus. Here, we provide a molecular basis for the breastfeeding recommendation through mass spectrometry (MS)-based proteomics and glycosylation analysis of immune-related proteins in both colostrum and mature breastmilk collected from COVID-19 patients and healthy donors. The total protein amounts in the COVID-19 colostrum group were significantly higher than in the control group. While casein proteins in COVID-19 colostrum exhibited significantly lower abundances, immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, were upregulated. These proteins were detected with unique site-specific glycan structures and improved glycosylation diversity that are beneficial for recognizing epitopes and blocking viral entry. Such adaptive differences in milk from COVID-19 mothers tended to fade in mature milk from the same mothers one month postpartum. These results suggest that feeding infants colostrum from COVID-19 mothers confers both nutritional and immune benefits, and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.

Proteomic Analysis of Human Milk Reveals Nutritional and Immune Benefits in the Colostrum from Mothers with COVID-19

Despite the well-known benefits of breastfeeding and the World Health Organization's breastfeeding recommendations for COVID-19 infected mothers, whether these mothers should be encouraged to breastfeed is under debate due to concern about the risk of virus transmission and lack of evidence of breastmilk's protective effects against the virus. Here, we provide a molecular basis for the breastfeeding recommendation through mass spectrometry (MS)-based proteomics and glycosylation analysis of immune-related proteins in both colostrum and mature breastmilk collected from COVID-19 patients and healthy donors. The total protein amounts in the COVID-19 colostrum group were significantly higher than in the control group. While casein proteins in COVID-19 colostrum exhibited significantly lower abundances, immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, were upregulated. These proteins were detected with unique site-specific glycan structures and improved glycosylation diversity that are beneficial for recognizing epitopes and blocking viral entry. Such adaptive differences in milk from COVID-19 mothers tended to fade in mature milk from the same mothers one month postpartum. These results suggest that feeding infants colostrum from COVID-19 mothers confers both nutritional and immune benefits, and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.

Transparent Polyurethane Coating with Synergistically Enhanced Antibacterial Mechanism Composed of Low Surface Free Energy and Biocide

Recently, antibacterial coatings have gained great attention after the outbreak of COVID-19, thus durable transparent polyurethane (PU) coatings with anti-bacterial and anti-fingerprint performances are highly desired. In this work, the low surface free energy enables the hydroxyl-terminated polysiloxanes modified with quaternary ammonium salts (PQMS) enriched on the surface. The optimal PU-PQMS-40% coating with the thickness of 15 μm displayed 96% light transmittance and can be adopted to diverse substrates. This resultant coating exhibits excellent antibacterial activity against Gram-negative E. coli (99.2%) and Gram-positive S. aureus (98.6%) because of the synergistically enhanced antibacterial mechanism of both low surface free energy (27.54 ± 0.75 mJ·m−2) and quaternary ammonium salts (QAs). It is noteworthy that this antibacterial PU coating is capable of retaining its properties even after being subjected to 210 cycles of abrasion tests, manifesting a superior self-renewability. This coating system with combined features of transparency, antibacterial performance, chemical resistance, and durability make it a promising candidate for applications in the fields of electronic devices, automobile interiors, intelligent glass, and marine antifouling.

Low tricuspid annular plane systolic excursion is associated with a poor outcome in patients with COVID-19: A systematic review and meta-analysis.

ABSTRACT: Background: This systematic review and meta-analysis aimed to assess whether tricuspid annular plane systolic excursion (TAPSE) could be used as a prognostic tool in patients with coronavirus disease 19 (COVID-19). METHODS: Studies on the relationship between TAPSE and COVID-19 since February 2021. Standardized mean difference (SMD) and 95% confidence intervals were used to assess the effect size. The potential for publication bias was assessed using a contour-enhanced funnel plot and Egger test. A meta-regression was performed to assess if the difference in TAPSE between survivors and nonsurvivors was affected by age, sex, hypertension or diabetes. RESULTS: Sixteen studies comprising 1579 patients were included in this meta-analysis. TAPSE was lower in nonsurvivors (SMD -3.24 (-4.23, -2.26), P < .00001; I2 = 71%), and a subgroup analysis indicated that TAPSE was also lower in critically ill patients (SMD -3.85 (-5.31, -2.38,), P < .00001; I2 = 46%). Heterogeneity was also significantly reduced, I2 < 50%. Pooled results showed that patients who developed right ventricular dysfunction had lower TAPSE (SMD -5.87 (-7.81, -3.92), P = .004; I2 = 82%). There was no statistically significant difference in the TAPSE of patients who sustained a cardiac injury vs those who did not (SMD -1.36 (-3.98, 1.26), P = .31; I2 = 88%). No significant publication bias was detected (P = .8147) but the heterogeneity of the included studies was significant. A meta-regression showed that heterogeneity was significantly greater when the incidence of hypertension was <50% (I2 = 91%) and that of diabetes was <30% (I2 = 85%). CONCLUSION: Low TAPSE levels are associated with poor COVID-19 disease outcomes. TAPSE levels are modulated by disease severity, and their prognostic utility may be skewed by pre-existing patient comorbidities. TRIAL RETROSPECTIVELY REGISTERED FEBRUARY ,: PROSPERO CRD42021236731.

Current status of prevention and control of COVID-19 epidemic in elderly care institutions in Jiangsu Province

OBJECTIVE: To investigate the current status of prevention and control of COVID-19 epidemic and health status of elderly care institutions in Jiangsu Province so as to provide basis for better implementing the state's work deployment on the COVID-19 epidemic and improving the health status and disinfection quality of elderly care institutions. METHODS: From Oct 2020 to Dec 2020, a survey was conducted for the elderly care institutions in Jiangsu Province by using self-designed survey plans and questionnaires, the results of the survey were collected and summarized by "Questionnaire Star" platform, and statistical analysis was performed by using SPSS 23.0 software. RESULTS: The proportions of provision of anti-epidemic materials, indoor ventilation, environmental cleaning and disinfection, and staff's wearing masks were relatively high in 93 elderly care institutions, there was significant difference in the provision rate of hand-washing disinfectants between the medical treatment integrated care institutions and the non-medical treatment integrated care institutions (P < 0.05), there were no significant differences in other survey items.In terms of health monitoring, 719 samples were collected from environmental object surfaces for test of new coronavirus nucleic acid, and all of the results were negative;the average qualified rate of 1750 samples that were collected from air, object surfaces, tableware and staff' hands was 75.09%, the qualified rate of the tableware was the lowest, and there was significant difference in the qualified rate between the health care doctors' hands and the cleaning staff's hands (P < 0.05). There was significant difference in the qualified rate of air between the medical treatment integrated care institutions and the non-medical treatment integrated care institutions (P < 0.05), while there were no significant differences in the qualified rates of object surfaces, tableware and working staff' hands. CONCLUSION: In accordance with the requirements of the "Notice on Printing and Distributing the Technical Guidelines for the Prevention and Control of New Coronary Pneumonia Epidemic Prevention and Control in Key Units and Key Populations in Key Places", the implementation of state-issued notices needs to be strengthened in the elderly care institutions in Jiangsu Province and the environmental sanitation needs to be improved, it is suggested that the supervision and management of the environment should be strengthened in the elderly care institutions, and disinfection-related national standards and norms for elderly care institutions should be introduced as early as possible.

Chinese Parent Intention to Vaccinate Children With Special Diseases Against COVID-19.

Background: Information on the intention of parents of children with special diseases to vaccinate their children against coronavirus disease 2019 (COVID-19) is scarce. Methods: In this survey, all participants (n = 914) were enrolled from a tertiary children's hospital between September 2020 and April 2021. A face-to-face questionnaire interview was conducted to collect information on the special diseases of children and parental attitudes about the COVID-19 vaccine. We compared the demographic and disease factors between the group of parents who were willing to vaccinate their children against COVID-19 and the group who were unwilling to vaccinate. Results: Among 941 children, 58.1% (n = 547) were boys. The Mean age was 1.4 (SD 1.9) years. If the COVID-19 vaccine becomes available for the child, 470 (49.9%) of parents were willing to provide vaccination for their children. The less the education levels of the father or mother, the more likely they were to vaccinate their children (P = 0.003, P = 0.007). However, more intentions to vaccinate were provided in parents of children with COVID-19 prevention and control education (P < 0.001). Conclusion: Our findings provided evidence that some parents are willing to vaccinate their children with special diseases against COVID-19. Professional knowledge about COVID-19 prevention and control may contribute to increased parental intention.

Controlled Ovarian Hyperstimulation Protocol in Infertile Patients During the COVID-19 Pandemic.

Objectives: To explore the appropriate controlled ovarian hyperstimulation (COH) protocols in infertility patients who received the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments during the COVID-19 pandemic. Materials and Methods: This retrospective cohort study evaluated the efficiency of the early follicular-phase long-acting GnRH-agonist long (EFLL) protocol (a new protocol developed by Chinese clinicians), prolonged pituitary down-regulation of EFLL protocol (Pro-EFLL), and the GnRH-ant protocol for couples meeting the study criteria between February 2020 and June 2020 who were treated by the First Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic, and compared the pregnancy rates and miscarriage rates per fresh transfer cycle, number of retrieved oocytes, endometrial thickness on the day of hCG injection and the number of fertilized oocytes, mature oocytes, fertilized oocytes, and transferable embryos among the three protocols. Results: We found that the prolonged pituitary down-regulation during the COVID-19 pandemic by utilizing a full-dose of GnRH-a administrated in infertility patients were no differences in clinical outcomes than other protocols, The prolonged pituitary down-regulation protocol and EFLL protocol were associated with a higher Endometrial thickness on the day of hCG injection (12.67 ± 2.21 vs. 12.09 ± 2.35 vs. 10.79 ± 2.38, P < 0.001), retrieved oocytes (14.49 ± 6.30 vs. 15.02 ± 7.93 vs. 10.06 ± 7.63, P < 0.001), mature oocytes (11.60 ± 5.71 vs. 11.96 ± 6.00 vs. 7.63 ± 6.50, P < 0.001), fertilized oocytes (9.14 ± 5.43 vs. 8.44 ± 5.34 vs. 5.42 ± 5.20, P < 0.001), and transferable embryos (4.87 ± 2.96 vs. 6.47 ± 5.12 vs. 3.00 ± 3.28 vs. P < 0.001) in the GnRH-antagonist protocol. Conclusion: We recommend that patients start Gn injections 33-42 days after a pituitary downregulated full dose (3.75 mg) of gonadotropin-releasing hormone agonist during the COVID-19 pandemic, even a delay of 2-4 weeks does not affect the implantation rate. The study can provide a more detailed estimate and clinical management strategies for infertile couples during the COVID-19 pandemic.

Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Inflammatory Response and Viral Clearance in COVID-19 Patients.

Objectives: To evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the inflammatory response and viral clearance in coronavirus disease 2019 (COVID-19) patients. Methods: We included 229 patients with confirmed COVID-19 in a multicenter, retrospective cohort study. Propensity score matching at a ratio of 1:3 was introduced to eliminate potential confounders. Patients were assigned to the ACEI/ARB group (n = 38) or control group (n = 114) according to whether they were current users of medication. Results: Compared to the control group, patients in the ACEI/ARB group had lower levels of plasma IL-1ß [(6.20 ± 0.38) vs. (9.30 ± 0.31) pg/ml, P = 0.020], IL-6 [(31.86 ± 4.07) vs. (48.47 ± 3.11) pg/ml, P = 0.041], IL-8 [(34.66 ± 1.90) vs. (47.93 ± 1.21) pg/ml, P = 0.027], and TNF-α [(6.11 ± 0.88) vs. (12.73 ± 0.26) pg/ml, P < 0.01]. Current users of ACEIs/ARBs seemed to have a higher rate of vasoconstrictive agents (20 vs. 6%, P < 0.01) than the control group. Decreased lymphocyte counts [(0.76 ± 0.31) vs. (1.01 ± 0.45)*109/L, P = 0.027] and elevated plasma levels of IL-10 [(9.91 ± 0.42) vs. (5.26 ± 0.21) pg/ml, P = 0.012] were also important discoveries in the ACEI/ARB group. Patients in the ACEI/ARB group had a prolonged duration of viral shedding [(24 ± 5) vs. (18 ± 5) days, P = 0.034] and increased length of hospitalization [(24 ± 11) vs. (15 ± 7) days, P < 0.01]. These trends were similar in patients with hypertension. Conclusions: Our findings did not provide evidence for a significant association between ACEI/ARB treatment and COVID-19 mortality. ACEIs/ARBs might decrease proinflammatory cytokines, but antiviral treatment should be enforced, and hemodynamics should be monitored closely. Since the limited influence on the ACEI/ARB treatment, they should not be withdrawn if there was no formal contraindication.

Potential mechanism analysis of respiratory system treated by Tankejing based on network pharmacology

Objective: To study the potential mechanism of Tankejing in the treatment of respiratory system based on network pharmacology, and to evaluate the possibility of Tankejing in the prevention and treatment of COVID-19 pneumonia.

Coordination and Cooperation are Essential: A Call for a Global Network to Enhance Integrated Human Health Risk Resilience Based on China’s COVID-19 Pandemic Coping Practice

More than a year after its appearance and still rampant around the world, the COVID-19 pandemic has highlighted tragically how poorly the world is prepared to handle systemic risks in an increasingly hyper-connected global social-ecological system. The absence or clear inadequacy of global governance arrangements and mechanisms is painfully distinct and obvious. In this short article, we summarize a set of COVID-19 pandemic-related analyses and lessons that are inspired by Chinese practice. First, strong government response is one of the most important methods to control a pandemic. Second, countries should be concerned about human-to-frozen goods-to-human transmission. Third, sharing resources and experiences through cooperation is crucial to ensure an adequate health response. Based on these insights, we stress the critical importance of coordination and cooperation, and call for a global network to enhance integrated human health risk resilience.

A safety consideration of mesenchymal stem cell therapy on COVID-19.

Due to the multi-potential differentiation and immunomodulatory function, mesenchymal stem cells (MSCs) have been widely used in the therapy of chronic and autoimmune diseases. Recently, the novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency but no effective drug is available to date. Several studies investigated MSCs therapy for COVID-19 patients. However, it remains unclear whether MSCs could be the host cells of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) and whether they might affect the SARS-CoV-2 entry into other cells. Here, we report that human MSCs barely express ACE2 and TMPRSS2, two receptors required for the virus endocytosis, indicating that MSCs are free from SARS-CoV-2 infection. Furthermore, we observed that MSCs were unable to induce the expression of ACE2 and TMPRSS2 in epithelial cells and macrophages. Importantly, under different inflammatory challenge conditions, implanted human MSCs failed to up-regulate the expression of ACE2 and TMPRSS2 in the lung tissues of mice. Intriguingly, we showed that a SARS-CoV-2 pseudovirus failed to infect MSCs and co-cultured MSCs did not increase the risk of SARS-CoV-2 pseudovirus infection in epithelial cells. All these results suggest that human MSCs have no risk of assisting SARS-CoV-2 infection and the use of MSCs as the therapy for COVID-19 patients is feasible and safe.

Feasibility of Shengmai powder in convalescent patients with novel coronavirus pneumonia

As the number of discharged patients with novel coronavirus pneumonia (COVID-19) increased, TCM treatment received more attention. Some COVID-19 diagnosis and treatment plans issued by national health commission and local government recorded the syndrome differentiation and classification of TCM in the convalescent period and the treatment prescriptions. The clinical characteristics and TCM classification of convalescent period were also reported in recent literatures. Deficiency of Qi and Yin is the main syndrome in recovery period, and the Shengmai Powder (SMS) is the representative prescription. This paper reviews the studies of SMS in the treatment of deficiency of Qi and Yin, pulmonary fibrosis and vascular endothelial cell injury. The feasibility of SMS for the discharged patients with COVID-19 was discussed. This review will provide reference for clinical doctors and patients in the recovery period of TCM treatment.

Acute Kidney Injury in Patients with the Coronavirus Disease 2019: A Multicenter Study.

INTRODUCTION: Severe acute respiratory viral infections are frequency accompanied by multiple organ dysfunction, including acute kidney injury (AKI). In December 2019, the coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, Hubei Province, China, and rapidly spread worldwide. While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described. We assessed the incidence and clinical characteristics of AKI in patients with laboratory-confirmed COVID-19 and its effects on clinical outcomes. METHODS: We conducted a multicenter, retrospective, observational study of patients with COVID-19 admitted to two general hospitals in Wuhan from 5 January 2020 to 21 March 2020. Demographic data and information on organ dysfunction were collected daily. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 72 h after admission or after 72 h, respectively. RESULTS: Of the 116 patients, AKI developed in 21 (18.1%) patients. Among them, early and late AKI were found in 13 (11.2%) and 8 (6.9%) patients, respectively. Compared with patients without AKI, patients with AKI had more severe organ dysfunction, as indicated by a higher level of disease severity status, higher sequential organ failure assessment (SOFA) score on admission, an increased prevalence of shock, and a higher level of respiratory support. Patients with AKI had a higher SOFA score on admission (4.5 ± 2.1 vs. 2.8 ± 1.4, OR 1.498, 95% CI 1.047-2.143 ) and greater hospital mortality (57.1% vs. 12.6%, OR 3.998, 95% CI 1.088-14.613) than patients without AKI in both the univariate and multivariate analyses. Patients with late AKI, but not those with early AKI, had a significantly prolonged length of stay (19.6 vs. 9.6 days, p = 0.015). CONCLUSION: Our findings show that admission SOFA score was an independent risk factor for AKI in COVID-19 patients, and patients with AKI had higher in-hospital mortality. Moreover, AKI development after 72 h of admission was related to prolonged hospitalization time.