Key mutations in the spike protein of SARS-CoV-2 affecting neutralization resistance and viral internalization.

To control the ongoing COVID-19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin-converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.

How to reduce the exposure risk of medical staff from SARS-CoV-2 by reducing environmental contamination: Experience from designated hospitals in China.

Background: Using daily monitoring of environmental surfaces and personal protective equipment (PPE), we found an increase in environmental contamination since August 18, 2021, in a designated hospital for COVID-19 patients in China, which may lead to an increased risk of exposure to medical staff. Methods: To investigate the cause of increased environmental contamination and effect of our intervention, we obtained environmental samples at pre-intervention (August 18-21, 2021) and post-intervention (August 22-28, 2021) from six infection isolation rooms with windows for ventilation and other auxiliary areas at 105 and 129 sites before routine daily cleaning, respectively. In addition, we obtained PPE samples from 98 medical staff exiting the patient rooms/contaminated areas at 482 sites. Between August 22 and 24, 2021, we took measures to reduce environmental contamination based on sampling and inspection results. Findings: At pre-intervention, the positivity rates for contamination of environmental surfaces and PPE samples were significantly higher for critical patients (37.21 and 27.86%, respectively) than severely ill patients (25.00 and 12.50%, respectively) and moderately ill patients (0.00 and 0.00%, respectively) (Pearson's Chi-square: χ2 = 15.560, p = 0.000; Fisher's exact test: χ2 = 9.358, p = 0.007). Therefore, we inferred that the source of contamination of environmental surfaces and PPE was mainly the room of critically ill patients, likely through the hands of medical staff to the potentially contaminated areas. A critically ill patient had emergency tracheal intubation and rescue on August 18, 2021, due to worsened patient condition. The ventilator tube used for first aid did not match the ventilator, and the ventilator tube fell off multiple times on August 18-21, 2021, which may explain the increased contamination of environmental surfaces and PPE from critically ill patients, as well as lead to indirect contamination of potentially contaminated areas. The contamination positivity rates of environmental surfaces and PPE were reduced by replacing the appropriate ventilator catheter, limiting the number of people entering the isolation room simultaneously, increasing the frequency of environmental disinfection, standardizing the undressing process, setting up undressing monitoring posts to supervise the undressing process, and preventing the spread of virus infections in the hospital during an epidemic. Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spread on object surfaces in isolation rooms mainly by touch, and the contamination of environmental surfaces and PPE was greater in rooms of patients with greater disease severity and higher surface touch frequency. Therefore, strict protective measures for medical staff, frequent environmental cleaning for isolation rooms, and compliance with mask wearing by patients when conditions permit should be advised to prevent SARS-CoV-2 spread in hospitals.

Development of a thermostable SARS-CoV-2 variant-based bivalent protein vaccine with cross-neutralizing potency against Omicron subvariants.

SARS-CoV-2 variants have posed significant challenges to the hopes of using ancestral strain-based vaccines to address the risk of breakthrough infection by variants. We designed and developed a bivalent vaccine based on SARS-CoV-2 Alpha and Beta variants (named SCTV01C). SCTV01C antigens were stable at 25 ^oC for at least 6 months. In the presence of a squalene-based oil-in-water adjuvant SCT-VA02B, SCTV01C showed significant protection efficacy against antigen-matched Beta variant, with favorable safety profiles in rodents. Notably, SCTV01C exhibited cross-neutralization capacity against Omicron subvariants (BA.1, BA.1.1, BA.2, BA.3, and BA.4/5) in mice, superior to a WT (D614G)-based vaccine, which reinforced our previously published findings that SCTV01C exhibited broad-spectrum neutralizing potencies against over a dozen pre-Omicron variants and the Omicron BA.1 variant. In summary, variant-based multivalent protein vaccine could be a platform approach to address the challenging issues of emerging variants, vaccine hesitancy and the needs of affordable and thermal stable vaccines.

Development of a thermostable SARS-CoV-2 variant-based bivalent protein vaccine with cross-neutralizing potency against Omicron subvariants

SARS-CoV-2 variants have posed significant challenges to the hopes of using ancestral strain-based vaccines to address the risk of breakthrough infection by variants. We designed and developed a bivalent vaccine based on SARS-CoV-2 Alpha and Beta variants (named SCTV01C). SCTV01C antigens were stable at 25 oC for at least 6 months. In the presence of a squalene-based oil-in-water adjuvant SCT-VA02B, SCTV01C showed significant protection efficacy against antigen-matched Beta variant, with favorable safety profiles in rodents. Notably, SCTV01C exhibited cross-neutralization capacity against Omicron subvariants (BA.1, BA.1.1, BA.2, BA.3, and BA.4/5) in mice, superior to a WT (D614G)-based vaccine, which reinforced our previously published findings that SCTV01C exhibited broad-spectrum neutralizing potencies against over a dozen pre-Omicron variants and the Omicron BA.1 variant. In summary, variant-based multivalent protein vaccine could be a platform approach to address the challenging issues of emerging variants, vaccine hesitancy and the needs of affordable and thermal stable vaccines.

Expert consensus on prevention and control of infection in makeshift hospitals

Makeshift hospitals have played an important role in responding to the spread of the epidemic caused by the Omicron coronavirus variant, one of the novel coronavirus(SARS-CoV-2) strains with significantly enhanced infectiousness. In order to prevent the patients, healthcare workers and other staff against from infection, Healthcare-associated Infection Management Committee of Chinese Hospital Association organized domestic experts to jointly formulate this consensus according to the comprehensive consideration of national guidelines as well as the actual characteristics and needs of makeshift hospitals. This consensus is mainly applicable for makeshift hospitals where a large number of asymptomatic and mild cases of novel coronavirus disease 2019(COVID-19) are treated. It provides guidance for the managers and staff to implement prevention and control work in line with local conditions in makeshift hospitals based on a perfect organizational structure and efficient working mechanism, the prevention and control work includes training and assessment of infection control knowledge and skills, flowing in and out of the makeshift hospitals for staff and materials, infection monitoring and feedback, implementation of infection prevention and control measures, requirements for infection management in key areas, occupational protection of staff and terminal disinfection, etc. Meanwhile, this consensus particularly emphasizes that the infection prevention and control in makeshift hospitals is a systematic project, which requires not only multi-system and multi-department collaboration, but also uniting in a concrete effort among leaders and staff. In accordance with the national guidelines and evidence-based experiences, it is very important to combine theory with practice for ensuring efficient operation and safety of makeshift hospitals.

Rational Development of a Polysaccharide–Protein-Conjugated Nanoparticle Vaccine Against SARS-CoV-2 Variants and Streptococcus pneumoniae (Adv. Mater. 21/2022)

Nanoparticle Vaccines In article number 2200443, Liangzhi Xie, Chengfeng Qin, and co-workers develop a novel bivalent nanoparticle vaccine that confers protection against infection of multiple SARS-CoV-2 variants and Streptococcus pneumoniae. This universal polysaccharide?protein-conjugated vaccine platform provides a powerful tool to fight against cocirculating viral and bacterial pathogens worldwide.

Neurological aspects of SARS-CoV-2 infection: lipoproteins and exosomes as Trojan horses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets lipid-producing cells for viral tropism. In this review, we connect systemic lipid couriers, particularly high-density lipoproteins (HDLs) and exosomes, with the neurological facets of SARS-CoV-2 infection. We discuss how SARS-CoV-2 preferentially targets lipid-secreting cells and usurps host cell lipid metabolism for efficient replication and systemic spreading. Besides providing natural veils for viral materials against host immunity, the inherent properties of some of these endogenous lipid particles to traverse the blood-brain barrier (BBB) also offer alternative routes for SARS-CoV-2 neurotropism. Importantly, virus-driven neurological aberrations mediated by HDLs and exosomes are fueled by lipid rafts, which are implicated in the production and transmigration of these lipid particles across the BBB. Finally, we discuss how repurposing existing drugs targeting lipid rafts and cholesterol homeostasis may be beneficial toward alleviating the global coronavirus disease 2019 (COVID-19) disease burden.

Rational Development of a Polysaccharide-Protein-Conjugated Nanoparticle Vaccine Against SARS-CoV-2 Variants and Streptococcus pneumoniae.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide. Streptococcus pneumoniae (S. pneumoniae) remains a major cause of mortality in underdeveloped countries. A vaccine that prevents both SARS-CoV-2 and S. pneumoniae infection represents a long-sought "magic bullet". Herein, a nanoparticle vaccine, termed SCTV01B, is rationally developed by using the capsular polysaccharide of S. pneumoniae serotype 14 (PPS14) as the backbone to conjugate with the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The final formulation of conjugated nanoparticles in the network structure exhibits high thermal stability. Immunization with SCTV01B induces potent humoral and Type 1/Type 2 T helper cell (Th1/Th2) cellular immune responses in mice, rats, and rhesus macaques. In particular, SCTV01B-immunized serum not only broadly cross-neutralizes all SARS-CoV-2 variants of concern (VOCs), including the most recent Omicron variant, but also shows high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. Finally, SCTV01B vaccination confers protection against challenges with the SARS-CoV-2 mouse-adapted strain and the original strain in established murine models. Collectively, these promising preclinical results support further clinical evaluation of SCTV01B, highlighting the potency of polysaccharide-RBD-conjugated nanoparticle vaccine platforms for the development of vaccines for COVID-19 and other infectious diseases.

Changes in Incidence of Notifiable Infectious Diseases in China Under the Prevention and Control Measures of COVID-19.

Aim: The aim of this study was to analyze the changes in incidence of notifiable infectious diseases in China under the prevention and control measures of COVID-19. Methods: Using descriptive epidemiological methods, data were collected from the official website of the Health Commission of the People's Republic of China, and the prevalence characteristics of notifiable infectious diseases in the country in 2020 were analyzed and compared with the historical data in 2019. Monthly reporting data on influenza and tuberculosis from 2015 to 2019 were also collected. Results: Except for COVID-19, the total number of notifiable infectious diseases cases in 2020 was 6,366,176, a decrease of 41.38% year-on-year compared with 2019. Category B and C notifiable infectious diseases decreased by 14.84 and 54.98% year-on-year, respectively (P < 0.01). The top three incidence rates were influenza (87.63 cases/100,000), hepatitis B (81.36 cases/100,000) and other infectious diarrhea (76.33 cases/100,000). Three types of diseases with the largest decline were influenza (-2,280,502 cases), hand-foot-mouth disease (-1,174,588 cases), and other infectious diarrhea diseases (-275,746 cases). Compared with 2019, respiratory infectious diseases were reported to be in the largest decline in 2020, followed by intestinal infectious diseases, blood-borne and sexually transmitted diseases, natural foci, and insect-borne infectious diseases. The monthly reported incidences of influenza and tuberculosis in 2020 were lower than the average of the previous 5 years. Conclusion: In 2020, the incidence of most notifiable infectious diseases in China showed a downward trend, non-pharmaceutical interventions (NPIs)such as the wearing of masks, frequent hand-washing, more ventilation, less gathering, etc, played an positive role in the prevention and control of respiratory and intestinal infectious diseases. The various public health intervention strategies and measures adopted by China to contain COVID-19 can provide a reference for the prevention and control of infectious diseases in other countries.

Mental health status among Chinese healthcare-associated infection control professionals during the outbreak of coronavirus disease 2019: A national cross-sectional survey.

ABSTRACT: Recently, the coronavirus disease 2019 (COVID-19) epidemic has greatly threatened global public health. The responsibility of healthcare-associated infection control professionals (ICPs) is to prevent and control the nosocomial infections. The mental health status of ICPs deserves more attention, however, the correlational research is still lacking. This study aims to investigate the incidence and risk factors of mental health status among ICPs in China during the outbreak of COVID-19.A national cross-sectional survey was performed. The online questionnaire was completed by 9228 ICPs from 3776 hospitals throughout China. Data collection tools were used, including demographics data questionnaire, the Chinese version of the 12-item general health questionnaire (GHQ-12) and the Chinese version of the psychological capital questionnaire (PCQ) for medical staff. Univariate and multivariable analyses were conducted.The total score of mental health of Chinese ICPs was 3.45 ±â€Š2.57. 5608 (60.77%) ICPs might have mental health problems. The psychological capital was in the upper-middle level with an average score of 3.72 ±â€Š0.38. An increased mental health problem risk was associated with the greater self-efficacy and working in the public hospital; a significantly lower risk was obtained by working in the second-class hospital rather than in the third-class hospitals. Besides, mental health problem risk of ICPs working in hospitals of the western economic region or northeast economic region was more significant than that in hospitals of the central economic region. However, a lower risk was caused by the unmarried than married, and working years in department ≤1 year contributed to the lower risk than that >20 years. Moreover, fewer working hours per week, higher values of hope, and optimism each were contributed to a lower risk.Chinese healthcare-associated ICPs were under different levels of mental health problems in fighting against COVID-19. More importantly, we should actively deal with the mental health problem of ICPs and help them get rid of psychological disorders.

Experimental study and reflection on peacetime and wartime reconstruction of large general hospitals in public health emergencies. / å¤§åž‹ç»¼åˆåŒ»é™¢åœ¨çªå‘å ¬å ±å«ç”Ÿäº‹ä»¶ä¸­å¹³æˆ˜ç»“åˆæ”¹å»ºå®žè¯ä¸Žåæ€.

To propose the architectural layout for the big general hospital in the face of public health emergencies, we analyzed the conditions, methods, problems and countermeasures for the reconstruction of the isolation ward from the existing medical building layout of a general hospital. The affected areas met the requirements of isolation ward in the reconstruction, and realized the corresponding partition and separation of people. But the cost of occupying the medical room should be concerned. General hospital should be alerted to potential risks of public health emergencies. The characteristics of different construction types, defects, and the function of the hospital should be considered in the construction, rebuilding, and expansion of the hospital, which shouldnot only meet the needs of the development of the hospital daily usage but also consider dealing with emergent public health events. We can adopt the reasonable layout, including setting up a firewall-like device between the channel and the floor, an ordinary ward at ordinary times, and an independent space for emergency by pulling down the gate. This strategy can not only avoid the problem of low utilization rate of the space occupied by the corresponding area in the ward for diseases spread by air and droplets, maximizing the efficiency of the medical site, but also avoid the problem of emergency response to the temporary reconstruction.

BioAider: An efficient tool for viral genome analysis and its application in tracing SARS-CoV-2 transmission.

The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. Control of COVID-19 pandemic is vital for public health and is the prerequisite to maintain social stability. However, the origin and transmission route of SARS-CoV-2 is unclear, bringing huge difficult to virus control. Monitoring viral variation and screening functional mutation sites are crucial for prevention and control of infectious diseases. In this study, we developed a user-friendly software, named BioAider, for quick sequence annotation and mutation analysis on large-scale genome-sequencing data. Herein, we detected 14 substitution hotspots within 3,240 SARS-CoV-2 genome sequences, including 3 groups of potentially linked substitution. NSP13-Y541C was crucial substitution which might affect the unwinding activity of the viral helicase. In particular, we discovered a SR-rich region of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SSRX repeat fragments in SARS-CoV-2 provided further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of viral genome mutations which could facilitate viral genomic studies. Using this tool, we have found critical clues for the transmission route of SARS-CoV-2 which would provide theoretical support for the epidemic control of pathogenic coronaviruses.

Evaluation of the exposure risk of SARS-CoV-2 in different hospital environment.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant impact on social and economic activities. As a high infectious pathogen, the existence of SARS-CoV-2 in public space is very important for its transmission. During the COVID-19 pandemic, hospitals are the main places to deal with the diseases. In this work, we evaluated the exposure risk of SARS-CoV-2 in hospital environment in order to protect healthcare workers (HCWs). Briefly, air and surface samples from 6 different sites of 3 hospitals with different protection levels were collected and tested for the SARS-CoV-2 nucleic acid by reverse transcription real-time fluorescence PCR method during the COVID-19 epidemic. We found that the positive rate of SARS-CoV-2 nucleic acid was 7.7 % in a COVID-19 respiratory investigation wards and 82.6 % in a ICUs with confirmed COVID-19 patients. These results indicated that in some wards of the hospital, such as ICUs occupied by COVID-19 patients, the nucleic acid of SARS-CoV-2 existed in the air and surface, which indicates the potential occupational exposure risk of HCWs. This study has clarified retention of SARS-CoV-2 in different sites of hospital, suggesting that it is necessary to monitor and disinfect the SARS-CoV-2 in hospital environment during COVID-19 pandemic, and will help to prevent the iatrogenic infection and nosocomial transmission of SARS-CoV-2 and to better protect the HCWs.