Understanding the risk of transmission of respiratory viral infections in childcare centres: protocol for the DISeases TrANsmission in ChildcarE (DISTANCE) multicentre cohort study.

INTRODUCTION: Childcare centre is considered a high-risk setting for transmission of respiratory viruses. Further evidence is needed to understand the risk of transmission in childcare centres. To this end, we established the DISeases TrANsmission in ChildcarE (DISTANCE) study to understand the interaction among contact patterns, detection of respiratory viruses from environment samples and transmission of viral infections in childcare centres. METHODS AND ANALYSIS: The DISTANCE study is a prospective cohort study in multiple childcare centres of Jiangsu Province, China. Study subjects will be childcare attendees and teaching staff of different grades. A range of information will be collected from the study subjects and participating childcare centres, including attendance, contact behaviours (collected by onsite observers), respiratory viral infection (weekly respiratory throat swabs tested by multiplex PCR), presence of respiratory viruses on touch surfaces of childcare centres and weekly follow-up survey on respiratory symptoms and healthcare seeking among subjects tested positive for any respiratory viruses. Detection patterns of respiratory viruses from study subjects and environment samples, contact patterns, and transmission risk will be analysed by developing statistical and mathematical models as appropriate. The study has been initiated in September 2022 in 1 childcare centre in Wuxi City, with a total of 104 children and 12 teaching staff included in the cohort; data collection and follow-up is ongoing. One more childcare centre in Nanjing City (anticipated to include 100 children and 10 teaching staff) will start recruitment in 2023. ETHICS AND DISSEMINATION: The study has received ethics approval from Nanjing Medical University Ethics Committee (No. 2022-936) and ethics approval from Wuxi Center for Disease Control and Prevention Ethics Committee (No. 2022-011). We plan to disseminate the study findings mainly through publications in peer-reviewed journals and presentations in academic conferences. Aggregated research data will be shared freely to researchers.

Higher SARS-CoV-2 shedding in exhaled aerosol probably contributed to the enhanced transmissibility of Omicron BA.5 subvariant.

The global pandemic of the BA.5 subvariant had moved from prediction to reality. In this study, we compared SARS-CoV-2 aerosol emissions from patients with BA.2 or BA.5 subvariant infection. First, patients with BA.2 subvariant infection had higher upper respiratory viral loads than patients with BA.5 subvariant infection. However, the average breath emission rate (BER) of patients with BA.5 subvariant infection, which represented the concentration of exhaled SARS-CoV-2 aerosols, was nearly 40 times higher than that of patients with BA.2 subvariant. Second, aerosols exhaled by patients with BA.5 subvariant infection exhibited SARS-CoV-2 RNA detection positive rate than patients with BA.1 or BA.2 subvariant infection. Meanwhile, for BA.5 subvariant infection, patients that exhaled infectious SARS-CoV-2 aerosols accounted for 14.8% of all patients. Third, since the onset of COVID-19, the SARS-CoV-2 RNA detection signals of throat swabs showed a gradual decline trend, although the decline process was accompanied by fluctuations. Overall, the monitoring of infectious SARS-CoV-2 aerosols may provide the data support for the transmissibility evaluation of the Omicron BA.5 subvariant. This article is protected by copyright. All rights reserved.

Emerging Omicron subvariants evade neutralizing immunity elicited by vaccine or BA.1/BA.2 infection.

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.75 and BA.2.76 subvariants contained 35 and 29 additional mutations in its spike (S) protein compared with the reference SARS-CoV-2 genome, respectively. Here, we measured the evasion degree of the BA.1, BA.2, BA.4, BA.5, BA.2.75, and BA.2.76 subvariants from neutralizing immunity in people previously infected with the Omicron BA.1 and BA.2, determined the effect of vaccination on immune evasion, and compared the titers of neutralizing antibodies in serums between acute infection and convalescence. Results showed that the neutralization effect of serums from patients with different vaccination statuses and BA.1/BA.2 breakthrough infection decreased with the Omicron evolution from BA.1 to BA.2, BA.4, BA.5, BA.2.75, and BA.2.76. This study also indicated that the existing vaccines could no longer provide effective protection, especially for the emerging BA.2.75 and BA.2.76 subvariants. Therefore, vaccines against emerging epidemic strains should be designed specifically. In the future, we can not only focus on the current strains, but also predict and design new vaccines against potential mutant strains. At the same time, we can combine the virus strains' infection characteristics to develop protective measures for virus colonization areas, such as nasal protection spray. Besides, further studies on the Y248N mutation of BA.2.76 subvariant were also necessary to explore its contribution to the enhanced immune evasion ability.

Visualization of the infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward.

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections.

A Novel Strategy for the Detection of SARS-CoV-2 Variants Based on Multiplex PCR-Mass Spectrometry Minisequencing Technology.

The objective of this study was to construct a novel strategy for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants using multiplex PCR-mass spectrometry minisequencing technique (mPCR-MS minisequencing). Using the nucleic acid sequence of a SARS-CoV-2 nonvariant and a synthetic SARS-CoV-2 variant-carrying plasmid, a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method based on the single-base mass probe extension of multiplex PCR amplification products was established to detect 9 mutation types in 7 mutated sites (HV6970del, N501Y, K417N, P681H, D614G, E484K, L452R, E484Q, and P681R) in the receptor-binding domain of the spike protein of SARS-CoV-2 variants. Twenty-one respiratory tract pathogens (9 bacteria and 12 respiratory viruses) and nucleic acid samples from non-COVID-19 patients were selected for specific validation. Twenty samples from COVID-19 patients were used to verify the accuracy of this method. The 9 mutation types could be detected simultaneously by triple PCR amplification coupled with MALDI-TOF MS. SARS-CoV-2 and six variants, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.429 (Epsilon), B.1.526 (Iota), P.1 (Gamma) and B.1.617.2 (Delta), could be identified. The detection limit for all 9 sites was 1.5 × 103 copies. The specificity of this method was 100%, and the accuracy of real-time PCR cycle threshold (CT) values less than 27 among positive samples was 100%. This method is open and extensible, and can be used in a high-throughput manner, easily allowing the addition of new mutation sites as needed to identify and track new SARS-CoV-2 variants as they emerge. mPCR-MS minisequencing provides a new detection option with practical application value for SARS-CoV-2 and its variant infection. IMPORTANCE The emergence of SARS-CoV-2 variants is the key factor in the second wave of the COVID-19 pandemic. An all-in-one SARS-CoV-2 variant identification method based on a multiplex PCR-mass spectrometry minisequencing system was developed in this study. Six SARS-CoV-2 variants (Alpha, Beta, Epsilon, Iota, Gamma, and Delta) can be identified simultaneously. This method can not only achieve the multisite simultaneous detection that cannot be realized by PCR coupled with first-generation sequencing technology and quantitative PCR (qPCR) technology but also avoid the shortcomings of time-consuming, high-cost, and high technical requirements of whole-genome sequencing technology. As a simple screening assay for monitoring the emergence and spread of SARS-CoV-2 and variants, mPCR-MS minisequencing is expected to play an important role in the detection and monitoring of SARS-CoV-2 infection as a supplementary technology.

Delays in routine childhood vaccinations and their relationship with parental vaccine hesitancy: a cross-sectional study in Wuxi, China.

OBJECTIVES: This study aimed to examine childhood vaccination delay, explore the association between vaccination delay and parental vaccine hesitancy, and assess childhood vaccination delays during the coronavirus disease (COVID)-19 pandemic in China. METHODS: This cross-sectional survey was conducted in Wuxi City. Participants were recruited from local vaccination clinics. Questionnaires were used to collect information about socio-demographics, vaccine hesitancy, and immunization clinic evaluations. Vaccination records were obtained from the Jiangsu Information Management System of Vaccination Cases. RESULTS: Overall, 2728 participants were included. The coverage for seven category A vaccines (Expanded Program on Immunization (EPI)) was more than 95% at 24 months. The proportion of children vaccinated in a timely manner was the highest for the first dose of the hepatitis B vaccine (91.6%) and the lowest for the Bacillus-Calmette-Guerin vaccine (44.6%). More than 50% of the planned vaccinations were delayed in February and March 2020. The Vaccine Hesitancy Scale scores were not associated with vaccination delay (P = 0.842). Children's vaccination delays were negatively associated with parents who reported convenient access to clinics and satisfaction with immunization services (P = 0.020, P = 0.045). CONCLUSIONS: EPI is highly successful in China. Despite vaccination delays due to the COVID-19 pandemic, coverage was recovered after lockdown restrictions were eased.

Persistence of Antibody and Cellular Immune Responses in Coronavirus Disease 2019 Patients Over Nine Months After Infection.

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.

Non-EPI Vaccine Hesitancy among Chinese Adults: A Cross-Sectional Study.

Vaccination against coronavirus disease 2019 (COVID-19) is paramount to curtailing the pandemic. However, the impact of the Non-Expanded Program on Immunization (non-EPI) and COVID-19 vaccine hesitancy on vaccine uptake among Chinese adults remain unclear. This study was an online survey performed in Eastern, Central, and Western China between February 2021 and March 2021 using proportional sampling (n = 7381). Adults aged ≥ 18 years were included, especially younger people (aged < 65). Vaccine hesitancy was assessed using the 3C model and relative scales; logistic regression was used to explore the factors affecting vaccination uptake; structural equation modeling was used to evaluate the correlations between variables. Overall, 67.6% and 24.7% of adults reported vaccine hesitancy toward the non-EPI and COVID-19 vaccines, respectively. Participants (66.3%) reported taking the vaccine mainly based on recommendations from medical staff. Vaccine-hesitant participants (60.5%) reported a fear of side effects as the deciding factor in vaccine rejection. Vaccine hesitancy interacted negatively with confidence (ß = -0.349, p < 0.001) and convenience (ß = -0.232, p < 0.001), and positively with complacence (ß = 0.838, p < 0.001). Nonmedical personnel, adults who had previously received the influenza vaccine, and older people had lower vaccine hesitancy than their counterparts. Most Chinese adults have non-EPI but not COVID-19 vaccine hesitancy. Vaccine safety remains a concern.

Transmission and prevention of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19), caused by a novel virus of the ß-coronavirus genus (SARS-CoV-2), has been spreading globally. As of July 2020, there have been more than 17 million cases worldwide. Determining multiple transmission routes of SARS-CoV-2 is critical to improving safety practices for the public and stemming the spread of SARS-CoV-2 effectively. This article mainly focuses on published studies on the transmission routes of SARS-CoV-2 including contact transmission, droplet transmission, aerosol transmission and fecal-oral transmission, as well as related research approaches, such as epidemiological investigations, environmental sampling in hospitals and laboratories and animal models. We also provide four specific recommendations for the prevention and control of SARS-CoV-2 that may help reduce the risk of SARS-CoV-2 infection under different environmental conditions. First, social distancing, rational use of face masks and respirators, eye protection, and hand disinfection for medical staff and the general public deserve further attention and promotion. Second, aerodynamic characteristics, such as size distribution, release regularity, aerosol diffusion, survival and decline, infectious dose and spread distance, still require further investigation in order to identify the transmissibility of COVID-19. Third, background monitoring of the distribution of pathogenic microorganisms and environmental disinfection in crowded public places, such as railway stations, schools, hospitals and other densely populated areas, can give early warning of outbreaks and curb the transmission routes of SARS-CoV-2 in those high-risk areas. Forth, establishing novel predictive models can help us to not only assess transmission and impacts in communities, but also better implement corresponding emergency response measures.

Characteristics and evaluation of the effectiveness of monitoring and control measures for the first 69 Patients with COVID-19 from 18 January 2020 to 2 March in Wuxi, China.

BACKGROUND: The Coronavirus disease (COVID-19) has caused 91,305 confirmed cases and 4746 deaths in China by 13:50 on October 11, 2020. We analyzed data on 69 infections in Wuxi to describe the disease's characteristics, to analyze factors of cases clinical outcome and to evaluate the prevention and control measures. METHODS: The demographic characteristics, exposure history, time indicators and propagation dynamics in Wuxi were collected. RESULTS: The clinical severity of cases was mostly mild and normal (75.36 %). Aging (relative risk [RR] = 1.04, 95 % confidence interval [CI]: 1.001-1.08) and fever (RR = 10.33, 95 %CI: 2.75-38.78) were risk factors for disease severity. The mean incubation period was estimated to be 4.77 days (95 % CI: 3.61-5.94), with a mean serial interval of 6.31 days (95 % CI: 5.12-7.50). The controlled reproduction number was estimated to be 1.12 (95 %CI: 0.71-1.69). CONCLUSIONS: The incidence of COVID-19 in Wuxi has turned into a lower level, suggesting the early prevention and control measures have achieved effectiveness. Aging and fever of initial symptom were risk factors for severe clinical outcome. The family clusters provided further clues of the risk factors for COVID-19 transmission.

Morphology and Molecular Characterization of a Fungus from the Alternaria alternataSpecies Complex Causing Black Spots on Pyrus sinkiangensis(Koerle pear)

A small-spored Alternariawas found from black spots of storaged Koerle pear (Pyrus sinkiangensis), one of the economically important fruit in Xinjiang province, China. The morphology is similar to A. limoniasperaebut obviously different in secondary conidiophores and conidial septa. A phylogenetic analysis using sequence datasets of ITS, GAPDH, TEF1, RPB2, Alt a1, OPA10–2, and EndoPG genes revealed that it belonged to the Alternaria alternatacomplex group. Pathogenicity tests illustrated that the fungus was the causal pathogen of black spot on Koerle pear fruit.

Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020.

To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.