Enabling accurate and early detection of recently emerged SARS-CoV-2 variants of concern in wastewater.

As clinical testing declines, wastewater monitoring can provide crucial surveillance on the emergence of SARS-CoV-2 variant of concerns (VoCs) in communities. In this paper we present QuaID, a novel bioinformatics tool for VoC detection based on quasi-unique mutations. The benefits of QuaID are three-fold: (i) provides up to 3-week earlier VoC detection, (ii) accurate VoC detection (>95% precision on simulated benchmarks), and (iii) leverages all mutational signatures (including insertions & deletions).

Expert consensus on prevention and control of infection in COVID-19 designated hospitals

OBJECTIVE: To further standardize and guide the infection prevention and control(IPC) in designated hospitals so as to effectively ensure the stability, order and safety of medical treatment, ensure the safety of health care workers and patients, and reduce cross infections caused by the transmission of COVID-19. METHODS: The experts who repeatedly participated in the national COVID-19 medical treatment and IPC were invited to compile the consensus based on latest national norms, characteristics of the omicron and situation of epidemic prevention and control. RESULTS: The consensus consisted of two major parts: comprehensive coverage and control of infections in designated hospitals, with 47 recommendations involved. CONCLUSION: The expert consensus will provide guidance for the upcoming prevention and control of infection in designated hospitals.

Strategies and practice for prevention and control of infections in medical institutions due to COVID-19 epidemic

OBJECTIVE: To explore the key points of infection prevention and control in the transition process and early stage of closure of medical institutions that have been transferred to closed due to the outbreak of COVID-19. METHODS: Based on the national technical guidelines for the prevention and control of COVID-19 and relevant documents, combined with the experience of participating in the prevention and control of COVID-19 in various places, the author explored and analyzed the common problems and the key points of infection prevention and control during the transition to close management and the initial period of closure due to the COVID-19 epidemic. RESULTS: Hospitals transferred to closed-off management due to the outbreak of COVID-19 often encountered problems such as incompatibility of the original management system, lack of awareness of secondary control, and insufficient knowledge and skills. When transferred to closed management, epidemiological investigations should be actively carried out, management and control should be graded and classified, and various personnel in the hospital should be arranged reasonably. Infection prevention and control work should be quickly transferred into an anti-epidemic state. On the basis of meeting the needs of infection prevention and control, hospital reconstruction and air-condition use assessment should be carried out quickly, and attention should be paid to the infection risk prevention and control of personnel and treatment behaviors in the process of diagnosis and treatment. At the same time, it is necessary to pay attention to continuous infection risk monitoring, and achieve necessary terminal disinfection. CONCLUSION: When medical institutions are transferred to closed-off management due to the outbreak of COVID-19, the risk of infection prevention and control involved in the process of functional transformation should be fully considered to prepare for the COVID-19 outbreak actively, and to accumulate experience in preventing possible future infectious diseases transmitted through the respiratory tract.

Cyclophilin D-mediated angiotensin II-induced NADPH oxidase 4 activation in endothelial mitochondrial dysfunction that can be rescued by gallic acid.

Vascular endothelial dysfunction plays a central role in the most dreadful human diseases, including stroke, tumor metastasis, and the coronavirus disease 2019 (COVID-19). Strong evidence suggests that angiotensin II (Ang II)-induced mitochondrial dysfunction is essential for endothelial dysfunction pathogenesis. However, the precise molecular mechanisms remain obscure. Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2 and NADPH oxidase 4 (NOX 4) expression treated by Ang II. Interestingly, we first found that Ang II-induced NOX 4 binds with Poldip 2 was dependent on cyclophilin D (CypD). CypD knockdown (KD) significantly inhibited the binding of NOX 4 to Poldip 2, and mitochondrial ROS generation in human umbilical vein endothelial cells (HUVECs). Similar results were also found in cyclosporin A (CsA) treated HUVECs. Our previous study suggested a crosstalk between extracellular regulated protein kinase (ERK) phosphorylation and CypD expression, and gallic acid (GA) inhibited mitochondrial dysfunction in neurons depending on regulating the ERK-CypD axis. Here, we confirmed that GA inhibited Ang II-induced NOX 4 activation and mitochondrial dysfunction via ERK/CypD/NOX 4/Poldip 2 pathway, which provide novel mechanistic insight into CypD act as a key regulator of the NOX 4/Poldip 2 axis in Ang II-induced endothelial mitochondrial dysfunction and GA might be beneficial in the treatment of wide variety of diseases, such as COVID-19, which is worthy further research.

Mechanisms and strategies for operation of fever clinics in a general hospital during prevention and control of COVID-19

OBJECTIVE: To explore the mechanisms and strategies for operation of fever clinics of a general hospital during prevention and control of COVID-19. METHODS: The working characteristics and management modes of the fever clinic of the First Medical Center of Chinese PLA General Hospital were analyzed and summarized during the period of normalized prevention and control without cases and the period with local outbreak. RESULTS: During the period of normalized prevention and control, strict pre-job admission was carried out, the new recruits must pass the qualification test for special positions, the daily training was intensified, the treatment procedures were optimized, the step of identification of infectious diseases was moved forward to the triage;the closed-loop management of information was improved, the links such as identification of infectious diseases, treatment warning, prewarning and reporting have been achieved, and the standard prevention measures were taken. During the period of local outbreak, the application for demand of personnel and prevention supplies was put forward, fever clinic was designed and expanded, supporting personnel was trained, shifts were reasonably arranged, supervisors were added, and 24-hour logistic shifts wee also added. Zero infection of health care workers and zero case of nosocomial infection were achieved during the prevention and control of epidemic. CONCLUSION: The fever clinic is an outpost of prevention and control of infectious diseases. Combined with the characteristics, it is recommended that the construction of departments, personnel management and hardware configuration should be solidified and promoted.

Research progress on the application of antiseptics after mucosal exposure of SARS-CoV-2

The transmission routes of SARS-CoV-2 include droplet, air and contact transmission, but regardless of the transmission route, the virus must eventually be exposed through the oral, nasal and ocular mucous membranes to invade the human body. Guaranteeing the respiratory protection of front-line medical staff in the prevention and control of COVID-19 is one of the primary tasks of nosocomial infection management. According to "Technical Guidelines for Prevention and Control of COVID-19 in Healthcare Settings (3rd Edition)", oral/nasal cavity can be disinfected with hydrogen peroxide, iodophor, in the event of occupational respiratory exposure. But, at the moment, In the field of nosocomial management, compared with hand hygiene, "mucosal hygiene" is rarely mentioned, especially the treatment of respiratory mucosa after exposure to acute infectious respiratory pathogens, which is still blank in the domestic research. After a rapid literature review, it is found that some antiseptics have been widely used in clinical practices, such as gargling with bactericidal solution before the diagnosis and treatment procedure for dental patients under COVID-19 epidemic, nasal decolonization for patients undergoing elective surgery to prevent surgical site infection, and use of eye drops of antiseptics to prevent neonatal conjunctivitis. In view of the current lack of effective antiviral drugs for treatment of SARS-CoV-2, and the constantly emerging mutant strains can break through the immune barrier of human body, this paper recommends that medical personnel use antiseptics for emergency mucosal disinfection as an supporting measure for respiratory tract protection after accidental exposure to SARS-CoV-2 of oral, nasal and ocular mucosa.

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.

New evidence for aerosol transmission of SARS-CoV-2

Since the outbreak of COVID-19, the opinion that the aerosol plays a key role in the transmission of SARS-CoV-2 has been controversial. The COVID-19 pandemic has continued interpersonal transmission for more than two years, especially after the emergence of Delta and Omicron variants, making the situation of COVID-19 pandemic more severe. The transmission of SARS-COV-2 variants was significantly accelerated and the time of transmission between generations was significantly shortened. Therefore, it has been questioned to attribute the close-range infection to droplet transmission. The point that the aerosol can also has a close-range transmission and may play a dominant role is neglected under the influence of traditional transmission mode of respiratory infectious diseases. A large number of studies have shown that normal breath, talk and cough could release a large number of respiratory aerosol particles, and the virus particles were mainly tiny particles(=5.0 micro m). The biological activity and infectivity of the droplet nuclei have been questioned in the studies on their physicochemical properties. Animal models of ferrets and hamsters showed that SARS-COV-2 could transmit via aerosol. Therefore, the new evidence for the aerosol transmission of SARS-COV-2 was reviewed in the article so as to provide latest evidence-based evidence for prevention and control of COVID-19.

Patients with COVID-19 and HBV Coinfection are at Risk of Poor Prognosis.

INTRODUCTION: This study aimed to determine whether there is a difference in the risk of death/critical illness between different stages of hepatitis B virus (HBV) (resolved hepatitis B, HBeAg (-) chronic hepatitis B [CHB]/infection, HBeAg (+) CHB/infection, and HBV reactivation) coinfected with coronavirus disease 2019 (COVID-19); and if there is a difference, whether it is due to abnormal liver function and to what extent. METHODS: This cohort study included all COVID-19 inpatients of a single-center tertiary care academic hospital in Wuhan, Hubei, China, between February 4, 2020, and follow-up to April 14, 2020. A total of 2899 patients with COVID-19 were included as participants in this study, and they were divided into five groups based on hepatitis B infection status. Follow-up was conducted for mortality and ICU admission during hospitalization. RESULTS: The median follow-up time was 39 days (IQR, 30-50), with 66 deaths and 126 ICU admissions. After adjustment, compared with patients without CHB, the hazard ratio (HR) for ICU admission was 1.86 (95% CI: 1.05-3.31) for patients with HBeAg (+) CHB/infection. The HR for death was 3.19 (95% CI: 1.62-6.25) for patients with HBeAg (+) CHB/infection. The results for the mediating effect indicated that the total effect of HBeAg (+) CHB/infection on death/ICU stay was partially mediated by abnormal liver function, which accounted for 79.60% and 73.53%, respectively. CONCLUSION: Patients with COVID-19 coinfected with HBV at the HBeAg (+) CHB/infection stage have an increased risk of poor prognosis, and abnormal liver function partially mediates this increased risk of poor prognosis caused by the coinfection.

Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data.

Infectious disease monitoring on Oxford Nanopore Technologies (ONT) platforms offers rapid turnaround times and low cost. Tracking low frequency intra-host variants provides important insights with respect to elucidating within-host viral population dynamics and transmission. However, given the higher error rate of ONT, accurate identification of intra-host variants with low allele frequencies remains an open challenge with no viable computational solutions available. In response to this need, we present Variabel, a novel approach and first method designed for rescuing low frequency intra-host variants from ONT data alone. We evaluate Variabel on both synthetic data (SARS-CoV-2) and patient derived datasets (Ebola virus, norovirus, SARS-CoV-2); our results show that Variabel can accurately identify low frequency variants below 0.5 allele frequency, outperforming existing state-of-the-art ONT variant callers for this task. Variabel is open-source and available for download at: www.gitlab.com/treangenlab/variabel .

Consideration of the infection prevention and control mode in designated hospitals in response to local outbreaks of COVID-19

OBJECTIVE: To investigate the mode of prevention and control during local outbreaks of Corona virus disease 2019 (COVID-19), and to provide a basis for effective prevention of nosocomial infection. METHODS: Based on the working mode of the state council to prevent and control local outbreaks of COVID-19, the national technical guidelines on COVID-19 prevention and control, and the experience of fighting against COVID-19, working mode of nosocomial infection prevention and control team under the new mode were explored and analyzed. RESULTS: COVID-19 nosocomial infection prevention and control required scientific standards, multiple measures and precise control. Infection prevention and control teams should focus on environmental safety and personnel safety. Therefore, the effectiveness of the work should focus on improving the organizational structure, infection risk assessment in designated hospitals, establishing rules and regulations and working processes, establishing working mechanisms, standardizing information reporting and other aspects, and ensuring the implementation of prevention and control measures through supervision, monitoring, training and guidance. CONCLUSION: Nosocomial infection has a serious impact on COVID-19 response. Infection prevention and control teams need to establish a scientific and effective working mode to implement precise policies and scientific prevention and control, which can effectively prevent and control nosocomial infection incidents in COVID-19 response.

Progress of study on biology, epidemiology and prevention strategies for SARS-CoV-2 lambda variant

The emergence of SARS-COV-2 caused the global pandemic crisis.As the pandemic evolves, the mutation of novel coronavirus genome continues, resulting in several novel coronavirus variants. For example, Alpha (B.1.1.7), Beta (B.1.351), Gamma (p.1), Delta (B.1.617.2) and Lambda (C.37) variants may cause changes in biological characteristics of the virus, such as pathogenicity and infectivity, which may lead immune escape from vaccine protection and antibodies, even bring greater harm to epidemic prevention and control and also disease treatment. In this paper, the pandemic characteristics and relevant prevention and control measures of lambda variant are reviewed.

Research on control and prevention strategy of COVID-19 in metropolis

OBJECTIVE To discuss the core control strategy for the possible COVID-19 pandemic in the metropolis. METHODS Based on the national technical guidelines for COVID-19 Prevention and Control, this study summarized the experience in the fighting against the COVID-19 epidemic in Guangdong Province and explored the core strategy for the infection prevention and control under the new dynamic and precise' model. RESULTS Five key points played a great role in the control and prevention of COVID-19 epidemic in the metropolis, including the control of imported cases, management of isolation points, designated medical institutions,non-designated metical institutions and community control. The bundle measures of seven core measures may be effective, including strengthening the strict control over goods and staff of inbound personnel, management of designated hospitals, isolation points and residence, improving the construction of the associated teams, deploying tight check at the entrance of the community, enhancing comprehensive social governance, encouraging vaccination and propagating health education. CONCLUSION The epidemic COVID-19 seriously affects the economic and social life in the metropolis.We must rapidly control the situation by taking comprehensive measures decisively in order to achieve the fastest response.We expected that the most precise strategy, the shortest time and the minimum cost of control and prevention strategy can result in the optima effect on the COVID-19 prevention and control.

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

Susceptible-Infected-Removed Mathematical Model under Deep Learning in Hospital Infection Control of Novel Coronavirus Pneumonia.

Objective: This research aimed to explore the application of a mathematical model based on deep learning in hospital infection control of novel coronavirus (COVID-19) pneumonia. Methods: First, the epidemic data of Beijing, China, were utilized to make a definite susceptible-infected-removed (SIR) model fitting to determine the estimated value of the COVID-19 removal intensity ß, which was then used to do a determined SIR model and a stochastic SIR model fitting for the hospital. In addition, the reasonable ß and γ estimates of the hospital were determined, and the spread of the epidemic in hospital was simulated, to discuss the impact of basal reproductive number changes, isolation, vaccination, and so forth on COVID-19. Results: There was a certain gap between the fitting of SIR to the remover and the actual data. The fitting of the number of infections was accurate. The growth rate of the number of infections decreased after measures, such as isolation, were taken. The effect of herd immunity was achieved after the overall immunity reached 70.9%. Conclusion: The SIR model based on deep learning and the stochastic SIR fitting model were accurate in judging the development trend of the epidemic, which can provide basis and reference for hospital epidemic infection control.

SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission.

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq data sets and 6928 consensus genomes to contrast the intra-host and inter-host diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights intra-host single nucleotide variant (iSNV) and SNP similarity, albeit with differences in C > U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

Epidemiological investigation of a family cluster with 'diarrhea type' COVID-19

OBJECTIVE: To further explore the interpersonal transmission channels of SARS-CoV-2 through an epidemiological survey of one confirmed case of COVID-19 and six close family members and description of major clinical characteristics of 3 confirmed cases so as to provide theoretical basis for prevention and control of cluster outbreaks of the epidemic. METHODS: The surveys of individual case and clustered epidemic were conducted for 1 confirmed case of COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital, the forms were made by using Excel 2003, the data were entered, and the statistical description was performed by using SPPS software. RESULTS: During the family cluster outbreak, there were 4 persons who were infected and 3 persons who were not infected. 2 elderly patients had chronic underlying diseases. 3 cases had gastrointestinal symptoms which were the initial symptoms, 2 of whom had diarrhea, and 1 had nausea;2 cases had respiratory symptoms;3 cases had fever. The incubation periods of 3 cases were short, with an average period 5 days;the incubation period of 1 case was 20 days. The average interval between onset and consultation was 12.5 days;the average length of hospital stay was more than 14 days. The nasal and throat swab samples of all the patients were positive for nucleic acid tests, the stool samples of 2 cases were positive for the nucleic acid test. The average age of 3 close-contact persons without infection was 16 years old, 2 of whom were children. CONCLUSION: During the family cluster outbreak, the infection rate was 50% under the same exposure factor, and it is further confirmed that the elderly people are the population at high risk of infection. SARS-CoV-2 enters the human body and lead to infection through stool or inhaled aerosols. Adding the nucleic acid tests of stool and anal swab samples as one of the criteria for screening, release from quarantine and discharge should be taken into considerations.

Epidemiological survey and coping strategies for COVID-19 outbreak and pandemic

OBJECTIVE: To explore the epidemiological survey and coping strategies for Corona Virus Disease 2019(COVID-19) outbreak and pandemic. METHODS: The practical experience of the epidemiological survey of COVID-19 was analyzed, and the coping strategies were put forward under the circumstances of the pandemic abroad. RESULTS: The key points for the epidemiological survey and prevention and control of COVID-19 included the epidemiological evidence and chain of evidence, determination of sources of the epidemic, control of sources of infection, cutting off transmission routes and classification of high risk populations. The coping strategies for the COVID-19 pandemic such as strengthening the frontier health quarantine, enhancing the information collection and sharing, boosting the active monitoring, conducting the case-focused lead tracking and accelerating the development of vaccine were put forward. CONCLUSION: Adjusting and perfecting the coping strategies in a timely manner is crucial to the further improvement in the prevention and control of COVID-19.

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

Hospital biosecurity capacitation: Analysis and recommendations for the prevention and control of COVID-19.

The outbreak of the coronavirus disease 2019 (COVID-19) in December 2019 highlighted several concerns regarding hospital biosafety capacitation in the People's Republic of China, although the epidemic is now under control. This study examined the primary problems related to hospital biosecurity, including the absence of a hospital emergency system, inadequate management and control of nosocomial infection, limited hospital laboratory capacity, and poor hospital admission capacity. Accordingly, this study puts forward the following countermeasures and suggestions for hospitals to deal with future biosecurity events, such as a major epidemic: first, biosecurity management systems and emergency response mechanisms in hospitals need to be set up; second, the investment and guarantee mechanisms for hospital biosecurity construction should be improved; third, the capacity building of biosecurity incident management requires special attention in general hospitals; and finally, comprehensive plans need to be developed for the integrated construction of medical treatment and prevention facilities through disease-control systems.