SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling (preprint)

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since emerging in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV infections including murine coronavirus and Middle East respiratory syndrome (MERS)-CoV. To determine how nsp15 functions during SARS-CoV-2 infection, we constructed a mutant recombinant SARS-CoV-2 (nsp15mut) expressing a catalytically inactive nsp15. Infection with SARS-CoV-2 nsp15 mut led to increased activation of the IFN signaling and PKR pathways in lung-derived epithelial cell lines and primary nasal epithelial air-liquid interface (ALI) cultures as well as significant attenuation of replication in ALI cultures compared to wild-type (WT) virus. This replication defect was rescued when IFN signaling was inhibited with the Janus activated kinase (JAK) inhibitor ruxolitinib. Finally, to assess nsp15 function in the context of minimal (MERS-CoV) or moderate (SARS-CoV-2) innate immune induction, we compared infections with SARS-CoV-2 nsp15mut and previously described MERS-CoV nsp15 mutants. Inactivation of nsp15 had a more dramatic impact on MERS-CoV replication than SARS-CoV-2 in both Calu3 cells and nasal ALI cultures suggesting that SARS-CoV-2 can better tolerate innate immune responses. Taken together, SARS-CoV-2 nsp15 is a potent inhibitor of dsRNA-induced innate immune response and its antagonism of IFN signaling is necessary for optimal viral replication in primary nasal ALI culture. SIGNIFICANCESevere acute respiratory syndrome coronavirus (SARS-CoV)-2 causes a spectrum of respiratory disease ranging from asymptomatic infections to severe pneumonia and death. Innate immune responses during SARS-CoV-2 infection have been associated with clinical disease severity, with robust early interferon responses in the nasal epithelium reported to be protective. Thus, elucidating mechanisms through which SARS-CoV-2 induces and antagonizes host innate immune responses is crucial to understanding viral pathogenesis. CoVs encode various innate immune antagonists, including the conserved nonstructural protein 15 (nsp15) which contains an endoribonuclease (EndoU) domain. We demonstrate that SARS-CoV-2 EndoU is a crucial interferon antagonist, by providing further evidence for the role of the conserved CoV nsp15 in antagonizing innate immune activation, thereby optimizing CoV replication.

Using the increasing vaccination model and the moderating roles of chronic medical conditions and education to understand COVID-19 vaccination uptake in Singapore.

COVID-19 vaccination programmes have helped reduce deaths and morbidity from the pandemic and allowed for the resumption of normal life. However, vaccine hesitancy remains an issue even with recurrent surges in COVID-19 cases due to new SARS-CoV-2 variants. Purpose: To elucidate psychosocial factors that contribute to our understanding of vaccine hesitancy. 676 Participants in Singapore took part in an online survey on vaccine hesitancy and uptake between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected. The responses were analyzed using structural equation modeling (SEM). The study found that confidence in the COVID-19 vaccines and risk perception of the COVID-19 situation are significantly associated with vaccination intention, while vaccination intention is also significantly associated with reported vaccination status. Additionally, certain chronic medical conditions moderate the relationship between vaccine confidence/risk perception and vaccine intention. This study contributes to our understanding of factors behind vaccination uptake which can help anticipate challenges to future vaccination campaigns for the next pandemic.

COVID-19 vaccination programmes have helped reduce deaths from the pandemic and allowed for the resumption of normal life. However, vaccine hesitancy among the public remains an issue even with recurrent surges in COVID-19 cases due to new SARS-CoV-2 variants. To understand psychosocial factors that contribute to vaccine uptake, this study surveyed 676 participants in Singapore through an online survey on vaccine hesitancy and uptake between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness factors were collected. The responses were analyzed using structural equation modeling (SEM). The study found that confidence in the COVID-19 vaccines and risk perception of the COVID-19 situation are significantly associated with vaccination intention, while vaccination intention is also significantly associated with reported vaccination status. Additionally, certain chronic medical conditions moderate the relationship between vaccine confidence/risk perception and vaccine intention. This study contributes to our understanding of factors behind vaccination uptake which can help anticipate challenges to future vaccination campaigns for the next pandemic.

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses.

The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary human nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)] and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures, though replication is differentially modulated by temperature. Infections conducted at 33 °C vs. 37 °C (reflective of temperatures in the upper and lower airway, respectively) revealed that replication of both seasonal HCoVs (HCoV-NL63 and -229E) is significantly attenuated at 37 °C. In contrast, SARS-CoV-2 and MERS-CoV replicate at both temperatures, though SARS-CoV-2 replication is enhanced at 33 °C late in infection. These HCoVs also diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV receptor availability as well as replication. MERS-CoV receptor DPP4 expression increases with IL-13 treatment, whereas ACE2, the receptor used by SARS-CoV-2 and HCoV-NL63, is down-regulated. IL-13 treatment enhances MERS-CoV and HCoV-229E replication but reduces that of SARS-CoV-2 and HCoV-NL63, reflecting the impact of IL-13 on HCoV receptor availability. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.

Enhanced Recovery After Surgery Is Still Powerful for Colorectal Cancer Patients in COVID-19 Era.

Purpose: To figure out whether enhanced recovery after surgery (ERAS) could effectively improve the prognosis of colorectal cancer (CRC) patients and reduce hospitalization expenses under the shadow of COVID-19, furthermore to alleviate the current situation of medical resource for the whole society. Methods: Patients who underwent CRC surgery in the department of gastrointestinal surgery of the First Affiliated Hospital from January 2020 to March 2022 were retrospectively enrolled. According to protocol adherence, all patients were divided into the ERAS group and the non-ERAS group. Short-term outcomes were compared between the two groups. Results: A total of 918 patients were enrolled in the study. Based on protocol adherence ≥70%, 265 patients were classified into the ERAS group and the other 653 patients were classified into the non-ERAS group. Patients in the ERAS group had shorter operation time (P < .01), less intraoperative blood loss (P < .01), shorter overall hospital stay (P < .01) and postoperative hospital stay (P < .01), less hospital costs (P < .01), earlier first flatus (P < .01), earlier first stool (P < .01), earlier food tolerance (P < .01), and lower postoperative complications (P < .01). Univariate and multivariate logistic regression analysis manifested that ERAS and cerebrovascular disease were predictive factors of postoperative overall complications. In univariate analyses, cerebrovascular disease (P = .033, OR = 2.225, 95% CI = 1.066-4.748), time of the surgery (P = .026, OR = 1.417, 95% CI = 1.043-1.925), and ERAS (P < .01, OR = 0.450, 95% CI = 0.307-0.661) were predictive factors. Furthermore, in the multivariate analysis, ERAS (P < .01, OR = 0.440, 95% CI = 0.295-0.656) and cerebrovascular disease (P = .016, OR = 2.575, 95% CI = 1.190-5.575) were independent predictive factors of postoperative overall complications. Conclusion: In summary, under the impact of the COVID-19 pandemic, ERAS could still reduce the financial burden of patients and reduce the incidence of short-term postoperative complications. However, whether the effects of ERAS were enhanced after the pandemic and the long-term outcomes of CRC obey ERAS remained to be further explored.

Epidemiological characteristics of home enteral nutrition in patients from a Chinese tertiary hospital in 2021: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Home enteral nutrition was reported to be a treatment reducing malnutrition rates and improving the rational allocation of medical resources. We aim to investigate the epidemiological characteristics and improved the management of home enteral nutrition. METHODS AND STUDY DESIGN: 3953 patients with home enteral nutrition were enrolled in West China Hospital, located in Sichuan province, between January 1, 2021, and December 31, 2021. RESULTS: 7238 visit records (3429 females and 3809 males) were included. The median age was 59.0, with the age from 1 to 115. The top two diseases were oncologic disorders (40.3%) and digestive disorders (15.9%). Oral nutritional supplements (86.2%) was the major treatment of home enteral nutrition. The median daily energy intake and daily protein intake were 575.1 kcal and 31.2 g. 25.8%, 39.3%, 34.9% patients choose online clinic (1867), offline clinic (2843) and hospital to home (2528) respectively. Interestingly, 63.6% patients were revisited, and the rate of online clinic, offline clinic and hospital to home was increasingly lower (91.9%, 71.5%, 33.8%) among them, revealing online clinic improving the revisit rate. Most patients lived in Chengdu (60.5%), and 67.4% patients from Chengdu were revisited. The median monthly cost of hospital to home patients (¥ 1863.8) was higher than the total median monthly cost (¥ 1714.5), illustrating the cost may reduce the revisit rate. CONCLUSIONS: Distance, cost and convenience may be the key factors to determine the method of visit and revisit in patients of home enteral nutrition. Online clinic may enhance the patients' follow-up.

Postgraduate education in radiation oncology during the COVID-19 pandemic - What did we learn?

Introduction: During the COVID-19 pandemic the ESTRO School who provides international non-profit postgraduate education in Radiation Oncology and related disciplines, including Medical Physics and Radiation Technology, had to close down all live educational activities and turn online, although having only limited experience. The paper describes the experience, discusses the limitations and benefits of online education and suggests directions for the future. Materials and methods: Data about format and feedback from attendees and faculty members from the course activities held in 2019, 2020 and 2021 were made available from the ESTRO School. Results: In 2020, all but two out of thirty live courses that happened before the lockdown were canceled. Among the 18 courses scheduled in the second half of the year, seven went online with a short notice. Each course planned their activities quite differently, from compressed courses with consecutive full days online program to courses over several weeks with a few hours online a week. Both numbers of participants and different nationalities were higher than live courses in 2019 for the seven courses happening online, and courses were well evaluated by participants and faculties. Roughly-one-third of participants would prefer online courses in the future. Discussion: Although online education was well received by the majority, pros and cons exist and especially the personal discussions and networking were missed. Online education and live education are not comparable but can complement each other. Careful balancing these activities in the future is important and strategies for online andragogy are needed.

Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope.

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A∗02+ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Reciprocal effects between young children's negative emotions and mothers' mental health during the COVID-19 pandemic.

Objective: To investigate the relations between young children's negative emotions and their mothers' mental health during the COVID-19 pandemic. Background: The COVID-19 pandemic caused the public a certain degree of psychological symptoms, and family environments and relations have been changed dramatically as a result. The relations between young children's negative emotions and their mothers' mental health have not been sufficiently determined for the context of a pandemic or other large-scale crises. Method: A survey was administrated on 8119 Chinese mothers of 3- to 6-year-old children with the Symptom Checklist 90 and the Child Negative Emotion Questionnaire. Results: The canonical correlation results indicated that there were covariation trends between young children's anger and their mother's obsessive-compulsive symptoms and hostility, children's fear and mothers' phobic anxiety, and children's tension and mothers' interpersonal sensitivity and depression. These correlations were all positively significant. Conclusion: During the COVID-19 pandemic, the predictive power of young children's negative emotions to their mothers' mental health was greater than that of the reverse. Implications: This study provides a scientific guidance on the regulation of young children's negative emotions and the improvement of mothers' mental health during the pandemic as well as potential emergencies in the future.

MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells.

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into humans in 2012, causing highly lethal respiratory disease. The severity of disease may be, in part, because MERS-CoV is adept at antagonizing early innate immune pathways­interferon (IFN) production and signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L)­activated in response to viral double-stranded RNA (dsRNA) generated during genome replication. This is in contrast to severe acute respiratory syndrome CoV-2 (SARS-CoV-2), which we recently reported to activate PKR and RNase L and, to some extent, IFN signaling. We previously found that MERS-CoV accessory proteins NS4a (dsRNA binding protein) and NS4b (phosphodiesterase) could weakly suppress these pathways, but ablation of each had minimal effect on virus replication. Here we investigated the antagonist effects of the conserved coronavirus endoribonuclease (EndoU), in combination with NS4a or NS4b. Inactivation of EndoU catalytic activity alone in a recombinant MERS-CoV caused little if any effect on activation of the innate immune pathways during infection. However, infection with recombinant viruses containing combined mutations with inactivation of EndoU and deletion of NS4a or inactivation of the NS4b phosphodiesterase promoted robust activation of dsRNA-induced innate immune pathways. This resulted in at least tenfold attenuation of replication in human lung­derived A549 and primary nasal cells. Furthermore, replication of these recombinant viruses could be rescued to the level of wild-type MERS-CoV by knockout of host immune mediators MAVS, PKR, or RNase L. Thus, EndoU and accessory proteins NS4a and NS4b together suppress dsRNA-induced innate immunity during MERS-CoV infection in order to optimize viral replication.

Microplastics released from food containers can suppress lysosomal activity in mouse macrophages.

The ingestion and accumulation of microplastics is a serious threat to the health and survival of humans and other organisms given the increasing use of daily-use plastic products, especially during the COVID-19 pandemic. However, whether direct microplastic contamination from plastic packaging is a threat to human health remains unclear. We analyzed the market demand for plastic packaging in Asia-Pacific, North America, and Europe and identified the commonly used plastic food packaging products. We found that food containers exposed to high-temperature released more than 10 million microplastics per mL in water. Recycled plastic food packaging was demonstrated to continuously leach micro- and nanoplastics. In vitro cell engulfing experiments revealed that both micro- and nanoplastic leachates are readily taken up by murine macrophages without any preconditioning, and that short-term microplastic exposure may induce inflammation while exposure to nanoplastic substantially suppressed the lysosomal activities of macrophages. We demonstrated that the ingestion of micro- and nanoplastics released from food containers can exert differential negative effects on macrophage activities, proving that the explosive growth in the use of plastic packaging can poses significant health risks to consumers.

Total infectome characterization of respiratory infections in pre-COVID-19 Wuhan, China.

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.

Safety attitudes, burnout and wellbeing among healthcare workers during the COVID-19 pandemic: an Indo-Pacific regional cross-sectional study.

INTRODUCTION: The COVID-19 pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on safety attitudes among healthcare workers (HCWs) as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety. METHODS: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: Safety Attitudes Questionnaire (SAQ); Oldenburg Burnout Inventory; and Hospital and Anxiety Depression Scale. We performed multivariate mixed model regression to assess for independent associations with the SAQ Total Percentage Agree Rates (PAR). RESULTS: We obtained 3,163 responses. A SAQ Total PAR of 35.7%, 15.0%, 51.0% and 3.3% was calculated among respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest in respondents from India at 70.9%-85.4% versus 56.3%-63.6%, respectively. Multivariate analyses revealed that meeting burnout and depression thresholds, and shifts lasting ≥ 12 hours were significantly associated with lower SAQ Total PAR. CONCLUSION: Addressing factors contributing to high burnout and depression, and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities as this pandemic continues.

The road to achieving herd immunity: factors associated with Singapore residents' uptake and hesitancy of the COVID-19 vaccination.

OBJECTIVE: Achieving high vaccination rates is key to containing the coronavirus disease 2019 (COVID-19). This study evaluated the factors associated with uptake of the COVID-19 vaccine. METHODS: Six hundred and seventy-six respondents were surveyed online between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected. RESULTS: Approximately 54.6% of the respondents had received the COVID-19 vaccination. Age (p = 0.001), males (OR 1.7, 95% CI 1.1-2.6, p = 0.026), ethnicity (p = 0.004), occupation (p = 0.003)), working in healthcare (OR 6.1, 95% CI 2.8-13.2, p < 0.001), smoking (OR 3.3, 95% CI 1.3-8.8, p = 0.014), seeing vaccination as a social responsibility (OR 3.8, 95% CI 1.2-12.0, p = 0.022) and believing the vaccine is important to end the COVID-19 pandemic (OR 2.7, 95% CI 1.1-6.1, p = 0.020) were associated with greater vaccination uptake. CONCLUSION: Social responsibility and well-being of collective society are important values associated with vaccine uptake in an Asian society. Understanding factors behind vaccine uptake can help advise public health measures and strategies to achieve high levels of vaccination.

Impact of the COVID-19 pandemic on hospital admissions of nursing home residents.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has impacted nursing home care and activities in profound ways. We sought to understand whether the COVID-19 pandemic had any impact on hospital admissions of nursing home residents. METHODS: A retrospective analysis of hospital admissions of nursing home residents to a tertiary general hospital in Singapore during the COVID-19 pandemic in 2020 was conducted and compared to admissions in the preceding year. Patients' demographics, length of stay, primary diagnosis on admission, death and causes of death were recorded. RESULTS: Our study found reduced number of hospital admissions of nursing home residents to a tertiary hospital in Singapore. There was a significant decrease in pneumonia (p < 0.001) and fall (p = 0.001) as a primary diagnosis on admission and a decrease in pneumonia as the cause of death (p < 0.001) for nursing home residents admitted to hospital during the COVID-19 pandemic. CONCLUSIONS: This suggests that measures implemented during the pandemic may have impacted outcomes of nursing home residents. Further study is warranted to lead to practise changing outcomes for nursing home settings.

Clinical and epidemiological characteristics of children with COVID-19 in Selangor, Malaysia.

Objective: To describe the clinical and epidemiological characteristics of children diagnosed with coronavirus disease 2019 (COVID-19) at Hospital Sungai Buloh, Selangor, Malaysia. Methods: A retrospective observational study was performed on children aged <12 years diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between January 25 and December 31, 2020. A comparative analysis was undertaken between asymptomatic and symptomatic children, as well as a sub-analysis of their caretakers' COVID-19 status. Results: A total of 1498 children were included, 48.7% female and 51.3% male. Their mean age was 5.6 years (standard deviation 3.5 years). Overall, 82.3% were detected through contact tracing of positive family members or from the same household. Fifty-seven percent were asymptomatic. The most common symptoms reported were fever, nasal congestion/rhinorrhoea, and cough. Compared to asymptomatic children, those who were symptomatic had higher reported comorbidities, lower total white blood cell (WBC), absolute lymphocyte, and absolute neutrophil counts, raised C-reactive protein (CRP), and raised aspartate transaminase (P < 0.05). The median duration of illness was 10 days (interquartile range 3 days). Overall outcomes were good. Only 19 (8.2%) negative caretakers seroconverted prior to discharge. Conclusions: The majority of the children in the State of Selangor experienced mild COVID-19 illness in 2020, and they did not appear to be key drivers in the transmission of the disease.

High-Throughput Virtual Screening and Validation of a SARS-CoV-2 Main Protease Noncovalent Inhibitor.

Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel noncovalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (Mpro) by employing a scalable high-throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this Mpro inhibitor with an inhibition constant (Ki) of 2.9 µM (95% CI 2.2, 4.0). Furthermore, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft in the primary binding site of Mpro forming stable hydrogen bond and hydrophobic interactions. We then used multiple µs-time scale molecular dynamics (MD) simulations and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by Mpro, involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits Mpro and offers a springboard for further therapeutic design.

Effect of quantitative assessment of nosocomial infection management in normalized prevention and control phase of the COVID-19 pneumonia epidemic

OBJECTIVE To evaluate the implementation of normalization prevention and control measures for the COVID-2019 epidemic by quantitative assessment, and to evaluated the effectiveness of epidemic prevention and control and its impact on the quality of nosocomial infection management. METHODS The infection control measures of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were summarized and refined them into 16 quantitative assessment indicators, which will be inspected and assessed throughout the hospital from from Jul. to Dec. 2020. Data on epidemic prevention and control, incidence of nosocomial infection, hand hygiene related data during the same period were collected. RESULTS No confirmed cases of novel coronavirus pneumonia were found, and no asymptomatic infection cases were found to infect others. The incidence of nosocomial infection from July to December 2020 decreased compared with the same period in 2019. Stratified analysis showed that the infection of upper respiratory tract, urinary tract and gastrointestinal tract were significantly reduced, while there was no significant change in the infection rate of the type I incision surgical sites, the incidence of intravascular catheter related bloodstream infection, the incidence of ventilator-associated pneumonia and the incidence of catheter-related urinary tract infection. The compliance of hand hygiene, the accuracy of hand hygiene and the standard rate of hand disinfectant consumption were significantly improved, while there was no significant change in the consumption of dry hand tissue and hand sanitizer. CONCLUSION Quantitative assessment can effectively evaluate the implementation of normalized prevention and control measures of epidemic situation. The timely detection and elimination of potential epidemic hazards will have a positive impact on the improvement of the quality of nosocomial infection management.