Evaluation of BioFire Respiratory Panel 2 plus for Detection of Bordetella pertussis in Nasopharyngeal Swab Specimens from Children with Clinically Suspected Pertussis.

The objective of this study was to compare the performances of BioFire Respiratory Panel 2 (RP2) plus, quantitative real-time PCR (qPCR), and culture for the detection of Bordetella pertussis in nasopharyngeal swab (NPS) specimens. Consecutive NPS specimens were collected from patients with clinically suspected pertussis from 1 March 1 to 31 July 2018 in Shenzhen Children's Hospital. All the specimens were tested in parallel by RP2 plus, qPCR, and culture methods. A total of 464 children were enrolled in this study. The positive pertussis rates of culture, RP2 plus, and qPCR were 23.1%, 39.0%, and 38.4%, respectively. Compared to the combined reference standard, the sensitivity, specificity, positive predictive value, and negative predictive values were, respectively, 56.6% (95% confidence interval [CI], 49.2 to 63.7%), 100% (98.3 to 100%), 100% (95.7 to 100%), and 77.0% (72.2 to 81.2%) for culture, 89.9% (84.5 to 93.7%), 96.0% (92.8 to 97.9%), 93.9% (89.1 to 96.8%), and 93.3% (89.5 to 95.8%) for RP2 plus, and 86.8% (80.9 to 91.1%), 94.9% (91.4 to 97.1%), 92.1% (86.9 to 95.5%), and 91.3% (87.2 to 94.2%) for qPCR. The most prevalent codetected pathogen was human rhinovirus/enterovirus (n = 99, 52.4%), followed by parainfluenza virus (n =32, 16.9%) and respiratory syncytial virus (n = 29, 15.3%), in children with B. pertussis present, which was consistent with the top three pathogens previously found in children with B. pertussis absent. Turnaround times for RP2 plus, qPCR, and culture were 2 h, 8 h, and 120 h, respectively. RP2 plus quickly and accurately detected B. pertussis, providing valuable information for an early clinical diagnosis and optimal choice of therapy. IMPORTANCE In recent years, there have been some epidemic or local outbreaks of pertussis in countries with high vaccination rates. One of the crucial factors in controlling pertussis is early diagnosis, which is based on specific laboratory measurements, including culture, serological tests, and PCR assays. Compared to culture and serological tests, PCR is more suitable for clinical application, with a fast detection speed of several hours independent of the disease stage and individual vaccination status. BioFire Respiratory Panel 2 plus, a multiplex PCR assay for simultaneously detecting 22 respiratory pathogens, facilitates the quick detection of Bordetella pertussis and coinfecting respiratory pathogens. It also provides valuable information for an early clinical diagnosis and optimal choice of therapy for children with clinically suspected pertussis.

Factors associated with delaying medical care: cross-sectional study of Nebraska adults.

BACKGROUND: Delayed medical care may result in adverse health outcomes and increased cost. Our purpose was to identify factors associated with delayed medical care in a primarily rural state. METHODS: Using a stratified random sample of 5,300 Nebraska households, we conducted a cross-sectional mailed survey with online response option (27 October 2020 to 8 March 2021) in English and Spanish. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals. RESULTS: The overall response rate was 20.8% (n = 1,101). Approximately 37.8% of Nebraskans ever delayed healthcare (cost-related 29.7%, transportation-related 3.7%), with 22.7% delaying care in the past year (10.1% cost-related). Cost-related ever delay was associated with younger age [< 45 years aOR 6.17 (3.24-11.76); 45-64 years aOR 2.36 (1.29-4.32)], low- and middle-income [< $50,000 aOR 2.85 (1.32-6.11); $50,000-$74,999 aOR 3.06 (1.50-6.23)], and no health insurance [aOR 3.56 (1.21-10.49)]. Transportation delays were associated with being non-White [aOR 8.07 (1.54-42.20)], no bachelor's degree [≤ high school aOR 3.06 (1.02-9.18); some college aOR 4.16 (1.32-13.12)], and income < $50,000 [aOR 8.44 (2.18-32.63)]. Those who did not have a primary care provider were 80% less likely to have transportation delays [aOR 0.20 (0.05-0.80)]. CONCLUSIONS: Delayed care affects more than one-third of Nebraskans, primarily due to financial concerns, and impacting low- and middle-income families. Transportation-related delays are associated with more indicators of low socio-economic status. Policies targeting minorities and those with low- and middle-income, such as Medicaid expansion, would contribute to addressing disparities resulting from delayed care.

The ORF7a protein of SARS-CoV-2 initiates autophagy and limits autophagosome-lysosome fusion via degradation of SNAP29 to promote virus replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the SNAP29 protein at aspartic acid residue 30 (D30), ultimately impairing complete autophagy. Importantly, SARS-CoV-2 infection-induced accumulated autophagosomes promote progeny virus production, whereby ORF7a downregulates SNAP29, ultimately resulting in failure of autophagosome fusion with lysosomes to promote viral replication. Taken together, our study reveals a mechanism by which SARS-CoV-2 utilizes the autophagic machinery to facilitate its own propagation via ORF7a.

Driving the effectiveness of public health emergency management strategies through cross-departmental collaboration: Configuration analysis based on 15 cities in China.

Background: Owing to the complexity of and changes associated with modern public health emergencies, cross-departmental collaborative governance is an inevitable choice for ensuring effective emergency management. In the context of emergency management research, the way in which taking full advantage of synergy can be used to enhance the effectiveness of emergency prevention and control approaches is an important issue that must be addressed urgently. Methods: Combined with China's responses to the management of public health emergencies, in this study, we construct a theoretical analysis framework involving three dimensions: information, organization, and environment. Our proposed framework relies on the fuzzy-set qualitative comparative analysis (fsQCA) method to analyze the mechanisms behind the prevention and control of coronavirus disease 2019 (COVID-19) cases across 15 cities located in typical provinces throughout China and explore the roles of cross-departmental collaboration in the processing of various elements as well as the effects of their combination on the action mechanisms for ensuring the effectiveness of emergency management approaches. Findings: The results show a significant conditional correlation between the effectiveness of emergency management and the factors affecting cross-departmental coordination. Based on the characteristics of multiple concurrent paths, the driving paths can be classified into four categories: organizational, environmental, environment-balanced, and organization environment-based dual-core categories. Conclusions: The effectiveness of public health emergency management is the result of multiple factors. Local governments should strengthen the coordination and integration of information, organization, and environment, improve the coordinated system associated with emergency management, promote the "two-wheel drive" of high-quality development as well as accurate prevention and control, explore and perfect the adaptive combinatorial optimization path, and effectively transform the advantages of linking multi-dimensional factors with governance efficiency.

Adoption of Preventive Measures During the Very Early Phase of the COVID-19 Outbreak in China: National Cross-sectional Survey Study.

BACKGROUND: The outbreak of COVID-19 in China occurred around the Chinese New Year (January 25, 2020), and infections decreased continuously afterward. General adoption of preventive measures during the Chinese New Year period was crucial in driving the decline. It is imperative to investigate preventive behaviors among Chinese university students, who could have spread COVID-19 when travelling home during the Chinese New Year break. OBJECTIVE: In this study, we investigated levels of COVID-19-related personal measures undertaken during the 7-day Chinese New Year holidays by university students in China, and associated COVID-19-related cognitive factors. METHODS: A cross-sectional anonymous web-based survey was conducted during the period from February 1 to 10, 2020. Data from 23,863 students (from 26 universities, 16 cities, 13 provincial-level regions) about personal measures (frequent face-mask wearing, frequent handwashing, frequent home staying, and an indicator that combined the 3 behaviors) were analyzed (overall response rate 70%). Multilevel multiple logistic regression analysis was performed. RESULTS: Only 28.0% of respondents (6684/23,863) had left home for >4 hours, and 49.3% (11,757/23,863) had never left home during the 7-day Chinese New Year period; 79.7% (19,026/23,863) always used face-masks in public areas. The frequency of handwashing with soap was relatively low (6424/23,863, 26.9% for >5 times/day); 72.4% (17,282/23,863) had frequently undertaken ≥2 of these 3 measures. COVID-19-related cognitive factors (perceptions on modes of transmission, permanent bodily damage, efficacy of personal or governmental preventive measures, nonavailability of vaccines and treatments) were significantly associated with preventive measures. Associations with frequent face-mask wearing were stronger than those with frequent home staying. CONCLUSIONS: University students had strong behavioral responses during the very early phase of the COVID-19 outbreak. Levels of personal prevention, especially frequent home staying and face-mask wearing, were high. Health promotion may modify cognitive factors. Some structural factors (eg, social distancing policy) might explain why the frequency of home staying was higher than that of handwashing. Other populations might have behaved similarly; however, such data were not available to us.

Ventilation reconstruction in bathrooms for restraining hazardous plume: Mitigate COVID-19 and beyond.

Converging evidence reports that the probability of vertical transmission patterns via shared drainage systems, may be responsible for the huge contactless community outbreak in high-rise buildings. Publications indicate that a faulty bathroom exhaust fan system is ineffective in removing lifted hazardous virus-laden aerosols from the toilet bowl space. Common strategies (boosting ventilation capability and applying disinfection tablets) seem unsustainable and remain to date untested. Using combined simulation and experimental approaches, we compared three ventilation schemes in a family bathroom including the traditional ceiling fan, floor fan, and side-wall fan. We found that the traditional ceiling fan was barely functional whereby aerosol particles were not being adequately removed. Conversely, a side-wall fan could function efficiently and an enhanced ventilation capability can have increased performance whereby nearly 80.9% of the lifted aerosol particles were removed. There exists a common, and easily-overlooked mistake in the layout of the bathroom, exposing occupants to a contactless vertical pathogen aerosol transmission route. Corrections and dissemination are thus imperative for the reconstruction of these types of family bathrooms. Our findings provide evidence for the bathroom and smart ventilation system upgrade, promoting indoor public health and human hygiene.

The Potential Roles of BCG Vaccine in the Prevention or Treatment of COVID-19.

Coronavirus disease 2019 (COVID-19), which broke out at the end of 2019, is a global pandemic and seriously threatens human health. Vaccination is the most effective way to prevent and control COVID-19. At present, more than 13 COVID-19 vaccines have been urgently authorized for use, but the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has brought unprecedented challenges to the protective efficiency of these COVID-19 vaccines. In particular, the recent emergence of Delta and Omicron variants, which are rapidly spreading worldwide, may bring many challenges to the medical systems. Interestingly, previous studies have shown that the Bacillus Calmette-Guerin (BCG) vaccine used to prevent tuberculosis can induce non-specific trained immunity, protecting against infectious diseases caused by respiratory viruses. Therefore, there is a hypothesis that BCG plays an essential role in reducing the incidence, severity, hospitalization, and mortality of COVID-19 and enhancing the protection efficiency of the COVID-19 vaccine. To confirm this hypothesis, 56 clinical trials have been conducted globally to assess BCG's protective effectiveness against COVID-19 infection. Herein, this review discussed the trained immunity induced by BCG and its underlying mechanisms and summarised BCG's latest research progress in preventing COVID-19, especially the ongoing clinical trials. We hope this review will provide new strategies for fighting against COVID-19.

Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

BACKGROUND: The present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated. METHODS: Numerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve. RESULTS: The analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo. CONCLUSIONS: Overall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2021-6-0033/.

Life in a New Normal with a Self-Care Routine: A Cross-Sectional Study of Older Adults' Daily Health Behaviors (DHB) Performance during the Initial Outbreak of COVID-19 in China.

For older adults, self-care begins with daily health behaviors (DHB), which refers to a series of basic behaviors beneficial to health in daily life; it is the foundation for promoting health, preventing disease, and maintaining health with or without the support of a healthcare provider. Thus, this study aimed to observe the changes in DHB among older adults when the COVID-19 pan-demic first erupted in China (at the beginning of 2020) and explore the impact factors on self-care routines in daily life. We applied a cross-sectional study among 1256 (83.7%) valid older Chinese from 19 February 2020 to 19 March 2020, the score of DHB changes (mean ± SD, 14.70 ± 2.140; range, 8-18) presented a significant growth (t1256 = 44.636, p < 0.001) during COVID-19. From 3 hierarchical linear regression models, the older Chinese who received a higher education include high school (ß = 0.403, 95% CI [0.009, 0.797], p = 0.045) and college degree and above (ß = 0.488, 95% CI [0.034, 0.943], p = 0.035), and lived in the eastern China (ß = 0.771, 95% CI [0.392, 1.151], p < 0.001) took DHB more frequently. However, the high-risk infection (ß = -0.740, 95% CI [-1.248, -0.231], p = 0.004), overweight/obese character (ß = -0.265, 95% CI [-0.526, -0.004], p = 0.047), and alcohol consumption (ß = -0.350, 95% CI [-0.634, -0.065], p = 0.016) are significant factors in decreasing a senior's DHB performance. For China, self-care offers a straightforward strategy among the range of measures required to combat COVID-19 and future health threats. In summary, findings in this study can build a foundation for developing healthcare policy and services for the relevant government and departments on prompting DHB and the importance of self-care among the older population.

A single-cell transcriptomic landscape of the lungs of patients with COVID-19.

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.

SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy.

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe morbidity and mortality in humans. It is urgent to understand the function of viral genes. However, the function of open reading frame 10 (ORF10), which is uniquely expressed by SARS-CoV-2, remains unclear. In this study, we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon (IFN-I) genes and IFN-stimulated genes. Then, mitochondrial antiviral signaling protein (MAVS) was identified as the target via which ORF10 suppresses the IFN-I signaling pathway, and MAVS was found to be degraded through the ORF10-induced autophagy pathway. Furthermore, overexpression of ORF10 promoted the accumulation of LC3 in mitochondria and induced mitophagy. Mechanistically, ORF10 was translocated to mitochondria by interacting with the mitophagy receptor Nip3-like protein X (NIX) and induced mitophagy through its interaction with both NIX and LC3B. Moreover, knockdown of NIX expression blocked mitophagy activation, MAVS degradation, and IFN-I signaling pathway inhibition by ORF10. Consistent with our observations, in the context of SARS-CoV-2 infection, ORF10 inhibited MAVS expression and facilitated viral replication. In brief, our results reveal a novel mechanism by which SARS-CoV-2 inhibits the innate immune response; that is, ORF10 induces mitophagy-mediated MAVS degradation by binding to NIX.

Mental Health Status of the Elderly Chinese Population During COVID-19: An Online Cross-Sectional Study.

Background: COVID-19 not only threatened the public's physical health but also brought unbearable psychological pressure, especially for those vulnerable groups like the elderly. However, studies on the psychological status of older adults during this public health emergency remained scant. This study aims to investigate the mental health status among the elderly Chinese population during COVID-19 pandemic and determine the influencing factors of psychological symptoms. Methods: From February 19 to March 19, 2020, an online survey was administered to Chinese older adults using a convenience sampling method. Information on demographic data, health status and other epidemic related factors were collected. Specifically, the study defined the psychological status as five primary disorder-depression, neurasthenia, fear, anxiety, and hypochondria-which were assessed by the Psychological Questionnaire for Emergent Event of Public Health (PQEEPH). Standard descriptive statistics and multiple logistic regression analyses were conducted to analyze the data. Results: Of 1,501 participants recruited from 31 provinces in China, 1,278 were valid for further analysis. Participants' scores on each sub-scale were described in median and interquartile [M(Q)]: depression [0.00 (0.33)], neurasthenia [0.00 (0.40)], fear [1.00 (0.83)], anxiety [0.00 (0.17)], hypochondria [0.00 (0.50)]. Chronic diseases (depression p = 0.001; neurasthenia p < 0.001; fear p = 0.023; anxiety p < 0.001; hypochondria p = 0.001) and the BMI index (depression p = 0.015; neurasthenia p = 0.046; fear p = 0.016; anxiety p = 0.015; hypochondria p = 0.013) had significant impacts on all of the five sub-scales. Specifically, the rural dwellers had a higher level of neurasthenia, fear, and hypochondria. Besides, education level (p = 0.035) and outbreak risk level (p = 0.004) had significant impacts on the depression. Higher household monthly income per capita (p = 0.031), and the community-level entry/exit control (p = 0.011) are factors against anxiety. Conclusions: Most elderly residents reported mild negative emotions during COVID-19 and more attention should be paid to the recognition and alleviation of fear. Our findings also identified factors associated with the mental health status of the elderly, which is of practical significance in the design and implementation of psychological interventions for this vulnerable population during COVID-19 and future emerging diseases.

Bacterial Epidemiology and Antimicrobial Resistance Profiles in Children Reported by the ISPED Program in China, 2016 to 2020.

The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant Enterobacteriaceae (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. IMPORTANCE AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.

Molecular evidence suggesting the persistence of residual SARS-CoV-2 and immune responses in the placentas of pregnant patients recovered from COVID-19.

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.

Viral and Host Transcriptomes in SARS-CoV-2-Infected Human Lung Cells.

Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.

Nucleic acid visualization assay for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) by targeting the UpE and N gene.

Since its first emergence in 2012, cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV) have continued to occur. At the end of January 2020, 2519 laboratory confirmed cases with a case-fatality rate of 34.3% have been reported. Approximately 84% of human cases have been reported in the tropical region of Saudi Arabia. The emergence of MERS-CoV has highlighted need for a rapid and accurate assay to triage patients with a suspected infection in a timely manner because of the lack of an approved vaccine or an effective treatment for MERS-CoV to prevent and control potential outbreaks. In this study, we present two rapid and visual nucleic acid assays that target the MERS-CoV UpE and N genes as a panel that combines reverse transcription recombinase polymerase amplification with a closed vertical flow visualization strip (RT-RPA-VF). This test panel was designed to improve the diagnostic accuracy through dual-target screening after referencing laboratory testing guidance for MERS-CoV. The limit of detection was 1.2×101 copies/µl viral RNA for the UpE assay and 1.2 copies/µl viral RNA for the N assay, with almost consistent with the sensitivity of the RT-qPCR assays. The two assays exhibited no cross-reactivity with multiple CoVs, including the bat severe acute respiratory syndrome related coronavirus (SARSr-CoV), the bat coronavirus HKU4, and the human coronaviruses 229E, OC43, HKU1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the panel does not require sophisticated equipment and provides rapid detection within 30 min. This panel displays good sensitivity and specificity and may be useful to rapidly detect MERS-CoV early during an outbreak and for disease surveillance.

Factors Influencing Depression and Mental Distress Related to COVID-19 Among University Students in China: Online Cross-sectional Mediation Study.

BACKGROUND: The COVID-19 epidemic may elevate mental distress and depressive symptoms in various populations in China. OBJECTIVE: This study investigates the levels of depression and mental distress due to COVID-19, and the associations between cognitive, behavioral, and psychosocial factors, and depression and mental distress due to COVID-19 among university students in China. METHODS: A large-scale online cross-sectional study (16 cities in 13 provinces) was conducted among university students from February 1 to 10, 2020, in China; 23,863 valid questionnaires were returned. The Patient Health Questionnaire-9 was used to assess depression. Structural equation modeling was performed to test mediation and suppression effects. RESULTS: Of the 23,863 participants, 47.1% (n=11,235) reported high or very high levels of one or more types of mental distress due to COVID-19; 39.1% (n=9326) showed mild to severe depression. Mental distress due to COVID-19 was positively associated with depression. All but one factor (perceived infection risks, perceived chance of controlling the epidemic, staying at home, contacted people from Wuhan, and perceived discrimination) were significantly associated with mental distress due to COVID-19 and depression. Mental distress due to COVID-19 partially mediated and suppressed the associations between some of the studied factors and depression (effect size of 6.0%-79.5%). CONCLUSIONS: Both mental distress due to COVID-19 and depression were prevalent among university students in China; the former may have increased the prevalence of the latter. The studied cognitive, behavioral, and psychosocial factors related to COVID-19 may directly or indirectly (via mental distress due to COVID-19) affect depression. Interventions to modify such factors may reduce mental distress and depressive symptoms during the COVID-19 epidemic.