Age-related rhesus macaque models of COVID-19.

BACKGROUND: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. METHODS: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. RESULTS: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. CONCLUSION: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

Electrochemical biosensors based on saliva electrolytes for rapid detection and diagnosis.

In recent years, electrochemical biosensors (ECBSs) have shown significant potential for real-time disease diagnosis and in situ physical condition monitoring. As a multi-constituent oral fluid comprising various disease signaling biomarkers, saliva has drawn much attention in the field of point-of-care (POC) testing. In particular, during the outbreak of the COVID-19 pandemic, ECBSs which hold the simplicity of a single-step assay compared with the multi-step assay of traditional testing methods are expected to relieve the human and economic burden caused by the massive and long-term sample testing process. Noteworthily, ECBSs for the detection of SARS-CoV-2 in saliva have already been developed and may replace current testing methods. Furthermore, the detection scope has expanded from routine indices such as sugar and uric acid to abnormal biomarkers for early-stage disease detection and drug level monitoring, which further facilitated the evolution of ECBSs in the last 5 years. This review is divided into several main sections. First, we discussed the latest advancements and representative research on ECBSs for saliva testing. Then, we focused on a novel kind of ECBS, organic electrochemical transistors (OECTs), which hold great advantages of high sensitivity and signal-to-noise ratio and on-site detection. Finally, application of ECBSs with integrated portable platforms in oral cavities, which lead to powerful auxiliary testing means for telemedicine, has also been discussed.

Diagnosis of COVID-19 via acoustic analysis and artificial intelligence by monitoring breath sounds on smartphones.

Scientific evidence shows that acoustic analysis could be an indicator for diagnosing COVID-19. From analyzing recorded breath sounds on smartphones, it is discovered that patients with COVID-19 have different patterns in both the time domain and frequency domain. These patterns are used in this paper to diagnose the infection of COVID-19. Statistics of the sound signals, analysis in the frequency domain, and Mel-Frequency Cepstral Coefficients (MFCCs) are then calculated and applied in two classifiers, k-Nearest Neighbors (kNN) and Convolutional Neural Network (CNN), to diagnose whether a user is contracted with COVID-19 or not. Test results show that, amazingly, an accuracy of over 97% could be achieved with a CNN classifier and more than 85% on kNN with optimized features. Optimization methods for selecting the best features and using various metrics to evaluate the performance are also demonstrated in this paper. Owing to the high accuracy of the CNN model, the CNN model was implemented in an Android app to diagnose COVID-19 with a probability to indicate the confidence level. The initial medical test shows a similar test result between the method proposed in this paper and the lateral flow method, which indicates that the proposed method is feasible and effective. Because of the use of breath sound and tested on the smartphone, this method could be used by everybody regardless of the availability of other medical resources, which could be a powerful tool for society to diagnose COVID-19.

Beyond Mere Surviving: The role of host country support and gratitude in thriving during the pandemic.

While the ensuing COVID-19 pandemic has significantly altered individuals' lives worldwide, it has been perhaps especially disruptive to the lives of sojourners as many have been unable to return home and are absent from their families, a familiar culture, and normal social support systems. While it is important to ask how such individuals can successfully survive in such a crisis, we were interested in extending our knowledge and understanding by asking "how can such individuals move beyond mere surviving to a state of thriving?" In answering this question, we utilized a positive psychology framework to develop a theoretical model wherein we expected higher/lower levels of perceived social support from host country people (i.e., host country support) to result in higher/lower levels of perceived gratitude, which would then result in higher/lower levels of thriving, and ethnocentrism moderated this indirect effect. To test our model, we utilized a sample of sojourners who responded to a survey measuring ethnocentrism (February 2020). We then administered daily surveys measuring perceived host country support, gratitude, and thriving over a nine-day period during the COVID-19 crisis (March 26-April 3, 2020). Results supported the indirect effect of host country support on thriving via gratitude. Further, we found that sojourners with lower levels of ethnocentrism exhibited stronger host country support- gratitude link, hence stronger indirect effect of host country support on thriving via gratitude. We close by offering implications for the existing literature, future research, and organizational practices.

Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques.

Variants of concern (VOCs) like Delta and Omicron, harbor a high number of mutations, which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies (NAbs). In this study, Rhesus macaques immunized with 2-dose inactivated vaccines (Coronavac) were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine, or a bivalent inactivated vaccine (Beta and Delta) to determine the effectiveness of sequential immunization. The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type, Beta, Delta, and Omicron. Animals administered with an indicated booster dose and subsequently challenged with Delta or Omicron variants showed markedly reduced viral loads and improved histopathological profiles compared to control animals, indicating that sequential immunization could protect primates against Omicron. These results suggest that sequential immunization of inactivated vaccines or polyvalent vaccines could be a potentially effective countermeasure against newly emerging variants.

A Systematic Review of Systematic Reviews on Blended Learning: Trends, Gaps and Future Directions.

Blended Learning (BL) is one of the most used methods in education to promote active learning and enhance students' learning outcomes. Although BL has existed for over a decade, there are still several challenges associated with it. For instance, the teachers' and students' individual differences, such as their behaviors and attitudes, might impact their adoption of BL. These challenges are further exacerbated by the COVID-19 pandemic, as schools and universities had to combine both online and offline courses to keep up with health regulations. This study conducts a systematic review of systematic reviews on BL, based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to identify BL trends, gaps and future directions. The obtained findings highlight that BL was mostly investigated in higher education and targeted students in the first place. Additionally, most of the BL research is coming from developed countries, calling for cross-collaborations to facilitate BL adoption in developing countries in particular. Furthermore, a lack of ICT skills and infrastructure are the most encountered challenges by teachers, students and institutions. The findings of this study can create a roadmap to facilitate the adoption of BL. The findings of this study could facilitate the design and adoption of BL which is one of the possible solutions to face major health challenges, such as the COVID-19 pandemic.

Students' Intention of Visiting Urban Green Spaces after the COVID-19 Lockdown in China.

This study addresses students' perceptions of using urban green spaces (UGSs) after the easing of COVID-19 lockdown in China. We questioned whether they are still mindful of the risks from the outdoor gathering, or conversely, starting to learn the restoration benefits from the green spaces. Online self-reported surveys were distributed to the Chinese students aging from 14 to 30 who study in Hunan and Jiangsu Provinces, China. We finally obtained 608 complete and valid questionnaire forms from all participants. Their intentions of visiting UGSs were investigated based on the extended theory of planned behavior model. Structural equation modeling was employed to test the hypothesized psychological model. The results have shown good estimation performance on risk perception and perceived knowledge to explain the variances in their attitudes, social norms, and perceived behavior control. Among these three endogenous variables, the perceived behavior control owns the greatest and positive influence on the behavioral intention, inferring that controllability is crucial for students to make decisions of visiting green spaces in a post-pandemic context.

Management of systemic risk factors ahead of dental implant therapy: A beard well lathered is half shaved.

As the most successful therapy for missing teeth, dental implant has become increasingly prevalent around the world. A lot of papers have reported diverse local risk factors affecting the success and survival rate of dental implants, either for a short or a long period. However, there are also many types of systemic disorders or relatively administrated medicine that may jeopardize the security and success of dental implant treatment. Additionally, the coronavirus disease 2019 pandemic also poses a challenge to dental implant clinicians. Some of these risk factors are clinically common but to some extent unfamiliar to dentists, thus optimal measurements are often lacking when they occur in dental clinics. In this review, we analyze potential systemic risk factors that may affect the success rate of dental implants. Some of them may affect bone mineral density or enhance the likelihood of local infection, thus impeding osseointegration. Others may even systemically increase the risk of the surgery and threaten patients' life. In order to help novices receive high-risk patients who need to get dental implant treatment in a more reasonable way, we accordingly review recent research results and clinical experiments to discuss promising precautions, such as stopping drugs that impact bone mineral density or the operation, and addressing any perturbations on vital signs.

Correlation between early features and prognosis of symptomatic COVID-19 discharged patients in Hunan, China.

To determine the correlation between the clinical, laboratory, and radiological findings and the hospitalization days in Coronavirus Infectious Disease-19 (COVID-19) discharged patients. We retrospectively identified 172 discharged patients with COVID-19 pneumonia from January 10, 2020, to February 28, 2020, in Hunan province. The patients were categorized into group 1 (≤ 19 days) and group 2 (> 19 days) based on the time from symptom onset to discharge. Cough during admission occurred more commonly in group 2 (68.4%) than in group 1 (53.1%, p = 0.042). White blood cell (p = 0.045), neutrophil counts (p = 0.023), Alanine aminotransferase (p = 0.029), Aspartate aminotransferase (p = 0.027) and Lactate dehydrogenase (p = 0.021) that were above normal were more common in group 2. Patients with single lesions were observed more in group 1(17.7%, p = 0.018) and multiple lesions observed more in group 2(86.8%, p = 0.012). The number of lobes involved (p = 0.008) in the CT score (p = 0.001) for each patient was all differences between the two groups with a statistically significant difference. Mixed ground-glass opacity (GGO) and consolidation appearances were observed in most patients. GGO components > consolidation appearance was more common in group 1 (25.0%) than in group 2 (8.0%) with a significant difference (0.015), GGO < consolidation was more common in group 2(71.1%, p = 0.012). From the logistic regression analysis, the CT score (OR, 1.223; 95% CI, 1.004 to 1.491, p = 0.046) and the appearance of GGO > consolidation (OR, 0.150; 95% CI, 0.034 to 0.660, p = 0.012) were independently associated with the hospitalization days. Thus, special attention should be paid to the role of radiological features in monitoring the disease prognosis.

Association between incubation period and clinical characteristics of patients with COVID-19.

PURPOSE: To investigate associations between the clinical characteristics and incubation periods of patients infected with coronavirus disease 2019 (COVID-19) in Wuhan, China. METHODS: Complete clinical and epidemiological data from 149 patients with COVID-19 at a hospital in Hunan Province, China, were collected and retrospectively analyzed. RESULTS: Analysis of the distribution and receiver operator characteristic curve of incubation periods showed that 7 days was the optimal cut-off value to assess differences in disease severity between groups. Patients with shorter (≤7 days) incubation periods (n = 79) had more severe disease, longer durations of hospitalization, longer times from symptom onset to discharge, more abnormal laboratory findings, and more severe radiological findings than patients with longer (>7 days) incubation periods. Regression and correlation analyses also showed that a shorter incubation period was associated with longer times from symptom onset to discharge. CONCLUSION: The associations between the incubation periods and clinical characteristics of COVID-19 patients suggest that the incubation period may be a useful marker of disease severity and prognosis.

Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1-7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1-7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.

Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques.

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.

Clinical and radiological changes of hospitalised patients with COVID-19 pneumonia from disease onset to acute exacerbation: a multicentre paired cohort study.

OBJECTIVES: To analyse clinical and radiological changes from disease onset to exacerbation in coronavirus infectious disease-19 (COVID-19) patients. METHODS: We reviewed clinical histories of 276 patients with confirmed COVID-19 pneumonia and extracted data on patients who met the diagnostic criteria for COVID-19 severe/fatal pneumonia and had an acute exacerbation starting with mild or common pneumonia. RESULTS: Twenty-four patients were included. Of these, 8% were smokers, 54% had been to Wuhan, and 46% had comorbidities. Before acute exacerbation, elevated lactate dehydrogenase (232.9 ± 88.7) was present, and chest CT scans showed the number of involved lobes was 4 (2-5) and total CT score was 6 (2-8). Following acute exacerbation, patients were likely to have more clinical symptoms (p < 0.01) and abnormal laboratory changes (p < 0.01). The number of involved lobes and CT score after an exacerbation significantly increased to 5 (5-5) and 12 (9-14), respectively. Receiver operating characteristic (ROC) curve showed that, when the cutoff value of CT score was 5, the sensitivity and specificity for severe pneumonia were 90% and 70%, respectively. CT findings of ground glass opacity with consolidations (91.7%), bilateral distribution (100.0%), and multifocal lesion (100.0%) were features in found in patients after exacerbation. CONCLUSIONS: There are significant changes in clinical, laboratory, and CT findings in patients from disease onset to exacerbation. An increase in the number of involved lobes or an increased CT score from the baseline may predict poor clinical outcomes. Combining an assessment of CT changes with clinical and laboratory changes could help clinical teams evaluate the prognosis. KEY POINTS: • The common chest CT signs of COVID-19 pneumonia after exacerbation were ground glass opacity (GGO) with consolidation, bilateral distribution, and multifocal lesions. • An increase in number of involved lobes or an increased CT score from the baseline may predict a poor clinical outcome. • Worsened symptoms and abnormal laboratory results are also associated with poor prognosis.