Viral Pneumonia during the COVID-19 Pandemic, 2019-2021 Evoking Needs for SARS-CoV-2 and Additional Vaccinations.

Coronaviruses can cause pneumonia, with clinical symptoms that may be similar to the symptoms of other viral pneumonias. To our knowledge, there have been no reports regarding cases of pneumonia caused by coronaviruses and other viruses among hospitalized patients in the past 3 years before and during coronavirus disease 2019 (COVID-19). Here, we analysed the causes of viral pneumonia among hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic (2019-2021). Between September 2019 and April 2021, patients hospitalized at Shuang Ho Hospital in north Taiwan with a diagnosis of pneumonia were enrolled in this study. Age, sex, onset date, and season of occurrence were recorded. Respiratory tract pathogens were identified with molecular detection using the FilmArray® platform from nasopharyngeal swabs. In total, 1147 patients (128 patients aged <18 years and 1019 patients aged ≥18 years) with pneumonia and identified respiratory tract pathogens were assessed. Among the 128 children with pneumonia, the dominant viral respiratory pathogen was rhinovirus (24.2%), followed by respiratory syncytial virus (RSV; 22.7%), parainfluenza virus (1 + 2 + 3 + 4) (17.2%), adenovirus (12.5%), metapneumovirus (9.4%), coronavirus (1.6%), and influenza virus (A + B) (1.6%). Among the 1019 adults with pneumonia, the dominant viral respiratory pathogen was rhinovirus (5.0%), followed by RSV (2.0%), coronavirus (2.0%), metapneumovirus (1.5%), parainfluenza virus (1 + 2 + 3 + 4) (1.1%), adenovirus (0.7%), and influenza virus (A + B) (0%). From 2019-2021, older patients (aged >65 years) with pneumonia tested positive for coronavirus most commonly in autumn. Coronavirus was not detected during summer in children or adults. Among children aged 0-6 years, RSV was the most common viral pathogen, and RSV infection occurred most often in autumn. Metapneumovirus infection occurred most often in spring in both children and adults. In contrast, influenza virus was not detected in patients with pneumonia in any season among children or adults from January 2020 to April 2021. Among all patients with pneumonia, the most common viral pathogens were rhinovirus in spring, adenovirus and rhinovirus in summer, RSV and rhinovirus in autumn, and parainfluenza virus in winter. Among children aged 0-6 years, RSV, rhinovirus, and adenovirus were detected in all seasons during the study period. In conclusion, the proportion of pneumonia cases caused by a viral pathogen was higher in children than the proportion in adults. The COVID-19 pandemic period evoked a need for SARS-CoV-2 (severe acute respiratory disease coronavirus 2) vaccination to prevent the severe complications of COVID-19. However, other viruses were also found. Vaccines for influenza were clinically applied. Active vaccines for other viral pathogens such as RSV, rhinovirus, metapneuomoccus, parainfluenza, and adenovirus may need to be developed for special groups in the future.

Effects of EEG burst suppression on cerebral oxygen metabolism and postoperative cognitive function in elderly surgical patients: A randomized clinical trial.

BACKGROUND: This randomized clinical trial determined the effects of electroencephalographic burst suppression on cerebral oxygen metabolism and postoperative cognitive function in elderly surgical patients. METHODS: The patients were placed into burst suppression (BS) and non-burst suppression (NBS) groups. All patients were under bispectral index monitoring of an etomidate target-controlled infusion for anesthesia induction and intraoperative combination sevoflurane and remifentanil for anesthesia maintenance. The cerebral oxygen extraction ratio (CERO2), jugular bulb venous saturation (SjvO2), and difference in arteriovenous oxygen (Da-jvO2) were measured at T0, T1, and T2. One day before surgery, and 1, 3, and 7 days after surgery, postoperative cognitive dysfunction was assessed using the mini-mental state examination (MMSE). RESULTS: Compared with T0, the Da-jvO2 and CERO2 values were decreased, and SjvO2 was increased in the 2 groups at T1 and T2 (P < .05). There was no statistical difference in the SjvO2, Da-jvO2, and CERO2 values between T1 and T2. Compared with the NBS group, the SjvO2 value increased, and the Da-jvO2 and CERO2 values decreased at T1 and T2 in the BS group (P < .05). The MMSE scores on the 1st and 3rd days postoperatively were significantly lower in the 2 groups compared to the preoperative MMSE scores (P < .05). The MMSE scores of the NBS group were higher than the BS group on the 1st and 3rd days postoperatively (P < .05). CONCLUSION: In elderly patients undergoing surgery, intraoperative BS significantly reduced cerebral oxygen metabolism, which temporarily affected postoperative neurocognitive function.

Machine Learning-Based 30-Day Hospital Readmission Predictions for COPD Patients Using Physical Activity Data of Daily Living with Accelerometer-Based Device.

Chronic obstructive pulmonary disease (COPD) is a significantly concerning disease, and is ranked highest in terms of 30-day hospital readmission. Generally, physical activity (PA) of daily living reflects the health status and is proposed as a strong indicator of 30-day hospital readmission for patients with COPD. This study attempted to predict 30-day hospital readmission by analyzing continuous PA data using machine learning (ML) methods. Data were collected from 16 patients with COPD over 3877 days, and clinical information extracted from the patients' hospital records. Activity-based parameters were conceptualized and evaluated, and ML models were trained and validated to retrospectively analyze the PA data, identify the nonlinear classification characteristics of different risk factors, and predict hospital readmissions. Overall, this study predicted 30-day hospital readmission and prediction performance is summarized as two distinct approaches: prediction-based performance and event-based performance. In a prediction-based performance analysis, readmissions predicted with 70.35% accuracy; and in an event-based performance analysis, the total 30-day readmissions were predicted with a precision of 72.73%. PA data reflect the health status; thus, PA data can be used to predict hospital readmissions. Predicting readmissions will improve patient care, reduce the burden of medical costs burden, and can assist in staging suitable interventions, such as promoting PA, alternate treatment plans, or changes in lifestyle to prevent readmissions.

Takotsubo Syndrome Occurring after mRNA COVID-19 Vaccination in a Patient with Graves' Disease.

Cardiovascular events such as myocarditis following mRNA COVID-19 vaccination are increasing. We present a 67-year-old postmenopausal woman with Takotsubo Syndrome and Graves' disease after mRNA COVID-19 vaccination. She developed chest pain and shortness of breath one week after vaccination. An electrocardiogram revealed ST elevation in the precordial leads. Coronary angiography revealed the absence of obstructive coronary artery disease, and the left ventriculography showed a typical feature with apical ballooning. Laboratory workup showed the elevation of free T4 and thyrotropin receptor antibodies. It was presumed that Takotsubo Syndrome and Graves' disease were probably related to the COVID-19 mRNA vaccination. The patient was treated with low-dose bisoprolol, diuretics, carbimazole, and steroid and discharged uneventfully. The mRNA COVID-19 vaccination is still safe and effective to defend against COVID-19 pandemic. However, clinicians should be aware of the possible cardiovascular adverse events other than myocarditis following vaccination.

Anticancer Therapy and Mortality of Adult Patients with Hematologic Malignancy and COVID-19: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) might affect cancer treatment outcomes. This systematic review and meta-analysis identified the prognostic predictors of adult patients with hematologic malignancies and COVID-19, and evaluated the effect of anticancer therapy on mortality. We performed a literature search of electronic databases and identified additional studies from the bibliographies of the articles that were retrieved. Two investigators independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. We evaluated study quality using the Newcastle-Ottawa Scale and performed a meta-analyses in order to evaluate the effect of anticancer therapy on mortality among adult patients with hematologic malignancies and COVID-19. Heterogeneity was assessed with the I2 statistic. The meta-analysis included 12 studies. The overall mortality rate was 36.3%. The pooled risk difference (RD) in mortality between patients receiving and not receiving anticancer therapy was 0.14 (95% confidence interval [CI]: 0.02-0.26; I2 = 76%). The pooled RD in mortality associated with chemotherapy was 0.22 (95% CI: 0.05-0.39; I2 = 48%), and with immunosuppression was 0.20 (95% CI: 0.05-0.34; I2 = 67%). In the subgroup analyses, anticancer-therapy-associated mortality was higher in females (RD = 0.57; 95% CI: 0.29-0.85; I2 = 0%) than in males (RD = 0.28; 95% CI: 0.04-0.52; I2 = 0%). Among patients with hematologic malignancies and COVID-19, those receiving anticancer therapy had a higher mortality risk, regardless of sex. The mortality risk was higher in females than in males. These results indicate that caution should be exercised when administering anticancer therapy to patients with hematologic malignancies and COVID-19.

Trend in healthcare-associated infections due to vancomycin-resistant Enterococcus at a hospital in the era of COVID-19: More than hand hygiene is needed.

BACKGROUND: Variable control measures for vancomycin-resistant Enterococcus (VRE) infections were adopted among different hospitals and areas. We investigated the burden and patient characteristics of healthcare-associated VRE infections in 2018-2019 and 2020, when multiple preventive measures for COVID-19 were taken. METHODS: During the COVID-19 pandemic, mask waring and hand hygiene were enforced in the study hospital. The incidence densities of healthcare-associated infections (HAIs), including overall HAIs, methicillin-resistant Staphylococcus aureus (MRSA) HAIs, VRE HAIs, and VRE healthcare-associated bloodstream infections (HABSIs), consumption of broad-spectrum antibiotics and hygiene products, demographic characteristics and medical conditions of affected patients, were compared before and after the pandemic. RESULTS: The incidence density of both VRE HAIs and VRE HABSIs did not change statistically significantly, however, the highest in 2020 than that in 2018 and 2019. This was in spite of universal mask waring and increased consumption of 75% alcohol in 2020 and consistent implementation of an antibiotic stewardship program in three observed years. The increased prescriptions of broad-spectrum cephalosporins might partially explain the increase of VRE infection. CONCLUSION: Increased mask wearing and hand hygiene may not result in the decline in the development of VRE HAIs in the hospital during the COVID-19 pandemic, and continued monitoring of the dynamics of HAIs remains indispensable.

Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model.

Background: Drug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease. Methods: Here, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC50 = 0.4 µM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms. Results: Our in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals. Conclusions: We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Effective multipurpose sewage sludge and food waste reduction strategies: A focus on recent advances and future perspectives

Energy crisis and increasing rigorous management standards pose significant challenges for solid waste management worldwide. Several emerging diseases such as COVID-19 aggravated the already complex solid waste management crisis, especially sewage sludge and food waste streams, because of the increasingly large production year by year. As mature waste disposal technologies, landfills, incineration, composting, and some other methods are widespread for solid wastes management. This paper reviews recent advances in key sewage sludge disposal technologies. These include incineration, anaerobic digestion, and valuable products oriented-conversion. Food waste disposal technologies comprised of thermal treatment, fermentation, value-added product conversion, and composting have also been described. The hot topic and dominant research foci of each area are summarized, simultaneously compared with conventional technologies in terms of organic matter degradation or conversion performance, energy generation, and renewable resources production. Future perspectives of each technology that include issues not well understood and predicted challenges are discussed with a positive effect on the full-scale implementation of the discussed disposal methods.

Structural insights into Nirmatrelvir (PF-07321332)-3C-like SARS-CoV-2 protease complexation: a ligand Gaussian accelerated molecular dynamics study.

Coronavirus 3C-like protease (3CLpro) is found in SARS-CoV-2 virus, which causes COVID-19. 3CLpro controls virus replication and is a major target for target-based antiviral discovery. As reported by Pfizer, Nirmatrelvir (PF-07321332) is a competitive protein inhibitor and a clinical candidate for orally delivered medication. However, the binding mechanisms between Nirmatrelvir and 3CLpro complex structures remain unknown. This study incorporated ligand Gaussian accelerated molecular dynamics, the one-dimensional and two-dimensional potential of mean force, normal molecular dynamics, and Kramers' rate theory to determine the binding and dissociation rate constants (koff and kon) associated with the binding of the 3CLpro protein to the Nirmatrelvir inhibitor. The proposed approach addresses the challenges in designing small-molecule antiviral drugs.

Clinical features and characteristics of pediatric patients with COVID-19 infection: Experiences in a Tertiary Taiwan Hospital.

Coronavirus disease 2019 (COVID-19) patients have distinct clinical features in the pediatric groups. However, there is a paucity of research focused on clinical manifestation within pediatric group in Taiwan. This study is to conduct a retrospective study of the clinical features of COVID-19 in Taiwan pediatric patients. A retrospective study was conducted on pediatric patients (Aged ≤ 18 years) in a Northern Taiwan hospital from May 1st, 2021 to June 30th, 2021. Thirty-eight patients were included from emergency room. They were laboratory confirmed COVID-19 through specimens from nasopharyngeal swab by real-time reverse-transcription polymerase chain reaction (RT-PCR). Data including RT-PCR cycle threshold (Ct) values, clinical and epidemiological features were collected and analyzed. Thirty-eight patients aged from 7-month to 18-year-old were included. The median age of patients was 15-year-old. The patients had sex ratio of 23 males to 15 females. More than half patients were infected from family members. Asymptomatic patients were 47.37%. In the symptomatic patients, fever (34.21%) was the most predominant symptom. Cough, nasal obstruction and sore throat were also common. Asymptomatic children had significantly higher Ct-values than symptomatic children, and diagnosed patients with Ct-values more than 19 were associated with asymptomatic infection (P = .0084). Ct-values higher than 19 were associated with asymptomatic infection, which may be a predictor of pediatric disease severity. Our results highlight the distinct clinical manifestations and outcomes in pediatric COVID-19 patients. Compared to the adults, pediatric patients aged ≤ 18 years with COVID-19 in Taiwan mainly had mild disease.

Effort-reward imbalance and job strain index associated with health-related quality of life for civil servants in a national survey: the mediation effect of job support and over-commitment.

OBJECTIVES: Work-related stress (WRS) is significantly associated with health-related quality of life (HRQoL), but the amounts of evidence on differences of effort-reward imbalance (ERI) and job strain index (JSI) remain sparse and have limited generalizability. Therefore, we aimed to assess the association between ERI and JSI with HRQoL and assess the mediation effect of social support (JS) and over-commitment (OC) on this association in Taiwan's civil servants. MATERIAL AND METHODS: A cross-sectional national survey was given to registered civil servants in Taiwan - 20 046 civil servants from 647 institutions were enrolled using multistage stratified random cluster sampling. A web-questionnaire collected demographic information, job characteristics, and different indexes of ERI and job-control-demand-support (JCDS) models. Structural equation model (SEM) was used to examine the association between ERI and JSI with HRQoL, and the mediation effect of JS and OC on the associations. RESULTS: In the ERI model, ERI and OC were consistently negatively associated with the mental component score (MCS) (r = -0.46 and r = -0.37) and physical component score (PCS) (r = -0.45 and r = -0.34), which were higher than job demand (r = -0.28 and r = -0.22) and JSI (r = -0.38 and r = -0.29). Using hierarchical multiple regression analyses, ERI was significantly correlated with MCS and PCS, which was consistently higher than JSI. The ERI and JSI were significantly correlated with MCS (ß = -0.170 and ß = -0.140) and PCS (ß = -0.150 and ß = -0.082) using SEM analysis, whereas ERI was considerably higher than in JSI. In addition, OC and JS mediated the association between The ERI and JSI with HRQoL. CONCLUSIONS: We found the ERI index is significantly correlated with HRQoL superior to JSI, in particular among Taiwan civil servants. Further longitudinal studies are needed to determine the causality and spatiotemporal relation of these differences. Int J Occup Med Environ Health. 2022;35(4):425-36.

Non-Arteritic Anterior Ischemic Optic Neuropathy Following COVID-19 Vaccination.

People are advised to receive a vaccine booster as the Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge, but various adverse ocular reactions after vaccination have been reported. NAION following COVID-19 vaccination appears extremely rarely. Here, we report a case of a 61-year-old female with sudden painless blurred vision developing NAION after receiving ChAdOx1 nCoV-19 (AstraZeneca) vaccination and provide an in-depth explanation of the possible mechanisms regarding the hypercoagulable state after vaccination. Our report adds to the literature on potential adverse ocular effects after COVID-19 vaccination, and we as ophthalmologists recommend that clinicians should increase awareness of this possible ocular complication when evaluating patients with sudden visual disturbance with a recent history of vaccination.

Rapid sentinel surveillance for COVID-19 - Santa Clara County, California, March 2020

On February 27, 2020, Santa Clara County, California, identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission. During March 5-14, among patients with respiratory symptoms evaluated at one of four Santa Clara County urgent care centers serving as sentinel surveillance sites, 23% had positive test results for influenza. Among a subset of patients with negative test results for influenza, 11% had positive test results for COVID-19. COVID-19 cases identified through this sentinel surveillance system helped confirm community transmission in the county. Local health departments can use sentinel surveillance to understand the level of community transmission of COVID-19 and to better guide the selection and implementation of community mitigation measures.

Genomic Epidemiology and Transmission Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Congregate Healthcare Facilities in Santa Clara County, California.

BACKGROUND: Outbreaks of SARS-CoV-2 in long-term care facilities (LTCFs) cause significant morbidity and mortality. Mapping viral transmission within and between facilities by combining genomic sequencing with epidemiologic investigations enables targeting infection-control interventions. METHODS: We conducted weekly surveillance of residents and staff in LTCFs in Santa Clara County, California, with ≥1 confirmed COVID-19 case between March and July 2020. Positive samples were referred for whole-genome sequencing. Epidemiological investigations and phylogenetic analyses of the largest outbreaks (>30 cases) were carried out in 6 LTCFs (Facilities A through F). RESULTS: Among the 61 LTCFs in the county, 41 had ≥1 confirmed case during the study period, triggering weekly SARS-CoV-2 testing. The 6 largest outbreaks accounted for 60% of cases and 90% of deaths in LTCFs, although the bed capacity of these facilities represents only 11% of the LTCF beds in the county. Phylogenetic analysis of 196 whole-genome sequences recovered from those facilities showed that each outbreak was monophyletic, with staff and residents sharing a common viral lineage. Outbreak investigations revealed that infected staff members often worked at multiple facilities, and in 1 instance, a staff member infected while working in 1 facility was the likely index case in another. CONCLUSIONS: We detected a pattern of rapid and sustained transmission after a single introduction of SARS-CoV-2 in 6 large LTCF outbreaks, with staff playing a key role in transmission within and between facilities. Infection control, testing, and occupational policies to reduce exposure and transmission risk for staff are essential components to keeping facility residents safe.

Dynamic Changes of the Blood Chemistry in Syrian Hamsters Post-Acute COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 2019 (COVID-19). However, the long-term health consequences of COVID-19 are not fully understood. We aimed to determine the long-term lung pathology and blood chemistry changes in Syrian hamsters infected with SARS-CoV-2. Syrian hamsters (Mesocricetus auratus) were inoculated with 105 PFU of SARS-CoV-2, and changes post-infection (pi) were observed for 20 days. On days 5 and 20 pi, the lungs were harvested and processed for pathology and viral load count. Multiple blood samples were collected every 3 to 5 days to observe dynamic changes in blood chemistry. Infected hamsters showed consistent weight loss until day 7 pi At day 5 pi, histopathology of the lungs showed moderate to severe inflammation and the virus could be detected. These results indicate that SARS-CoV-2 has an acute onset and recovery course in the hamster infection model. During the acute onset, blood triglyceride levels increased significantly at day 3 pi During the recovery course, uric acid and low-density lipoprotein levels increased significantly, but the total protein and albumin levels decreased. Together, our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. IMPORTANCE COVID-19 is now considered a multiorgan disease with a wide range of manifestations. There are increasing reports of persistent and long-term effects after acute COVID-19, but the long-term health consequences of COVID-19 are not fully understood. This study reported for the first time the use of blood samples collected continuously in a SARS-CoV-2-infected hamster model, which provides more information about the dynamic changes in blood biochemistry during the acute and recovery phases of SARS-CoV-2 infection. Our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. The study may be used by several researchers and clinicians, especially those who are studying potential treatments for patients with post-acute COVID-19 syndrome.

A study investigating user adoptive behavior and the continuance intention to use mobile health applications during the COVID-19 pandemic era: Evidence from the telemedicine applications utilized in Indonesia

During the COVID-19 pandemic era that began in 2020, there has been a growing trend in the literature to tackle the problem of health stress (HS) for promoting a sense of public health. In turn, this developing area of research has a high level of relevancy linked to business and economic recovery (Čvirik, 2020). Since HS has increased sharply during the COVID-19 pandemic era, there has been a need to further investigate the balance between coping with HS and the positive continuous intention to use mobile health applications (mHealth apps) among the public. This is the first study that takes the Asia-Pacific region as its case study and empirically investigates the validity of extensions based on the theories of expectation confirmation theory (ECT) (Bhattacherjee, 2001) on user continuous behavior relating to mHealth apps during the COVID-19 pandemic. Results reveal that HS as an emotion can positively affect perceived usefulness and satisfaction in relation to the continuous intention to use mHealth apps. The differences between new and frequent users are confirmed. Discussion and implications for practices are provided in the end.