The photolytic behavior of COVID-19 antivirals ribavirin in natural waters and the increased environmental risk

Increasing drug residues in aquatic environments have been caused by the abuse of antivirals since the global spread of the COVID-19 epidemic, whereas research on the photolytic mechanism, pathways and toxicity of these drugs is limited. The concentration of COVID-19 antivirals ribavirin in rivers has been reported to increase after the epidemic. Its photolytic behavior and environmental risk in actual waters such as wastewater treatment plant (WWTP) effluent, river water and lake water were first investigated in this study. Direct photolysis of ribavirin in these media was limited, but indirect photolysis was promoted in WWTP effluent and lake water by dissolved organic matter and NO3−. Identification of photolytic intermediates suggested that ribavirin was photolyzed mainly via C−N bond cleavage, splitting of the furan ring and oxidation of the hydroxyl group. Notably, the acute toxicity was increased after ribavirin photolysis owing to the higher toxicity of most of the products. Additionally, the overall toxicity was greater when ARB photolysis in WWTP effluent and lake water. These findings emphasize the necessity to concern about the toxicity of ribavirin transformation in natural waters, as well as to limit its usage and discharge. Graphical

The photolytic behavior of COVID-19 antivirals ribavirin in natural waters and the increased environmental risk.

Increasing drug residues in aquatic environments have been caused by the abuse of antivirals since the global spread of the COVID-19 epidemic, whereas research on the photolytic mechanism, pathways and toxicity of these drugs is limited. The concentration of COVID-19 antivirals ribavirin in rivers has been reported to increase after the epidemic. Its photolytic behavior and environmental risk in actual waters such as wastewater treatment plant (WWTP) effluent, river water and lake water were first investigated in this study. Direct photolysis of ribavirin in these media was limited, but indirect photolysis was promoted in WWTP effluent and lake water by dissolved organic matter and NO3-. Identification of photolytic intermediates suggested that ribavirin was photolyzed mainly via C-N bond cleavage, splitting of the furan ring and oxidation of the hydroxyl group. Notably, the acute toxicity was increased after ribavirin photolysis owing to the higher toxicity of most of the products. Additionally, the overall toxicity was greater when ARB photolysis in WWTP effluent and lake water. These findings emphasize the necessity to concern about the toxicity of ribavirin transformation in natural waters, as well as to limit its usage and discharge.

Midwest rural-urban disparities in use of patient online services for COVID-19.

PURPOSE: Rural populations are disproportionately affected by the COVID-19 pandemic. We characterized urban-rural disparities in patient portal messaging utilization for COVID-19, and, of those who used the portal during its early stage in the Midwest. METHODS: We collected over 1 million portal messages generated by midwestern Mayo Clinic patients from February to August 2020. We analyzed patient-generated messages (PGMs) on COVID-19 by urban-rural locality and incorporated patients' sociodemographic factors into the analysis. FINDINGS: The urban-rural ratio of portal users, message senders, and COVID-19 message senders was 1.18, 1.31, and 1.79, indicating greater use among urban patients. The urban-rural ratio (1.69) of PGMs on COVID-19 was higher than that (1.43) of general PGMs. The urban-rural ratios of messaging were 1.72-1.85 for COVID-19-related care and 1.43-1.66 for other health care issues on COVID-19. Compared with urban patients, rural patients sent fewer messages for COVID-19 diagnosis and treatment but more messages for other reasons related to COVID-19-related health care (eg, isolation and anxiety). The frequent senders of COVID-19-related messages among rural patients were 40+ years old, women, married, and White. CONCLUSIONS: In this Midwest health system, rural patients were less likely to use patient online services during a pandemic and their reasons for its use differ from urban patients. Results suggest opportunities for increasing equity in rural patient engagement in patient portals (in particular, minority populations) for COVID-19. Public health intervention strategies could target reasons why rural patients might seek health care in a pandemic, such as social isolation and anxiety.

Research advances on coronavirus disease 2019

This article reviewed the global research advances of corona virus disguise 2019 (COVID-19) from December 1st, 2019 to February 23rd, 2020, including etiology, clinical characteristics, diatomic and treatment and epidemiology. The main issues that remain unclear had been raised.

Allosteric aptasensor-initiated target cycling and transcription amplification of light-up RNA aptamer for sensitive detection of protein.

The early detection of biomarker proteins in clinical samples is of great significance for the diagnosis of diseases. However, it is still a challenge to detect low-concentration protein. Herein, a label-free aptamer-based amplification assay, termed the ATC-TA system, that allows fluorescence detection of very low numbers of protein without time-consuming washing steps and pre-treatment was developed. The target induces a conformational change in the allosteric aptasensor, triggers the target cycling and transcription amplification, and ultimately converts the input of the target protein into the output of the light-up aptamer (R-Pepper). It exhibits ultrahigh sensitivity with a detection limit of 5.62 fM at 37 â„ƒ and the accuracy is comparable to conventional ELISA. ATC-TA has potential application for the detection of endogenous PDGF-BB in serum samples to distinguish tumor mice from healthy mice at an early stage. It also successfully detects exogenous SARS-CoV-2 spike proteins in human serum. Therefore, this high-sensitive, universality, easy-to-operate and cost-effective biosensing platform holds great clinical application potential in early clinical diagnosis.

Treatment of MDA5-positive dermatomyositis complicated by gangrenous cholecystitis with tofacitinib.

BACKGROUND: Dermatomyositis is a rare idiopathic inflammatory disease with diverse presentations that can have varying degrees of cutaneous and systemic involvement. This phenotypic heterogeneity makes DM a therapeutic challenge. Some therapeutic drugs, such as hormones and immunosuppressants, have poor therapeutic effects. In recent years, tofacitinib has been reported to be effective in the treatment of dermatomyositis. CASE PRESENTATION: We report a case of anti-MDA5 antibody-positive dermatomyositis that was relieved after treatment with tofacitinib, during which gallbladder gangrene and suppurative cholecystitis occurred. After cholecystectomy, we continued to use tofacitinib and achieved a good therapeutic effect. CONCLUSIONS: Tofacitinib is effective in the treatment of anti-MDA5 antibody-positive dermatomyositis, but the risk of infection is increased. It can still be used after infection control. Close follow-up should be performed during the use of tofacitinib.

Patient Portal Messaging for Asynchronous Virtual Care During the COVID-19 Pandemic: Retrospective Analysis.

BACKGROUND: During the COVID-19 pandemic, patient portals and their message platforms allowed remote access to health care. Utilization patterns in patient messaging during the COVID-19 crisis have not been studied thoroughly. In this work, we propose characterizing patients and their use of asynchronous virtual care for COVID-19 via a retrospective analysis of patient portal messages. OBJECTIVE: This study aimed to perform a retrospective analysis of portal messages to probe asynchronous patient responses to the COVID-19 crisis. METHODS: We collected over 2 million patient-generated messages (PGMs) at Mayo Clinic during February 1 to August 31, 2020. We analyzed descriptive statistics on PGMs related to COVID-19 and incorporated patients' sociodemographic factors into the analysis. We analyzed the PGMs on COVID-19 in terms of COVID-19-related care (eg, COVID-19 symptom self-assessment and COVID-19 tests and results) and other health issues (eg, appointment cancellation, anxiety, and depression). RESULTS: The majority of PGMs on COVID-19 pertained to COVID-19 symptom self-assessment (42.50%) and COVID-19 tests and results (30.84%). The PGMs related to COVID-19 symptom self-assessment and COVID-19 test results had dynamic patterns and peaks similar to the newly confirmed cases in the United States and in Minnesota. The trend of PGMs related to COVID-19 care plans paralleled trends in newly hospitalized cases and deaths. After an initial peak in March, the PGMs on issues such as appointment cancellations and anxiety regarding COVID-19 displayed a declining trend. The majority of message senders were 30-64 years old, married, female, White, or urban residents. This majority was an even higher proportion among patients who sent portal messages on COVID-19. CONCLUSIONS: During the COVID-19 pandemic, patients increased portal messaging utilization to address health care issues about COVID-19 (in particular, symptom self-assessment and tests and results). Trends in message usage closely followed national trends in new cases and hospitalizations. There is a wide disparity for minority and rural populations in the use of PGMs for addressing the COVID-19 crisis.

Effective degradation of COVID-19 related drugs by biochar-supported red mud catalyst activated persulfate process: Mechanism and pathway.

With the global spread of the COVID-19 pandemic, the water pollution caused by extensive production and application of COVID-19 related drugs has aroused growing attention. Herein, a novel biochar-supported red mud catalyst (RM-BC) containing abundant free hydroxyl groups was synthesized. The RM-BC activated persulfate process was firstly put forward to degrade COVID-19 related drugs, including arbidol (ARB), chloroquine phosphate, hydroxychloroquine sulfate, and acyclovir. Highly effective removal of these pharmaceuticals was achieved and even 100% of ARB was removed within 12 min at optimum conditions. Mechanism study indicated that SO4 •- and HO• were the predominant radicals, and these radicals were responsible for the formation of DMPOX in electron spin resonance experiments. Fe species (Fe0 and Fe3O4) and oxygen-containing functional groups in RM-BC played crucial roles in the elimination of ARB. Effects of degradation conditions and several common water matrices were also investigated. Finally, the degradation products of ARB were identified by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and possible degradation pathways were proposed. This study demonstrated that RM-BC/PS system would have great potential for the removal of COVID-19 related drug residues in water by the catalyst synthesized from the solid waste.

Comparison of Clinical Characteristics for Distinguishing COVID-19 From Influenza During the Early Stages in Guangdong, China.

Background: To explore the differences in clinical manifestations and infection marker determination for early diagnosis of coronavirus disease-2019 (COVID-19) and influenza (A and B). Methods: A hospital-based retrospective cohort study was designed. Patients with COVID-19 and inpatients with influenza at a sentinel surveillance hospital were recruited. Demographic data, medical history, laboratory findings, and radiographic characteristics were summarized and compared between the two groups. The chi-square test or Fisher's exact test was used for categorical variables, and Kruskal-Wallis H-test was used for continuous variables in each group. Receiver operating characteristic curve (ROC) was used to differentiate the intergroup characteristics. The Cox proportional hazards model was used to analyze the predisposing factors. Results: About 23 patients with COVID-19 and 74 patients with influenza were included in this study. Patients with influenza exhibited more symptoms of cough and sputum production than COVID-19 (p < 0.05). CT showed that consolidation and pleural effusion were more common in influenza than COVID-19 (p < 0.05). Subgroup analysis showed that patients with influenza had high values of infection and coagulation function markers, but low values of blood routine and biochemical test markers than patients with COVID-19 (mild or moderate groups) (p < 0.05). In patients with COVID-19, the ROC analysis showed positive predictions of albumin and hematocrit, but negative predictions of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and erythrocyte sedimentation rate. Multivariate analysis revealed that influenza might associate with risk of elevated CRP, PCT, and LDH, whereas COVID-19 might associated with high HBDH. Conclusion: Patients with influenza had more obvious clinical symptoms but less common consolidation lesions and pleural effusion than those with COVID-19. These findings suggested that influenza likely presents with stronger inflammatory reactions than COVID-19, which provides some insights into the pathogenesis of these two contagious respiratory illnesses.

Reopening International Borders without Quarantine: Contact Tracing Integrated Policy against COVID-19.

With the COVID-19 vaccination widely implemented in most countries, propelled by the need to revive the tourism economy, there is a growing prospect for relieving the social distancing regulation and reopening borders in tourism-oriented countries and regions. This need incentivizes stakeholders to develop border control strategies that fully evaluate health risks if mandatory quarantines are lifted. In this study, we have employed a computational approach to investigate the contact tracing integrated policy in different border-reopening scenarios in Hong Kong, China. Explicitly, by reconstructing the COVID-19 transmission from historical data, specific scenarios with joint effects of digital contact tracing and other concurrent measures (i.e., controlling arrival population and community nonpharmacological interventions) are applied to forecast the future development of the pandemic. Built on a modified SEIR epidemic model with a 30% vaccination coverage, the results suggest that scenarios with digital contact tracing and quick isolation intervention can reduce the infectious population by 92.11% compared to those without contact tracing. By further restricting the inbound population with a 10,000 daily quota and applying moderate-to-strong community nonpharmacological interventions (NPIs), the average daily confirmed cases in the forecast period of 60 days can be well controlled at around 9 per day (95% CI: 7-12). Two main policy recommendations are drawn from the study. First, digital contact tracing would be an effective countermeasure for reducing local virus spread, especially when it is applied along with a moderate level of vaccination coverage. Second, implementing a daily quota on inbound travelers and restrictive community NPIs would further keep the local infection under control. This study offers scientific evidence and prospective guidance for developing and instituting plans to lift mandatory border control policies in preparing for the global economic recovery.

Detection of Virus-Related Sequences Associated With Potential Etiologies of Hepatitis in Liver Tissue Samples From Rats, Mice, Shrews, and Bats.

Hepatitis is a major global health concern. However, the etiology of 10-20% hepatitis cases remains unclear. Some hepatitis-associated viruses, like the hepatitis E virus, are zoonotic pathogens. Rats, shrews, and bats are reservoirs for many zoonotic pathogens. Therefore, understanding the virome in the liver of these animals is important for the investigation of the etiologies of hepatitis and monitoring the emerging zoonotic viruses. In this study, viral metagenomics and PCR methods were used to investigate viral communities in rats, mice, house shrews, and bats livers. Viral metagenomic analysis showed a diverse set of sequences in liver samples, comprising: sequences related to herpesviruses, orthomyxoviruses, anelloviruses, hepeviruses, hepadnaviruses, flaviviruses, parvoviruses, and picornaviruses. Using PCR methods, we first detected hepatovirus sequences in Hipposideros larvatus (3.85%). We also reported the first detection of Zika virus-related sequences in rats and house shrews. Sequences related to influenza A virus and herpesviruses were detected in liver. Higher detection rates of pegivirus sequences were found in liver tissue and serum samples from rats (7.85% and 15.79%, respectively) than from house shrews. Torque teno virus sequences had higher detection rates in the serum samples of rats and house shrews (52.72% and 5.26%, respectively) than in the liver. Near-full length genomes of pegivirus and torque teno virus were amplified. This study is the first to compare the viral communities in the liver of bats, rats, mice, and house shrews. Its findings expand our understanding of the virome in the liver of these animals and provide an insight into hepatitis-related viruses.

An aberration detection-based approach for sentinel syndromic surveillance of COVID-19 and other novel influenza-like illnesses.

Coronavirus Disease 2019 has emerged as a significant global concern, triggering harsh public health restrictions in a successful bid to curb its exponential growth. As discussion shifts towards relaxation of these restrictions, there is significant concern of second-wave resurgence. The key to managing these outbreaks is early detection and intervention, and yet there is a significant lag time associated with usage of laboratory confirmed cases for surveillance purposes. To address this, syndromic surveillance can be considered to provide a timelier alternative for first-line screening. Existing syndromic surveillance solutions are however typically focused around a known disease and have limited capability to distinguish between outbreaks of individual diseases sharing similar syndromes. This poses a challenge for surveillance of COVID-19 as its active periods tend to overlap temporally with other influenza-like illnesses. In this study we explore performing sentinel syndromic surveillance for COVID-19 and other influenza-like illnesses using a deep learning-based approach. Our methods are based on aberration detection utilizing autoencoders that leverages symptom prevalence distributions to distinguish outbreaks of two ongoing diseases that share similar syndromes, even if they occur concurrently. We first demonstrate that this approach works for detection of outbreaks of influenza, which has known temporal boundaries. We then demonstrate that the autoencoder can be trained to not alert on known and well-managed influenza-like illnesses such as the common cold and influenza. Finally, we applied our approach to 2019-2020 data in the context of a COVID-19 syndromic surveillance task to demonstrate how implementation of such a system could have provided early warning of an outbreak of a novel influenza-like illness that did not match the symptom prevalence profile of influenza and other known influenza-like illnesses.