Protocol for an OpenSAFELY cohort study collecting patient-reported outcome measures using the TPP Airmid smartphone application and linked big data to quantify the health and economic costs of long COVID (OpenPROMPT).

INTRODUCTION: The impact of long COVID on health-related quality of-life (HRQoL) and productivity is not currently known. It is important to understand who is worst affected by long COVID and the cost to the National Health Service (NHS) and society, so that strategies like booster vaccines can be prioritised to the right people. OpenPROMPT aims to understand the impact of long COVID on HRQoL in adults attending English primary care. METHODS AND ANALYSIS: We will ask people to participate in this cohort study through a smartphone app (Airmid), and completing a series of questionnaires held within the app. Questionnaires will ask about HRQoL, productivity and symptoms of long COVID. Participants will be asked to fill in the questionnaires once a month, for 90 days. Questionnaire responses will be linked, where possible, to participants' existing health records from primary care, secondary care, and COVID testing and vaccination data. Analysis will take place using the OpenSAFELY data platform and will estimate the impact of long COVID on HRQoL, productivity and cost to the NHS. ETHICS AND DISSEMINATION: The Proportionate Review Sub-Committee of the South Central-Berkshire B Research Ethics Committee has reviewed and approved the study and have agreed that we can ask people to take part (22/SC/0198). Our results will provide information to support long-term care, and make recommendations for prevention of long COVID in the future. TRIAL REGISTRATION NUMBER: NCT05552612.

SARS-CoV-2 NSP12 utilizes various host splicing factors for replication and splicing regulation (preprint)

Background The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses SARS-CoV-2, SARS-CoV, and MARS-CoV have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. Results In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8), suggesting that the polymerase activity and stability of SARS-CoV-2 RdRp were affected by them to varying degrees. Furthermore, the entry efficacy of SARS-CoV-2 pseudovirus considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. In addition, NSP12 and its homologues from SARS-CoV and MARS-CoV suppressed thealternative splicing (AS) of cellular genes, which were influenced by the three splicing factors. Conclusions Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.

Study on Education Inequality of Differentiated Groups in Remote Learning During COVID-19

In the COVID-19 pandemic, schooling systems across all levels have been forced into remote teaching dramatically and massively. It is critical to examine how education practitioners and students have responded to the goals and practices of schooling, and the progress of education equity issues in educational institutions against the background of such significant social change. Therefore, this article first focuses on the controversy of equity in the policy of citizen mobilization in times of pandemic, to underline the errors of different pandemic measures. Second, scrutinize the challenges faced by group differences in schooling in the context of the current pandemic from the angle of educational equity. Finally, we urge schooling systems to introduce the principle of inclusion of group differences from the very beginning of education provision. By so doing, the existing conditions of group differences can be recognized and the rights of different groups can be supported.

Validation of Viral Inactivation Protocols for Therapeutic Blood Products against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2).

Therapeutic blood products including convalescent plasma/serum and immunoglobulins concentrated from convalescent plasma, such as intravenous immunoglobulins or hyperimmune globulins, and monoclonal antibodies are passive immunotherapy options for novel coronavirus disease 2019 (COVID-19). They have been shown to improve the clinical status and biological and radiological parameters in some groups of COVID-19 patients. However, blood products are still potential sources of virus transmission in recipients. The use of pathogen reduction technology (PRT) should increase the safety of the products. The purpose of this study was to determine the impact of solvent/detergents (S/D) procedures on SARS-COV-2 infectivity elimination in the plasma of donors but also on COVID-19 convalescent serum (CCS) capacity to neutralize SARS-COV-2 infectivity. In this investigation, S/D treatment for all experiments was performed at a shortened process time (30 min). We first evaluated the impact of S/D treatments (1% TnBP/1% TritonX-45 and 1% TnBP/1% TritonX-100) on the inactivation of SARS-COV-2 pseudoparticles (SARS-COV-2pp)-spiked human plasma followed by S/D agent removal using a Sep-Pak Plus C18 cartridge. Both treatments were able to completely inactivate SARS-COV-2pp infectivity to an undetectable level. Moreover, the neutralizing activity of CCS against SARS-COV-2pp was preserved after S/D treatments. Our data suggested that viral inactivation methods using such S/D treatments could be useful in the implementation of viral inactivation/elimination processes of therapeutic blood products against SARS-COV-2.

15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions: 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.

The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank.

BACKGROUND: Recent studies indicate that vitamin D supplementation may decrease respiratory tract infections, but the association between vitamin D and COVID-19 is still unclear. OBJECTIVE: To explore the association between vitamin D status and infections, hospitalisation, and mortality due to COVID-19. METHODS: We used UK Biobank, a nationwide cohort of 500,000 individuals aged between 40 and 69 years at recruitment between 2006 and 2010. We included people with at least one serum vitamin D test, living in England with linked primary care and inpatient records. The primary exposure was serum vitamin D status measured at recruitment, defined as deficiency at <25 nmol/L, insufficiency at 25-49 nmol/L and sufficiency at ≥ 50 nmol/L. Secondary exposures were self-reported or prescribed vitamin D supplements. The primary outcome was laboratory-confirmed or clinically diagnosed SARS-CoV-2 infections. The secondary outcomes included hospitalisation and mortality due to COVID-19. We used multivariable Cox regression models stratified by summertime months and non-summertime months, adjusting for demographic factors and underlying comorbidities. RESULTS: We included 307,512 participants (54.9% female, 55.9% over 70 years old) in our analysis. During summertime months, weak evidence existed that the vitamin D deficiency group had a lower hazard of being diagnosed with COVID-19 (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77-0.95). During non-summertime, the vitamin D deficiency group had a higher hazard of COVID-19 compared with the vitamin D sufficient group (HR = 1.14, 95% CI = 1.01-1.30). No evidence was found that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time strata. CONCLUSION: We found no evidence of an association between historical vitamin D status and hospitalisation or mortality due to COVID-19, along with inconsistent results for any association between vitamin D and diagnosis of COVID-19. However, studies using more recent vitamin D measurements and systematic COVID-19 testing are needed.

A Comparative Study of Positive and Negative Electronic Word-of-Mouth on the SERVQUAL Scale under the COVID-19 epidemic -Taking a Regional Teaching Hospital in Taiwan as an Example (preprint)

Background In recent years, studies have disclosed that electronic WOM (eWOM) more directly reflects consumers' post-purchase psychological perception, and directly affects repurchase behavior, which is valued by institutions in various fields. Within the scope of service characteristic evaluation, medical service is the most invisible and difficult to evaluate service attribute. They are service organizations that must have high trust attributes. Therefore, the eWOM review will significantly influence people's decision-making process for choosing a healthcare provider. The purpose of this research is to combine eWOM reviews with the SERVQUAL scale in a comparative study of positive and negative eWOM reviews of a certain regional teaching hospital in Taiwan.Methods This research obtained data of eWOM reviews publicly available on Google maps from a Regional Teaching hospital in Taiwan in the past 10 years (from June 24, 2011, to December 31, 2021) by using website scraping technology. The semantic content analysis method was used in this study to classify WOM reviews according to the revised PZB SERVQUAL scale.Results Statistical analysis is then conducted. During the COVID-19 pandemic, the positive reviews have shown a downward trend. Among the five determiners of SERVQUAL of PZB, positive WOM reviews performed best in “Assurance”, with a positive review rate of 60.00%, followed by 42.11% of “Reliability”. In negative WOM reviews, “Assurance” performed the worst, with a positive rate of 72.34%, followed by “Responsiveness” at 28.37% and “Reliability” at 26.95%.Conclusion Since the onset of the COVID-19 in 2020, negative eWOM has increased significantly and exceeded the numbers of positive eWOM. Regardless of the positive and negative reviews, what patients care most about is “Assurance” of the professional attitude and skills of the medical staff, which needs to be strengthened most urgently. In addition, good “Reliability” will help to build up positive eWOM. However, the "Responsiveness" of poor service waiting time can easily lead to the spread of negative eWOM. This study suggests that the hospital management should focus on these few service-oriented qualities.

Pandemic strategies with computational and structural biology against COVID-19: A retrospective.

The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic, has dominated all aspects of life since of 2020. Research studies on the virus and exploration of therapeutic and preventive strategies has been moving at rapid rates to control the pandemic. In the field of bioinformatics or computational and structural biology, recent research strategies have used multiple disciplines to compile large datasets to uncover statistical correlations and significance, visualize and model proteins, perform molecular dynamics simulations, and employ the help of artificial intelligence and machine learning to harness computational processing power to further the research on COVID-19, including drug screening, drug design, vaccine development, prognosis prediction, and outbreak prediction. These recent developments should help us better understand the viral disease and develop the much-needed therapies and strategies for the management of COVID-19.

Analysis of factors affecting virus survival on object surface and in air

The contagion of the new coronavirus pneumonia (COVID-19) not only seriously endangers the safety of human, but also affects the development of the national economy. There are few reports on factors influencing the transmission of 2019-nCoV, such as environmental conditions (humidity and temperature), air pollution, and human activities. It is difficult to sample and research 2019-nCoV directly. Therefore, it is significant to investigate the factors influencing the spread and survival of other similar viruses, which is instructional for the prevention of epidemics and the control of 2019-nCoV transmission. The results show that: (1) Low temperature and low humidity could prolong the lifetime and increase the transmission of coronavirus, especially on dry surfaces. For example, coronavirus can survive on a smooth surface at a temperature of 22-25 degrees C and a relative humidity (RH) of 40%-45% for more than 5 days. (2) Similarly, the survival rates of the aerosolized coronavirus is also high in a closed environment at low temperature and low humidity, 2019-nCoV may hold high survival rates at a temperature of 20-25 degrees C and a relative humidity of 30%-50%. (3) The higher the particle concentration, the risk of 2019-nCoV transmission may increase. (4) The behavior of infected people also plays a important role in the transmission of 2019-nCoV. The transmission of virus can be reduced by avoiding sneezing and coughing in the crowd, and blocking the transmission of droplets using hands, elbows or other objects. Considering the above analysis, some suggestions for the prevention and control the epidemics are made, such as improving the indoor microenvironment, investigating the detection, inactivation, influence factors and propagation characteristics of 2019-nCoV.

Elevation in viral entry genes and innate immunity compromise underlying increased infectivity and severity of COVID-19 in cancer patients.

Multiple studies have reported a doubling in risk of Coronavirus Disease-2019 (COVID-19) among cancer patients. Here, we examine the potential biological rationale behind this recurrent epidemiological observation. By leveraging large-scale genome-wide transcriptional data of normal and malignant tissues from adults and children, we found evidence of increased expression of SARS-CoV-2 viral entry genes in the cancer state, particularly in respiratory, gastrointestinal, and genitourinary tract tissues, with decreased expression in pediatric vs. adult samples. Additionally, by interrogating the temporal effects of radiotherapy on human peripheral blood mononuclear and mucosal cells, we observed important treatment-related alterations in host innate immunity, specifically type I interferon responses. Overall, cancers enhance expression of critical viral entry genes, and innate viral defenses can be dysregulated transiently during radiation treatments. These factors may contribute to the observed increased susceptibility to SARS-CoV-2 entry and severity of COVID-19 in cancer patients.

Update on Antiviral Strategies Against COVID-19: Unmet Needs and Prospects.

By December 2020, the COVID-19 pandemic had caused more than 74 million confirmed cases and 1.6 million related deaths around the world. However, only a few drugs have been approved in certain areas and for use in conditional patients, and the vaccine candidates were only recently approved or authorized for emergency use without being fully implemented worldwide, suggesting that we are yet to reach effective control of the current outbreak as its uninhibited transmission continues precariously. Over the past few months, several therapeutic candidates have been proven ineffective in large clinical trials, while some other agents exhibited promising preliminary results. Meanwhile, the investigation of SARS-CoV-2-specific antivirals is underway. Despite still being preclinical, these agents could be beneficial for the long-term control of COVID-19 and deserve more research focus. In this article, we update the current status of therapeutic candidates that have been examined for COVID-19 management, including the virus-targeting inhibitors and host-targeting agents, with their antiviral efficacy in vitro, in vivo, and in clinical studies. Finally, we highlight the current challenges and future prospect of developing potent therapeutic agents against COVID-19.

Covid-19 mortality is associated with test number and government effectiveness (preprint)

Objectives: A question central to the Covid-19 pandemic is why the Covid-19 mortality rate varies so greatly across countries. This study aims to investigate factors associated with cross-country variation in Covid-19 mortality.Methods: Covid-19 mortality rate was calculated as number of deaths per 100 Covid-19 cases. To identify factors associated with Covid-19 mortality rate, a multivariable linear regression model was applied to a cross-sectional dataset comprising 78 countries and 1,790,550 patients infected by Covid-19. We retrieved data from the Worldometer website and the Worldwide Governance Indicators and World Development Indicators databases.Results: Covid-19 mortality rate was negatively associated with Covid-19 test number per 1,000 population (RR=0.97; 95% CI 0.96 to 0.99, P=0.013) and government effectiveness indicator (RR=0.96; 95% CI 0.93 to 0.98, P=0.001). Covid-19 mortality rate was positively associated with number of critical cases per 100 Covid-19 cases, Covid-19 case number per 10,000 population, proportion of population aged 65 or older and proportion of deaths attributable to communicable diseases in previous years (all with P<0.05). Predicted mortality rates were highly associated with observed mortality rates (r = 0.74; P<0.001).Conclusions: Multiple factors were associated with Covid-19 mortality rates. Increasing Covid-19 testing and improving government effectiveness may have the potential to attenuate Covid-19 mortality.Authors Li-Lin Liang and Chun-Ying Wu contributed equally to this work.

Use of radiographic features in COVID-19 diagnosis: Challenges and perspectives.

The rapid surge and wide spread of the coronavirus disease-2019 (COVID-19) overshadows the entire medical industries worldwide. The stringent medical resources hinder the diagnostic capacity globally, while 84 000 of new cases confirmed within a single day of April 14, 2020. Real-time reverse-transcription polymerase chain reaction (RT-PCR) with is the current first-line diagnosis, but the false-negative rate remains concerned. Radiographic technologies and tools, including computed tomography (CT) and chest X-ray, were applied for initial screening and follow-up, from which the tools provide detail diagnosis with specific pathologic features for staging and treatment arrangement. Although the radiographic imaging is found less sensitive, numerous CT-positive patients were not screened out by RT-PCR initially and later confirmed as COVID-19 positive. Besides, the shortage of sampling kits and the longer turn-over time of PCR examinations in some areas were noticed due to logistic issues and healthcare burden. In this review, we will discuss the challenges and the future perspectives of using radiographic modalities for COVID-19 diagnosis in view of securing human lives amid the crisis.