Transcription regulation of SARS-CoV-2 receptor ACE2 by Sp1: a potential therapeutic target (preprint)

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of ACE2 expression may represent an effective tactic employed by SARS-CoV-2 to facilitate its own propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. By employing an array of 45 different luciferase reporters, we identify that the transcription factor Sp1 positively and HNF4 negatively regulate the expression of ACE2 at the transcriptional levels in HPAEpiC cells, a human lung epithelial cell line. SARS-CoV-2 infection promotes and inhibits the transcription activity of Sp1 and HNF4, respectively. The PI3K/AKT signaling pathway, which is activated by SARS-CoV-2 infection, is a crucial node for induction of ACE2 expression by increasing Sp1 phosphorylation, an indicator of its activity, and reducing HNF4 nuclear location. Furthermore, we show that colchicine could inhibit the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. Inhibition of Sp1 by either its inhibitor mithramycin A or colchicine reduces viral replication and tissue injury in Syrian hamsters infected with SARS-CoV-2. In summary, our study uncovers a novel function of Sp1 in regulating ACE2 expression and suggests that Sp1 is a potential target to reduce SARS-CoV-2 infection.

Summary of global surveillance data of infectious diseases in April 2022

In April 2022, a total of 69 infectious diseases were reported globally, affecting 232 countries and regions. Except for influenza, the top five infectious diseases affecting greatest number of countries and regions were COVID-19 (232), dengue fever (29), measles (25), cholera (11) and leptospirosis (9). The top five infectious diseases with highest case fatality rates were Ebola virus disease (100.0%), Crimean-Congo hemorrhagic fever (40.0%), Middle East Respiratory Syndrome (34.4%), Lassa fever (19.3%) and monkeypox (5.3%). The top five infectious diseases with greatest number of deaths were COVID-19, malaria, dengue fever, cholera and measles. The prevalent infectious diseases in Asia were COVID-19 and dengue fever, the prevalent infectious diseases in Africa were COVID-19, Ebola virus disease, cholera, yellow fever, Lassa fever, malaria and measles, the prevalent infectious diseases in America were COVID-19, dengue fever, chikungunya fever and Zika virus disease, the prevalent infectious disease in Europe were COVID-19 and acute hepatitis of unknown aetiology.

A retrospective cohort study: vaccination status and safety analysis of SARS-CoV-2 vaccine in patients with Wilson's disease (preprint)

Background Wilson's disease (WD) is a rare hepatic and neurological disorder that tends to worsen slowly. However, traumatic injuries, surgeries, and severe infections can dramatically worsen the disease. No studies have reported whether SARS-CoV-2 vaccination affects disease progression in patients with WD. Vaccination decisions in this population are affected by the potential adverse events following vaccination. This study aimed to determine SARS-CoV-2 vaccination status and post-vaccination adverse events in patients with WD. To assess the correlation between vaccination status and Unified Wilson's Disease Rating Scale (UWDRS) scores. Methods This was a multicenter, retrospective, observational cohort study. Data on patient characteristics, current vaccination status, vaccine type, vaccine dose, and adverse events of the vaccine were collected. We evaluated the vaccination rates in various regions of China. Subjective reasons for non-vaccination were analyzed. To compare the baseline data between the two groups, age, male, liver cirrhosis, hypersplenism, post-splenectomy, kidney damage, bone damage, and cholecystitis were used as confounding factors to compare the differences between the vaccinated and unvaccinated groups. Differences in UWDRS scores between vaccinated and unvaccinated patients were analyzed using independent-sample t-tests. Paired sample t-tests were used to analyze whether there were differences in UWDRS scores before and after vaccination in vaccinated patients. Logistic regression analysis was used to assess the correlation between vaccination status and increased UWDRS scores. Results Among the 554 patients with WD included in the study, the mean age was 25.3±10.85 years. A total of 368 (66.4%) patients received at least one dose of the SARS-CoV-2 vaccine (1 dose, n=10; 2 doses, n=161; 3 doses, n=197). A total of 186 patients (33.6%) were unvaccinated. The subjective reasons why patients did not receive the vaccine were advice from the medical center (n=83,44.6%), fear of worsening WD symptoms (n=63, 33.9%), and doubts about the effectiveness and safety of the vaccine (n=40, 21.5%). There was no significant difference in confounding factors between the vaccinated and unvaccinated groups (P>0.05). This indicated that the baseline data of the two groups maintained a certain balance. Multifactorial regression analysis showed no correlation between the confounding factors and vaccination status. There was no statistically significant difference in the UWDRS scores between the two groups (P>0.05). There was no statistically significant difference in the UWDRS scores before and after vaccination (P>0.05). Logistic regression analysis showed that vaccination against SARS-CoV-2 was not significantly associated with increased scores on the UWDRS (OR=0.924, 95% CI:0.336-2.540, P=0.879), hepatic subscale (OR=0.170, 95% CI:0.148-3.027, P=0.603), neurological subscale (OR=1.322, 95% CI:0.219-7.984, P=0.761), and psychiatric subscale (OR=1.011, 95% CI:0.183-5.571, P=0.990). A total of 78 (21.2%) of the 368 patients who received at least one dose of the vaccine had adverse events. Eight patients (2.2%) showed worsening symptoms of extrapyramidal damage. Local and systemic adverse reactions occurred in 70 (19.0 %) patients, 48 (13.0%) had local pain at the injection site, 6 (1.6%) had swelling of the vaccination arm, 6 (1.6%) had fever, 4 (1.1%) had headache, 3 (0.8%) had weakness, 2 (0.5%) had stomach ache, and 1 (0.3%) had palpitations. Conclusion In this cohort study, vaccination against SARS-CoV-2 was safe in patients with WD, providing evidence for the safety of vaccination in patients with WD. It also provides a reference for patients with other heavy metal metabolism disorders, nervous system damage, and similar diseases to be vaccinated against SARS-CoV-2.

Cloud Computing-based Higher Education Platforms during the COVID-19 Pandemic (preprint)

Cloud computing has become the infrastructure that supports people's daily activities, business operations, and education delivery around the world. Cloud computing-based education platforms have been widely applied to assist online teaching during the COVID-19 pandemic. This paper examines the impact and importance of cloud computing in remote learning and education. This study conducted multiple-case analyses of 22 online platforms of higher education in Chinese universities during the epidemic. A comparative analysis of the 22 platforms revealed that they applied different cloud computing models and tools based on their unique requirements and needs. The study results provide strategic insights to higher education institutions regarding effective approaches to applying cloud computing-based platforms for remote education, especially during crisis situations.

Analysis of the clinical characteristics of novel coronavirus pneumonia and the influencing factors of severe disease progress

Objective: To analyze the clinical characteristics of patients with novel coronavirus pneumonia (COVID-19) and the factors influencing mild eases developing into severe cases, so as to provide a basis for clinical screening, prevention and treatment of potential severe cases.

Promoting, seeking, and reaching vaccination services: A systematic review of costs to immunization programs, beneficiaries, and caregivers.

INTRODUCTION: Understanding the costs to increase vaccination demand among under-vaccinated populations, as well as costs incurred by beneficiaries and caregivers for reaching vaccination sites, is essential to improving vaccination coverage. However, there have not been systematic analyses documenting such costs for beneficiaries and caregivers seeking vaccination. METHODS: We searched PubMed, Scopus, and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the costs for beneficiaries and caregivers to 1) seek and know how to access vaccination (i.e., costs to immunization programs for social mobilization and interventions to increase vaccination demand), 2) take time off from work, chores, or school for vaccination (i.e., productivity costs), and 3) travel to vaccination sites. We assessed if these costs were specific to populations that faced other non-cost barriers, based on a framework for defining hard-to-reach and hard-to-vaccinate populations for vaccination. RESULTS: We found 57 studies describing information, education, and communication (IEC) costs, social mobilization costs, and the costs of interventions to increase vaccination demand, with mean costs per dose at $0.41 (standard deviation (SD) $0.83), $18.86 (SD $50.65) and $28.23 (SD $76.09) in low-, middle-, and high-income countries, respectively. Five studies described productivity losses incurred by beneficiaries and caregivers seeking vaccination ($38.33 per person; SD $14.72; n = 3). We identified six studies on travel costs incurred by beneficiaries and caregivers attending vaccination sites ($11.25 per person; SD $9.54; n = 4). Two studies reported social mobilization costs per dose specific to hard-to-reach populations, which were 2-3.5 times higher than costs for the general population. Eight studies described barriers to vaccination among hard-to-reach populations. CONCLUSION: Social mobilization/IEC costs are well-characterized, but evidence is limited on costs incurred by beneficiaries and caregivers getting to vaccination sites. Understanding the potential incremental costs for populations facing barriers to reach vaccination sites is essential to improving vaccine program financing and planning.

Summary of global surveillance data of infectious diseases in April 2020

In April 2020, a total of 61 infectious diseases were reported globally, affecting 214 countries and regions. Except for influenza, the top five infectious diseases affecting greatest number of countries and regions were Novel coronavirus disease 2019(COVID-19)(214), measles (30), dengue fever (19), poliomyelitis (12) and rubella (9). The top four infectious diseases with highest case fatality rates were Ebola virus disease (65.8%), Middle East respiratory syndrome (34.2%), Lassa fever (19.0%) and COVID-19 (7.0%). The top five infectious diseases with greatest number of deaths were COVID-19, measles, dengue fever, cholera and Ebola virus disease. The prevalent infectious diseases in Asia were COVID-19, Middle East respiratory syndrome and dengue fever, the prevalent infectious diseases in Africa were COVID-19, Ebola virus disease, cholera, yellow fever, Lassa fever and measles, the prevalent infectious diseases in America were COVID-19 and dengue fever, the prevalent infectious diseases in Europe were COVID-19 and measles and measles.