A single-administration therapeutic interfering particle reduces SARS-CoV-2 viral shedding and pathogenesis in hamsters.

The high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a primary driver of the COVID-19 pandemic. While existing interventions prevent severe disease, they exhibit mixed efficacy in preventing transmission, presumably due to their limited antiviral effects in the respiratory mucosa, whereas interventions targeting the sites of viral replication might more effectively limit respiratory virus transmission. Recently, intranasally administered RNA-based therapeutic interfering particles (TIPs) were reported to suppress SARS-CoV-2 replication, exhibit a high barrier to resistance, and prevent serious disease in hamsters. Since TIPs intrinsically target the tissues with the highest viral replication burden (i.e., respiratory tissues for SARS-CoV-2), we tested the potential of TIP intervention to reduce SARS-CoV-2 shedding. Here, we report that a single, postexposure TIP dose lowers SARS-CoV-2 nasal shedding, and at 5 days postinfection, infectious virus shed is below detection limits in 4 out of 5 infected animals. Furthermore, TIPs reduce shedding of Delta variant or WA-1 from infected to uninfected hamsters. Cohoused "contact" animals exposed to infected, TIP-treated animals exhibited significantly lower viral loads, reduced inflammatory cytokines, no severe lung pathology, and shortened shedding duration compared to animals cohoused with untreated infected animals. TIPs may represent an effective countermeasure to limit SARS-CoV-2 transmission.

Economic hardships from COVID-19 and its association with socioeconomic factors and diabetes management indicators: A cross-sectional study.

Aims: The three objectives of this study were to determine the economic hardships of COVID-19 pandemic, their socio-economic predictors, and their association with diabetes management indicators in three cities in a middle-income country. Methods: A community-based cross-sectional survey of 309 people with diabetes aged 34-85 was carried out in 10 communities during July and August 2020. Face-to-face surveys were conducted by trained community physicians. Economic hardship was assessed by income loss and "financial toxicity" during the COVID-19 pandemic, where financial toxicity was defined as experiencing economic difficulties in accessing diabetes management resources. Indicators of diabetes management was assessed by blood glucose and Hemoglobin A1c (HbA1c) monitoring frequency. Results: Among all respondents, 38.5% reported having income loss, and 15.5% experiencing financial toxicity during the pandemic. Younger and self-employed people living suburban areas were more likely to experience income loss. Similarly, suburban area residency and lower household income were associated with financial toxicity. Patients with financial toxicity were less likely to monitor HbA1c in the past three months (OR = 0.20; 95% CI, 0.07-0.48). Conclusion: Diabetes management as indicated by less frequent HbA1c monitoring was associated with experiencing COVID-19 related financial toxicity. Our findings identified vulnerable groups in need of additional support for diabetes management.

Investigating time, strength, and duration of measures in controlling the spread of COVID-19 using a networked meta-population model.

Policy makers around the world are facing unprecedented challenges in making decisions on when and what degrees of measures should be implemented to tackle the COVID-19 pandemic. Here, using a nationwide mobile phone dataset, we developed a networked meta-population model to simulate the impact of intervention in controlling the spread of the virus in China by varying the effectiveness of transmission reduction and the timing of intervention start and relaxation. We estimated basic reproduction number and transition probabilities between health states based on reported cases. Our model demonstrates that both the time of initiating an intervention and its effectiveness had a very large impact on controlling the epidemic, and the current Chinese intense social distancing intervention has reduced the impact substantially but would have been even more effective had it started earlier. The optimal duration of the control measures to avoid resurgence was estimated to be 2 months, although would need to be longer under less effective controls.

Identification of a therapeutic interfering particle-A single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance.

Viral-deletion mutants that conditionally replicate and inhibit the wild-type virus (i.e., defective interfering particles, DIPs) have long been proposed as single-administration interventions with high genetic barriers to resistance. However, theories predict that robust, therapeutic DIPs (i.e., therapeutic interfering particles, TIPs) must conditionally spread between cells with R0 >1. Here, we report engineering of TIPs that conditionally replicate with SARS-CoV-2, exhibit R0 >1, and inhibit viral replication 10- to 100-fold. Inhibition occurs via competition for viral replication machinery, and a single administration of TIP RNA inhibits SARS-CoV-2 sustainably in continuous cultures. Strikingly, TIPs maintain efficacy against neutralization-resistant variants (e.g., B.1.351). In hamsters, both prophylactic and therapeutic intranasal administration of lipid-nanoparticle TIPs durably suppressed SARS-CoV-2 by 100-fold in the lungs, reduced pro-inflammatory cytokine expression, and prevented severe pulmonary edema. These data provide proof of concept for a class of single-administration antivirals that may circumvent current requirements to continually update medical countermeasures against new variants.

The effect of anticancer treatment on cancer patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The relationship between cancer and COVID-19 has been revealed during the pandemic. Some anticancer treatments have been reported to have negative influences on COVID-19-infected patients while other studies did not support this hypothesis. METHODS: A literature search was conducted in WOS, PubMed, Embase, Cochrane Library, CNKI and VIP between Dec 1, 2019 and Sept 23, 2020 for studies on anticancer treatments in patients with COVID-19. Cohort studies involving over 20 patients with cancer were included. The characteristics of the patients and studies, treatment types, mortality, and other additional outcomes were extracted and pooled for synthesis. RRs and forest plots were adopted to present the results. The literature quality and publication bias were assessed using NOS and Egger's test, respectively. RESULTS: We analyzed the data from 29 studies, with 5121 cancer patients with COVID-19 meeting the inclusion criteria. There were no significant differences in mortality between patients receiving anticancer treatment and those not (RR 1.17, 95%CI: 0.96-1.43, I2 =66%, p = 0.12). Importantly, in patients with hematological malignancies, chemotherapy could markedly increase the mortality (RR 2.68, 95% CI: 1.90-3.78, I2 =0%, p < 0.00001). In patients with solid tumors, no significant differences in mortality were observed (RR 1.16, 95% CI: 0.57-2.36, I2 =72%, p = 0.67). In addition, our analysis revealed that anticancer therapies had no effects on the ICU admission rate (RR 0.87, 95% CI: 0.70-1.09, I2 =25%, p = 0.23), the severe rate (RR 1.04, 95% CI: 0.95-1.13, I2 =31%, p = 0.42), or respiratory support rate (RR 0.92, 95% CI: 0.70-1.21, I2 =32%, p = 0.55) in COVID-19-infected patients with cancer. Notably, patients receiving surgery had a higher rate of respiratory support than those without any antitumor treatment (RR 1.87, 95%CI: 1.02-3.46, I2 =0%, p = 0.04). CONCLUSIONS: No significant difference was seen in any anticancer treatments in the solid tumor subgroup. Chemotherapy, however, will lead to higher mortality in patients with hematological malignancies. Multicenter, prospective studies are needed to re-evaluate the results.

Quality Analysis of Chinese Popular Scientific Articles Pertaining to Novel Coronavirus Pneumonia (preprint)

Background: To evaluate the quality, reliability, comprehensiveness and accuracy of the popular science information related to the Corona Virus Disease 2019 (COVID-19) on the Chinese website.Methods: Searching for scientific articles with the keywords of "novel coronavirus pneumonia" in Baidu, Sogou and 360 search engine at 14:00 on May 22, 2020, and collecting information such as article source, length, upload time, etc. Using JAMA score and 5-point DISCERN scale, two specialists independently analyzed the reliability and quality of scientific articles. Combined with the "Novel Coronavirus Pneumonia Diagnosis and Treatment Program (Trial Version 6)", we made corresponding evaluation on the comprehensiveness and accuracy of articles. Results: A total of 45 scientific articles were included in the study. The average number of words is 2692.27±1267.61, and the average upload time is 11.8±10.80 days. Those popular scientific articles are mainly uploaded by government agencies and individuals. However, the JAMA score, DISCERN score, content comprehensiveness and accuracy of the articles were generally low. Among the 45 popular scientific articles, 27 articles were classified as accurate-content group and 18 articles were classified as misleading-content group. Scientific articles of accurate-content groups mainly came from government agencies, universities and hospitals. The publication date of articles in the accurate-content group is closer, the scores of JAMA, DISCERN and content comprehensiveness were higher (P<0.05). The results also showed that JAMA score, DISCERN score, content comprehensiveness and accuracy of popular science articles uploaded by government agencies, universities and hospitals were higher (P<0.05). The results indicated that there was a significant positive correlation between the scores of JAMA, DISCERN, comprehensiveness and accuracy (P<0.05). Conclusion: Although there are many scientific articles related to the novel coronavirus pneumonia on the Chinese website, the overall detection rate of high-quality scientific articles were low. We are Looking forward to more high-quality medical scientific articles published by government agencies, universities and hospitals. It is suggested that search engines adopt a more optimized sorting method to help more readers get high-quality information.