Distinct effectiveness in containing COVID-19 epidemic: Comparative analysis of two cities in China by mathematical modeling

For better preparing future epidemic/pandemic, important lessons can be learned from how different parts of China responded to the early COVID-19 epidemic. In this study, we comparatively analyzed the effectiveness and investigated the mechanistic insight of two highly representative cities of China in containing this epidemic by mathematical modeling. Epidemiological data of Wuhan and Wenzhou was collected from local health commission, media reports and scientific literature. We used a deterministic, compartmental SEIR model to simulate the epidemic. Specific control measures were integrated into the model, and the model was calibrated to the recorded number of hospitalized cases. In the epicenter Wuhan, the estimated number of unisolated or unidentified cases approached 5000 before the date of city closure. By implementing quarantine, a 40% reduction of within-population contact was achieved initially, and continuously increased up to 70%. The expansion of emergency units has finally reduced the mean duration from disease onset to hospital admission from 10 to 3.2 days. In contrast, Wenzhou is characterized as an emerging region with large number of primarily imported cases. Quick response effectively reduced the duration from onset to hospital admission from 20 to 6 days. This resulted in reduction of R values from initial 2.3 to 1.6, then to 1.1. A 40% reduction of contact through within-population quarantine further decreased R values until below 1 (0.5;95% CI: 0.4–0.65). Quarantine contributes to 37% and reduction of duration from onset to hospital admission accounts for 63% to the effectiveness in Wenzhou. In Wuhan, these two strategies contribute to 54% and 46%, respectively. Thus, control measures combining reduction of duration from disease onset to hospital admission and within-population quarantine are effective for both epicenters and settings primarily with imported cases.

Treating SARS-CoV-2 Omicron variant infection by molnupiravir for pandemic mitigation and living with the virus: a mathematical modeling study.

Treating severe COVID-19 patients and controlling the spread of SARS-CoV-2 are concurrently important in mitigating the pandemic. Classically, antiviral drugs are primarily developed for treating hospitalized COVID-19 patients with severe diseases to reduce morbidity and/or mortality, which have limited effects on limiting pandemic spread. In this study, we simulated the expanded applications of oral antiviral drugs such as molnupiravir to mitigate the pandemic by treating nonhospitalized COVID-19 cases. We developed a compartmental mathematical model to simulate the effects of molnupiravir treatment assuming various scenarios in the Omicron variant dominated settings in Denmark, the United Kingdom and Germany. We found that treating nonhospitalized cases can limit Omicron spread. This indirectly reduces the burden of hospitalization and patient death. The effectiveness of this approach depends on the intrinsic nature of the antiviral drug and the strategies of implementation. Hypothetically, if resuming pre-pandemic social contact pattern, extensive application of molnupiravir treatment would dramatically (but not completely) mitigate the COVID-19 burden, and thus there remains lifetime cost of living with the virus.

Distinct effectiveness in containing COVID-19 epidemic: Comparative analysis of two cities in China by mathematical modeling.

For better preparing future epidemic/pandemic, important lessons can be learned from how different parts of China responded to the early COVID-19 epidemic. In this study, we comparatively analyzed the effectiveness and investigated the mechanistic insight of two highly representative cities of China in containing this epidemic by mathematical modeling. Epidemiological data of Wuhan and Wenzhou was collected from local health commission, media reports and scientific literature. We used a deterministic, compartmental SEIR model to simulate the epidemic. Specific control measures were integrated into the model, and the model was calibrated to the recorded number of hospitalized cases. In the epicenter Wuhan, the estimated number of unisolated or unidentified cases approached 5000 before the date of city closure. By implementing quarantine, a 40% reduction of within-population contact was achieved initially, and continuously increased up to 70%. The expansion of emergency units has finally reduced the mean duration from disease onset to hospital admission from 10 to 3.2 days. In contrast, Wenzhou is characterized as an emerging region with large number of primarily imported cases. Quick response effectively reduced the duration from onset to hospital admission from 20 to 6 days. This resulted in reduction of R values from initial 2.3 to 1.6, then to 1.1. A 40% reduction of contact through within-population quarantine further decreased R values until below 1 (0.5; 95% CI: 0.4-0.65). Quarantine contributes to 37% and reduction of duration from onset to hospital admission accounts for 63% to the effectiveness in Wenzhou. In Wuhan, these two strategies contribute to 54% and 46%, respectively. Thus, control measures combining reduction of duration from disease onset to hospital admission and within-population quarantine are effective for both epicenters and settings primarily with imported cases.

Repurposing dyphylline as a pan-coronavirus antiviral therapy.

Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.

Differing pan-coronavirus antiviral potency of boceprevir and GC376 in vitro despite discordant molecular docking predictions.

Given the structural similarities of the viral enzymes of different coronaviruses (CoVs), we investigated the potency of the anti-SARS-CoV-2 agents boceprevir and GC376 for counteracting seasonal coronavirus infections. In contrast to previous findings that both boceprevir and GC376 are potent inhibitors of the main protease (Mpro) of SARS-CoV-2, we found that GC376 is much more effective than boceprevir in inhibiting SARS-CoV-2 and three seasonal CoVs (NL63, 229E, and OC43) in cell culture models. However, these results are discordant with a molecular docking analysis that suggested comparable affinity of boceprevir and GC376 for the different Mpro enzymes of the four CoVs. Collectively, our results support future development of GC376 but not boceprevir (although it is an FDA-approved antiviral medication) as a pan-coronavirus antiviral agent. Furthermore, we caution against overinterpretation of in silico data when developing antiviral therapies.

Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models.

Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS-CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. We first successfully modelled the 3D structure of HCoV-NL63 RNA-dependent RNA polymerase (RdRp) based on the experimentally solved SARS-CoV-2 RdRp structure. Molecular docking indicated that favipiravir has similar binding affinities to SARS-CoV-2 and HCoV-NL63 RdRp with LibDock scores of 75 and 74, respectively. The LibDock scores of remdesivir to SARS-CoV-2 and HCoV-NL63 were 135 and 151, suggesting that remdesivir may have a higher affinity to HCoV-NL63 compared to SARS-CoV-2 RdRp. In cell culture models infected with HCoV-NL63, both favipiravir and remdesivir significantly inhibited viral replication and production of infectious viruses. Overall, remdesivir compared to favipiravir is more potent in inhibiting HCoV-NL63 in cell culture. Importantly, there is no evidence of resistance development upon long-term exposure to remdesivir. Furthermore, combining favipiravir or remdesivir with the clinically used antiviral cytokine interferon-alpha resulted in synergistic effects. These findings provided a proof-of-concept that anti-SARS-CoV-2 drugs, in particular remdesivir, have the potential to be repurposed for treating HCoV-NL63 infection.

Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses.

Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, ß-D-N4-hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV-OC43 and HCoV-229E. In cell culture models, treatment of molnupiravir effectively inhibited viral replication and production of infectious viruses of the three seasonal coronaviruses. A time-of-drug-addition experiment indicates the specificity of molnupiravir in inhibiting viral components. Furthermore, combining molnupiravir with the protease inhibitor GC376 resulted in enhanced antiviral activity. Our findings highlight that the great potential of repurposing molnupiravir for treating seasonal coronavirus infected patients.

COVID-19 impact on high school student's education and mental health: A cohort survey in China.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic and the universal implementation of control measures are fundamentally affecting every aspect of our society and daily lives. AIM: To evaluate the prevalence of post-traumatic stress disorder symptoms and their associated factors as well as the effects and attitudes towards online education in Chinese high school students. METHODS: A total of 883 students were included. The first, second and third-year students of a high school in Lanzhou, Gansu province of China were invited to participate in this study. They were requested to involve their parents to complete the survey together. A detailed questionnaire of 65 questions was designed and divided into five sections. The survey was anonymously conducted via WeChat, a Chinese multipurpose messaging, social media and mobile payment app. RESULTS: Overall, 32.94% of students experienced post-traumatic stress disorder due to the COVID-19 epidemic. The majority of students (60.82%) felt that online education was not (10.76%) or less effective (50.06%) in terms of gaining knowledge and improving practical and communications skills. Correlation analysis revealed that the class level, residential background and whether living with parents were significantly linked with the effectiveness and satisfaction of the online education system. Of the final year students, 74.2% said that the COVID-19 outbreak has negatively affected their preparation for the college entrance exam, and 68% of students felt that this outbreak increased psychological pressure for their college entrance examination preparation. In case of having COVID-19 symptoms during the exam, 50.7%, 13.3%, and 10.2% would notify the proctor, teacher and parents, respectively. CONCLUSION: We found a high prevalence rate of post-traumatic stress disorder symptoms in high school students. Thus, our results call for urgent attention from both government and schools to implement effective interventions to cope with the psychological effects and the disturbance of education by COVID-19 on children.

COVID-19 knowledge, risk perception, and information sources among Chinese population.

BACKGROUND: Measures for effective control of the coronavirus disease 2019 (COVID-19) pandemic include identifying the causal organisms, applying appropriate therapies, and developing vaccines, as well as improving understanding among the general public. AIM: To evaluate the knowledge, awareness, perception, and response of the general public to COVID-19 in China. METHODS: A detailed questionnaire comprising 47 questions designed in both English and Chinese was developed. The survey was conducted via WeChat, a multipurpose messaging, social media, and mobile payment app that is widely used by the Chinese population. In total, 1006 participants responded, and most of them were from different provinces of mainland China. RESULTS: Overall, this comprehensive survey revealed that the general public in China is highly aware of the basic information concerning COVID-19 and its precautions. Interestingly, more respondents (99.3%) were aware of the term severe acute respiratory syndrome (SARS) than COVID-19 (97.2%) and Middle East respiratory syndrome (MERS) (73.4%). Among them, 2.4%, 1.6%, and 0.9% said that they or their family members or friends were affected by COVID-19, SARS, and MERS, respectively. The majority of the respondents (91.2%) indicated that knowledge about COVID-19 was received mainly from WeChat, followed by TV (89%), friends (76.1%), and QQ (a Chinese instant messaging software service) (57.7%). CONCLUSION: The general public in China is highly aware of COVID-19 and the necessary precautions. Unexpectedly, 2.8% of the participants were unaware of the current epidemic. The remaining information gaps highlight the necessity of further enhancing awareness and preparedness.

The impact of COVID-19 pandemic outbreak on education and mental health of Chinese children aged 7-15 years: an online survey.

BACKGROUND: The emerging of psychological problems triggered by COVID-19 particularly in children have been extensively highlighted and emphasized, but original research in this respect is still lagging behind. Therefore, we designed this study to evaluate the impact of COVID-19 pandemic on mental health and the effectiveness and attitudes towards online education among Chinese children aged 7-15 years. METHODS: A detailed questionnaire, comprising of 62 questions was designed and parents or caretakers of 7 to 15 years old children were invited to participate via WeChat, a multi-purpose messaging, social media and mobile payment app, which is widely used by the Chinese population. A total of 668 parents across different regions of China were included. RESULTS: During COVID-19 pandemic, 20.7 and 7.2% children report experiencing post-traumatic stress disorder (PTSD) and depressive symptoms due to the COVID-19 pandemic. PTSD and SMFQ-P scores are significantly higher in middle school and boarding school students compared to primary and day school students. Multiple logistic regression analysis revealed that school system and province of origin are factors significantly associated with developing PSTD symptoms. 44.3% respondents feel online education is effective in gaining knowledge and improving practical and communications skills. 78.0% believe the online education system is efficient. Overall 79.8% respondents are satisfied and children can adapt to this new education system. During the COVID-19 pandemic, we found 1 in five children have PTSD and 1 in 14 children have depressive symptoms. CONCLUSION: In summary, COVID-19 epidemic has caused PTSD and depression symptoms among Chinese children aged 7 to 15 years. In general, a large proportion of respondents are satisfied with online education, but still a substantial proportion of students are not comfortable with this new form of learning. Authorities should optimize online education systems and implement effective interventions to cope with the psychological effects of COVID-19 on children, as it is affecting the global population and remains uncertain when it will end.

Systematically comparing COVID-19 with the 2009 influenza pandemic for hospitalized patients.

OBJECTIVES: This study aimed to comprehensively compare the clinical features of hospitalized COVID-19 patients with hospitalized 2009 influenza pandemic patients. METHODS: Medline, Embase, Web of Science, Cochrane CENTRAL, and Google scholar were systematically searched to identify studies related to COVID-19 and the 2009 influenza pandemic. The pooled incidence rates of clinical features were estimated using the DerSimonian-Laird random-effects model with the Freeman-Tukey double arcsine transformation method. RESULTS: The incidence rates of fever, cough, shortness of breath, sore throat, rhinorrhea, myalgia/muscle pain, or vomiting were found to be significantly higher in influenza patients when compared with COVID-19 patients. The incidence rates of comorbidities, including cardiovascular disease/hypertension and diabetes, were significantly higher in COVID-19 compared with influenza patients. In contrast, comorbidities such as asthma, chronic obstructive pulmonary disease, and immunocompromised conditions were significantly more common in influenza compared with COVID-19 patients. Unexpectedly, the estimated rates of intensive care unit admission, treatment with extracorporeal membrane oxygenation, treatment with antibiotics, and fatality were comparable between hospitalized COVID-19 and 2009 influenza pandemic patients. CONCLUSIONS: This study comprehensively estimated the differences and similarities of the clinical features and burdens of hospitalized COVID-19 and 2009 influenza pandemic patients. This information will be important to better understand the current COVID-19 pandemic.

Unique challenges to control the spread of COVID-19 in the Middle East.

The COVID-19 pandemic is spreading at unprecedented pace among the Middle East and neighboring countries. This region is geographically, economically, politically, culturally and religiously a very sensitive area, which impose unique challenges for effective control of this epidemic. These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. These factors are interrelated and collectively determine the response to the pandemic in this region. Here, we in-depth emphasize these challenges and take a glimpse of possible solutions towards mitigating the spread of COVID-19.