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We found that the overall second infection rate of SARS-COV-2 was 32.4% within household. The estimated median incubation period and serial interval were 4.3 days and 5.1 days, respectively. Early isolation of patients and contact investigation should be initiated urgently. AbstractBackground: To illustrate the extent of transmission, identify affecting risk factors and estimate epidemiological modeling parameters of SARS-CoV-2 in household setting. Methods:We enrolled 35 confirmed index cases and their 148 household contacts, January 2020-February 2020, in Zhuhai, China. All participants were interviewed and asked to complete questionnaires. Household contacts were then prospectively followed active symptom monitoring through the 21-day period and nasopharyngeal and/or oropharyngeal swabs were collected at 3-7 days intervals. Epidemiological, demographic and clinical data (when available) were collected. Results:Assuming that all these secondary cases were infected by their index cases, the second infection rate (SIR) in household context is 32.4% (95% confidence interval [CI] 22.4%-44.4%), with 10.4% of secondary cases being asymptomatic. Multivariate analysis showed that household contacts with underlying medical conditions, a history of direct exposure to Wuhan and its surrounding areas, and shared vehicle with an index patient were associated with higher susceptibility. Household members without protective measures after illness onset of the index patient seem to increase the risk for SARS-CoV-2 infection. The median incubation period and serial interval within household were estimated to be 4.3 days (95% CI; 3.4 to 5.3 days) and 5.1 days (95% CI; 4.3 to 6.2 days), respectively. Conclusion:Early isolation of patients with COVID-19 and prioritizing rapid contact investigation, followed by active symptom monitoring and periodic laboratory evaluation, should be initiated immediately after confirming patients to address the underlying determinants driving the continuing pandemic.

Background Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. Method In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. Results A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Conclusions Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.

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7Background Effective therapies are urgently needed for the SARS-CoV-2 7 8pandemic. Chloroquine has been proved to have antiviral effect against 7 9coronavirus in vitro. In this study, we aimed to assess the efficacy and safety 8 0of chloroquine with different doses in COVID-19. 8 1 MethodIn this multicenter prospective observational study, we enrolled 8 2

The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, only a few have been characterized for their antiviral potential, target specificity and mechanisms of action. In this work, we focused our investigation on the possible antiviral effect of a novel ISG, C19orf66 in response to ZIKV infection and the associated mechanisms. We found that ZIKV infection could induce C19orf66 expression in ZIKV-permissive cells, and such an overexpression of C19orf66 remarkably suppressed ZIKV replication. Conversely, the depletion of C19orf66 led to a significant increase in viral replication. Furthermore, C19orf66 was found to interact and co-localize with ZIKV nonstructural protein 3 (NS3), thus inducing NS3 degradation via a lysosome-dependent pathway. Taken together, this study identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically degrading a viral nonstructural protein. These findings uncovered an intriguing mechanism of C19orf66 that targeting NS3 protein of ZIKV, providing clues for understanding the actions of innate immunity, and affording the possible availability of new drug targets that can be used for therapeutic intervention. "Guangdong Te Zhi program" youth science and technology talent of project (2015TQ01R281); Guangdong MEDP Fund Author summary ZIKV represents a serious threat to global health with particular relevance to microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. Despite the global health threat of Zika virus infection, there is currently no vaccine or effective antiviral therapy available for the disease. As widely recognized, interferon signaling is key to establishing a strong antiviral state in host cells, mainly mediated through the anti-viral effects of numerous interferon-stimulated genes (ISGs). This work described our novel finding of the antiviral effect of a novel ISG, C19orf66, and its underlying mechanisms. We identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically interacting and colocalizing with the ZIKV nonstructural (NS) protein NS3, which inducing NS3 degradation via a lysosome-dependent pathway. Thus, this work broadens the understanding of the pivotal roles of C19orf66 in the interaction between the host and ZIKV, which might further provide a rational basis for developing novel anti-ZIKV strategies. PLOS NEGLECTED TROPICAL DISEASESC19orf66 suppresses ZIKV replication by target viral NS3 PLOS Neglected Tropical Diseases | https://doi.org/10.

Recent studies have investigated the roles of FXR deficiency in the pathogenesis of alcoholic liver disease (ALD). However, the underlined molecular mechanisms remain unclear. In this study, FXR knockout (FXR −/−) and wild-type (WT) mice were subjected to chronic-plus-binge alcohol feeding to study the effect of FXR deficiency on ALD development. The degree of liver injury was greater in FXR −/− mice compared to WT mice. Ethanol feeding enhanced hepatic steatosis in FXR −/− mice, accompanied by decreased mRNA levels of Pparα and Srebp-1c. The expression of Lcn2 was increased by ethanol treatment, despite unchanged expression of pro-inflammatory cytokines Tnfα, II6 and II-1 β. Furthermore, ethanol treatment altered bile acid (BA) homeostasis to a greater extent in FXR −/− mice, as well as serum and hepatic BA pool composition. The mRNA levels of hepatic Cyp7a1 and Shp, as well as intestinal Fgf15, were decreased in WT mice with ethanol feeding, which were further reduced in FXR −/− mice. Levels of both primary and