Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.

Osteosarcoma (OS) is the most common type of primary bone tumor in children and adolescents and has been associated with a high degree of malignancy, early metastasis, rapid progression and poor prognosis. However, the use of adjuvant chemotherapy improves the prognosis of patients with OS. OS chemotherapy is based primarily on the use of adriamycin, cisplatin (DDP), methotrexate (MTX), ifosfamide (IFO), epirubicin (EPI) and other drugs. Previous studies have revealed that the survival rate for patients with OS appears to have plateaued: 5-year survival rates remain close to 60%, even with the use of combined chemotherapy. The most limiting factors include complications and fatal toxicity associated with chemotherapy agents, particularly high-dose MTX (HD-MTX), for which high toxicity and great individual variation in responses have been observed. Docetaxel (TXT) is a representative member of the relatively recently developed taxane class of drugs, which function to inhibit OS cell proliferation and induce apoptosis. Recently, more clinical studies have reported that TXT combined with gemcitabine (GEM) is effective in the treatment of OS (relapse/refractory and progressive), providing evidence in support of potential novel treatment strategies for this patient population. However, there is still no global consensus on this type of chemotherapy approach. The present review summarizes current studies surrounding progress in the chemotherapeutic treatment of OS and discusses the advantages and potential feasibility of TXT+GEM in the treatment of OS.

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Alteration in hepatitis B virus (HBV) secretion efficiency may have pathological consequences. Naturally occurring mutations that regulate virion secretion have not been defined. We recently identified HBV genomes displaying high (4B), substantially reduced (3.4), or negative (4C) virion secretion. In the present study, the underlying mutations were mapped. A T552C point mutation in the 4B genome was responsible for its enhanced virion secretion, whereas a G510A mutation in 3.4 and G660C in 4C impaired virus secretion. The three point mutations generate M133T, G119E, and R169P substitutions in the S domains of viral envelope proteins, respectively, without modifying the coding capacity of the overlapping polymerase gene. The mutated residues are predicted to lie in the luminal side of the endoplasmic reticulum (ER) or to be embedded in the ER membrane and thus are not involved in contact with core particles during envelopment. Of the two mutations inhibitory of virion secretion, G510A greatly reduced small envelope protein (hepatitis B surface antigen [HBsAg]) levels both inside cells and in culture medium, whereas G660C specifically abolished HBsAg secretion. Surprisingly, a T484G mutation in the 4B genome, generating an I110M substitution in the S domain, could also reduce HBsAg secretion and block virion secretion. However, its inhibitory effect was suppressed in the 4B genome by the T552C mutation, the enhancer of virion secretion. T552C can also override the inhibitory G510A mutation, but not the G660C mutation. These findings suggest a hierarchy in the regulation of virion secretion and a close link between defective virion secretion and impaired HBsAg formation or secretion.

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Importance Several parameters driving the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear, including age-specific differences in infectivity and susceptibility, and the contribution of inapparent infections to transmission. Robust estimates of key time-to-event distributions remain scarce as well. Objective Illustrate SARS-CoV-2 transmission patterns and risk factors, and estimate key time-to-event distributions. Design, Setting, and Participants Individual-based data on 1,178 SARS-CoV-2 infected individuals and their 15,648 contacts identified by contact tracing monitoring over the period from January 13-April 02, 2020 were extracted from the notifiable infectious diseases reporting system in Hunan Province, China. Demographic characteristics, severity classification, exposure and travel history, and key clinical timelines were retrieved. Exposures Confirmed SARS-CoV-2 infection by positive polymerase chain reaction test result of respiratory samples, and exposure to SARS-CoV-2 infected individuals via household, relative, social, and other types of contacts. Main Outcomes and Measures The relative contribution of pre-symptomatic and asymptomatic transmission, key time-to-event parameters, and the effect of biological, demographic, and behavioral factors on SARS-CoV-2 infectivity and susceptibility were quantified. Results Among SARS-CoV-2 infected individuals, the estimated mean serial interval was 5.5 days (95%CI -5.0, 19.9) and the mean generation time was 5.5 days (95%CI 1.7, 11.6). Infectiousness was estimated to peak 1.8 days before symptom onset, with 95% of transmission events occurring between -7.6 days and 7.3 days from the date of symptom onset. The proportion of pre-symptomatic transmission was estimated at 62.5%, while a lower bound for the proportion of asymptomatic transmission was 3.5%. Infectiousness of SARS-CoV-2 was not significantly different between working-age adults (15-59 years old) and other age groups (0-14 years old: p-value=0.16; 60 years and over: p-value=0.33), whilst susceptibility to SARS-CoV-2 infection was estimated to increase with age (p-value=0.03). In addition, transmission risk was higher for household contacts (p-value<0.001), but decreased in later generations of a cluster (second generation: OR=0.13, p-value<0.001; generations 3-4: OR=0.05, p-value<0.001, relative to generation 1) and for those exposed to infectors with a larger number of contacts (p-value=0.04). Conclusions and Relevance These findings support the contribution of children to transmission and the importance of pre-symptomatic transmission, in turn highlighting the importance of large-scale testing, contact tracing activities, and the use of personnel protective equipment during the COVID-19 pandemic.