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.

Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel.

Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods:The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources.Results: This study found that the suitable temperature range for 2019-nCoV survival is (13-24 °C), among which 19°C lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-19 °C. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 °C, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Conclusions:A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 °C are all high-risk cities for 2019-nCoV transmission before June.

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Background We aimed to describe the epidemiological, virological and serological features of coronavirus disease 2019 (COVID-19) cases in people living with HIV (PLWH). Methods This population-based cohort study identified all COVID-19 cases among the whole PLWH in Wuhan city, China, by April 16, 2020. The epidemiological, virological and serological features were analyzed based on the demographic data, temporal profile of nucleic acid test for SARS-CoV-2 during the disease, and SARS-CoV-2-specific IgM and IgG after recovery. Results From January 1 to April 16, 2020, 35 of 6001 PLWH have experienced COVID-19, with the cumulative incidence of COVID-19 to be 0.58% (95%CI: 0.42%-0.81%). Among the COVID-19 cases, 15 (42.86%) had severe illness, with 2 deaths. The incidence, case-severity and case-fatality of COVID-19 in PLWH were comparable to that in the entire population in Wuhan. 197 persons had cART discontinuation, of whom 4 persons experienced COVID-19. Risk factors for COVID-19 were age ≥50 years old and cART discontinuation. The median duration of SARS-CoV-2 viral shedding among confirmed COVID-19 cases in PLWH was 30 (IQR: 20-46) days. Cases with high HIV viral load (≥20 copies/ml) had lower IgM and IgG levels than those with low HIV viral load (<20 copies/ml) (median S/CO for IgM, 0.03 vs. 0.11, P<0.001; median S/CO for IgG, 10.16 vs. 17.04, P=0.069). Conclusions Efforts need to maintain the persistent supply of antiretroviral treatment to elderly PLWH aged 50 years or above during the COVID-19 epidemic. The coinfection of HIV and SARS-CoV-2 might change the progression and prognosis of COVID-19 patients in PLWH.

The novel coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, where the initial wave of intense community transmissions was cut short by interventions. Using multiple data sources, here we estimate the disease burden and clinical severity by age of COVID-19 in Wuhan from December 1, 2019 to March 31, 2020. Our estimates account for the sensitivity of the laboratory assays, prospective community screenings, and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95% CI: 703–977), 489 (472–509), 370 (358–384), and 36.2 (35.0–37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had a higher burden than the 2009 influenza pandemic or seasonal influenza in terms of hospitalization and mortality rates, and clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.

Background Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are two important cellular components in the tumor microenvironment, which may modify the cancer phenotype and affect patient survival. However, the crosstalk between MDSCs and multiple myeloma stem cells (MMSCs) are relatively poorly understood. Methods The frequencies of granulocytic-MDSCs (G-MDSCs) in MM patients were detected by flow cytometry and their association with the disease stage and patient survival were analyzed. RT-PCR, flow cytometry, western blot and sphere formation assays were performed to investigate the effects of G-MDSCs, piRNA-823 and DNA methylation on the maintenance of stemness in MM. Then a subcutaneous tumor mouse model was constructed to analyze tumor growth and angiogenesis after G-MDSCs induction and/or piRNA-823 knockdown in MM cells. Results Our clinical dataset validated the association between high G-MDSCs levels and poor overall survival in MM patients. In addition, for the first time we showed that G-MDSCs enhanced the side population, sphere formation and expression of CSCs core genes in MM cells. Moreover, the mechanism study showed that G-MDSCs triggered piRNA-823 expression, which then promoted DNA methylation and increased the tumorigenic potential of MM cells. Furthermore, silencing of piRNA-823 in MM cells reduced the stemness of MMSCs maintained by G-MDSCs, resulting in decreased tumor burden and angiogenesis in vivo. Conclusion Altogether, these data established a cellular, molecular, and clinical network among G-MDSCs, piRNA-823, DNA methylation and CSCs core genes, suggesting a new anti-cancer strategy targeting both G-MDSCs and CSCs in MM microenvironment.

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.