Epidemiological features of COVID-19 patients with prolonged incubation period and its implications for controlling the epidemics in China.

BACKGROUND: COVID-19 patients with long incubation period were reported in clinical practice and tracing of close contacts, but their epidemiological or clinical features remained vague. METHODS: We analyzed 11,425 COVID-19 cases reported between January-August, 2020 in China. The accelerated failure time model, Logistic and modified Poisson regression models were used to investigate the determinants of prolonged incubation period, as well as their association with clinical severity and transmissibility, respectively. RESULT: Among local cases, 268 (10.2%) had a prolonged incubation period of > 14 days, which was more frequently seen among elderly patients, those residing in South China, with disease onset after Level I response measures administration, or being exposed in public places. Patients with prolonged incubation period had lower risk of severe illness (ORadjusted = 0.386, 95% CI: 0.203-0.677). A reduced transmissibility was observed for the primary patients with prolonged incubation period (50.4, 95% CI: 32.3-78.6%) than those with an incubation period of ≤14 days. CONCLUSIONS: The study provides evidence supporting a prolonged incubation period that exceeded 2 weeks in over 10% for COVID-19. Longer monitoring periods than 14 days for quarantine or persons potentially exposed to SARS-CoV-2 should be justified in extreme cases, especially for those elderly.

Epidemiological parameters of COVID-19 and its implication for infectivity among patients in China, 1 January to 11 February 2020.

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

Clinical outcomes of doxycycline, azithromycin and chloramphenicol for the treatment of patients with severe scrub typhus.

BACKGROUND: Previous studies have evaluated treatment efficacy of various antibiotics for patients with mild-to-moderate scrub typhus (ST). However, the efficacy of different antibiotics for treating severe ST remains uncertain. METHODS: A retrospective study of patients with severe ST was undertaken in China. The treatment efficacy rates of doxycycline, azithromycin and chloramphenicol were compared, using treatment failure and time to defervescence as primary outcomes. RESULTS: In total, 876 patients with severe ST who initially received doxycycline, azithromycin or chloramphenicol were recruited. The treatment failure rate did not differ significantly between patients receiving doxycycline and patients receiving azithromycin (6.0% vs 11.4%; P=0.109). However, a higher treatment failure rate was observed for chloramphenicol compared with doxycycline (14.6% vs 6.0%; P=0.004). No significant difference in time to defervescence was observed between patients receiving doxycycline, azithromycin or chloramphenicol. Further subgroup analysis revealed a higher risk of treatment failure for chloramphenicol compared with doxycycline in patients with acute kidney injury, pneumonia and shock; and a higher risk of treatment failure for azithromycin compared with doxycycline in patients with meningitis. Significant correlation was found between azithromycin resistance and meningitis (P=0.009), and between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (P<0.001) using Cramer's V correlation coefficient. Multi-variate Cox regression analysis revealed significant associations between time to defervescence and presence of ARDS, shock, myocarditis, meningitis and acute kidney injury. CONCLUSION: Azithromycin and doxycycline were found to have significant therapeutic effects in patients with severe ST. In contast, chloramphenicol was less efficacious for the treatment of these patients.

Clinical characteristics and risk factors for severe scrub typhus in pediatric and elderly patients.

BACKGROUND: Scrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear. METHODS: Clinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients. RESULTS: A total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%-16.1%) and 10.3% (95% CI 9.0%-11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96-152.67, p<0.001) and 13.22 (1.54-113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33-18.64, p<0.001) and 3.17 (1.97-5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001). CONCLUSION: The disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.

Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study.

BACKGROUND: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. METHODS: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. FINDINGS: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. INTERPRETATION: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. FUNDING: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

[Correlation between the airway inflammations and levels of stromal cell-derived factor 1 in induced sputum of asthmatic patients].

OBJECTIVE: To evaluate concentrations of stromal cell-derived factor 1 (SDF-1) and IL-17 in induced sputum supernatants from asthmatic patients before and after treatment with glucocorticosteroids. METHODS: Induced sputum was collected from 30 healthy controls and 99 patients with chronic persistent asthma from 2009-2010. Sputum samples were obtained before and after 4 week treatment with inhaled glucocorticosteroids. The sputum concentrations of SDF-1 and IL-17 were measured by ELISA. RESULTS: The FEV(1)% and the asthma control score of patients with severe asthma were decreased as compared with patients with moderate persistent and mild persistent asthma (F = 457.448 and 79.271, all P < 0.01). The concentrations of SDF-1, IL-17 and the percentage of eosinophils were increased in asthma group compared with control subjects (all P < 0.01), but the percentage of sputum neutrophils was lower than that in the healthy controls (P < 0.01). The percentage of sputum neutrophils and eosinophils and the level of SDF-1 and IL-17 in patients with severe persistent asthma were significantly higher than those in patients with mild persistent asthma (all P < 0.05). The percentage of sputum neutrophils and eosinophils were negatively correlated with FEV(1)% (r = -0.409 and -0.316, all P < 0.05). The levels of IL-17 and SDF-1 were positively correlated with the percentage of sputum neutrophils and eosinophils (all P < 0.01). The levels of IL-17 were positively correlated with the levels of SDF-1 (r = 0.872, P < 0.01). After glucocorticosteroid therapy, the percentage of eosinophils and neutrophils, the levels of IL-17 and SDF-1 decreased significantly in all patients (all P < 0.01), while the percentage of sputum neutrophils and the levels of IL-17 and SDF-1 in uncontrolled patients increased significantly compared with the controlled and partly controlled groups (all P < 0.05). CONCLUSIONS: SDF-1 and IL-17 may contribute to airway inflammation in asthma by chemotactic activity towards neutrophils. The concentration of SDF-1 may be used to evaluate the inflammation and the therapeutic effects.

[Effect of Autophagy to Drug Resistance of B-cell Lymphoma Cells].

OBJECTIVE: To investigate the effect of autophagy on the drug resistance of different human lymphoma cells. METHODS: Human Burkitt's lymphoma cell Daudi, human B lymphoma cell SUDHL-4, and human mantle cell lymphoma cell JeKo-1 were taken as the research subjects. The expression of Atg5 was inhibited by the treatments of autophagy inhibitors or stable interference via lentivirus infection. The autophagy activity of B lymphoma cell was changed, and the changes of lymphoma cells to the drug resistance of ADR and VCR was observed. RESULTS: JeKo-1 cells showed the strongest resistance to ADR and VCR, followed by SUDHL-4, and Daudi cells showed the weakest resistance to ADR and VCR. At the same time, JeKo-1 cells showed the strongest autophagy activity, followed by SUDHL-4, and Daudi cells showed the weakest autophagy activity. After the treatments of autophagy inhibitors or stable Atg5 interference, the resistance of lymphoma cells to ADR and VCR was significantly weakened, and there was the positive correlation at the drug resistance and the autophagy activity of B lymphoma cell. CONCLUSION: The higher autophagy activity in lymphoma cells, the lower chemotherapy resistance of the lymphoma cells after autophagy was inhibited.

Mapping ticks and tick-borne pathogens in China.

Understanding ecological niches of major tick species and prevalent tick-borne pathogens is crucial for efficient surveillance and control of tick-borne diseases. Here we provide an up-to-date review on the spatial distributions of ticks and tick-borne pathogens in China. We map at the county level 124 tick species, 103 tick-borne agents, and human cases infected with 29 species (subspecies) of tick-borne pathogens that were reported in China during 1950-2018. Haemaphysalis longicornis is found to harbor the highest variety of tick-borne agents, followed by Ixodes persulcatus, Dermacentor nutalli and Rhipicephalus microplus. Using a machine learning algorithm, we assess ecoclimatic and socioenvironmental drivers for the distributions of 19 predominant vector ticks and two tick-borne pathogens associated with the highest disease burden. The model-predicted suitable habitats for the 19 tick species are 14‒476% larger in size than the geographic areas where these species were detected, indicating severe under-detection. Tick species harboring pathogens of imminent threats to public health should be prioritized for more active field surveillance.

Characteristics of diarrheagenic Escherichia coli among patients with acute diarrhea in China, 2009‒2018.

Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China. Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples. Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas. Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.

The changing pattern of enteric pathogen infections in China during the COVID-19 pandemic: a nation-wide observational study.

BACKGROUND: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. METHODS: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. FINDINGS: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012-2019, with a relative decrease of 71•75% for adenovirus, 58•76% for norovirus, 53•50% for rotavirus A, and 72•07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012-2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66•53% and 90•48% increase respectively. This increase was larger for pediatric patients than for adult patients. INTERPRETATION: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. FUNDING: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

[Biological Characteristics of Immunophenotype, Stem Cell Gene and Colony Forming Ability in Side-Population Cells of Jeko-1 Cell Line].

AbstractObjective: To investigate the in vitro biological characteristics of side-population(SP) cells in mantle cell lymphoma(MCL). METHODS: The SP cells in JeKo-1 cells were enriched by continuous culture and sorted by flow cytometry（FCM）, and the expression of CD19 and IgM were analyzed. The differences of gene expression and their self-renewal ability between SP cells and non-SP cells were estimated by qRT-PCR and colony-forming assay(CFA) respectively. RESULTS: SP cells in JeKo-1 cells could be enriched by continuous sorting and in vitro cultureing, and it was found that CD19-/IgM- accounted for (2.79±0.82)%,CD19-/IgM+accounted for (70.99±13.61)%,CD19+/IgM-accounted for (0.55±0.25)%, and CD19+/IgM+accounted for (25.67±14)%. Bmi-1,CD133, C-MYC and Nanog genes were highly expressed in SP cells, but were low expressed in non-SP cells (P<0.05). Compared with non-SP cells, SP cells had stronger colony forming ability (P<0.05). CONCLUSION: JeKo-1 cell line of mantle cell lymphoma contains SP cells, which can be enriched by continuous sorting and culture for research. The SP cells in JeKo-1 contain four different cell populations with different immunophenotypes： CD19-/IgM-、CD19-/IgM+、CD19+/IgM-、CD19+/IgM+, and show stronger gene expression of stem cells and self-renewal ability in vitro.

Epidemiology of imported infectious diseases, China, 2014-18.

BACKGROUND: The frequent movement of population between countries brings an increasing number of travel-related infections. This study aims to define the spectrum and dynamics of imported infections observed from international travel in the Chinese mainland. METHODS: Sick travellers were screened by inbound sentinel surveillance and post-travel clinic visits from 2014 to 18. The infections were classified as respiratory, gastrointestinal, vector-borne, blood/sexually transmitted and mucocutaneous. The analysed variables included the place of origin of the travellers (Chinese or foreign) and the time when travel-related infection was present (at the time of return, during travel and post-travel visits to the clinic). RESULTS: In total, 58 677 cases were identified amongst 1 409 265 253 travellers, with an incidence of 41.64/million, comprising during-travel incidence of 27.44/million and a post-travel incidence of 14.20/million. Respiratory infections constituted the highest proportion of illnesses during travel (81.19%, 31 393 of 38 667), which mainly came from Asian countries and tourists; with influenza virus and rhinovirus infections being mainly diagnosed. Vector-borne diseases constituted the highest proportion of post-travel illnesses (98.14%, 19 638 of 20 010), which were mainly diagnosed from African countries and labourers; with malaria and dengue fever being mainly diagnosed. The differential infection spectrum varied in terms of the traveller's demography, travel destination and travel purpose. As such, a higher proportion of foreign travellers had blood/sexually transmitted diseases (89.85%, 2832 of 3152), while Chinese citizens had a higher prevalence of vector-borne diseases (85.98%, 19 247 of 22 387) and gastrointestinal diseases (79.36%, 1115 of 1405). The highest incidence rate was observed amongst travellers arriving from Africa, while the lowest was observed amongst travellers arriving from Europe. CONCLUSIONS: The findings might help in preparing recommendations for travellers and also aid in primary care or other clinics that prepare travellers before trips abroad. The findings will also help to identify locations and the associated types of infections that might require attention.