Regional-based within-year seasonal variations in influenza-related health outcomes across mainland China: a systematic review and spatio-temporal analysis.

BACKGROUND: China experiences large variations in influenza seasonal activity. We aim to update and improve the current understanding of regional-based within-year variations of influenza activity across mainland China to provide evidence for the planning and optimisation of healthcare strategies. METHODS: We conducted a systematic review and spatio-temporal meta-analysis to assess regional-based within-year variations of ILI outpatient consultation rates, influenza test positivity rates amongst both ILI outpatients and SARI inpatients, and influenza-associated excess mortality rates. We searched English and Chinese databases for articles reporting time-series data on the four influenza-related outcomes at the sub-national and sub-annual level. After synthesising the data, we reported on the mean monthly rate, epidemic onset, duration, peak and intensity. RESULTS: We included 247 (7.7%) eligible studies in the analysis. We found within-year influenza patterns to vary across mainland China in relation to latitude and geographic location. High-latitude provinces were characterised by having short and intense annual winter epidemics, whilst most mid-latitude and low-latitude provinces experience semi-annual epidemics or year-round activity. Subtype activity varied across the country, with A/H1N1pdm09 and influenza B occurring predominantly in the winter, whereas A/H3N2 activity exhibited a latitudinal divide with high-latitude regions experiencing a winter peak, whilst mid and low-latitude regions experienced a summer epidemic. Epidemic onsets and peaks also varied, occurring first in the north and later in the southeast. We found positive associations between all influenza health outcomes. In addition, seasonal patterns at the prefecture and county-level broadly resembled their wider province. CONCLUSIONS: This is the first systematic review to simultaneously examine the seasonal variation of multiple influenza-related health outcomes at multiple spatial scales across mainland China. The seasonality information provided here has important implications for the planning and optimisation of immunisation programmes and healthcare provision, supporting the need for regional-based approaches to address variations in local epidemiology.

The effect of travel restrictions on the geographical spread of COVID-19 between large cities in China: a modelling study.

BACKGROUND: To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China. METHODS: We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to February 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios to simulate the effect of local non-pharmaceutical interventions. RESULTS: We find that in the four cities, given the potentially high prevalence of COVID-19 in Wuhan between December 2019 and early January 2020, local transmission may have been seeded as early as 1-8 January 2020. By the time the cordon sanitaire was imposed, infections were likely in the thousands. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. Reduced transmissibility resulted in a notable decrease in the incidence of infection in the four studied cities. CONCLUSIONS: Our results indicate that sustained transmission was likely occurring several weeks prior to the implementation of the cordon sanitaire in four major cities of mainland China and that the observed decrease in incidence was likely attributable to other non-pharmaceutical, transmission-reducing interventions.

Multi-organ abnormalities assessed by a single MRI scan in individuals with blood cancer.

BACKGROUND: During the COVID-19 pandemic individuals with all blood cancers were classified as clinically vulnerable and at high risk of complications and death. Our study sought to determine if individuals with specific blood cancers were at a heightened risk of longer term organ impairment, secondary to SARS-CoV-2 infection. METHODS: We set up a prospective observational study, utilising quantitative multi-parametric MRI to determine organ health over time in patients with specific blood cancers who had recovered from COVID-19. RESULTS: Multi-organ abnormality was more prevalent in blood cancer patients than in healthy controls (42 % vs 6 % p < 0.001) but comparable to the long COVID controls (42 % vs 33 %, p > 0.05). At 6 month follow up scans, organ abnormalities persisted in most individuals with blood cancer (71 % ≥1 organ and 52 % multi-organ). CONCLUSION: A multi-organ MRI platform offers the capacity to accurately evaluate organ health dynamically in blood cancers and detect asymptomatic organ impairment. The application of multi-organ MRI could aid early detection and longitudinal monitoring of organ impairment, potentially guiding more personalised treatment strategies and improving clinical outcomes in many rare diseases.

Quantitative imaging reveals steatosis and fibro-inflammation in multiple organs in people with type 2 diabetes: a real-world study.

We aimed to determine the extent of multi-organ fat accumulation and fibro-inflammation in individuals living with type 2 diabetes. We deeply phenotyped individuals with type 2 diabetes (134 from secondary care, 69 from primary care) with multi-organ, quantitative multi-parametric MRI and compared with 134 matched controls and 92 normal weight controls. We examined the impact of diabetes duration, obesity status and glycemic control. Ninety-three of the individuals with type 2 diabetes were re-evaluated at 7 months (median). Multi-organ abnormalities were more common in individuals with type 2 diabetes (94%) than in age, BMI-matched healthy or healthy normal weight people. We demonstrated a high burden of combined steatosis and fibro-inflammation, within the liver, pancreas and kidneys (41, 17 and 10%), associated with visceral adiposity (73%) and poor vascular health (82%). Obesity was most closely associated with advanced liver disease, renal and visceral steatosis, and multi-organ abnormalities whilst poor glycaemic control was associated with pancreatic fibro-inflammation. Pharmacological therapies with proven cardiorenal protection improved liver and vascular health unlike conventional glucose-lowering treatments, whilst weight loss or improved glycaemic control reduced multi-organ adiposity (p≤0.01). Quantitative imaging in people with type 2 diabetes highlights widespread organ abnormalities and may provide useful risk and treatment stratification.

Changing travel patterns in China during the early stages of the COVID-19 pandemic.

Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigate the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020, and discuss their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower healthcare capacity. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and did not lead to structural reorganisation of the transportation network during the study period.

Early dynamics of transmission and control of COVID-19: a mathematical modelling study.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. METHODS: We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. FINDINGS: We estimated that the median daily reproduction number (Rt) in Wuhan declined from 2·35 (95% CI 1·15-4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41-2·39) 1 week after. Based on our estimates of Rt, assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. INTERPRETATION: Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually. FUNDING: Wellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.