Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Prevalence and Etiological Characteristics of Norovirus Infection in China: A Systematic Review and Meta-Analysis.

Norovirus is a common cause of sporadic cases and outbreaks of gastroenteritis worldwide, although its prevalence and the dominant genotypes responsible for gastroenteritis outbreaks remain obscure. A systematic review was conducted on norovirus infection in China between January 2009 and March 2021. A meta-analysis and beta-binomial regression model were used to explore the epidemiological and clinical characteristics of norovirus infection and the potential factors contributing to the attack rate of the norovirus outbreaks, respectively. A total of 1132 articles with 155,865 confirmed cases were included, with a pooled positive test rate of 11.54% among 991,786 patients with acute diarrhea and a pooled attack rate of 6.73% in 500 norovirus outbreaks. GII.4 was the predominant genotype in both the etiological surveillance and outbreaks, followed by GII.3 in the etiological surveillance, and GII.17 in the outbreaks, with the proportion of recombinant genotypes increasing in recent years. A higher attack rate in the norovirus outbreaks was associated with age group (older adults), settings (nurseries, primary schools, etc.) and region (North China). The nation-wide pooled positive rate in the etiological surveillance of norovirus is lower than elsewhere in the global population, while the dominant genotypes are similar in both the etiological surveillance and the outbreak investigations. This study contributes to the understanding of norovirus infection with different genotypes in China. The prevention and control of norovirus outbreaks during the cold season should be intensified, with special attention paid to and enhanced surveillance performed in nurseries, schools and nursing homes from November to March.

Decline of onset-to-diagnosis interval and its impacts on clinical outcome of COVID-19 in China: a nation-wide observational study.

BACKGROUND: To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China's National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. RESULTS: As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10-11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8-9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. CONCLUSION: The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.

Mapping the viruses belonging to the order Bunyavirales in China.

BACKGROUND: Viral pathogens belonging to the order Bunyavirales pose a continuous background threat to global health, but the fact remains that they are usually neglected and their distribution is still ambiguously known. We aim to map the geographical distribution of Bunyavirales viruses and assess the environmental suitability and transmission risk of major Bunyavirales viruses in China. METHODS: We assembled data on all Bunyavirales viruses detected in humans, animals and vectors from multiple sources, to update distribution maps of them across China. In addition, we predicted environmental suitability at the 10 km × 10 km pixel level by applying boosted regression tree models for two important Bunyavirales viruses, including Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV). Based on model-projected risks and air travel volume, the imported risk of RVFV was also estimated from its endemic areas to the cities in China. RESULTS: Here we mapped all 89 species of Bunyavirales viruses in China from January 1951 to June 2021. Nineteen viruses were shown to infect humans, including ten species first reported as human infections. A total of 447,848 cases infected with Bunyavirales viruses were reported, and hantaviruses, Dabie bandavirus and Crimean-Congo hemorrhagic fever virus (CCHFV) had the severest disease burden. Model-predicted maps showed that Xinjiang and southwestern Yunnan had the highest environmental suitability for CCHFV occurrence, mainly related to Hyalomma asiaticum presence, while southern China had the highest environmental suitability for Rift Valley fever virus (RVFV) transmission all year round, mainly driven by livestock density, mean precipitation in the previous month. We further identified three cities including Guangzhou, Beijing and Shanghai, with the highest imported risk of RVFV potentially from Egypt, South Africa, Saudi Arabia and Kenya. CONCLUSIONS: A variety of Bunyavirales viruses are widely distributed in China, and the two major neglected Bunyavirales viruses including CCHFV and RVFV, both have the potential for outbreaks in local areas of China. Our study can help to promote the understanding of risk distribution and disease burden of Bunyavirales viruses in China, and the risk maps of CCHFV and RVFV occurrence are crucial to the targeted surveillance and control, especially in seasons and locations at high risk.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

OBJECTIVES: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). METHOD: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. RESULTS: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). CONCLUSION: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Mapping the risk distribution of Borrelia burgdorferi sensu lato in China from 1986 to 2020: a geospatial modelling analysis.

Lyme borreliosis, recognized as one of the most important tick-borne diseases worldwide, has been increasing in incidence and spatial extent. Currently, there are few geographic studies about the distribution of Lyme borreliosis risk across China. Here we established a nationwide database that involved Borrelia burgdorferi sensu lato (B. burgdorferi) detected in humans, vectors, and animals in China. The eco-environmental factors that shaped the spatial pattern of B. burgdorferi were identified by using a two-stage boosted regression tree model and the model-predicted risks were mapped. During 1986-2020, a total of 2,584 human confirmed cases were reported in 25 provinces. Borrelia burgdorferi was detected from 35 tick species with the highest positive rates in Ixodes granulatus, Hyalomma asiaticum, Ixodes persulcatus, and Haemaphysalis concinna ranging 20.1%-24.0%. Thirteen factors including woodland, NDVI, rainfed cropland, and livestock density were determined as important drivers for the probability of B. burgdorferi occurrence based on the stage 1 model. The stage 2 model identified ten factors including temperature seasonality, NDVI, and grasslands that were the main determinants used to distinguish areas at high or low-medium risk of B. burgdorferi, interpreted as potential occurrence areas within the area projected by the stage 1 model. The projected high-risk areas were not only concentrated in high latitude areas, but also were distributed in middle and low latitude areas. These high-resolution evidence-based risk maps of B. burgdorferi was first created in China and can help as a guide to future surveillance and control and help inform disease burden and infection risk estimates.

Human infections with neglected vector-borne pathogens in China: A systematic review.

Background: Emerging vector-borne pathogens (VBPs) pose a continuous background threat to the global health. Knowledge of the occurrence, distributions and epidemiological characteristics of VBP are lacking in many countries. Outbreaks of novel VBP are of increasing global interest including those arising in China. Methods: A systematic review of published literature was undertaken to characterize the spectrum of VBPs causing human illness in China. We searched five databases for VBP-related articles in English and Chinese published between January 1980 and June 2021, that excluded those listed in the National Notifiable Diseases Surveillance System of China. The study is registered with PROSPERO, CRD42021259540. Findings: A total of 906 articles meeting the selection criteria were included in this study. A total of 44,809 human infections with 82 species of VBPs including 40 viruses, 33 bacteria (20 Rickettsiales bacteria, eight Spirochaetales bacteria, and five other bacteria) and nine parasites, were identified in China. Rickettsiales bacteria were the most common and widely distributed pathogens with 18,042 cases reported in 33 provinces by 347 reviewed articles, followed by Spirochaetales bacteria with 15,745 cases in 32 provinces (299 articles), viruses with 8455 cases in 30 provinces (139 articles), other bacteria with 2053 cases in 19 provinces (65 articles), parasites with 514 cases in 17 provinces (44 articles), and multiple pathogens with 3626 cases in 14 provinces (23 articles). Coxiella burnetii, Bartonella henselae and Rickettsia sibirica were the most frequently reported pathogens. A total of 18 new pathogens were reported in China during this period (these also represented their first identification globally). Based on 419 articles with clinical information, a meta-analysis revealed that flu-like illness was the most common manifestation among infections with VBPs. Interpretation: This review helps improve the understanding of VBPs in China, demonstrating the need to consider a wider surveillance of VBPs in many different settings, thus helping to inform future research and surveillance efforts. Funding: Natural Science Foundation of China.

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.

Changes in notifiable infectious disease incidence in China during the COVID-19 pandemic.

Nationwide nonpharmaceutical interventions (NPIs) have been effective at mitigating the spread of the novel coronavirus disease (COVID-19), but their broad impact on other diseases remains under-investigated. Here we report an ecological analysis comparing the incidence of 31 major notifiable infectious diseases in China in 2020 to the average level during 2014-2019, controlling for temporal phases defined by NPI intensity levels. Respiratory diseases and gastrointestinal or enteroviral diseases declined more than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Early pandemic phases with more stringent NPIs were associated with greater reductions in disease incidence. Non-respiratory diseases, such as hand, foot and mouth disease, rebounded substantially towards the end of the year 2020 as the NPIs were relaxed. Statistical modeling analyses confirm that strong NPIs were associated with a broad mitigation effect on communicable diseases, but resurgence of non-respiratory diseases should be expected when the NPIs, especially restrictions of human movement and gathering, become less stringent.

The differential demographic pattern of coronavirus disease 2019 fatality outside Hubei and from six hospitals in Hubei, China: a descriptive analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. METHODS: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. RESULTS: The overall HCFR in China was estimated to be 4.6% (95% CI 4.5-4.8%, P < 0.001). It increased with age and was higher in males than females. Although the highest HCFR observed was in male patients ≥70 years old, the relative risks for death outcome by sex varied across age groups, and the greatest HCFR risk ratio for males vs. females was shown in the age group of 50-60 years, higher than age groups of 60-70 and ≥ 70 years. Differential age/sex HCFR patterns across geographical regions were found: the age effect on HCFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher HCFR was associated with older age (both P < 0.001), and male sex (both P < 0.001). Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher HCFR. CONCLUSIONS: This up-to-date and comprehensive picture of COVID-19 HCFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

Association between fatality rate of COVID-19 and selenium deficiency in China.

BACKGROUND: COVID-19 has impacted populations around the world, with the fatality rate varying dramatically across countries. Selenium, as one of the important micronutrients implicated in viral infections, was suggested to play roles. METHODS: An ecological study was performed to assess the association between the COVID-19 related fatality and the selenium content both from crops and topsoil, in China. RESULTS: Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019-13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas (P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas (P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21-12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14-4.98) for moderate-selenium-deficient cities and 3.06 (1.49-6.27) for severe-selenium-deficient cities. CONCLUSIONS: Regional selenium deficiency might be related to an increased CFR of COVID-19. Future studies are needed to explore the associations between selenium status and disease outcome at individual-level.

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.

Meteorological conditions and nonpharmaceutical interventions jointly determined local transmissibility of COVID-19 in 41 Chinese cities: A retrospective observational study.

BACKGROUND: Before effective vaccines become widely available, sufficient understanding of the impacts of climate, human movement and non-pharmaceutical interventions on the transmissibility of COVID-19 is needed but still lacking. METHODS: We collected by crowdsourcing a database of 11 003 COVID-19 cases from 305 cities outside Hubei Province from December 31, 2019 to April 27, 2020. We estimated the daily effective reproduction numbers (Rt ) of COVID-19 in 41 cities where the crowdsourced case data are comparable to the official surveillance data. The impacts of meteorological variables, human movement indices and nonpharmaceutical emergency responses on Rt were evaluated with generalized estimation equation models. FINDINGS: The median Rt was 0•46 (IQR: 0•37-0•87) in the northern cities, higher than 0•20 (IQR: 0•09-0•52) in the southern cities (p=0•004). A higher local transmissibility of COVID-19 was associated with a low temperature, a relative humidity near 70-75%, and higher intracity and intercity human movement. An increase in temperature from 0℃ to 20℃ would reduce Rt by 30% (95 CI 10-46%). A further increase to 30℃ would result in another 17% (95% CI 5-27%) reduction. An increase in relative humidity from 40% to 75% would raise the transmissibility by 47% (95% CI 9-97%), but a further increase to 90% would reduce the transmissibility by 12% (95% CI 4-19%). The decrease in intracity human movement as a part of the highest-level emergency response in China reduced the transmissibility by 36% (95% CI 27-44%), compared to 5% (95% CI 1-9%) for restricting intercity transport. Other nonpharmaceutical interventions further reduced Rt by 39% (95% CI 31-47%). INTERPRETATION: Climate can affect the transmission of COVID-19 where effective interventions are implemented. Restrictions on intracity human movement may be needed in places where other nonpharmaceutical interventions are unable to mitigate local transmission. FUNDING: China Mega-Project on Infectious Disease Prevention; U.S. National Institutes of Health and National Science Foundation.