9:00 AM 7/8/2020 - WHO confirms there's 'emerging evidence' of airborne transmission of coronavirus - CNN | #floods and #epidemics

Michael Novakhov@mikenov

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Michael Novakhov - SharedNewsLinks: From environmental variability to disease prevention largely based on data from China
Michael_Novakhov shared this story . Abstract Hantaviruses can cause hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In recent decades, repeated outbreaks of hantavirus disease have led to public concern and have created a global public health burden. Hantavirus spillover from natural hosts into human populations could be considered an ecological process, in which environmental forces, behavioral determinants of exposure, and dynamics at the humananimal interface affect human susceptibility and the epidemiology of the disease. In this review, we summarize the progress made in understanding hantavirus epidemiology and rodent reservoir population biology. We mainly focus on three species of rodent hosts with longitudinal studies of sufficient scale: the striped field mouse (Apodemus agrarius, the main reservoir host for Hantaan virus [HTNV], which causes HFRS) in Asia, the deer mouse (Peromyscus maniculatus, the main reservoir host for Sin Nombre virus [SNV], which causes HPS) in North America, and the bank vole (Myodes glareolus, the main reservoir host for Puumala virus [PUUV], which causes HFRS) in Europe. Moreover, we discuss the influence of ecological factors on human hantavirus disease outbreaks and provide an overview of research perspectives. Citation: Tian H, Stenseth NC (2019) The ecological dynamics of hantavirus diseases: From environmental variability to disease prevention largely based on data from China. PLoS Negl Trop Dis 13(2): e0006901. <a href="https://doi.org/10.1371/journal.pntd.0006901" rel="nofollow">https://doi.org/10.1371/journal.pntd.0006901</a> Editor: Patricia V. Aguilar, University of Texas Medical Branch, UNITED STATES Published: February 21, 2019 Copyright: © 2019 Tian, Stenseth. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding for this study was provided by the Beijing Natural Science Foundation (JQ18025) (http://kw.beijing.gov.cn/jjb/), the National Natural Science Foundation of China (81673234,81460520,31870400,41476161) (http://www.nsfc.gov.cn/), the Young Elite Scientist Sponsorship Program by CAST(YESS)(2018QNRC001) (http://www.cast.org.cn/), the Fundamental Research Funds for the Central Universities (http://www.moe.gov.cn/), the National Key Research and Development Program of China (2016YFA0600104) (http://www.most.gov.cn/), and the health industrys special research funds for public welfare projects (Grant 201502020) (http://www.nhfpc.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Introduction Hantaviruses are enveloped RNA viruses belonging to the family Hantaviridae, genus Orthohantavirus [1]. They can cause serious diseases in humans, with some outbreaks resulting in case fatality rates of 12% (for hemorrhagic fever with renal syndrome [HFRS] in Europe and Asia) and up to 40% (for hantavirus pulmonary syndrome [HPS] in the Americas), depending on the hantavirus type and the resulting clinical syndrome [2,3]. Hantavirus disease came to global attention when two major outbreaks were reported during the last century. The first, an HFRS outbreak, occurred during the Korean War (1950 to 1953), when more than 3,000 United Nations troops fell ill [4]. The second was an outbreak of HPS that occurred in the Four Corners region of the southwestern United States in 1993 [5]. Hantaviruses remain a global threat to public health; they have been estimated to affect approximately 200,000 humans annually worldwide in recent years [6]. Moreover, the number of countries reporting human cases of hantavirus infection is still on the rise [7]. Human infections with hantaviruses result from contact with infected rodents or exposure to virus-contaminated aerosols; Andes virus (ANDV) is the only hantavirus in which person-to-person transmission has been documented so far [811]. Outbreaks of hantavirus disease are therefore considered to be associated with the primary rodent host and pathogen dynamics [12,13]. However, the mechanism of zoonotic pathogen dynamics is complex, and the relationships between or among environmental change, hostpathogen dynamics, and human spillover is far from clear [14,15]. For example, variations in incidence rates are not simply, as expected, a result of changes in rodent demography or virus prevalence [1618]. Furthermore, although numerous research efforts have been undertaken, no WHO-licensed vaccine against hantavirus infection is available [19] (except Hantavax, which is only licensed for human use in the Republic of Korea). Current efforts to curb hantavirus transmission focus on avoiding contact between humans and host rodents [20,21]. Due to the complexity of these systems, hantaviruses deserve the attention of research scientists in the contexts of both public health and wildlife conservation. Here, we present a review of the ecology of hantavirus diseases in an attempt to improve our understanding of the mechanisms underlying disease outbreaks. We mainly focus on three species of rodent hosts, on which there have been a wealth of longitudinal studies of population and prevalence dynamics: the striped field mouse (Apodemus agrarius, the main reservoir host for Hantaan virus [HTNV] [2225]) in Asia, the deer mouse (Peromyscus maniculatus, the main reservoir host for Sin Nombre virus [SNV] [12,18,2628]) in North America, and the bank vole (Myodes glareolus, the main reservoir host for Puumala virus [PUUV] [2932]) in Europe. A deeper understanding of the natural ecological dynamics of hostpathogen interactions would be of great value in developing future strategies for disease prevention and control. Methods Search strategy and selection criteria We searched the MEDLINE (via PubMed) online database and Google Scholar for articles with the key words hantavirus, ecology, or modelling in the title, with no date limit, published before 31 July 2017, with restriction to mainly English papers. Key words used in Medical Subject Headings were hantavirus, hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome, and rodent reservoir. Inclusion criteria were predefined as research providing information on viral infections (including human incidence, prevalence of hantavirus infections in rodent hosts, and/or hostpathogen interactions), environmental change and rodent reservoir population dynamics, and information on environmental factors that may trigger hantavirus disease outbreaks. Study data extracted included study year, location, hantavirus type, main rodent reservoir, study design, and environmental factors. Results Geographic distribution Hantaviruses that cause illness in humans have been identified across the globe [3,7,33] (Fig 1). The major hantavirus disease burden in the Old World is HFRS, and in the New World it is HPS. HTNV in Asia, PUUV and Dobrava virus in Europe, and Seoul virus (SEOV) worldwide are the causative agents of HFRS. SNV, ANDV, and related viruses have been identified as causative agents of HPS in the Americas [3,12]. Recent studies indicate that the medical problem caused by hantavirus infections may be underestimated in Africa, India, Southeast Asia (where Thailand virus [THAIV] has been isolated), and even Europe [25,31,3437] and North America [38,39]. It is estimated that hantavirus diseases are heavily underdiagnosed in Europe; only 20% of PUUV infections have been diagnosed, and no human infections data exist in several countries [31]. Fig 1. Map of Old World and New World hantavirus genotypes reported to be pathogenic for humans. Hantaviruses that have been shown to cause HFRS are shown in red, and those that cause HPS are shown in green. PUUV, which causes a milder form of HFRS (NE), is found in Europe. The described African hantavirus, Sangassou virus, was found in Guinea in 2016. In recent studies, THAIV is considered to act as an additional causative agent of HFRS. It should be noted that SEOV is harbored by Rattus norvegicus (brown rat) worldwide, but only those locations where reports of human infections with SEOV are shown. The map was created specifically for this manuscript and was generated by ArcGIS 9.2 (ESRI, Redlands, CA, USA) based on World Countries (http://www.arcgis.com/home/item.html?id=d974d9c6bc924ae0a2ffea0a46d71e3d). HFRS, hemorrhagic fever with renal syndrome; HPS, hantavirus pulmonary syndrome; NE, nephropathia epidemica; PUUV, Puumala virus; SEOV, Seoul virus; THAIV, Thailand virus. https://doi.org/10.1371/journal.pntd.0006901.g001 Environment variation and hantavirus reservoir population dynamics A bottom-up trophic cascade hypothesis has been proposed to explain the chain reactions resulting from climatic conditions, primary productivity, and host demography [27,40,41]. A bottom-up trophic cascade suggests that a change in nutrient supply could lead to similar changes in equilibrium abundances at all trophic levels [42,43]. In rodent host-hantavirus systems, climatic conditions are one of the many factors that can affect rodent population dynamics and, consequently, the prevalence of virus infection in rodent reservoirs and risk of virus exposure in humans [44] (see example shown in Fig 2). A review of the available longitudinal studies of rodent communities supports the hypothesis that hantavirus reservoir populations in both the Old World and New World are significantly influenced by climate, either directly (via winter survival) or indirectly (through food limitation). Fig 2. An overview of the ecological dynamics of HFRS caused by HTNV infection. Arrows represent connections affected by environment: the green line represents rainfall, and the orange line represents temperature. The solid line indicates available data, used in models linking the ENSO (Nino3.4 index) with local climate (rainfall and temperature), rodent population density (capture rate), and human HTNV infections. The rectangles delimit the seasonal, interannual, and zoonotic cycles of HTNV. Source: Adapted from [46]. ENSO, El Niño Southern Oscillation; HFRS, hemmorrhagic fever with renal syndrome; HTNV, Hantaan virus. https://doi.org/10.1371/journal.pntd.0006901.g002 In Central China, an environmentally induced cascading effect on the population dynamics of the striped field mouse (A. agrarius, the main reservoir host for HTNV) was found by combining 30 years of field surveillance and satellite images. The normalized difference vegetation index (NDVI) value for farmland, and precipitation two months previously, were important in determining striped field mouse survival and recruitment rates, respectively [45]. An extreme drought-induced food shortage is thought to increase mortality in striped field mouse populations, as they are a species that relies on farm crops [45]. Furthermore, winter temperature was found to exert complex effects on overwinter survival, thereby affecting the population growth rate in the following year [46]. In South China, the population density of the main reservoir host for SEOV, the brown rat (Rattus norvegicus), is correlated with temperature, precipitation, and the NDVI value for farmland [47]. In northeastern China, in Huludao City, an endemic area for HFRS due to SEOV, climate is considered to affect HFRS epidemics mainly through its effect on the population density of the brown rat (the most abundant rodent species present, accounting for more than 80% of the total rodent population) [48]. In Europe, food-related factors (seed production, climate affecting vegetation biomass) have been linked to rodent populations in deciduous forests [30,49]. Outbreaks of nephropathia epidemica (NE; a mild form of HFRS caused by PUUV infection) are hypothesized to have an ecological causal connection with the staple food source for the main carrier of PUUV, the bank vole, in mast years [32,50,51]. Population densities of bank voles were found to be associated with summer temperature and autumn temperature, both of which favor seed development [52,53]. A higher average winter temperature is believed to reduce winter survival of bank voles in Scandinavia because of a shorter period of protective snow cover against predators. On the contrary, increasing winter temperatures are found to provide a survival benefit to increasing populations of striped field mouse in the spring in Central China; subsequently, a large population of rodents might be accompanied by intraspecific competition due to food or space limitation, resulting in a negative-feedback effect of population density [46]. In North America, the HPS outbreak in 1993 in the Four Corners region of the southwestern US was considered to be driven by increased precipitation induced by an El Niño-Southern Oscillation (ENSO) event. The HPS outbreaks in 1997 in the same region were also preceded by an ENSO event, which brought increased precipitation, favoring deer mouse host populations [26,27]. NDVI is also used to identify locations that can be monitored for the abundance of deer mouse and presence of SNV by examining the seasonal dynamics of vegetative patterns [54]. In central Montana, US, the survival and recruitment rates of the deer mouse were found to be associated with precipitation and temperature, implying a complex relationship between climate and population dynamics [55]. Rodent population dynamics and risk to humans Long-term observations on the prevalence of hantavirus infection in rodent hosts are critical to understanding the dynamics of hantavirus diseases in humans. Similarly, analysis of hostpathogen interactions is important to successfully implement disease control strategies [56]. Hantaviruses are known to be directly transmitted from infected to susceptible hosts (horizontal transmission). Therefore, changes in rodent population densities are expected to increase or decrease the transmission and prevalence of hantavirus infection in rodent reservoir populations, resulting in greater or lower levels of spillover to humans [28]. The dynamics of rodent population density and hantavirus infection prevalence are linked by contact rates; the virus may become extinct below a certain host density, corresponding to the minimum number of hosts required for virus maintenance in a population [57]. A critical population density threshold of striped field mice has been observed in Central China, below which HTNV cannot invade and persist in the population [45]. A similar population density threshold has been observed in the SNV reservoir, the deer mouse, in North America [58,59]. Rodent community composition has also been found to affect the risk of human hantavirus infection among different landscapes [60]. Studies have demonstrated positive correlations between relative population density of bank voles and prevalence of PUUV infection among rodent populations [61]. Bank vole density indices were also positively correlated with risk of HFRS in humans in northern Sweden, Finland, and Norway [6264]. However, the relationship between rodent demography and disease dynamics in China and North America is more complicated. In Central China, fluctuation in HFRS incidence is highly correlated with striped field mouse population density and the prevalence of HFRS infection in Shaanxi Province, an endemic area for HFRS due to HTNV [13]. In northeastern China, HFRS cases are associated with a virus-carrying index, an indicator to describe the combined effects of rodent population density and prevalence of virus infection, with a one-month lag, in the SEOV endemic area of HFRS [48]. However, in South China, the number of HFRS cases is not associated with rodent population density in Chenzhou and Changsha (the main species captured are R. norvegicus, R. flavipectus, and Mus musculus), which are mixed HTNV and SEOV endemic areas [65,66]. In North America, different relationships have been found between deer mouse population density and SNV infection prevalence in the deer mouse populationpositive correlations [17,27,67], no linear correlation [59,68,69], and even negative correlations [18,70,71]. (It should also be noted that the different correlational relationship may be due to temporal issues; e.g., some studies take account of time lags when analyzing the data while others do not.) Because hantaviruses are horizontally transmitted, these inconsistent results may be due to two conflicting effects of population dynamics on prevalence [28]. During breeding seasons, rapid population growth of juveniles not yet infected may increase the proportion of uninfected rodents and potentially decrease hantavirus prevalence [72,73], whereas the resulting higher population size may eventually increase contact between individuals and prevalence. Taken together, these studies point to several issues that could be of importance to understanding the relationship between reservoir population dynamics and pathogen transmission [57]. Future demographic studies should aim to establish causal mechanisms linking behavior, demography, and virus prevalence dynamics. Environmental factors that trigger hantavirus disease outbreaks Environmental factors are major triggers that affect reservoir ecology and virus ecology and thus are likely to affect hantavirus transmission from rodent reservoir to humans (or risk of virus exposure in humans). However, although outbreaks appear to be a result of these factors, it is difficult to predict the exact outcome, chiefly due to the complex and multifactorial mechanisms that drive hantavirus disease outbreaks. Studies have highlighted the importance of the interplay between extrinsic and intrinsic factors in determining hantavirus disease dynamics [45,46,74], e.g., when the size of outbreaks is small due to low population susceptibility levels as the result of vaccination or the rodent reservoir population density is below the threshold level required to maintain the virus due to environmental limitations. In this section, studies addressing environmental variability and human hantavirus infections were included (Table 1), and we mainly review three factors that play an important role in altering hantavirus disease dynamics and have been documented sufficientlyprecipitation, temperature, and landscape alteration. It is becoming increasingly more apparent that climatic variations have profound impacts on infectious disease dynamics [75,76], especially for climate-sensitive infectious diseases; e.g., human hantavirus diseases are considered climate-sensitive infectious diseases [77]. Understanding the influence of climatic drivers on hantavirus disease ecology can help in forecasting and prevention, which is even more urgently needed in this era of climate change. Recently, Tian and colleagues [46] investigated the role extrinsic factors (climatic conditions) play in determining hantavirus disease dynamics in Central China. A unique data set from Central China covering half a century showed the existence of a climate-driven transmission mechanism for HTNV from the striped field mouse to humans [21]. HFRS outbreaks were highly correlated with specific environmental conditionslow summer temperature and abundant summer precipitation. Conversely, very few disease outbreaks occurred under conditions of high summer temperatures and drought (Fig 3A) [46]. In South China, HFRS incidence was also found to be positively correlated with annual precipitation and absolute humidity during 1991 to 2010 [78]. HPS outbreaks in the Four Corners region of the US are considered to be driven by ENSO-associated precipitation events as well [26,79]. Fig 3. Environmental factors associated with hantavirus disease outbreaks. (A) Relationship between summer temperature, summer rainfall, and HFRS cases in Weihe Plain, North China, 1960 to 2013. Circle size is proportionate to the number of HFRS cases [46]. (B) Contribution of the environmental variables to the explained variance of hantavirus-antibodypositive in rodents using a multivariate principal component analysis in Hunan Province, South China, 2007 to 2010. Dimensions 1 and 2 are the spaces where variables are expressed. The length (angle) of the arrows represents the magnitude (direction) of the correlation coefficient between the variable and the principal components. The contributions of the variables to the hantavirus-antibodypositive in rodents are ranked with colors ranging from green to red, respectively (reproduced from Xiao 2016 with permission of the publisher [127]). Dim, dimension; HFRS, hemorrhagic fever with renal syndrome; NDVI, normalized difference vegetation index. https://doi.org/10.1371/journal.pntd.0006901.g003 However, precipitation can also negatively affect or have no effect on the incidence of hantavirus disease, depending on magnitude and region [80]. In Europe, no clear relationship of rainfall with human hantavirus infections was shown [77], except that one study illustrated rainfall in the summer three years before hantavirus disease incidence increased [50]. Other studies also demonstrated no significant association between rainfall and hantavirus disease [52,81,82]. In Cascade and Polson, Montana, US, increases in primary productivity, deer mouse population densities, and human disease risk are less sensitive to changes in the amount of rainfall [83]. In low-lying regions of China, such as Anhui Province, HFRS incidence and rodent population density (dominated by the striped field mouse) are all negatively correlated with the total precipitation [8486]. Heavy precipitation there may kill rodents by flooding their burrows and nests, thereby reducing host population density and the risk of human exposure to pathogens. Floods could also cause movement of rodent populations (even community-level changes [87]) to new habitats and eventually disease emergence in new sites. Temperature could influence disease dynamics through its impact on the rodent reservoir population dynamics and pathogen survival in the external environment, subsequently influencing humananimal contact patterns. However, compared to precipitation, the effects of temperature have been less investigated, and contradictory findings make it difficult to draw firm conclusions. For example, in Central China, higher summer temperatures were followed by a lower incidence of HFRS in autumn (Fig 3A) [46]this was presumably due to a reduced frequency of contacts between rodents and between rodents and humans, coupled with an unfavorable environment for virus survival [88]whereas in Belgium, a higher summer temperature two years before led to higher NE incidence [50,52]. A potential explanation is that the higher temperature two years before might have stimulated bud formation that contributed to heavy masting one year before. Likewise, opposite associations between mean temperature and hantavirus infection incidence were found across China [20,66,89,90]. In South America, HPS caused by ANDV was also negatively associated with winter temperature [91]. Conversely, in North America, a positive relationship between hantavirus disease incidence and temperature was reported [80]. There is a need for more studies to investigate the mechanisms behind these relationships. Humananimal interface Humananimal interface constitutes the boundary/barrier for cross species transmission of disease and the environment (including ecological and anthropological factors) within which these species exist [92,93]. In the preceding sections, we have summarized the ecological factors and processes that affect hantavirus diseases dynamics; hereafter, anthropological factors will be reviewed, including agricultural activity, human-driven land-use change, and vaccination. In HPS endemic regions of America, agriculture-associated activities were also most commonly reported as potential risk factors [9497], and seropositive rodents were found with high frequency in agricultural landscapes [98,99]. In the HTNV-type endemic area of central China, seasonal pattern of HFRS dynamics is found to coincide with the increase in potential contact between rodents and humans in the dry season due to seasonal agricultural activities [45,100]. Besides, the breeding season of striped field mouse, the local rodent host, is closely associated with agricultural activity. Moreover, it could be concluded that agricultural activity may influence the activity and life cycles of local striped field mouse and in turn shape disease dynamics. Human-driven landscape change could influence rodent host behavior and the composition of reservoir communities in such a way as to impact pathogen transmission [101,102]. The major consequences of landscape alteration are habitat loss and changes in species composition due to the loss of specialist species and the increase in generalist species [74], and these consequences either increase or decrease the risk of disease transmission at the humananimal interface. For example, HFRS epidemics in China peaked in autumn and winter in the area where the dominant hantavirus is the Apodemus-borne HTNV, whereas the area with Rattus-borne SEOV saw epidemic peaks in spring [103]. These two distinct rodent species have different breeding sites with special landscape attributes [104], which changes the epidemiological characteristics of hantavirus disease. Human disturbance also affects survival probabilities and reproduction of rodent hosts [105]. Another consequence of landscape alteration is loss of biodiversity, which is considered to affect the transfer of pathogens among species and influence the risk of infection to humans. Biodiversity loss may result in increased hantavirus infection prevalence in host populations [106], affecting the dynamics of SNV in the US, Choclo hantavirus in Panama, and PUUV in Europe [68,107111]. For some directly transmitted and vector-borne zoonotic diseases, it has been hypothesized that increased species diversity would result in a lower pathogen prevalence in competent hosts and therefore lower risk of infection to humans by a mechanism called the dilution effect [112], although there is still a debate about the (positive or negative) relationship between biodiversity and zoonotic disease transmission, e.g., SNV and deer mice system in America [113]. To our knowledge, few attempts have been made to evaluate this effect with regards to HTNV/striped field mouse system in China. Further testing of this theory is therefore still required. Another human-driven landscape change is induced by urbanization (i.e., urban expansion). However, the relationship between the diffusion of zoonotic pathogens and urbanization is complex because of the contrasting effects (Fig 4): cities with faster economic growth may attract more immigrants and reach their endemic turning points later (endemic turning point defined as point at which incidence changes from increasing to decreasing), whereas economic growth that contributes towards improvements in the living conditions may decrease contact between rats and humans [114]. Fig 4. Urbanization, immigration, and hantavirus disease epidemics in an endemic area of south China. (A) Urbanization and HFRS incidence in Hunan Province. A biphasic inverted U-shaped relationship was found between hantavirus disease epidemics and urbanization. (B) The number of immigrants and HFRS incidence. This result indicates that the effect of urbanization on HFRS epidemics changed, whereas the effect of immigration remained constant. Source: Adapted from [114]. HFRS, hemorrhagic fever with renal syndrome. https://doi.org/10.1371/journal.pntd.0006901.g004 Vaccination programs against HFRS have been in practice for more than 20 years in China, where the incidence of HFRS has decreased with occasional small fluctuations. It has been reported that the age distribution of HFRS infections has clearly changed in recent years, ever since the Expanded Program of Immunization for regions with high HFRS incidence was implemented in 2008 [115]. Simulations conducted on data from a county in Central China have shown that vaccination will alter the dynamics of HFRS outbreaks [45]. The vaccination-induced reduction in susceptible human population gradually led to the reduction of human hantavirus infections and successfully averted further epidemics. The findings in China therefore highlight the necessity for a vaccination strategy and provide important insights for other countries. Discussion The dynamics of hantavirus epidemics involve multiple phases, including environmental drivers that influence infectious diseases, transmission in the animal reservoir, and spillover transmission to humans. The complexity of disease dynamics has been highlighted in recent decades by contradicting trends; the incidence of HFRS has decreased in China [22,116] and increased in Europe [31]. Although pioneering research efforts to study both New World and Old World strains of hantaviruses in rodents have been undertaken, as well as related prevention strategies, it is evident that much work remains to be done. By further studying the transmission dynamics of hantaviruses, better prediction and prevention measures can be implemented to protect human health, and critical insight can be obtained into the ecology of hantaviruses and their rodent hosts. The geographic distributions of hantaviruses reflect the distributions of their reservoir hosts [3], and our knowledge of the host associations of hantaviruses is expanding. For example, the hantavirus isolated in Africa, Sangassou virus, was recently found in the African wood mouse (Hylomyscus simus) [117]. Although, in general, each hantavirus has been considered to be associated with a specific reservoir host, there have been cases that suggest rodent host expansion (e.g., pathogens that can infect multiple host species) for both HTNV and SEOV in China [22,118120]. This challenges the strict rodentvirus coevolution theory and demonstrates that at least some hantaviruses can infect other susceptible rodents in addition to primary hosts, expanding the number of potential animal hosts [121]. These cases raise the question as to what role undetected or potential hosts play in hantavirus ecology and further influence the risk of human infectionsa question largely ignored in the past and an area of further research. Further research is also needed to clarify the relationships between diversity and prevalence across types of ecosystems and host species, in particular, as the dilution effect on prevalence dynamics has broad potential applicability in predicting virus prevalence among rodent hosts. To the best of our knowledge, this is the first systematic review to compare hantavirus disease dynamics, from environmental variability to rodent reservoir and to public health, among the main endemic areas across the globe. This review is timely because of the increasing public awareness of hantavirus diseases in Europe, in particular, over the last years. Limitations of this systematic review were that individual studies had differencessurveillance strategies for hantavirus infections, rodent sampling methods, rodent community compositions, socioeconomic factors, and environmental conditions. Therefore, studies were not all directly comparable, especially among China, European countries, and the US. Additionally, it should be noted that unusual human exposure (like war-induced exposure) to otherwise normal environment is an often forgotten risk factor for limited outbreaks [122]. Besides, there are more recent studies on ANDV-like viruses in South America that explore the environment conditions relevant to the occurrence of the host and the circulation of the virus, scrutinize the evidence for climate sensitivity of related disease risk, and recognize those areas of high risk for humans [91,123126]. However, in this review, more attention was paid to longitudinal studies of sufficient scale. Finally, our focus on China in the review reflects the fact that for this country highly comprehensive data exist. Establishing a mechanistically determined predictive framework for rodent-borne hantavirus disease prediction and prevention is urgently required to proactively protect the public from the increasing threat of hantaviruses. Such a framework would also provide insight into climate change, landscape alteration, rodent community composition, and pathogen spillover. Key Learning Points With this review we have demonstrated the following: The complex seasonality and interannual cycles of hantavirus disease dynamics are a direct result of the (nonlinear) interaction between the population dynamics of the rodent host, environmental forcing, and humanwildlife contact patterns. Specific environmental conditions can trigger hantavirus disease outbreaks, but the outcomes may differ among strains or areas mediated by the underlying mechanisms of hantavirus transmission. For example, in Weihe Plain of Central China, higher summer temperatures were followed by a lower incidence of HFRS in autumn; conversely, in North America, a positive relationship between hantavirus disease incidence and temperature was reported, indicating the complexity across different systems. Current efforts to curb hantavirus transmission focus on avoiding contact between humans and host rodents as there is no WHO-licensed vaccine against hantavirus infections available (except Hantavax, which is licensed for human use only in the Republic of Korea). Hence, a broader appreciation for the epidemiological links among human beings, animals, and environment can result in more effective control of disease outbreak. Top Five Papers Yates TL, Mills JN, Parmenter CA, Ksiazek TG, Parmenter RR, et al. (2002) The ecology and evolutionary history of an emergent disease: hantavirus pulmonary syndrome. Bioscience 52: 989998. Glass GE, Yates TL, Fine JB, Shields TM, Kendall JB, et al. (2002) Satellite imagery characterizes local animal reservoir populations of Sin Nombre virus in the southwestern United States. Proc Natl Acad Sci USA 99: 1681716822. Clement J, Vercauteren J, Verstraeten W, Ducoffre G, Barrios J, et al. (2009) Relating increasing hantavirus incidences to the changing climate: the mast connection. International Journal of Health Geographics 8: 1. Jonsson CB, Figueiredo LTM, Vapalahti O (2010) A global perspective on hantavirus ecology, epidemiology, and disease. Clinical Microbiology Reviews 23: 412441. Yan L, Fang LQ, Huang HG, Zhang LQ, Feng D, et al. (2007) Landscape elements and Hantaan virus-related hemorrhagic fever with renal syndrome, People's Republic of China. Emerging Infectious Diseases 13(9): 13011306. Acknowledgments We thank Jan Clement and James N. Mills for their valuable comments, which have been very helpful in improving the manuscript. References 1. Maes P, Alkhovsky SV, Bào Y, Beer M, Birkhead M, et al. 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Ecohealth 8: 332348. pmid:22130568 124. Piudo L, Monteverde MJ, Walker RS, Douglass RJ (2011) Rodent community structure and Andes virus infection in sylvan and peridomestic habitats in northwestern Patagonia, Argentina. Vector Borne Zoonotic Dis 11: 315324. pmid:21332352 125. Medina RA, Torres-Perez F, Galeno H, Navarrete M, Vial PA, et al. (2009) Ecology, genetic diversity, and phylogeographic structure of Andes virus in humans and rodents in Chile. J Virol 83: 24462459. pmid:19116256 126. Astorga F, Escobar LE, Poo-Muñoz D, Escobar-Dodero J, Rojas-Hucks S, et al. (2018) Distributional ecology of Andes hantavirus: a macroecological approach. Int J Health Geogr 17: 22. pmid:29929522 127. Xiao H, Huang R, Gao L, Huang C, Lin X, et al. (2016) Effects of humidity variation on the hantavirus infection and hemorrhagic fever with renal syndrome occurrence in subtropical China. Am J Trop Med Hyg 94: 420427. pmid:26711521 128. Prist PR, Uriarte M, Tambosi LR, Prado A, Pardini R, et al. (2016) Landscape, environmental and social predictors of Hantavirus risk in São Paulo, Brazil. PLoS ONE 11: e0163459. pmid:27780250 129. Li C, Cui Z, Li S, Magalhaes RJS, Wang B, et al. (2013) Association between hemorrhagic fever with renal syndrome epidemic and climate factors in Heilongjiang Province, China. Am J Trop Med Hyg 89: 10061012. pmid:24019443 130. Han SS, Kim S, Choi Y, Kim S, Kim YS (2013) Air pollution and hemorrhagic fever with renal syndrome in South Korea: an ecological correlation study. BMC Public Health 13: 347. pmid:23587219 131. Donalisio MR, Peterson AT (2011) Environmental factors affecting transmission risk for hantaviruses in forested portions of southern Brazil. Acta Tropica 119: 125130. pmid:21605537 132. Nsoesie EO, Mekaru SR, Ramakrishnan N, Marathe MV, Brownstein JS (2014) Modeling to predict cases of hantavirus pulmonary syndrome in Chile. PLoS Negl Trop Dis 8: e2779. pmid:24763320 133. Lin H, Zhang Z, Lu L, Li X, Liu Q (2014) Meteorological factors are associated with hemorrhagic fever with renal syndrome in Jiaonan County, China, 20062011. Int J Biometeorol 58: 10311037. pmid:23793957 134. Lin H, Liu Q, Guo J, Zhang J, Wang J, et al. (2007) Analysis of the geographic distribution of HFRS in Liaoning Province between 2000 and 2005. BMC Public Health 7: 207. pmid:17697362 135. Bi P, Parton KA, Tong S (2005) El Ninosouthern oscillation and vector-borne diseases in Anhui, China. Vector Borne Zoonotic Dis 5: 95100. pmid:16011424 136. Hjelle B, Glass GE (2000) Outbreak of hantavirus infection in the Four Corners region of the United States in the wake of the 19971998 El NinoSouthern Oscillation. J Infect Dis 181: 15691573. pmid:10823755 137. Fang LQ, Zhao WJ, de Vlas SJ, Zhang WY, Liang S, et al. (2009) Spatiotemporal dynamics of hemorrhagic fever with renal syndrome, Beijing, Peoples Republic of China. Emerg Infect Dis 15: 20432045. pmid:19961697 138. Clement J, Maes P, Van Ypersele de Strihou C, van der Groen G, Barrios JM, et al. (2010) Beechnuts and outbreaks of nephropathia epidemica (NE): of mast, mice and men. Nephrol Dial Transplant 25: 17401746. pmid:20237057 139. Heyman P, Cochez C, Ducoffre G, Mailles A, Zeller H, et al. (2007) Haemorrhagic fever with renal syndrome: an analysis of the outbreaks in Belgium, France, Germany, the Netherlands and Luxembourg in 2005. Euro Surveill 12: 1516. 140. Hofmann J, Meisel H, Klempa B, Vesenbeckh SM, Beck R, et al. (2008) Hantavirus outbreak, Germany, 2007. Emerg Infect Dis 14: 850852. pmid:18439382 141. Reil D, Imholt C, Eccard JA, Jacob J (2015) Beech fructification and bank vole population dynamics-combined analyses of promoters of human Puumala virus infections in Germany. PLoS One 10: e0134124. pmid:26214509 142. Yan L, Huang H, Zhang W, Wang J, Ren Y, et al. (2009) The relationship between hemorrhagic fever with renal syndrome cases and time series of NDVI in Dayangshu District. Journal of Remote Sensing 13: 873886. 143. Fang L-Q, Goeijenbier M, Zuo S-Q, Wang L-P, Liang S, et al. (2015) The association between hantavirus infection and selenium deficiency in mainland China. Viruses 7: 333351. pmid:25609306 Michael Novakhov - SharedNewsLinks
Michael Novakhov - SharedNewsLinks: hantavirus outbreaks after floods - Google Search
Michael_Novakhov shared this story . Search Results Web results Rodent-borne infectious disease outbreaks after flooding ... www.ncbi.nlm.nih.gov pubmed <a href="http://www.ncbi.nlm.nih.gov" rel="nofollow">www.ncbi.nlm.nih.gov</a> pubmed Similar CONCLUSIONS: Healthcare providers should maintain high levels of suspicion for LS in patients developing febrile illnesses after contaminated freshwater exposures following heavy rainfall, flooding, and even freshwater recreational events; and for Hantavirus-caused infectious diseases in patients with hemorrhagic ... by JH Diaz - 2015 - Cited by 11 - Related articles Rodent-borne Infectious Disease Outbreaks After Flooding ... pubmed.ncbi.nlm.nih.gov ... pubmed.ncbi.nlm.nih.gov ... Conclusions: Healthcare providers should maintain high levels of suspicion for LS in patients developing febrile illnesses after contaminated freshwater exposures following heavy rainfall, flooding, and even freshwater recreational events; and for Hantavirus-caused infectious diseases in patients with hemorrhagic ... by JH Diaz - 2015 - Cited by 11 - Related articles Rodent-borne infectious disease outbreaks after flooding ... www.researchgate.net publication 307808285_Rodent... <a href="http://www.researchgate.net" rel="nofollow">www.researchgate.net</a> publication 307808285_Rodent... Download Citation | Rodent-borne infectious disease outbreaks after flooding ... Another zoonotic viral disease after heavy rainfall and flooding is hantavirus ... Michael Novakhov - SharedNewsLinks
Michael Novakhov - SharedNewsLinks: floods and epidemics - Google Search
Michael_Novakhov shared this story . Search Results Scholarly articles for floods and epidemics Diarrheal epidemics in Dhaka, Bangladesh, during - Schwartz - Cited by 196 diarrhoea epidemics in the 1998 Bangladesh floods - Kunii - Cited by 171 seeking hospital care during floods in 1998, 2004, and - Harris - Cited by 108 Web results Flooding and communicable diseases fact sheet - WHO www.who.int hac techguidance ems flood_cds <a href="http://www.who.int" rel="nofollow">www.who.int</a> hac techguidance ems flood_cds Cached The lag time is usually around 6-8 weeks before the onset of a malaria epidemic. Malaria epidemics in the wake of flooding are a well-known phenomenon in ... People also search for Relationship between Flooding and Out Break of Infectious ... www.ncbi.nlm.nih.gov pmc articles PMC6207902 <a href="http://www.ncbi.nlm.nih.gov" rel="nofollow">www.ncbi.nlm.nih.gov</a> pmc articles PMC6207902 Cached Oct 17, 2018 - Flooding can potentially increase the spread of infectious diseases. ... Other studies that have linked flooding to explosive epidemic malaria ... by FO Okaka - 2018 - Cited by 10 - Related articles Abstract · Introduction · Results · Discussion People also search for Epidemics after Natural Disasters - NCBI www.ncbi.nlm.nih.gov pmc articles PMC2725828 <a href="http://www.ncbi.nlm.nih.gov" rel="nofollow">www.ncbi.nlm.nih.gov</a> pmc articles PMC2725828 Cached Similar After a flooding-related outbreak of leptospirosis in Brazil in 1996, spatial analysis indicated that incidence rates of leptospirosis doubled inside the flood-prone ... by JT Watson - 2007 - Cited by 606 - Related articles Abstract · Dead Bodies and Disease · Communicable Diseases ... · Discussion People also search for Preventing epidemics is yet another challenge after floods ... www.onmanorama.com Lifestyle Health <a href="http://www.onmanorama.com" rel="nofollow">www.onmanorama.com</a> Lifestyle Health New Delhi: After battling the worst flood disaster in Kerala the state is now fearing break out of epidemics ... Jun 24, 2020 Recurrent epidemics and floods following heavy rains in ... www.researchgate.net publication 270508689_Recurr... <a href="http://www.researchgate.net" rel="nofollow">www.researchgate.net</a> publication 270508689_Recurr... Request PDF | Recurrent epidemics and floods following heavy rains in Albertine Region Uganda: A desk review of the vulnerability factors and adaptive ... Michael Novakhov - SharedNewsLinks
Saved Stories - None: Deutsche Welle: DW.com - Business: Danish nod gives Nord Stream 2 gas pipeline fresh traction
The Danish Energy Agency has greenlighted the use of Russian ships that could speed up execution of the controversial Nord Stream 2 gas pipeline. US sanctions, however, may still put a dampener on the project.  Deutsche Welle: DW.com - Business Saved Stories - None
Saved Stories - None: Deutsche Welle: Germany's Angela Merkel in Brussels for talks on EU coronavirus recovery
Merkel's trip to Brussels is her first abroad since the pandemic caused lockdowns across the continent. Her talks with the presidents of the three main EU institutions will be dominated by the coronavirus stimulus deal.  Deutsche Welle Saved Stories - None
Saved Stories - None: Young Black voters say they aren't enthusiastic about a Joe Biden presidency - USA TODAY
Young Black voters say they aren't enthusiastic about a Joe Biden presidency  USA TODAY Why this area may seal Trump's 2020 fate  CNN Why Trump is right and wrong about America  Al Jazeera English Biden Should Not Debate Trump Unless   The New York Times Trump's last line of defense is the economy. Biden and Democrats must knock it down.  USA TODAY View Full Coverage on Google News Saved Stories - None
Saved Stories - None: Trump's Drive On Division And Fear May Not Be A Winning Strategy Come November - NPR
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Saved Stories - None: COVID-19: Uzbekistan Plans Second Lockdown Starting July 10
The global death toll from the coronavirus is approaching 547,000, with almost 12 million infections confirmed, causing mass disruptions as governments continue to try to slow the spread of the respiratory illness. Here's a roundup of COVID-19 developments in RFE/RL's broadcast regions. Saved Stories - None
Michael Novakhov - SharedNewsLinks: WHO confirms there's 'emerging evidence' of airborne transmission of coronavirus - CNN
Michael_Novakhov shared this story from Top stories - Google News. WHO confirms there's 'emerging evidence' of airborne transmission of coronavirus  CNN Is the coronavirus airborne? What we know about COVID-19 transmission  CNET Is Coronavirus More Airborne Than We Thought? Scientists Speak Out | TODAY  TODAY Airborne spread another goalpost move in battle against coronavirus? (opinion)  SILive.com Scientists say coronavirus can be spread farther than 6 feet in tiny airborne particles  CBS This Morning View Full Coverage on Google News Michael Novakhov - SharedNewsLinks
Saved Stories - None: WHO confirms there's 'emerging evidence' of airborne transmission of coronavirus - CNN
WHO confirms there's 'emerging evidence' of airborne transmission of coronavirusCNN Is the coronavirus airborne? What we know about COVID-19 transmissionCNET Airborne spread another goalpost move in battle against coronavirus? (opinion)SILive.com Is Coronavirus More Airborne Than We Thought? Scientists Speak Out | TODAYTODAY Airborne spread another goalpost move in battle against coronavirus? (opinion)SILive.com Is the coronavirus airborne? What we know about COVID-19 transmissionCNET Scientists say coronavirus can be spread farther than 6 feet in tiny airborne particlesCBS This Morning View Full Coverage on Google News Saved Stories - None
Saved Stories - None: Dutch police discover criminal gang's 'torture chamber' during drugs raid
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Saved Stories - None: Deutsche Welle: Merkel's CDU aim to fill half of party posts with women by 2025
Chancellor Angela Merkel's party has said it plans to introduce quotas to increase female representation in the party. An initial quota will go into effect next year, with gradual increases to follow.  Deutsche Welle Saved Stories - None
Saved Stories - None: Coronavirus: Biden vows to reverse Trump WHO withdrawal
President Trump's Democratic rival will put the US back in "on day one" if he wins November's poll. Saved Stories - None
Saved Stories - None: Dog meat: First Cambodian province bans sale and consumption
The decision in Siem Reap follows similar moves in parts of China and India in recent months. Saved Stories - None
Saved Stories - None: Tajik Prosecutors Summon Journalists Family After His Coverage Of Coronavirus
The Prosecutor-Generals Office in Tajikistan has summoned for questioning close relatives of an independent journalist who has led critical coverage of the governments response to the coronavirus pandemic, in a sign of the increased efforts by authorities to stifle free speech.

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Saved Stories - None: Deutsche Welle: US exit from the WHO: German minister calls move a 'setback' for cooperation

German Health Minister Jens Spahn said more international cooperation is needed now more than ever. China has also heavily criticized the US decision to withdraw from the WHO during a global pandemic.

 Deutsche Welle

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Saved Stories - None: Deutsche Welle: Lockdown and racism go hand in hand in Catalonia

All access to the Catalan region of Lleida has been closed again after a surge in COVID-19 clusters. Most of the new outbreaks are linked to the chaotic situation of 30,000 foreign day laborers.

 Deutsche Welle

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Saved Stories - None: Deutsche Welle: Can India really have a coronavirus vaccine ready by August?

India's top health agency has said the country should have a coronavirus vaccine ready in time for Independence Day on August 15. Experts warn the short timeline is both unrealistic and dangerous.

 Deutsche Welle

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Michael Novakhov - SharedNewsLinks: 7:35 AM 7/8/2020 - Bat virus? Bioweapon? What the science says about Covid-19 origins - Sars-Cov-2 origins: Six months into coronavirus pandemic, scientists say exact source may never be identified

Michael_Novakhov shared this story from Covid-19-Review.

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7:35 AM 7/8/2020

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mikenov on Twitter: Over 6 months into Covid-19 crisis, 5 mysteries that still shroud coronavirus - world news - Hindustan Times hindustantimes.com/world-news/ove
mikenov on Twitter: Merkel looks east as ties fray between Germany and U.S. - POLITICO politico.com/news/2020/07/0
mikenov on Twitter: Six months into coronavirus pandemic, scientists say exact source may never be identified sg.news.yahoo.com/six-months-cor via @yahoosg
Saved Stories - None: Google Alert - Sars-Cov-2 origins: Six months into coronavirus pandemic, scientists say exact source may never be identified
Saved Stories - None: Google Alert - Sars-Cov-2 origins: WHO Researchers to Investigate Animal Origin of COVID-19 in China
Saved Stories - None: Google Alert - Sars-Cov-2 origins: Scientists Continue the Search for the Source of COVID-19
mikenov on Twitter: RT @FrankFigliuzzi1: UPENN needs to investigate and if true, revoke his degree: Trump cheated on SAT by paying someone to take it for him.
mikenov on Twitter: 6:18 AM 7/8/2020 - Coronavirus origins: Coronavirus spreading now in Korea has its origin in Europe, US Tweets And News - From Michael Novakhov: 6:18 AM 7/8/2020 - Coronavirus origins: Coronaviru... tweetsandnews.blogspot.com/2020/07/618-am
Michael Novakhov - SharedNewsLinks: Why not to worry about it amid coronavirus
Saved Stories - None: Google Alert - coronavirus origins: Coronavirus spreading now in Korea has its origin in Europe, US
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Saved Stories - None: Google Alert - coronavirus origins: FACTBOX-China suspends meat imports from various origins amid COVID-19 pandemic
Saved Stories - None: Google Alert - Sars-Cov-2 origins: Yet another stunning revelation about the true origin of COVID-19
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Saved Stories - None: Google Alert - coronavirus origins: Coronavirus: world treating symptoms, not cause of pandemics, says UN
Saved Stories - None: Google Alert - Sars-Cov-2 origins: Preventing the next pandemic - Zoonotic diseases and how to break the chain of transmission
Saved Stories - None: Google Alert - coronavirus origins: Flooding follows coronavirus disaster in China's 'cursed' city of Wuhan
Saved Stories - None: Google Alert - coronavirus origins: Here's one 'remarkable' difference between COVID-19 and the 1918 Spanish flu
Saved Stories - None: Google Alert - coronavirus origins: North American bats may be susceptible to SARS-CoV-2
Saved Stories - None: Google Alert - coronavirus origins: Hong Kong facing coronavirus community outbreak - health official
Saved Stories - None: Google Alert - coronavirus origins: Coronavirus: Anger over US decision on foreign students' visas

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Michael Novakhov - SharedNewsLinks: 7:58 AM 7/8/2020 - Merkel looks east as ties fray between Germany and U.S. - POLITICO - Saved, Shared Stories, Tweets

Michael_Novakhov shared this story from Covid-19-Review.

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Merkel looks east as ties fray between Germany and U.S. - POLITICO https://www.politico.com/news/2020/07/07/germany-china-trade-coronavirus-us-351922 
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» mikenov on Twitter: Covid-19-Review: 7:35 AM 7/8/2020 - Bat virus? Bioweapon? What the ... covid-19-review.blogspot.com/2020/07/735-am
08/07/20 07:40 from TWEETS BY MIKENOV from mikenova (1 sites)
Covid-19-Review: 7:35 AM 7/8/2020 - Bat virus? Bioweapon? What the ... covid-19-review.blogspot.com/2020/07/735-am Posted by mikenov on Wednesday, July 8th, 2020 11:40am mikenov on Twitter

» mikenov on Twitter: Over 6 months into Covid-19 crisis, 5 mysteries that still shroud coronavirus - world news - Hindustan Times hindustantimes.com/world-news/ove
08/07/20 06:55 from TWEETS BY MIKENOV from mikenova (1 sites)
Over 6 months into Covid-19 crisis, 5 mysteries that still shroud coronavirus - world news - Hindustan Times hindustantimes.com/world-news/ove Posted by mikenov on Wednesday, July 8th, 2020 10:55am mikenov on Twitter

» mikenov on Twitter: Merkel looks east as ties fray between Germany and U.S. - POLITICO politico.com/news/2020/07/0
08/07/20 06:48 from TWEETS BY MIKENOV from mikenova (1 sites)
Merkel looks east as ties fray between Germany and U.S. - POLITICO politico.com/news/2020/07/0 Posted by mikenov on Wednesday, July 8th, 2020 10:48am mikenov on Twitter

» mikenov on Twitter: Six months into coronavirus pandemic, scientists say exact source may never be identified sg.news.yahoo.com/six-months-cor via @yahoosg
08/07/20 06:44 from TWEETS BY MIKENOV from mikenova (1 sites)
Six months into coronavirus pandemic, scientists say exact source may never be identified sg.news.yahoo.com/six-months-cor via @yahoosg Posted by mikenov on Wednesday, July 8th, 2020 10:44am mikenov on Twitter

» mikenov on Twitter: RT @FrankFigliuzzi1: UPENN needs to investigate and if true, revoke his degree: Trump cheated on SAT by paying someone to take it for him.
08/07/20 06:25 from TWEETS BY MIKENOV from mikenova (1 sites)
UPENN needs to investigate and if true, revoke his degree: Trump cheated on SAT by paying someone to take it for him. @Wharton businessinsider.com/donald-trump-c Posted by FrankFigliuzzi1 on Wednesday, July 8th, 2020 12:23am Retweet...

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Saved Stories - None: Google Alert - coronavirus origins: Russia, China Say They Support WHO's Coronavirus Efforts Amid US Exit

"China will continue supporting scientists from all countries in researching the origin and transmission routes of the coronavirus." Secretary of State Mike ...

 Google Alert - coronavirus origins

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