Over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. Several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. With the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in Africa. Hantavirus infection in humans can result in two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) caused by Old World and New World hantaviruses, respectively. The clinical presentation of HFRS varies from subclinical, mild, and moderate to severe, depending in part on the causative agent of the disease. In general, HFRS caused by Hantaan virus, Amur virus and Dobrava virus are more severe with mortality rates from 5 to 15%, whereas Seoul virus causes moderate and Puumala virus and Saaremaa virus cause mild forms of disease with mortality rates <1%. The central phenomena behind the pathogenesis of both HFRS and HCPS are increased vascular permeability and acute thrombocytopenia. The pathogenesis is likely to be a complex multifactorial process that includes contributions from immune responses, platelet dysfunction and the deregulation of endothelial cell barrier functions. Also a genetic predisposition, related to HLA type, seems to be important for the severity of the disease. As there is no effective treatment or vaccine approved for use in the USA and Europe, public awareness and precautionary measures are the only ways to minimize the risk of hantavirus disease.

No abstract

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus (EBOV)2,3. Here, we have for the first time evaluated the physiology of the human T cell immune response in EVD patients at the time of admission at the Ebola Treatment Center (ETC) in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we have identified an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by high percentage of CD4 and CD8 T cells expressing the inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1), which was correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation despite comparable overall T cell activation. Concommittant with virus clearance, survivors mounted a robust EBOV-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

19Laboratories are currently witnessing extraordinary demand globally for sampling devices, 20 reagents, consumables, and diagnostic instruments needed for timely diagnosis of SARS-CoV-2 21 infection. To meet diagnostic needs as the pandemic grows, the US Food and Drug 22 Administration (FDA) recently granted several commercial SARS-CoV-2 tests Emergency Use 23 Authorization (EUA), but manufacturer-independent evaluation data are scarce. We performed 24 the first manufacturer-independent evaluation of the fully automated sample-to-result two-25 target test cobas 6800 SARS-CoV-2 (cobas) (Roche Molecular Systems, Branchburg, NJ), which 26 received US FDA EUA on March 12, 2020. The comparator was a standardized 3-hour SARS-CoV-27 2 protocol, consisting of RNA extraction using an automated portable instrument, followed by a 28 two-target RT-PCR, which our laboratory has routinely used since January 2020 (Corman VM et 29 al. EuroSurveill 25(3):2000045). Cobas and the comparator showed overall agreement of 98.1% 30 and a kappa value of 0.95 on an in-house validation panel consisting of 217 well-characterized 31 retrospective samples. Immediate prospective head-to-head comparative evaluation followed 32 on 502 samples, and the diagnostic approaches showed overall percent agreement of 99.6% 33 and a kappa value of 0.98. A good correlation (r² = 0.96) between cycle threshold values for 34 SARS-CoV-2 specific targets obtained by cobas and the comparator was observed. Our results 35 showed that cobas is a reliable assay for qualitative detection of SARS-CoV-2 in nasopharyngeal 36 swab samples collected in the UTM-RT system. Under the extraordinary circumstances that 37 laboratories are facing worldwide, a safe diagnostic platform switch is feasible in only 48 hours 38 and in the midst of the COVID-19 pandemic if carefully planned and executed. 39 on June 9, 2020 by guest http://jcm.asm.org/ Downloaded from 3 40 Keywords: SARS-CoV-2, COVID-19, cobas, cobas 6800 41 on June 9, 2020 by guest http://jcm.asm.org/ Downloaded from 58 12), followed by the launch of a range of commercial SARS-CoV-2 PCR-based assays in the last 3 59 months. Despite the fact that the US Food and Drug Administration (FDA) granted several 60 commercial SARS-CoV-2 amplification assays Emergency Use Authorization (EUA), as of March 61 29, 2020 no manufacturer-independent evaluation data for any commercial SARS-CoV-2 assay 62 with US FDA EUA is available in peer-reviewed literature. 63 on June 9, 2020 by guest http://jcm.asm.org/ Downloaded from 5 Here we present the results of the first manufacturer-independent evaluation of the fully 64 automated sample-to-result two-target test cobas 6800 SARS-CoV-2 (cobas) (Roche Molecular 65 Systems, Branchburg, NJ, USA), which received US FDA EUA on March 12, 2020. The 66 performance of cobas was first evaluated on a well-characterized in-house validation panel 67 consisting of 217 samples. The comparator was a standardized 3-hour SARS-CoV-2 detection 68 protocol, consisting of RNA extraction using an automated por...

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Human granulocytic ehrlichiosis (HGE) was recently described in North America. It is caused by an Ehrlichia species closely related to Ehrlichia phagocytophila and Ehrlichia equi, recognized to infect mostly ruminants and horses, respectively. The vector in North America is the tick Ixodes scapularis, which is also the vector of the Lyme disease agent, Borrelia burgdorferi. Previous serologic studies in patients with a diagnosis of Lyme borreliosis indicate that HGE may exist in Europe. We report the first documented case of HGE in Europe. The diagnosis was established by seroconversion to E. equi and the HGE agent and by PCR with sequence analysis of the gene encoding the HGE agent 16S rRNA. Interestingly, the patient presented with a self-limited but moderately severe illness. Thus, European physicians need to be aware that HGE exists in Europe and that the diagnosis should be considered in febrile patients with tick bites in areas where Lyme disease is endemic.

Tick-borne encephalitis virus (TBEV) causes one of the most dangerous human neuroinfections in Europe and Asia. To infect neurons it must cross the blood-brain-barrier (BBB), and presumably also cells adjacent to the BBB, such as astrocytes, the most abundant glial cell type. However, the knowledge about the viral infection of glial cells is fragmental. Here we studied whether TBEV infects rat astrocytes. Rats belong to an animal group serving as a TBEV amplifying host. We employed high resolution quantitative fluorescence microscopy to investigate cell entry and cytoplasmic mobility of TBEV particles along with the effect on the cell cytoskeleton and cell survival. We report that infection of astrocytes with TBEV increases with time of exposure to TBEV and that with post-infection time TBEV particles gained higher mobility. After several days of infection actin cytoskeleton was affected, but cell survival was unchanged, indicating that rat astrocytes resist TBEV-mediated cell death, as reported for other mammalian cells. Therefore, astrocytes may present an important pool of dormant TBEV infections and a new target for therapeutic intervention.