Publications by authors named "Victor Max Corman"

63 Publications

Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died.

JAMA Neurol 2021 Jun 11. Epub 2021 Jun 11.

Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Importance: Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19.

Objective: To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died.

Design, Setting, And Participants: This case-control autopsy series was conducted in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included. Individuals for whom informed consent to autopsy was available and the postmortem interval was less than 6 days were randomly selected. Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19.

Main Outcomes And Measures: Inflammation of skeletal muscle tissue was assessed by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma, and a blinded evaluation on a visual analog scale ranging from absence of pathology to the most pronounced pathology. Inflammation of cardiac muscles was assessed by quantification of immune cell infiltrates.

Results: Forty-three patients with COVID-19 (median [interquartile range] age, 72 [16] years; 31 men [72%]) and 11 patients with diseases other than COVID-19 (median [interquartile range] age, 71 [5] years; 7 men [64%]) were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95% CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95% CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8 [8] vs 3 [4] cells per 10 high-power fields; 95% CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription-polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry and electron microscopy.

Conclusions And Relevance: In this case-control study of patients who had died with and without COVID-19, most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation. Detection of viral load was low or negative in most skeletal and cardiac muscles and probably attributable to circulating viral RNA rather than genuine infection of myocytes. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.
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http://dx.doi.org/10.1001/jamaneurol.2021.2004DOI Listing
June 2021

COVID-19: Autopsy findings in six patients between 26 and 46 years of age.

Int J Infect Dis 2021 Jun 2. Epub 2021 Jun 2.

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.

Objectives: Studies on the coronavirus disease 2019 (COVID-19) usually focus on middle aged and older adults. However, younger patients may present with severe COVID-19 and potentially fatal outcomes. For optimized, more specialized therapeutic regimens in this particular patient group, a better understanding of underlying pathomechanisms is of uttermost importance.

Methods: This study investigates relevant pre-existing medical conditions, clinical histories and autopsy findings, together with SARS-CoV-2-RNA, determined by qPCR, and laboratory data in six COVID-19 decedents at an age of 50 years or younger who were autopsied at the Charité University Hospital.

Results: From a total of 76 COVID-19 patients who underwent an autopsy at our institution, 6 (7.9%) were 50 years old or younger. Most COVID-19 decedents of younger age presented with pre-existing medical conditions prior to SARS-CoV-2 infection. These included overweight and obesity, arterial hypertension, asthma, obstructive sleep apnea as well as graft-versus-host disease following cancer and bone marrow transplantation. Furthermore, clinical histories and autopsy results revealed a disproportionally high prevalence of thromboembolism and ischemic organ damage in this patient cohort. Histopathology and laboratory results indicated coagulopathies, signs of immune dysregulation and liver damage.

Conclusions: In conclusion, pre-existing health conditions may increase the risk of severe and fatal COVID-19 in younger patients who may be especially prone to developing thromboembolic complications, immune dysregulation and liver damage.
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http://dx.doi.org/10.1016/j.ijid.2021.05.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172269PMC
June 2021

Estimating infectiousness throughout SARS-CoV-2 infection course.

Science 2021 May 25. Epub 2021 May 25.

Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25,381 German SARS-CoV-2 cases, including 6110 from test centres attended by pre-symptomatic, asymptomatic, and mildly-symptomatic (PAMS) subjects, 9519 who were hospitalised, and 1533 B.1.1.7 lineage infections. The youngest had mean log viral load 0.5 (or less) lower than older subjects and an estimated ~78% of the peak cell culture replication probability, due in part to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 10 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with mean age 37.6. We estimate 4.3 days from onset of shedding to peak viral load (8.1) and cell culture isolation probability (0.75). B.1.1.7 subjects had mean log viral load 1.05 higher than non-B.1.1.7, with estimated cell culture replication probability 2.6 times higher.
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http://dx.doi.org/10.1126/science.abi5273DOI Listing
May 2021

Characterization of the SARS-CoV-2 Neutralization Potential of COVID-19-Convalescent Donors.

J Immunol 2021 06 12;206(11):2614-2622. Epub 2021 May 12.

Department of Transfusion Medicine, Ulm University, Ulm, Germany.

The current SARS-CoV-2 pandemic has triggered the development of various SARS-CoV-2 neutralization tests. A wild-type virus (using African green monkey VeroE6 cells), a pseudovirus (using human Caco-2 cells), and a surrogate neutralization test platform were applied to characterize the SARS-CoV-2 neutralization potential of a cohort of 111 convalescent plasma donors over a period of seven months after diagnosis. This allowed an in-depth validation and assay performance analysis of these platforms. More importantly, we found that SARS-CoV-2 neutralization titers were stable or even increased within the observation period, which contradicts earlier studies reporting a rapid waning of Ab titers after three to four months. Moreover, we observed a positive correlation of neutralization titers with increasing age, number of symptoms reported, and the presence of the Rhesus Ag RhD. Validation of the platforms revealed that highest assay performances were obtained with the wild-type virus and the surrogate neutralization platforms. However, our data also suggested that selection of cutoff titers had a strong impact on the evaluation of neutralization potency. When taking strong neutralization potency, as demonstrated by the wild-type virus platform as the gold standard, up to 55% of plasma products had low neutralization titers. However, a significant portion of these products were overrated in their potency when using the surrogate assay with the recommended cutoff titer. In summary, our study demonstrates that SARS-CoV-2 neutralization titers are stable for at least seven months after diagnosis and offers a testing strategy for rapid selection of high-titer convalescent plasma products in a biosafety level 1 environment.
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http://dx.doi.org/10.4049/jimmunol.2100036DOI Listing
June 2021

Detection and genomic characterization of hepatitis E virus genotype 3 from pigs in Ghana, Africa.

One Health Outlook 2020 20;2:10. Epub 2020 Jul 20.

Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute of Virology, Berlin, Germany.

Background: Hepatitis E virus (HEV) is a major cause of human hepatitis worldwide. Zoonotic genotypes of the virus have been found in diverse animal species with pigs playing a major role. Putative risk of zoonotic infection from livestock particularly swine in Sub-Saharan Africa including Ghana is poorly understood due to scarcity of available data, especially HEV sequence information.

Methods: Serum samples were collected from cattle, sheep, goats and pigs from Kumasi in the Ashanti region of Ghana. Samples were subjected to nested RT-PCR screening and quantification of HEV RNA-positive samples using real-time RT-PCR and the World Health Organization International Standard for HEV. Testing of all pig samples for antibodies was done by ELISA. Sanger sequencing and genotyping was performed and one representative complete genome was generated to facilitate genome-wide comparison to other available African HEV sequences by phylogenetic analysis.

Results: A total of 420 samples were available from cattle ( = 105), goats ( = 124), pigs ( = 89) and sheep ( = 102). HEV Viral RNA was detected only in pig samples (10.1%). The antibody detection rate in pigs was 77.5%, with positive samples from all sampling sites. Average viral load was 1 × 10 (range 1.02 × 10 to 3.17 × 10) International Units per mL of serum with no statistically significant differences between age groups (≤ 6 month, > 6 months) by a T-test comparison of means (t = 1.4272, df = 7,  = 0.1966). Sequences obtained in this study form a monophyletic group within HEV genotype 3. Sequences from Cameroon, Ghana, Burkina Faso and Madagascar were found to share a most recent common ancestor; however this was not the case for other African HEV sequences.

Conclusion: HEV genotype 3 is highly endemic in pigs in Ghana and likely poses a zoonotic risk to people exposed to pigs. HEV genotype 3 in Ghana shares a common origin with other virus strains from Sub-Saharan Africa.
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http://dx.doi.org/10.1186/s42522-020-00018-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993477PMC
July 2020

SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.

Nat Commun 2021 03 30;12(1):1961. Epub 2021 Mar 30.

Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.

The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.
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http://dx.doi.org/10.1038/s41467-021-22210-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010106PMC
March 2021

Impaired performance of SARS-CoV-2 antigen-detecting rapid diagnostic tests at elevated and low temperatures.

J Clin Virol 2021 05 16;138:104796. Epub 2021 Mar 16.

Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; German Centre for Infection Research (DZIF), Associated Partner Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Antigen-detecting rapid diagnostic tests (Ag-RDTs) can complement molecular diagnostics for COVID-19. The recommended temperature for storage of SARS-CoV-2 Ag-RDTs ranges between 2-30 °C. In the global South, mean temperatures can exceed 30 °C. In the global North, Ag-RDTs are often used in external testing facilities at low ambient temperatures. We assessed analytical sensitivity and specificity of eleven commercially-available SARS-CoV-2 Ag-RDTs using different storage and operational temperatures, including short- or long-term storage and operation at recommended temperatures or at either 2-4 °C or at 37 °C. The limits of detection of SARS-CoV-2 Ag-RDTs under recommended conditions ranged from 1.0×10- 5.5×10 genome copies/mL of infectious SARS-CoV-2 cell culture supernatant. Despite long-term storage at recommended conditions, 10 min pre-incubation of Ag-RDTs and testing at 37 °C resulted in about ten-fold reduced sensitivity for five out of 11 SARS-CoV-2 Ag-RDTs, including both Ag-RDTs currently listed for emergency use by the World Health Organization. After 3 weeks of storage at 37 °C, eight of the 11 SARS-CoV-2 Ag-RDTs exhibited about ten-fold reduced sensitivity. Specificity of SARS-CoV-2 Ag-RDTs using cell culture supernatant from common respiratory viruses was not affected by storage and testing at 37 °C, whereas false-positive results occurred at outside temperatures of 2-4 °C for two out of six tested Ag-RDTs, again including an Ag-RDT recommended by the WHO. In summary, elevated temperatures impair sensitivity, whereas low temperatures impair specificity of SARS-CoV-2 Ag-RDTs. Consequences may include false-negative test results at clinically relevant virus concentrations compatible with transmission and false-positive results entailing unwarranted quarantine assignments. Storage and operation of SARS-CoV-2 Ag-RDTs at recommended conditions is essential for successful usage during the pandemic.
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http://dx.doi.org/10.1016/j.jcv.2021.104796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962993PMC
May 2021

Transmission of SARS-CoV-2 in northern Ghana: insights from whole-genome sequencing.

Arch Virol 2021 May 15;166(5):1385-1393. Epub 2021 Mar 15.

Kumasi Centre for Collaborative Research in Tropical Medicine, PMB, UPO, 00233, Kumasi, Ghana.

Following the detection of the first imported case of COVID-19 in the northern sector of Ghana, we molecularly characterized and phylogenetically analysed sequences, including three complete genome sequences, of severe acute respiratory syndrome coronavirus 2 obtained from nine patients in Ghana. We performed high-throughput sequencing on nine samples that were found to have a high concentration of viral RNA. We also assessed the potential impact that long-distance transport of samples to testing centres may have on sequencing results. Here, two samples that were similar in terms of viral RNA concentration but were transported from sites that are over 400 km apart were analyzed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Three complete genome sequences and another nearly complete genome sequence with 95.6% coverage were obtained. Sequences with coverage in excess of 80% were found to belong to three lineages, namely A, B.1 and B.2. Our sequences clustered in two different clades, with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23, which was collected 9 km from the testing site, than in sample TTH6, which was collected and transported over a distance of 400 km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be a need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.
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http://dx.doi.org/10.1007/s00705-021-04986-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959303PMC
May 2021

Causes of death and comorbidities in hospitalized patients with COVID-19.

Sci Rep 2021 02 19;11(1):4263. Epub 2021 Feb 19.

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.
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http://dx.doi.org/10.1038/s41598-021-82862-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895917PMC
February 2021

At Least Seven Distinct Rotavirus Genotype Constellations in Bats with Evidence of Reassortment and Zoonotic Transmissions.

mBio 2021 01 19;12(1). Epub 2021 Jan 19.

KU Leuven-University of Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Leuven, Belgium

Bats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses. The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents sheds light on the vast genetic diversity of rotaviruses and also hints at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.
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http://dx.doi.org/10.1128/mBio.02755-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845630PMC
January 2021

B cell depletion and signs of sepsis-acquired immunodeficiency in bone marrow and spleen of COVID-19 deceased.

Int J Infect Dis 2021 Feb 2;103:628-635. Epub 2021 Jan 2.

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Objectives: In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified.

Methods: This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden.

Results: In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events. Signs of sepsis-acquired immunodeficiency were found in the setting of an abscess-forming superinfection of viral COVID-19 pneumonia. Furthermore, a severe B cell loss was observed in the bone marrow and/or spleen in 64% of COVID-19 patients. This was reflected by lymphocytopenia in the peripheral blood. As compared to B cell preservation, B cell loss was associated with a higher pulmonary SARS-CoV-2 burden and only a marginal decrease of of T cell counts.

Conclusions: The results of this study suggest the presence of sepsis-related immunodeficiency in severe COVID-19 pneumonia with superinfection. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, which might impede the durability of the humoral immune response to SARS-CoV-2.
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http://dx.doi.org/10.1016/j.ijid.2020.12.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776126PMC
February 2021

Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19.

Nat Biotechnol 2021 Jun 24;39(6):705-716. Epub 2020 Dec 24.

Center for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.
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http://dx.doi.org/10.1038/s41587-020-00796-1DOI Listing
June 2021

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.

Nat Neurosci 2021 02 30;24(2):168-175. Epub 2020 Nov 30.

Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.
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http://dx.doi.org/10.1038/s41593-020-00758-5DOI Listing
February 2021

Low Seroprevalence of SARS-CoV-2 Antibodies during Systematic Antibody Screening and Serum Responses in Patients after COVID-19 in a German Transplant Center.

J Clin Med 2020 Oct 23;9(11). Epub 2020 Oct 23.

Department of Nephrology and Medical Intensive Care, Charité- Universitätsmedizin Berlin, 13353 Berlin, Germany.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 denotes a global health issue. Data regarding COVID-19 incidence in kidney transplant recipients (KTR) are sparse. From 19 March to 19 May 2020, we performed a systematic screening for COVID-19 in KTR. Tests included serum analysis for SARS-CoV-2 antibodies using S protein-based immunofluorescence, anti-SARS-CoV-2 S1 immunoglobulin G (IgG) and immunoglobulin A (IgA) enzyme-linked immunosorbent assays (ELISA), and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR) from nasal-throat swabs. Outpatient serum samples from KTR with PCR confirmed COVID-19, and swab samples from recipients (+donors) undergoing kidney transplantation were analyzed. Out of 223 samples from outpatients, 13 patients were positive with solely anti-SARS-CoV-2-IgA and 3 with both anti-IgA and anti-IgG. In total, 53 patients were symptomatic in the past, but positive results could be found in both symptomatic and asymptomatic patients. After an in depth analysis using immunofluorescence and neutralization tests in 2 KTR, recent COVID-19 infection remained highly suspicious. Apart from outpatient visits, only 5 out of 2044 KTR were symptomatic and tested positive via PCR, of which 4 recovered and one died. All patients showed seroconversion during the course of the disease. This study demonstrated a low seroprevalence in a German KTR cohort, and seroconversion of IgA and IgG after COVID-19 could be demonstrated. Effective containment strategies enabled us to continue our transplant program.
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http://dx.doi.org/10.3390/jcm9113401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690804PMC
October 2020

Independent Side-by-Side Validation and Comparison of 4 Serological Platforms for SARS-CoV-2 Antibody Testing.

J Infect Dis 2021 03;223(5):796-801

Department of Transfusion Medicine, Ulm University, Ulm, Germany.

Highly sensitive and specific platforms for the detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are becoming increasingly important for evaluating potential SARS-CoV-2 convalescent plasma donors, studying the spread of SARS-CoV-2 infections, and identifying individuals with seroconversion. This study provides a comparative validation of 4 anti-SARS-CoV-2 platforms. A unique feature of the study is the use of a representative cohort of convalescent patients with coronavirus disease 2019 and a mild to moderate disease course. All platforms showed significant correlations with a SARS-CoV-2 plaque reduction neutralization test, with highest sensitivities for the Euroimmun and the Roche platforms, suggesting their preferential use for screening persons at increased risk of SARS-CoV-2 infections.
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http://dx.doi.org/10.1093/infdis/jiaa656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665624PMC
March 2021

A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.

Cell 2020 11 23;183(4):1058-1069.e19. Epub 2020 Sep 23.

Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20359 Hamburg, Germany.

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC value of 3.1 ng/mL. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2-neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss, and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
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http://dx.doi.org/10.1016/j.cell.2020.09.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510528PMC
November 2020

A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model.

bioRxiv 2020 Aug 16. Epub 2020 Aug 16.

Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 A revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
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http://dx.doi.org/10.1101/2020.08.15.252320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430590PMC
August 2020

Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent .

Proc Natl Acad Sci U S A 2020 07 10;117(30):17977-17983. Epub 2020 Jul 10.

Institute of Virology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;

Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection.
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http://dx.doi.org/10.1073/pnas.2006750117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395443PMC
July 2020

Pathogen-associated selection on innate immunity genes (TLR4, TLR7) in a neotropical rodent in landscapes differing in anthropogenic disturbance.

Heredity (Edinb) 2020 10 2;125(4):184-199. Epub 2020 Jul 2.

Institute of Evolutionary Ecology and Conservation Genomics, Ulm University, 89069, Ulm, Germany.

Toll-like receptors (TLRs) form part of the innate immune system and can recognize structurally conserved pathogen-associated molecular pattern (PAMP) molecules. Their functional importance in the resistance to pathogens has been documented in laboratory experimental settings and in humans. TLR diversity, however, has been rarely investigated in wildlife species. How the genetic diversity of TLRs is associated with various pathogens and how it is shaped by habitat disturbance are understudied. Therefore, we investigated the role of genetic diversity in the functionally important parts of TLR4 and TLR7 genes in resistance towards gastrointestinal nematodes and Hepacivirus infection. We chose a generalist study species, the rodent Proechimys semispinosus, because it is highly abundant in three Panamanian landscapes that differ in their degree of anthropogenic modification. We detected only two TLR7 haplotypes that differed by one synonymous single-nucleotide polymorphism (SNP) position. The TLR4 variability was higher, and we detected four TLR4 haplotypes that differed at one synonymous SNP and at three amino acid positions within the leucine-rich repeat region. Only TLR4 haplotypes had different frequencies in each landscape. Using generalized linear models, we found evidence that nematode loads and virus prevalence were influenced by both specific TLR4 haplotypes and landscape. Here, the variable "landscape" served as a surrogate for the important influential ecological factors distinguishing landscapes in our study, i.e. species diversity and host population density. Individuals carrying the common TLR4_Ht1 haplotype were less intensely infected by the most abundant strongyle nematode. Individuals carrying the rare TLR4_Ht3 haplotype were all Hepacivirus-positive, where those carrying the rare haplotype TLR4_Ht4 were less often infected by Hepacivirus than individuals with other haplotypes. Our study highlights the role of TLR diversity in pathogen resistance and the importance of considering immune genetic as well as ecological factors in order to understand the effects of anthropogenic changes on wildlife health.
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http://dx.doi.org/10.1038/s41437-020-0331-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490709PMC
October 2020

Specialist laboratory networks as preparedness and response tool - the Emerging Viral Diseases-Expert Laboratory Network and the Chikungunya outbreak, Thailand, 2019.

Euro Surveill 2020 04;25(13)

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

We illustrate the potential for specialist laboratory networks to be used as preparedness and response tool through rapid collection and sharing of data. Here, the Emerging Viral Diseases-Expert Laboratory Network (EVD-LabNet) and a laboratory assessment of chikungunya virus (CHIKV) in returning European travellers related to an ongoing outbreak in Thailand was used for this purpose. EVD-LabNet rapidly collected data on laboratory requests, diagnosed CHIKV imported cases and sequences generated, and shared among its members and with the European Centre for Disease Prevention and Control. Data across the network showed an increase in CHIKV imported cases during 1 October 2018-30 April 2019 vs the same period in 2018 (172 vs 50), particularly an increase in cases known to be related to travel to Thailand (72 vs 1). Moreover, EVD-LabNet showed that strains were imported from Thailand that cluster with strains of the ECSA-IOL E1 A226 variant emerging in Pakistan in 2016 and involved in the 2017 outbreaks in Italy. CHIKV diagnostic requests increased by 23.6% between the two periods. The impact of using EVD-LabNet or similar networks as preparedness and response tool could be improved by standardisation of the collection, quality and mining of data in routine laboratory management systems.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.13.1900438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140599PMC
April 2020

Monitoring of free-ranging and captive populations in Western Europe for avian bornaviruses, circoviruses and polyomaviruses.

Avian Pathol 2020 Apr 1;49(2):119-130. Epub 2019 Nov 1.

Institute of Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Avian pathogens such as bornaviruses, circoviruses and polyomaviruses are widely distributed in captive collections of psittacine birds worldwide and can cause fatal diseases. In contrast, only little is known about their presence in free-ranging psittacines and their impact on these populations. Rose-ringed parakeets () and Alexandrine parakeets () are non-native to Europe, but have established stable populations in parts of Western Europe. From 2012-2017, we surveyed free-ranging populations in Germany and France as well as captive individuals from Germany and Spain for avian bornavirus, circovirus and polyomavirus infections. Samples from two out of 469 tested free-ranging birds (0.4%; 95% confidence interval [CI-95]: 0.1-1.5%) were positive for beak and feather disease virus (BeFDV), whereas avian bornaviruses and polyomaviruses were not detected in the free-ranging populations. In contrast, avian bornaviruses and polyomaviruses, but not circoviruses were detected in captive populations. Parrot bornavirus 4 (PaBV-4) infection was detected by RT-PCR in four out of 210 captive parakeets (1.9%; CI-95: 0.7-4.8%) from four different holdings in Germany and Spain and confirmed by detection of bornavirus-reactive antibodies in two of these birds. Three out of 160 tested birds (1.9%; CI-95: 0.5-5.4%) possessed serum antibodies directed against budgerigar fledgling disease virus (BuFDV). PaBV-4 and BuFDV were also detected in several psittacines of a mixed holding in Germany, which had been in contact with free-ranging parakeets. Our results demonstrate that parakeets are susceptible to common psittacine pathogens and their populations in Western Europe are exposed to these viruses. Nevertheless, the prevalence of avian bornaviruses, circoviruses and polyomaviruses in those populations is very low. parakeets are susceptible to bornavirus, circovirus and polyomavirus infection.Introduced populations in Europe have been exposed to these viruses.Nevertheless, they may be absent or present at only low levels in free-ranging populations.Free-ranging populations in Europe pose a minor threat of transmitting these viruses to captive Psittaciformes.
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http://dx.doi.org/10.1080/03079457.2019.1681359DOI Listing
April 2020

Proficiency Testing of Virus Diagnostics Based on Bioinformatics Analysis of Simulated High-Throughput Sequencing Data Sets.

J Clin Microbiol 2019 08 26;57(8). Epub 2019 Jul 26.

Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Quality management and independent assessment of high-throughput sequencing-based virus diagnostics have not yet been established as a mandatory approach for ensuring comparable results. The sensitivity and specificity of viral high-throughput sequence data analysis are highly affected by bioinformatics processing using publicly available and custom tools and databases and thus differ widely between individuals and institutions. Here we present the results of the COMPARE [llaborative anagement latform for Detection and nalyses of (e-)emerging and Foodborne Outbreaks in urope] virus proficiency test. An artificial, simulated data set of Illumina HiSeq sequences was provided to 13 different European institutes for bioinformatics analysis to identify viral pathogens in high-throughput sequence data. Comparison of the participants' analyses shows that the use of different tools, programs, and databases for bioinformatics analyses can impact the correct identification of viral sequences from a simple data set. The identification of slightly mutated and highly divergent virus genomes has been shown to be most challenging. Furthermore, the interpretation of the results, together with a fictitious case report, by the participants showed that in addition to the bioinformatics analysis, the virological evaluation of the results can be important in clinical settings. External quality assessment and proficiency testing should become an important part of validating high-throughput sequencing-based virus diagnostics and could improve the harmonization, comparability, and reproducibility of results. There is a need for the establishment of international proficiency testing, like that established for conventional laboratory tests such as PCR, for bioinformatics pipelines and the interpretation of such results.
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http://dx.doi.org/10.1128/JCM.00466-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663916PMC
August 2019

Hepatitis E Virus Infection in European Brown Hares, Germany, 2007-2014.

Emerg Infect Dis 2019 06;25(6):1233-1235

Rabbit-associated hepatitis E viruses (HEVs) cause zoonotic infections. We investigated 2,389 hares in Germany during 2007-2014. Complete genome characterization of a hare-associated HEV strain revealed close genomic relatedness to rabbit-associated HEV strains. Although hare-specific HEV seroprevalence was low, at 2.6%, hares represent a potential source of sporadic HEV infections.
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http://dx.doi.org/10.3201/eid2506.181618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537731PMC
June 2019

Shiga toxin-producing (STEC) isolated from fecal samples of African dromedary camels.

One Health 2019 Jun 7;7:100087. Epub 2019 Mar 7.

Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Switzerland.

Shiga toxin-producing (STEC) cause gastrointestinal illnesses including non-bloody or bloody diarrhoea, haemorrhagic colitis (HC), and the haemolytic uremic syndrome (HUS). To investigate the occurrence of STEC among grazing dromedaries from Kenya, isolated from fecal matter collected from 163 dromedaries on a large ranch were screened for the presence of and . STEC strains were isolated and serotyped. Isolates were subjected to PCR for the subtyping of genes and for the detection of and . In addition, whole genome sequencing (WGS) was carried out to detect further virulence genes and to determine the multilocus sequence types (MLST). Antimicrobial resistance profiles were determined by disk diffusion. STEC was isolated from 20 (12.3%) of the fecal samples. Thereof, nine (45%) isolates were STEC O156:H25, three (15%) isolates typed STEC O43:H2. The remaining isolates occurred as single serotypes or were O non-typeable. Eleven (55%) of the isolates harboured , nine (45%) , and 14 (70%) , respectively. WGS revealed the presence of in 16 (80%), in four (20%) and in two (10%) of the isolates, Furthermore, , , , , , and were found exclusively among STEC O156:H25. Eleven different sequence types (ST) were detected. The most prominent was ST300/ST5343, which comprised STEC O156:H25. All STEC isolates were pan susceptible to a panel of 16 antimicrobial agents. Overall, the results indicate that dromedary camels in Kenya may be reservoirs of STEC, including serotypes possessing virulence markers associated to disease in humans, such as STEC O156:H25. STEC in camels may represent a health hazard for humans with close contact to camels or to consumers of camel derived foodstuffs, such as unpasteurised camel milk.
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http://dx.doi.org/10.1016/j.onehlt.2019.100087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416407PMC
June 2019

Evolutionary biology of human hepatitis viruses.

J Hepatol 2019 03 23;70(3):501-520. Epub 2018 Nov 23.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, 10117 Berlin, Germany; German Center for Infection Research (DZIF), Germany. Electronic address:

Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human hepatitis viruses and their animal homologues, including transmission routes, liver tropism, oncogenesis, chronicity, pathogenesis and envelopment. We discuss the potential for translation of newly discovered hepatitis viruses into preclinical animal models for drug testing, studies on pathogenesis and vaccine development. Finally, we re-evaluate the evolutionary origins of human hepatitis viruses and discuss the past and present zoonotic potential of their animal homologues.
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http://dx.doi.org/10.1016/j.jhep.2018.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114834PMC
March 2019

Countrywide Survey for MERS-Coronavirus Antibodies in Dromedaries and Humans in Pakistan.

Virol Sin 2018 Oct 11;33(5):410-417. Epub 2018 Oct 11.

CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic pathogen capable of causing severe respiratory disease in humans. Although dromedary camels are considered as a major reservoir host, the MERS-CoV infection dynamics in camels are not fully understood. Through surveillance in Pakistan, nasal (n = 776) and serum (n = 1050) samples were collected from camels between November 2015 and February 2018. Samples were collected from animal markets, free-roaming herds and abattoirs. An in-house ELISA was developed to detect IgG against MERS-CoV. A total of 794 camels were found seropositive for MERS-CoV. Prevalence increased with the age and the highest seroprevalence was recorded in camels aged > 10 years (81.37%) followed by those aged 3.1-10 years (78.65%) and ≤ 3 years (58.19%). Higher prevalence was observed in female (78.13%) as compared to male (70.70%). Of the camel nasal swabs, 22 were found to be positive by RT-qPCR though with high Ct values. Moreover, 2,409 human serum samples were also collected from four provinces of Pakistan during 2016-2017. Among the sampled population, 840 humans were camel herders. Although we found a high rate of MERS-CoV antibody positive dromedaries (75.62%) in Pakistan, no neutralizing antibodies were detected in humans with and without contact to camels.
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http://dx.doi.org/10.1007/s12250-018-0051-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235758PMC
October 2018

Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission.

Sci Rep 2018 10 11;8(1):15177. Epub 2018 Oct 11.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117, Berlin, Germany.

A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (-29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.
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http://dx.doi.org/10.1038/s41598-018-33487-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181990PMC
October 2018

Ecological drivers of Hepacivirus infection in a neotropical rodent inhabiting landscapes with various degrees of human environmental change.

Oecologia 2018 Sep 23;188(1):289-302. Epub 2018 Jun 23.

Institute of Evolutionary Ecology and Conservation Genomics, University of Ulm, Ulm, Germany.

Anthropogenic environmental change can impact community and population traits such as species diversity and population densities, which have been shown to influence the prevalence of viruses in wildlife reservoirs. In particular, host species resilient to changes in their natural habitat may increase in numbers, which in turn can affect the prevalence of directly transmitted viruses. We have carried out a survey of small mammal communities in three tropical landscapes differing in their degree of environmental change in Central Panama and investigated the effects of community changes on Hepacivirus prevalence. The modification of continuous habitat into partly connected or isolated habitat patches during the past century was linked to changes in species diversity and species assemblages, which was further associated with shifts in the abundance of generalist marsupial (Didelphis marsupialis, Philander opossum) and rodent (Proechimys semispinosus) species. The latter has become dominant in isolated habitat patches and was the only identified Hepacivirus host in our study system. Our analyses suggest that, in addition to the effects of host age and sex, host population density in interaction with sex ratio is a crucial predictor of infection probability. Although we found no significant relationships between species diversity per se and infection probability, the lowest prevalence detected in the landscape with the highest species diversity indicates that shifts in species assemblages (e.g. changes in the presence and abundance of marsupial predators) impact the host's intraspecific contact rates, the probability of virus transmission and, thus, the virus prevalence. Our study additionally provides important data on the influence of human-induced landscape changes on infection probability and, therefore, on virus prevalence in wildlife and emphasizes the importance of a landscape-scale approach with concomitant consideration of the complex interactions between ecological factors.
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http://dx.doi.org/10.1007/s00442-018-4210-7DOI Listing
September 2018

Evolutionary Origins of Enteric Hepatitis Viruses.

Cold Spring Harb Perspect Med 2018 12 3;8(12). Epub 2018 Dec 3.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin 10117, Germany.

The enterically transmitted hepatitis A (HAV) and hepatitis E viruses (HEV) are the leading causes of acute viral hepatitis in humans. Despite the discovery of HAV and HEV 40-50 years ago, their evolutionary origins remain unclear. Recent discoveries of numerous nonprimate hepatoviruses and hepeviruses allow revisiting the evolutionary history of these viruses. In this review, we provide detailed phylogenomic analyses of primate and nonprimate hepatoviruses and hepeviruses. We identify conserved and divergent genomic properties and corroborate historical interspecies transmissions by phylogenetic comparisons and recombination analyses. We discuss the likely non-recent origins of human HAV and HEV precursors carried by mammals other than primates, and detail current zoonotic HEV infections. The novel nonprimate hepatoviruses and hepeviruses offer exciting new possibilities for future research focusing on host range and the unique biological properties of HAV and HEV.
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http://dx.doi.org/10.1101/cshperspect.a031690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280709PMC
December 2018