ResearchPad - 530 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures]]> https://www.researchpad.co/article/elastic_article_8299 The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explicit type, suggested by the wave of infections spreading from the initial foci to the rest of Italy. We estimate parameters of a metacommunity Susceptible–Exposed–Infected–Recovered (SEIR)-like transmission model that includes a network of 107 provinces connected by mobility at high resolution, and the critical contribution of presymptomatic and asymptomatic transmission. We estimate a generalized reproduction number (R0 = 3.60 [3.49 to 3.84]), the spectral radius of a suitable next-generation matrix that measures the potential spread in the absence of containment interventions. The model includes the implementation of progressive restrictions after the first case confirmed in Italy (February 21, 2020) and runs until March 25, 2020. We account for uncertainty in epidemiological reporting, and time dependence of human mobility matrices and awareness-dependent exposure probabilities. We draw scenarios of different containment measures and their impact. Results suggest that the sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Averted hospitalizations are measured by running scenarios obtained by selectively relaxing the imposed restrictions and total about 200,000 individuals (as of March 25, 2020). Although a number of assumptions need to be reexamined, like age structure in social mixing patterns and in the distribution of mobility, hospitalization, and fatality, we conclude that verifiable evidence exists to support the planning of emergency measures.

]]>
<![CDATA[Effectiveness of convalescent plasma therapy in severe COVID-19 patients]]> https://www.researchpad.co/article/N1f6f671d-8823-406a-b910-0c222f4b76c0 Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

]]>
<![CDATA[Phylogenetic network analysis of SARS-CoV-2 genomes]]> https://www.researchpad.co/article/N87de2df2-e17d-447b-a2d2-d2d221ff8e49 In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.

]]>
<![CDATA[Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors]]> https://www.researchpad.co/article/N5eb3f905-aaa0-45e0-93d7-2100d8d4672e

Significance

Cells carry sensors that are primed to detect invading viruses. To avoid being recognized, coronaviruses express factors that interfere with host immune sensing pathways. Previous studies revealed that a coronavirus endoribonuclease (EndoU) delays activation of the host sensor system, but the mechanism was not known. Here, we report that EndoU cleaves a viral polyuridine sequence that would otherwise activate host immune sensors. This information may be used in developing inhibitors that target EndoU activity and prevent diseases caused by coronaviruses.

]]>
<![CDATA[Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak]]> https://www.researchpad.co/article/Nd3b4ad2f-5d47-4b8c-a749-0385fc3d8cbf

Significance

To contain the global spread of the 2019 novel coronavirus epidemic (COVID-19), border control measures, such as airport screening and travel restrictions, have been implemented in several countries. Our results show that these measures likely slowed the rate of exportation from mainland China to other countries, but are insufficient to contain the global spread of COVID-19. With most cases arriving during the asymptomatic incubation period, our results suggest that rapid contact tracing is essential both within the epicenter and at importation sites to limit human-to-human transmission outside of mainland China.

]]>
<![CDATA[Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells]]> https://www.researchpad.co/article/N6f02d160-a345-4e57-8ae6-1f96eb2e3453

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.

]]>
<![CDATA[Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection]]> https://www.researchpad.co/article/Nc65fb86e-dfbd-43f2-bcc4-b63fbf657a5e

Significance

Middle East Respiratory Syndrome, caused by the MERS coronavirus (MERS-CoV), continues to cause severe respiratory disease with a high case fatality rate. To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China.

]]>
<![CDATA[Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans]]> https://www.researchpad.co/article/N3a021e5a-1556-476c-8d9e-c18cd3db3026

Significance

We report here a 3.3-Å cryo-EM structure of feline infectious peritonitis virus (FIPV) S protein derived from the serotype I FIPV UU4 strain. The near-atomic EM map enabled ab initio modeling of 27 out of the 33 experimentally verified high-mannose and complex-type N-glycans that mask most of the protein surface. We demonstrated the feasibility to directly visualize the core fucose of a complex-type glycan, which was independently cross-validated by glycopeptide mass spectrometry analyses. There exist 3 N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV-UU4 S protein, resulting in a propeller-like conformation unique to all reported CoV S proteins. The results highlight a structural role of glycosylation in maintaining complex protein structures.

]]>