Project description:In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.
Project description:The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. Host responses to the three SARS-CoV strains were similar and only apparent early during infection with the majority of genes associated with interferon signalling pathways.This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use 4 strains, time course, lungs
Project description:We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal (HCoV-NL63, -229E, -OC43 and -HKU1) and epidemic coronaviruses (SARS-CoV, hCoV-MERS) at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed IgG antibody reactivity to nucleocapsid and spike antigens using protein microarray. A cutoff was set at the average plus 3 times the SD of 20 nonreactive cultures with a minimum MFI of 1000.
Project description:The ongoing COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people worldwide and has significant implications for public health. Host transcriptomics profiling provides comprehensive understanding of how the virus interacts with host cells and how the host responds to the virus. COVID-19 disease alters the host transcriptome, affecting cellular pathways and key molecular functions. To contribute to the global effort to understand the virus’s effect on host cell transcriptome, we have generated a dataset from nasopharyngeal swabs of 35 individuals infected with SARS-CoV-2 from the Campania region in Italy during the three outbreaks, with different clinical conditions. This dataset will help to elucidate the complex interactions among genes and can be useful in the development of effective therapeutic pathways
Project description:The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak have accentuated the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2-subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, expanding on our previous work with S2-based vaccines, we developed a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protected female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc- receptor knockout mice revealed that antibody-based cellular effector mechanisms played a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.
Project description:The SARS-CoV-2 virus is continuously evolving, with appearance of new variants characterized by multiple genomic mutations, some of which can affect functional properties, including infectivity, interactions with host immunity, and disease severity. The rapid spread of new SARS-CoV-2 variants has highlighted the urgency to trace the virus evolution, to help limit its diffusion, and to assess effectiveness of containment strategies. We propose here a PCR-based rapid, sensitive and low-cost allelic discrimination assay panel for the identification of SARS-CoV-2 genotypes, useful for detection in different sample types, such as nasopharyngeal swabs and wastewater. The tests carried out demonstrate that this in-house assay, whose results were confirmed by SARS-CoV-2 whole-genome sequencing, can detect variations in up to 10 viral genome positions at once and is specific and highly sensitive for identification of all tested SARS-CoV-2 clades, even in the case of samples very diluted and of poor quality, particularly difficult to analyze.
Project description:In India, 100,340 confirmed cases and 3155 confirmed deaths due to COVID-19 were reported as of May 18, 2020. Due to absence of specific vaccine or therapy, non-pharmacological interventions including so- cial distancing, contact tracing are essential to end the worldwide COVID-19. We propose a mathematical model that predicts the dynamics of COVID-19 in 17 provinces of India and the overall India. A complete scenario is given to demonstrate the estimated pandemic life cycle along with the real data or history to date, which in turn divulges the predicted inflection point and ending phase of SARS-CoV-2. The proposed model monitors the dynamics of six compartments, namely susceptible (S), asymptomatic (A), recovered (R), infected (I), isolated infected ( I q ) and quarantined susceptible ( S q ), collectively expressed SARII q S q . A sensitivity analysis is conducted to determine the robustness of model predictions to parameter values and the sensitive parameters are estimated from the real data on the COVID-19 pandemic in India. Our re- sults reveal that achieving a reduction in the contact rate between uninfected and infected individuals by quarantined the susceptible individuals, can effectively reduce the basic reproduction number. Our model simulations demonstrate that the elimination of ongoing SARS-CoV-2 pandemic is possible by combining the restrictive social distancing and contact tracing. Our predictions are based on real data with reason- able assumptions, whereas the accurate course of epidemic heavily depends on how and when quaran- tine, isolation and precautionary measures are enforced.
Project description:A recombinant SARS-CoV lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major virulence determinant in vivo. Elimination of SARS-CoV E protein PBM by using reverse genetics led to attenuated viruses (SARS-CoV-mutPBM) and to a reduction in the deleterious exacerbate immune response triggered during infection with the parental virus (SARS-CoV-wt). Cellular protein syntenin bound E protein PBM during SARS-CoV infection. Syntenin activates p38 MAPK leading to overexpression of inflammatory cytokines, and we have shown that active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM (SARS-CoV-mutPBM) as compared with the parental virus (SARS-CoV-wt), leading to a decreased expression of inflammatory cytokines and to viral attenuation. Therefore, E protein PBM is a virulence factor that activates pathogenic immune response most likely by using syntenin as a mediator of p38 MAPK induced inflammation. Three biological replicates were independently hybridized (one channel per slide) for each sample type (SARS-CoV-wt, SARS-CoV-mutPBM, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)
Project description:The novel coronavirus SARS-CoV-2 has rapidly caused a global pandemic, due to higher transmission rates and lower mortality than previous epidemic CoVs. Here, we systematically analysed changes in the proteome of HEK293 cells upon overexpression of key SARS-CoV-2 encoded proteins and compared them to changes upon SARS-CoV-2 infection.