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1.
Transbound Emerg Dis ; 68(6): 3443-3452, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1526424

ABSTRACT

The recently emerged novel coronavirus, SARS-CoV-2, is phylogenetically related to bat coronaviruses (CoVs), specifically SARS-related CoVs from the Eurasian bat family Rhinolophidae. As this human pandemic virus has spread across the world, the potential impacts of SARS-CoV-2 on native North American bat populations are unknown, as is the ability of North American bats to serve as reservoirs or intermediate hosts able to transmit the virus to humans or to other animal species. To help determine the impacts of the pandemic virus on North American bat populations, we experimentally challenged big brown bats (Eptesicus fuscus) with SARS-CoV-2 under BSL-3 conditions. We inoculated the bats both oropharyngeally and nasally, and over the ensuing three weeks, we measured infectivity, pathology, virus concentrations in tissues, oral and rectal virus excretion, virus transmission, and clinical signs of disease. We found no evidence of SARS-CoV-2 infection in any examined bat, including no viral excretion, no transmission, no detectable virus in tissues, and no signs of disease or pathology. Based on our findings, it appears that big brown bats are resistant to infection with the SARS-CoV-2. The potential susceptibility of other North American bat species to SARS-CoV-2 remains to be investigated.


Subject(s)
COVID-19 , Chiroptera , Coronaviridae , Animals , COVID-19/veterinary , Humans , North America/epidemiology , Phylogeny , SARS-CoV-2
2.
Science ; 374(6567): eabj3624, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1440797
3.
Int J Biol Sci ; 17(14): 3717-3727, 2021.
Article in English | MEDLINE | ID: covidwho-1417291

ABSTRACT

SARS-CoV-2 belongs to the coronavirus family. Comparing genomic features of viral genomes of coronavirus family can improve our understanding about SARS-CoV-2. Here we present the first pan-genome analysis of 3,932 whole genomes of 101 species out of 4 genera from the coronavirus family. We found that a total of 181 genes in the pan-genome of coronavirus family, among which only 3 genes, the S gene, M gene and N gene, are highly conserved. We also constructed a pan-genome from 23,539 whole genomes of SARS-CoV-2. There are 13 genes in total in the SARS-CoV-2 pan-genome. All of the 13 genes are core genes for SARS-CoV-2. The pan-genome of coronaviruses shows a lower level of diversity than the pan-genomes of other RNA viruses, which contain no core gene. The three highly conserved genes in coronavirus family, which are also core genes in SARS-CoV-2 pan-genome, could be potential targets in developing nucleic acid diagnostic reagents with a decreased possibility of cross-reaction with other coronavirus species.


Subject(s)
Coronaviridae/genetics , Genome, Viral , Phylogeny
4.
Infect Genet Evol ; 95: 105075, 2021 11.
Article in English | MEDLINE | ID: covidwho-1401708

ABSTRACT

T-cell-mediated immunity to SARS-CoV-2-derived peptides in individuals unexposed to SARS-CoV-2 has been previously reported. This pre-existing immunity was suggested to largely derive from prior exposure to 'common cold' endemic human coronaviruses (HCoVs). To test this, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the full proteome of the Coronaviridae family. 54.8% of these epitopes had no homology to any of the HCoVs. Further, the proportion of SARS-CoV-2-derived epitopes with any level of sequence homology to the proteins encoded by any of the coronaviruses tested is well-predicted by their alignment-free phylogenetic distance to SARS-CoV-2 (Pearson's r = -0.958). No coronavirus in our dataset showed a significant excess of T-cell epitope homology relative to the proportion of expected random matches, given their genetic similarity to SARS-CoV-2. Our findings suggest that prior exposure to human or animal-associated coronaviruses cannot completely explain the T-cell repertoire in unexposed individuals that recognise SARS-CoV-2 cross-reactive epitopes.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coronaviridae/immunology , Disease Resistance , Immunologic Memory , SARS-CoV-2/immunology , Animals , Antibodies, Viral/genetics , Antibodies, Viral/immunology , Antigens, Viral/genetics , Antigens, Viral/immunology , Asymptomatic Diseases , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Chiroptera/virology , Coronaviridae/classification , Coronaviridae/genetics , Coronaviridae/pathogenicity , Cross Reactions , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Eutheria/virology , Humans , Immunity, Cellular , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/virology
6.
Virology ; 563: 20-27, 2021 11.
Article in English | MEDLINE | ID: covidwho-1356482

ABSTRACT

Viruses of the subfamily Orthocoronavirinae can cause mild to severe disease in people, including COVID-19, MERS and SARS. Their most common natural hosts are bat and bird species, which are mostly split across four virus genera. Molecular clock analyses of orthocoronaviruses suggested the most recent common ancestor of these viruses might have emerged either around 10,000 years ago or, using models accounting for selection, many millions of years. Here, we reassess the evolutionary history of these viruses. We present time-aware phylogenetic analyses of a RNA-dependent RNA polymerase locus from 123 orthocoronaviruses isolated from birds and bats, including those in New Zealand, which were geographically isolated from other bats around 35 million years ago. We used this age, as well as the age of the avian-mammals split, to calibrate the molecular clocks, under the assumption that these ages are applicable to the analyzed viruses. We found that the time to the most recent ancestor common for all orthocoronaviruses is likely 150 or more million years, supporting clock analyses that account for selection.


Subject(s)
Birds/virology , Chiroptera/virology , Coronaviridae Infections/virology , Coronaviridae , Genome, Viral , Animals , Coronaviridae/classification , Coronaviridae/genetics , Evolution, Molecular , New Zealand/epidemiology
7.
Sci Rep ; 11(1): 16145, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1349686

ABSTRACT

The genetic element s2m has been acquired through horizontal transfer by many distantly related viruses, including the SARS-related coronaviruses. Here we show that s2m is evolutionarily conserved in these viruses. Though several lineages of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) devoid of the element can be found, these variants seem to have been short lived, indicating that they were less evolutionary fit than their s2m-containing counterparts. On a species-level, however, there do not appear to be any losses and this pattern strongly suggests that the s2m element is essential to virus replication in SARS-CoV-2 and related viruses. Further experiments are needed to elucidate the function of s2m.


Subject(s)
Coronaviridae/genetics , Interspersed Repetitive Sequences/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Virus Replication/genetics , Animals , Base Sequence , COVID-19/virology , Coronaviridae/classification , Evolution, Molecular , Gene Transfer, Horizontal , Humans , Phylogeny , SARS-CoV-2/physiology , Sequence Homology, Nucleic Acid , Species Specificity
8.
Biomed Res Int ; 2021: 8856018, 2021.
Article in English | MEDLINE | ID: covidwho-1303204

ABSTRACT

Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.


Subject(s)
Antiviral Agents , Coronaviridae , Models, Biological , Viral Tropism , Virus Internalization , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19 , Cells, Cultured , Coronaviridae/drug effects , Coronaviridae/metabolism , Coronaviridae/pathogenicity , Coronaviridae/physiology , Coronaviridae Infections , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
9.
Nat Struct Mol Biol ; 28(7): 573-582, 2021 07.
Article in English | MEDLINE | ID: covidwho-1279891

ABSTRACT

SARS-CoV-2 ORF3a is a putative viral ion channel implicated in autophagy inhibition, inflammasome activation and apoptosis. 3a protein and anti-3a antibodies are found in infected patient tissues and plasma. Deletion of 3a in SARS-CoV-1 reduces viral titer and morbidity in mice, suggesting it could be an effective target for vaccines or therapeutics. Here, we present structures of SARS-CoV-2 3a determined by cryo-EM to 2.1-Å resolution. 3a adopts a new fold with a polar cavity that opens to the cytosol and membrane through separate water- and lipid-filled openings. Hydrophilic grooves along outer helices could form ion-conduction paths. Using electrophysiology and fluorescent ion imaging of 3a-reconstituted liposomes, we observe Ca2+-permeable, nonselective cation channel activity, identify mutations that alter ion permeability and discover polycationic inhibitors of 3a activity. 3a-like proteins are found across coronavirus lineages that infect bats and humans, suggesting that 3a-targeted approaches could treat COVID-19 and other coronavirus diseases.


Subject(s)
Cryoelectron Microscopy , Nanostructures , SARS-CoV-2 , Viroporin Proteins/chemistry , Viroporin Proteins/ultrastructure , Animals , Calcium/metabolism , Chiroptera/virology , Coronaviridae , Electrophysiology , Fluorescence , Humans , Ion Transport , Liposomes , Models, Molecular , Nanostructures/chemistry , Nanostructures/ultrastructure , Open Reading Frames , Optical Imaging , Reproducibility of Results , SARS-CoV-2/chemistry , SARS-CoV-2/ultrastructure , Sequence Homology , Viral Proteins/chemistry , Viral Proteins/ultrastructure , Viroporin Proteins/antagonists & inhibitors
10.
J Vet Diagn Invest ; 33(3): 457-468, 2021 May.
Article in English | MEDLINE | ID: covidwho-1264088

ABSTRACT

Every day, thousands of samples from diverse populations of animals are submitted to veterinary diagnostic laboratories (VDLs) for testing. Each VDL has its own laboratory information management system (LIMS), with processes and procedures to capture submission information, perform laboratory tests, define the boundaries of test results (i.e., positive or negative), and report results, in addition to internal business and accounting applications. Enormous quantities of data are accumulated and stored within VDL LIMSs. There is a need for platforms that allow VDLs to exchange and share portions of laboratory data using standardized, reliable, and sustainable information technology processes. Here we report concepts and applications for standardization and aggregation of data from swine submissions to multiple VDLs to detect and monitor porcine enteric coronaviruses by RT-PCR. Oral fluids, feces, and fecal swabs were the specimens submitted most frequently for enteric coronavirus testing. Statistical algorithms were used successfully to scan and monitor the overall and state-specific percentage of positive submissions. Major findings revealed a consistently recurrent seasonal pattern, with the highest percentage of positive submissions detected during December-February for porcine epidemic diarrhea virus, porcine deltacoronavirus, and transmissible gastroenteritis virus (TGEV). After 2014, very few submissions tested positive for TGEV. Monitoring VDL data proactively has the potential to signal and alert stakeholders early of significant changes from expected detection. We demonstrate the importance of, and applications for, data organized and aggregated by using LOINC and SNOMED CTs, as well as the use of customized messaging to allow inter-VDL exchange of information.


Subject(s)
Coronaviridae Infections/veterinary , Coronaviridae/isolation & purification , Laboratories/standards , Swine Diseases/virology , Animals , COVID-19 Testing/veterinary , Coronaviridae Infections/diagnosis , Coronaviridae Infections/virology , Disease Outbreaks , Feces/virology , Reference Standards , Seasons , Swine , Swine Diseases/diagnosis
11.
Int Rev Immunol ; 40(1-2): 5-53, 2021.
Article in English | MEDLINE | ID: covidwho-1236148

ABSTRACT

Coronavirus infections are responsible for mild, moderate, and severe infections in birds and mammals. These were first isolated in humans as causal microorganisms responsible for common cold. The 2002-2003 SARS epidemic caused by SARS-CoV and 2012 MERS epidemic (64 countries affected) caused by MERS-CoV showed their acute and fatal side. These two CoV infections killed thousands of patients infected worldwide. However, WHO has still reported the MERS case in December 2019 in middle-eastern country (Saudi Arabia), indicating the MERS epidemic has not ended completely yet. Although we have not yet understood completely these two CoV epidemics, a third most dangerous and severe CoV infection has been originated in the Wuhan city, Hubei district of China in December 2019. This CoV infection called COVID-19 or SARS-CoV2 infection has now spread to 210 countries and territories around the world. COVID-19 has now been declared a pandemic by the World Health Organization (WHO). It has infected more than 16.69 million people with more than 663,540 deaths across the world. Thus the current manuscript aims to describe all three (SARS, MERS, and COVID-19) in terms of their causal organisms (SARS-CoV, MERS-CoV, and SARS-CoV2), similarities and differences in their clinical symptoms, outcomes, immunology, and immunopathogenesis, and possible future therapeutic approaches.


Subject(s)
COVID-19/pathology , Coronaviridae/ultrastructure , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/pathology , Animals , COVID-19/diagnosis , COVID-19/mortality , Camelus/virology , Chiroptera/virology , Coronaviridae/classification , Disease Reservoirs/virology , Disease Susceptibility/virology , Humans , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Virus Replication/physiology
12.
Viruses ; 13(5)2021 05 18.
Article in English | MEDLINE | ID: covidwho-1234835

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had devastating health and socio-economic impacts. Human activities, especially at the wildlife interphase, are at the core of forces driving the emergence of new viral agents. Global surveillance activities have identified bats as the natural hosts of diverse coronaviruses, with other domestic and wildlife animal species possibly acting as intermediate or spillover hosts. The African continent is confronted by several factors that challenge prevention and response to novel disease emergences, such as high species diversity, inadequate health systems, and drastic social and ecosystem changes. We reviewed published animal coronavirus surveillance studies conducted in Africa, specifically summarizing surveillance approaches, species numbers tested, and findings. Far more surveillance has been initiated among bat populations than other wildlife and domestic animals, with nearly 26,000 bat individuals tested. Though coronaviruses have been identified from approximately 7% of the total bats tested, surveillance among other animals identified coronaviruses in less than 1%. In addition to a large undescribed diversity, sequences related to four of the seven human coronaviruses have been reported from African bats. The review highlights research gaps and the disparity in surveillance efforts between different animal groups (particularly potential spillover hosts) and concludes with proposed strategies for improved future biosurveillance.


Subject(s)
Coronavirus Infections/epidemiology , Epidemiological Monitoring/veterinary , Africa/epidemiology , Animals , Animals, Wild/virology , COVID-19/epidemiology , Chiroptera/virology , Coronaviridae/genetics , Coronavirus/pathogenicity , Ecosystem , Genetic Variation , Genome, Viral , Pandemics , Phylogeny , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics
14.
Exp Mol Med ; 53(5): 723-736, 2021 05.
Article in English | MEDLINE | ID: covidwho-1217695

ABSTRACT

The innate immune system is the first line of the host defense program against pathogens and harmful substances. Antiviral innate immune responses can be triggered by multiple cellular receptors sensing viral components. The activated innate immune system produces interferons (IFNs) and cytokines that perform antiviral functions to eliminate invading viruses. Coronaviruses are single-stranded, positive-sense RNA viruses that have a broad range of animal hosts. Coronaviruses have evolved multiple means to evade host antiviral immune responses. Successful immune evasion by coronaviruses may enable the viruses to adapt to multiple species of host organisms. Coronavirus transmission from zoonotic hosts to humans has caused serious illnesses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease-2019 (COVID-19), resulting in global health and economic crises. In this review, we summarize the current knowledge of the mechanisms underlying host sensing of and innate immune responses against coronavirus invasion, as well as host immune evasion strategies of coronaviruses.


Subject(s)
Coronaviridae/immunology , Coronavirus Infections/immunology , Immune Evasion , Immunity, Innate , Animals , COVID-19/immunology , Humans , Interferons/immunology , SARS-CoV-2/immunology
15.
PLoS Pathog ; 17(4): e1009149, 2021 04.
Article in English | MEDLINE | ID: covidwho-1194504

ABSTRACT

The COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. We obtained a set of 650 spike protein and 511 whole genome nucleotide sequences from 222 and 185 viruses belonging to the family Coronaviridae, respectively. We then trained random forest models independently on genome composition biases of spike protein and whole genome sequences, including dinucleotide and codon usage biases in order to predict animal host (of nine possible categories, including human). In hold-one-out cross-validation, predictive accuracy on unseen coronaviruses consistently reached ~73%, indicating evolutionary signal in spike proteins to be just as informative as whole genome sequences. However, different composition biases were informative in each case. Applying optimised random forest models to classify human sequences of MERS-CoV and SARS-CoV revealed evolutionary signatures consistent with their recognised intermediate hosts (camelids, carnivores), while human sequences of SARS-CoV-2 were predicted as having bat hosts (suborder Yinpterochiroptera), supporting bats as the suspected origins of the current pandemic. In addition to phylogeny, variation in genome composition can act as an informative approach to predict emerging virus traits as soon as sequences are available. More widely, this work demonstrates the potential in combining genetic resources with machine learning algorithms to address long-standing challenges in emerging infectious diseases.


Subject(s)
Biological Evolution , Coronaviridae Infections/diagnosis , Coronaviridae Infections/virology , Coronaviridae/pathogenicity , Genome, Viral , Machine Learning , Spike Glycoprotein, Coronavirus/metabolism , Animals , Coronaviridae Infections/genetics , Coronaviridae Infections/metabolism , Phylogeny , Spike Glycoprotein, Coronavirus/genetics
16.
Emerg Infect Dis ; 27(4): 1015-1022, 2021 04.
Article in English | MEDLINE | ID: covidwho-1150678

ABSTRACT

The ongoing global pandemic caused by coronavirus disease has once again demonstrated the role of the family Coronaviridae in causing human disease outbreaks. Because severe acute respiratory syndrome coronavirus 2 was first detected in December 2019, information on its tropism, host range, and clinical manifestations in animals is limited. Given the limited information, data from other coronaviruses might be useful for informing scientific inquiry, risk assessment, and decision-making. We reviewed endemic and emerging infections of alphacoronaviruses and betacoronaviruses in wildlife, livestock, and companion animals and provide information on the receptor use, known hosts, and clinical signs associated with each host for 15 coronaviruses detected in humans and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.


Subject(s)
Coronaviridae/isolation & purification , Coronavirus Infections/veterinary , Disease Reservoirs/veterinary , Zoonoses/virology , Alphacoronavirus/isolation & purification , Animals , Animals, Wild , Betacoronavirus/isolation & purification , COVID-19/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Outbreaks , Disease Reservoirs/virology , Host Specificity , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , SARS-CoV-2 , Zoonoses/epidemiology
17.
ACS Infect Dis ; 7(6): 1596-1606, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1135641

ABSTRACT

The presence of antibodies against endemic coronaviruses has been linked to disease severity after SARS-CoV-2 infection. Assays capable of concomitantly detecting antibodies against endemic coronaviridae such as OC43, 229E, NL63, and SARS-CoV-2 may help to elucidate this question. We developed a serum screening platform using a bead-based Western blot system called DigiWest, capable of running hundreds of assays using microgram amounts of protein prepared directly from different viruses. Characterization of the immunoassay for detection of SARS-CoV-2 specific antibodies revealed a sensitivity of 90.3% and a diagnostic specificity of 98.1%. Concordance analysis with the SARS-CoV-2 immunoassays available by Roche, Siemens, and Euroimmun indicates comparable assay performances (Cohen's κ ranging from 0.8874 to 0.9508). Analogous assays for OC43, 229E, and NL63 were established and combined into one multiplex with the SARS-CoV-2 assay. Seroreactivity for different coronaviruses was detected with high incidence, and the multiplex assay was adapted for serum screening.


Subject(s)
COVID-19 , Coronaviridae , COVID-19 Testing , Humans , Plant Extracts , SARS-CoV-2
18.
Clin Exp Rheumatol ; 39(5): 1119-1125, 2021.
Article in English | MEDLINE | ID: covidwho-1102871

ABSTRACT

OBJECTIVES: The results of the RECOVERY trial identified dexamethasone as the first pharmacological therapy that reduces mortality in patients with COVID-19. The aim of this paper is to conduct a systematic literature review on safety and efficacy of pulse glucocorticoid therapy for Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV), Middle East Respiratory Syndrome (MERS)-CoV or SARS-CoV-2 infections and describe a case-series of COVID-19 patients treated with off-label pulse doses of methylprednisolone. METHODS: We performed a systematic literature review on safety and efficacy of pulse therapy for betacoronaviridae infections as described in the protocol registered on PROSPERO (CRD42020190183). All consecutive patients admitted to Arcispedale Santa Maria Nuova di Reggio Emilia or Guastalla Hospital with COVID-19 between March 1st and April 30th, 2020 and treated with methylprednisolone 1 gram/day for at least three days were included in the case series. A retrospective review of available computed tomography (CT) scan and chest x-ray was performed independently by two radiologists blinded to clinical data, and discordances were resolved by consensus. RESULTS: Twenty papers were included for SARS, but only two were comparative and were included in the primary endpoint analysis. Likewise, eleven papers were included for COVID-19, four of which were comparative and were considered for the primary outcome analysis. Included studies for both SARS and COVID-19 are mostly retrospective and highly heterogeneous, with lethality ranging from 0% to 100% and ICU admission rate ranging from 9% to 100%. Fourteen patients were included in our case series, 7 males and 7 females. CONCLUSIONS: No randomised controlled trial is available yet for corticosteroids pulse-therapy defined as at least ≥500mg/day methylprednisolone in patients with emerging coronavirus pneumonia. Lethality among our cohort is high (4/14), but this finding should be interpreted with caution due to the fact that in our setting pulse-steroids were used in patients not eligible for other treatments because of comorbidities or as rescue therapy. The incidence of steroid-related adverse events seems low in our cohort. The quality of the evidence on glucocorticoid pulse-therapy in SARS, MERS and COVID-19 is poor. Randomised controlled trials are greatly needed.


Subject(s)
COVID-19 , Coronaviridae , Female , Glucocorticoids/adverse effects , Humans , Male , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
19.
Epidemiol Prev ; 44(5-6 Suppl 2): 169-182, 2020.
Article in English | MEDLINE | ID: covidwho-1068137

ABSTRACT

As the Coronavirus situation (COVID-19) continues to evolve, many questions concerning the factors relating to the diffusion and severity of the disease remain unanswered.Whilst opinions regarding the weight of evidence for these risk factors, and the studies published so far are often inconclusive or offer contrasting results, the role of comorbidities in the risk of serious adverse outcomes in patients affected with COVID-19 appears to be evident since the outset. Hypertension, diabetes, and obesity are under discussion as important factors affecting the severity of disease. Air pollution has been considered to play a role in the diffusion of the virus, in the propagation of the contagion, in the severity of symptoms, and in the poor prognosis. Accumulating evidence supports the hypothesis that environmental particulate matter (PM) can trigger inflammatory responses at molecular, cellular, and organ levels, sustaining respiratory, cardiovascular, and dysmetabolic diseases.To better understand the intricate relationships among pre-existing conditions, PM, and viral infection, we examined the response at the molecular level of T47D human breast adenocarcinoma cells exposed to different fractions of PM. T47D cells express several receptors, including the aryl hydrocarbon receptor (AhR), and ACE2, the main - but not the only - receptor for SARS-CoV-2 entry.PM samples were collected in an urban background site located in the Northern area of the City of Bologna (Emilia-Romagna Region, Northern Italy) during winter 2013. T47D cells were exposed to organic or aqueous (inorganic) extracts at the final concentration of 8 m3 for a 4-hour duration. Both the concentration and the exposure time were chosen to resemble an average outdoor exposure. RNA was extracted from cells, purified and hybridised on 66k microarray slides from Agilent.The lists of differentially expressed genes in PM organic extracts were evaluated by using Metacore, and an enrichment analysis was performed to identify pathways maps, process networks, and disease by biomarkers altered after T47D treatment.The analysis of the modulated genes gave evidence for the involvement of PM in dysmetabolic diseases, including diabetes and obesity, and hypertension through the activation of the aryl hydrocarbon receptor (AhR) canonical pathway.On the basis of current knowledge, existing data, and exploratory experimental evidence, we tease out the likely molecular interplay that can ultimately tip the disease outcome into severity. Looking beyond ACE2, several additional key markers are identified. Disruption of these targets worsens pre-existing conditions and/or exacerbates the adverse effects induced by SARS-CoV-2 infection. Whilst appropriately designed, epidemiological studies are very much needed to investigate these associations based on our hypothesis of investigation, by reviewing recent experimental and epidemiological evidence, here we speculate and provide new insights on the possible role of environmental pollution in the exacerbation of effects by SARS-CoV-2 and other respiratory viruses. This work is intended to assist in the development of appropriate investigative approaches to protect public health.


Subject(s)
Air Pollution/adverse effects , COVID-19/epidemiology , Particulate Matter/adverse effects , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/physiology , COVID-19/etiology , Cell Line, Tumor , Comorbidity , Coronaviridae/physiology , Cytochrome P-450 CYP1A1/physiology , Diabetes Mellitus/epidemiology , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Disease Susceptibility , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Hypertension/epidemiology , Hypertension/genetics , Hypertension/metabolism , Inflammation/epidemiology , Inflammation/genetics , Inflammation/metabolism , Italy , Obesity/epidemiology , Obesity/genetics , Obesity/metabolism , Particulate Matter/pharmacology , Receptors, Aryl Hydrocarbon/physiology , Receptors, Virus/physiology , Risk , SARS-CoV-2/ultrastructure , Signal Transduction
20.
Sci Rep ; 11(1): 3209, 2021 02 05.
Article in English | MEDLINE | ID: covidwho-1065951

ABSTRACT

Viral co-infections occur in COVID-19 patients, potentially impacting disease progression and severity. However, there is currently no dedicated method to identify viral co-infections in patient RNA-seq data. We developed PACIFIC, a deep-learning algorithm that accurately detects SARS-CoV-2 and other common RNA respiratory viruses from RNA-seq data. Using in silico data, PACIFIC recovers the presence and relative concentrations of viruses with > 99% precision and recall. PACIFIC accurately detects SARS-CoV-2 and other viral infections in 63 independent in vitro cell culture and patient datasets. PACIFIC is an end-to-end tool that enables the systematic monitoring of viral infections in the current global pandemic.


Subject(s)
COVID-19/diagnosis , Coinfection/diagnosis , Deep Learning , RNA Virus Infections/diagnosis , RNA Viruses/isolation & purification , SARS-CoV-2/isolation & purification , COVID-19 Testing , Coinfection/virology , Coronaviridae/isolation & purification , Humans , Metapneumovirus/classification , Metapneumovirus/isolation & purification , Neural Networks, Computer , Orthomyxoviridae/classification , Orthomyxoviridae/isolation & purification , RNA Virus Infections/virology , RNA Viruses/classification , RNA-Seq , Rhinovirus/classification , Rhinovirus/isolation & purification , SARS-CoV-2/classification , Sensitivity and Specificity
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