Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 74
Filter
2.
Signal Transduct Target Ther ; 5(1): 220, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1387194
4.
J Hosp Infect ; 105(4): 625-627, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1385923

ABSTRACT

SARS-CoV-2 is mainly transmitted by respiratory droplets and contact with contaminated surfaces. It can be retrieved in faeces but there is no evidence of faecal-oral transmission, which is the main route of contamination in recreational waters. Standard cleaning and disinfecting procedures, microbiological control and health rules aim to prevent infectious risk regardless of the micro-organisms. In the context of progressive lockdown exit and hospital activities recovery, we assessed the risk of SARS-CoV-2 transmission in rehabilitation pools and therapeutic water environments in order to provide specific recommendations to control the spread of SARS-CoV-2 while ensuring essential rehabilitation care for patients.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Guidelines as Topic , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Rehabilitation Centers/standards , Safety Management/standards , Swimming Pools/standards , COVID-19 , Humans , SARS-CoV-2
5.
J Mol Evol ; 88(5): 421-423, 2020 07.
Article in English | MEDLINE | ID: covidwho-1342961

ABSTRACT

Transmission of viruses from one species to another is not unusual in nature. Despite this, evolutionarily successful transmissions are rare. Such events can cause pandemics and are followed by host-virus coevolution procedures that can increase the fitness potential of viruses. In this perspective article, I recognize eight main types of trans-species viral transmission. I consider two of them as evolutionarily successful, explaining why coronavirus SARS-CoV-2 could be one of them.


Subject(s)
Betacoronavirus/genetics , Biological Coevolution , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Animals , Betacoronavirus/growth & development , Betacoronavirus/pathogenicity , COVID-19 , Genetic Fitness , Host-Pathogen Interactions/genetics , Humans , SARS-CoV-2
7.
Molecules ; 25(19)2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-1302391

ABSTRACT

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Peptides/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory System Agents/therapeutic use , Acute Disease , Anti-Inflammatory Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Betacoronavirus/drug effects , Betacoronavirus/growth & development , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Host-Pathogen Interactions/drug effects , Humans , Immunologic Factors/chemical synthesis , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Pandemics , Peptides/chemical synthesis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/prevention & control , Respiratory Insufficiency/virology , Respiratory System Agents/chemical synthesis , SARS-CoV-2 , Structure-Activity Relationship
8.
Afr J Prim Health Care Fam Med ; 12(1): e1-e3, 2020 Oct 02.
Article in English | MEDLINE | ID: covidwho-1073604

ABSTRACT

Early in the course of the coronavirus infection disease 2019 (COVID-19) pandemic in South Africa, the Department of Health implemented a policy of community screening and testing (CST). This was based on a community-orientated primary care approach and was a key strategy in limiting the spread of the pandemic, but it struggled with long turnaround times (TATs) for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction test. The local experience at Symphony Way Community Day Centre (Delft, Cape Town), highlighted these challenges. The first positive tests had a median TAT of 4.5 days, peaking at 29 days in mid-May 2020. Issues that contributed to long TATs were unavailability of viral transport medium, sample delivery and storage difficulties, staffing problems, scarcity of testing supplies and other samples prioritised over CST samples. At Symphony Way, many patients who tested COVID-19 positive had abandoned their self-isolation because of the delay in results. Employers were unhappy with prolonged sick leave whilst waiting for results and patients were concerned about not getting paid or job loss. The CST policy relies on a rapid TAT to be successful. Once the TAT is delayed, the process of contacting patients, and tracing and quarantining contacts becomes ineffective. With hindsight, other countries' difficulties in upscaling testing should have served as warning. Community screening and testing was scaled back from 18 May 2020, and testing policy was changed to only include high-risk patients from 29 May 2020. The delayed TATs meant that the CST policy had no beneficial impact at local level.


Subject(s)
Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Health Services Accessibility , Mass Screening , Pneumonia, Viral/diagnosis , Policy , Betacoronavirus/growth & development , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Mass Screening/methods , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome , South Africa , Time Factors
9.
Clin Microbiol Infect ; 26(8): 1094.e1-1094.e5, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1023515

ABSTRACT

OBJECTIVES: To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.


Subject(s)
Betacoronavirus/growth & development , Fomites/virology , RNA-Dependent RNA Polymerase/genetics , Viral Envelope Proteins/genetics , Animals , Betacoronavirus/genetics , Chlorocebus aethiops , Coronavirus Envelope Proteins , Equipment Contamination , Humans , Intensive Care Units , Microbial Viability , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Vero Cells , Viral Proteins/genetics
10.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 605-611, 2020 Apr 25.
Article in Chinese | MEDLINE | ID: covidwho-1024807

ABSTRACT

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections , Coronavirus/drug effects , Coronavirus/growth & development , Cyclophilin A/antagonists & inhibitors , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Pandemics , Pneumonia, Viral , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/growth & development , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cyclosporine/chemistry , Humans , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , SARS-CoV-2 , Virus Replication/drug effects
11.
J Clin Microbiol ; 58(8)2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-1006147

ABSTRACT

Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the specter of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestral origin emerged to infect humans in Wuhan, China, in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died. Coronavirus disease 2019 (COVID-19) in severely affected patients includes atypical pneumonia characterized by a dry cough, persistent fever, and progressive dyspnea and hypoxia, sometimes accompanied by diarrhea and often followed by multiple organ failure, especially of the respiratory and cardiovascular systems. In this minireview, we focus on two endemic respiratory CoV infections of livestock: bovine coronavirus (BCoV) and porcine respiratory coronavirus (PRCV). Both animal respiratory CoVs share some common features with SARS-CoV and SARS-CoV-2. BCoV has a broad host range including wild ruminants and a zoonotic potential. BCoV also has a dual tropism for the respiratory and gastrointestinal tracts. These aspects, their interspecies transmission, and certain factors that impact disease severity in cattle parallel related facets of SARS-CoV or SARS-CoV-2 in humans. PRCV has a tissue tropism for the upper and lower respiratory tracts and a cellular tropism for type 1 and 2 pneumocytes in lung but is generally a mild infection unless complicated by other exacerbating factors, such as bacterial or viral coinfections and immunosuppression (corticosteroids).


Subject(s)
Betacoronavirus/growth & development , Cattle Diseases/physiopathology , Coronavirus Infections/veterinary , Coronavirus, Bovine/growth & development , Pneumonia, Viral/physiopathology , Respiratory Tract Infections/veterinary , Swine Diseases/physiopathology , Animals , Betacoronavirus/pathogenicity , COVID-19 , Cattle , Cattle Diseases/pathology , Cattle Diseases/virology , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Coronavirus, Bovine/pathogenicity , Host Specificity , Humans , Pandemics , Pneumonia, Viral/pathology , Porcine Respiratory Coronavirus/growth & development , Porcine Respiratory Coronavirus/pathogenicity , Respiratory Tract Infections/pathology , Respiratory Tract Infections/physiopathology , SARS-CoV-2 , Swine , Swine Diseases/pathology , Swine Diseases/virology , Viral Tropism
12.
J Clin Microbiol ; 58(8)2020 07 23.
Article in English | MEDLINE | ID: covidwho-999208

ABSTRACT

Real-time reverse transcription-PCR (RT-PCR) is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs and two sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log10 genome copies/ml sample for detecting the nsp12, E, and N genes, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and nonstructural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.


Subject(s)
Betacoronavirus/growth & development , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Virus Cultivation/methods , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Correlation of Data , Humans , Nasopharynx/virology , Pandemics , Pharynx/virology , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2
13.
Molecules ; 25(11)2020 Jun 11.
Article in English | MEDLINE | ID: covidwho-981163

ABSTRACT

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1ß, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiß as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus OC43, Human/drug effects , Flavonoids/pharmacology , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/chemistry , Betacoronavirus/chemistry , Betacoronavirus/growth & development , Binding Sites , COVID-19 , Chloroquine/chemistry , Chloroquine/pharmacology , Coronavirus Infections/genetics , Coronavirus OC43, Human/chemistry , Coronavirus OC43, Human/growth & development , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Flavonoids/chemistry , Humans , Interleukins/antagonists & inhibitors , Interleukins/chemistry , Interleukins/genetics , Interleukins/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/virology , Lung/drug effects , Lung/pathology , Lung/virology , Mice , Molecular Docking Simulation , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phytotherapy/methods , Pneumonia, Viral/genetics , Primary Cell Culture , Protein Binding , Protein Interaction Domains and Motifs , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/chemistry , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Virus Internalization/drug effects
14.
Clin Microbiol Rev ; 34(1)2020 12 16.
Article in English | MEDLINE | ID: covidwho-962931

ABSTRACT

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Adenosine Monophosphate/pharmacokinetics , Adenosine Monophosphate/pharmacology , Alanine/pharmacokinetics , Alanine/pharmacology , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Betacoronavirus/pathogenicity , COVID-19 , Clinical Trials as Topic , Compassionate Use Trials/methods , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Administration Schedule , Ebolavirus/drug effects , Ebolavirus/growth & development , Ebolavirus/pathogenicity , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/pathology , Hemorrhagic Fever, Ebola/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/growth & development , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Patient Safety , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
15.
Antimicrob Resist Infect Control ; 9(1): 167, 2020 10 29.
Article in English | MEDLINE | ID: covidwho-895032

ABSTRACT

OBJECTIVES: We performed an environmental sampling study to investigate the environmental contamination of SARS-CoV-2 by COVID-19 patients with prolonged PCR positive status of clinical samples. METHODS: We sampled the air from rooms for nine COVID-19 patients with illness or positive PCR > 30 days, before and after nasopharyngeal/oropharyngeal swabbing and before and after nebulization treatment. We also sampled patients' surroundings and healthcare workers' personal protection equipment (PPE) in a non-ICU ward. SARS-CoV-2 was detected by PCR. RESULTS: Eighty-eight samples were collected from high-touch surfaces and floors in patient rooms and toilets, with only the bedsheets of two patients and one toilet positive for SARS-CoV-2. All air samples (n = 34) were negative for SARS-CoV-2. Fifty-five samples collected from PPE were all negative. CONCLUSION: Contamination of near-patient surroundings was uncommon for COVID-19 patients with prolonged PCR positive status if environmental cleaning/disinfection were performed rigorously. Airborne transmission of SARS-CoV-2 was unlikely in these non-ICU settings.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Personal Protective Equipment , Pneumonia, Viral/virology , Betacoronavirus/growth & development , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Disinfection/methods , Environmental Microbiology , Environmental Monitoring/methods , Health Personnel , Hospitals , Humans , Pandemics/prevention & control , Patients' Rooms , Pneumonia, Viral/diagnosis , Polymerase Chain Reaction , RNA, Viral/isolation & purification , SARS-CoV-2
16.
Nat Commun ; 11(1): 5503, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894393

ABSTRACT

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Beijing/epidemiology , COVID-19 , Coronavirus Infections/epidemiology , Female , Genome, Viral , Genomics , Genotype , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Polymorphism, Single Nucleotide , SARS-CoV-2 , Travel , Young Adult
17.
Nat Commun ; 11(1): 5493, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894389

ABSTRACT

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/growth & development , Biomarkers/blood , C-Reactive Protein , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Female , Hospitalization , Humans , Inflammation/blood , Inflammation/virology , Interleukin-6/blood , Longitudinal Studies , Massachusetts/epidemiology , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , RNA, Viral/blood , SARS-CoV-2 , Severity of Illness Index , Viral Load , Viremia/blood , Viremia/virology
18.
Emerg Microbes Infect ; 9(1): 2433-2445, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-872909

ABSTRACT

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1-3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/pathology , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/pathology , SARS Virus/growth & development , Virus Replication/genetics , A549 Cells , Adenoviridae/genetics , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/metabolism , COVID-19 , Cell Line , Chlorocebus aethiops , Disease Models, Animal , Female , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Pandemics , SARS Virus/metabolism , SARS-CoV-2 , Vero Cells , Virus Attachment
19.
Rev Med Virol ; 30(5): e2140, 2020 09.
Article in English | MEDLINE | ID: covidwho-848179

ABSTRACT

A knowledge-based cybernetic framework model representing the dynamics of SARS-CoV-2 inside the human body has been studied analytically and in silico to explore the pathophysiologic regulations. The following modeling methodology was developed as a platform to introduce a predictive tool supporting a therapeutic approach to Covid-19 disease. A time-dependent nonlinear system of ordinary differential equations model was constructed involving type-I cells, type-II cells, SARS-CoV-2 virus, inflammatory mediators, interleukins along with host pulmonary gas exchange rate, thermostat control, and mean pressure difference. This formalism introduced about 17 unknown parameters. Estimating these unknown parameters requires a mathematical association with the in vivo sparse data and the dynamic sensitivities of the model. The cybernetic model can simulate a dynamic response to the reduced pulmonary alveolar gas exchange rate, thermostat control, and mean pressure difference under a very critical condition based on equilibrium (steady state) values of the inflammatory mediators and system parameters. In silico analysis of the current cybernetical approach with system dynamical modeling can provide an intellectual framework to help experimentalists identify more active therapeutic approaches.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Host-Pathogen Interactions/immunology , Lung/immunology , Nonlinear Dynamics , Pneumonia, Viral/immunology , Acute-Phase Proteins/antagonists & inhibitors , Acute-Phase Proteins/genetics , Acute-Phase Proteins/immunology , Angiotensin-Converting Enzyme 2 , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Body Temperature , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/virology , Gene Expression Regulation , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Lung/drug effects , Lung/virology , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/immunology , Macrophages, Alveolar/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pulmonary Gas Exchange/drug effects , Pulmonary Gas Exchange/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
20.
Curr Protoc Microbiol ; 59(1): e126, 2020 12.
Article in English | MEDLINE | ID: covidwho-847847

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, has been responsible for a million deaths worldwide as of September 2020. At the time of this writing, there are no available US FDA-approved therapeutics for the treatment of SARS-CoV-2 infection. Here, we describe a detailed protocol to generate recombinant (r)SARS-CoV-2 using reverse-genetics approaches based on the use of a bacterial artificial chromosome (BAC). This method will allow the production of mutant rSARS-CoV-2-which is necessary for understanding the function of viral proteins, viral pathogenesis and/or transmission, and interactions at the virus-host interface-and attenuated SARS-CoV-2 to facilitate the discovery of effective countermeasures to control the ongoing SARS-CoV-2 pandemic. © 2020 Wiley Periodicals LLC. Basic Protocol: Generation of recombinant SARS-CoV-2 using a bacterial artificial chromosome Support Protocol: Validation and characterization of rSARS-CoV-2.


Subject(s)
Betacoronavirus/genetics , Chromosomes, Artificial, Bacterial/genetics , Animals , Betacoronavirus/growth & development , Chlorocebus aethiops , Containment of Biohazards , SARS-CoV-2 , Transfection , Vero Cells
SELECTION OF CITATIONS
SEARCH DETAIL