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1.
Euro Surveill ; 25(28)2020 07.
Article in English | MEDLINE | ID: covidwho-647504

ABSTRACT

BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Animals , Betacoronavirus/genetics , Blotting, Western , COS Cells , Chlorocebus aethiops , Conserved Sequence , Coronavirus Infections/genetics , Coronavirus Infections/virology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay/methods , Fluorescent Antibody Technique/methods , Genome, Viral , Mice , Pandemics , Peptidyl-Dipeptidase A/immunology , Plasmids , Pneumonia, Viral/genetics , Recombinant Proteins/immunology , SARS Virus/genetics , Sequence Alignment , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/genetics , Transfection , Vero Cells , Virus Integration
2.
Virol Sin ; 35(3): 290-304, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-618224

ABSTRACT

The recent outbreak of coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Disease Models, Animal , Middle East Respiratory Syndrome Coronavirus , Pneumonia, Viral/virology , SARS Virus , Severe Acute Respiratory Syndrome/virology , Animals , Betacoronavirus/pathogenicity , Camelids, New World , Camelus , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Mice , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/physiopathology , Severe Acute Respiratory Syndrome/therapy , Swine
3.
In Vivo ; 34(5): 3029-3032, 2020.
Article in English | MEDLINE | ID: covidwho-740633

ABSTRACT

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.


Subject(s)
Coronavirus Infections/therapy , Diabetes Mellitus/therapy , Hyperglycemia/therapy , Insulin/metabolism , Pneumonia, Viral/therapy , Betacoronavirus/pathogenicity , Blood Glucose/metabolism , Coronavirus Infections/complications , Coronavirus Infections/virology , Diabetes Mellitus/genetics , Diabetes Mellitus/virology , Female , Hospitalization , Humans , Hyperglycemia/complications , Hyperglycemia/virology , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Respiration, Artificial , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/virology
4.
Cien Saude Colet ; 25(9): 3517-3554, 2020 Sep.
Article in English, Portuguese | MEDLINE | ID: covidwho-740424

ABSTRACT

This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.


Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antimalarials/administration & dosage , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , SARS Virus/drug effects , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/virology
5.
Cien Saude Colet ; 25(9): 3365-3376, 2020 Sep.
Article in English, Portuguese | MEDLINE | ID: covidwho-740421

ABSTRACT

OBJECTIVES: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. METHODS: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. RESULTS: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. CONCLUSION: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.


Subject(s)
Coronavirus Infections/prevention & control , Masks , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pneumonia, Viral/epidemiology , Randomized Controlled Trials as Topic , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/prevention & control , Severe Acute Respiratory Syndrome/virology
6.
BMC Infect Dis ; 20(1): 644, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-740367

ABSTRACT

BACKGROUND: To explore the clinical features and CT findings of clinically cured coronavirus disease 2019 (COVID-19) patients with viral RNA positive anal swab results after discharge. METHODS: Forty-two patients with COVID-19 who were admitted to Yongzhou Central Hospital, Hunan, China, between January 20, 2020, and March 2, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using anal swab viral RT-PCR. In this report, we present the clinical characteristics and chest CT features of six patients with positive anal swab results and compare the clinical, laboratory, and CT findings between the positive and negative groups. RESULTS: The anal swab positivity rate for SARS-CoV-2 RNA in discharged patients was 14.3% (6/42). All six patients were male. In the positive group, 40% of the patients (2/5) had a positive stool occult blood test (OBT), but none had diarrhea. The median duration of fever and major symptoms (except fever) in the positive patients was shorter than that of the negative patients (1 day vs. 6 days, 4.5 days vs. 10.5 days, respectively). The incidence of asymptomatic cases in the positive group (33.3%) was also higher than that of the negative group (5.6%). There were no significant differences in the CT manifestation or evolution of the pulmonary lesions between the two groups. CONCLUSION: In our case series, patients with viral RNA positive anal swabs did not exhibit gastrointestinal symptoms, and their main symptoms disappeared early. They had similar CT features to the negative patients, which may be easier to be ignored. A positive OBT may indicate gastrointestinal damage caused by SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnostic imaging , Patient Discharge/statistics & numerical data , Pneumonia, Viral/diagnostic imaging , RNA, Viral/analysis , Severe Acute Respiratory Syndrome/diagnostic imaging , Adolescent , Adult , Aged , Anal Canal/virology , Betacoronavirus/genetics , Child , Child, Preschool , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Fever , Hospitalization , Hospitals , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Reverse Transcriptase Polymerase Chain Reaction , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology , Tomography, X-Ray Computed , Young Adult
7.
Sci Rep ; 10(1): 14214, 2020 08 26.
Article in English | MEDLINE | ID: covidwho-733506

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major public health concern. A handful of static structures now provide molecular insights into how SARS-CoV-2 and SARS-CoV interact with its host target, which is the angiotensin converting enzyme 2 (ACE2). Molecular recognition, binding and function are dynamic processes. To evaluate this, multiple 500 ns or 1 µs all-atom molecular dynamics simulations were performed to better understand the structural stability and interfacial interactions between the receptor binding domain of the spike (S) protein of SARS-CoV-2 and SARS-CoV bound to ACE2. Several contacts were observed to form, break and reform in the interface during the simulations. Our results indicate that SARS-CoV-2 and SARS-CoV utilizes unique strategies to achieve stable binding to ACE2. Several differences were observed between the residues of SARS-CoV-2 and SARS-CoV that consistently interacted with ACE2. Notably, a stable salt bridge between Lys417 of SARS-CoV-2 S protein and Asp30 of ACE2 as well as three stable hydrogen bonds between Tyr449, Gln493 and Gln498 of SARS-CoV-2 and Asp38, Glu35 and Lys353 of ACE2 were observed, which were absent in the ACE2-SARS-CoV interface. Some previously reported residues, which were suggested to enhance the binding affinity of SARS-CoV-2, were not observed to form stable interactions in these simulations. Molecular mechanics-generalized Born surface area based free energy of binding was observed to be higher for SARS-CoV-2 in all simulations. Stable binding to the host receptor is crucial for virus entry. Therefore, special consideration should be given to these stable interactions while designing potential drugs and treatment modalities to target or disrupt this interface.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , SARS Virus/physiology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Sequence , Binding Sites , Conserved Sequence , Host-Pathogen Interactions , Humans , Models, Molecular , Pandemics , Peptidyl-Dipeptidase A/chemistry , Protein Binding , Protein Conformation , Spike Glycoprotein, Coronavirus/chemistry
8.
Nutrients ; 12(9)2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-731022

ABSTRACT

The 2019 novel coronavirus, SARS-CoV-2, producing the disease COVID-19 is a pathogenic virus that targets mostly the human respiratory system and also other organs. SARS-CoV-2 is a new strain that has not been previously identified in humans, however there have been previous outbreaks of different versions of the beta coronavirus including severe acute respiratory syndrome (SARS-CoV1) from 2002 to 2003 and the most recent Middle East respiratory syndrome (MERS-CoV) which was first identified in 2012. All of the above have been recognised as major pathogens that are a great threat to public health and global economies. Currently, no specific treatment for SARS-CoV-2 infection has been identified; however, certain drugs have shown apparent efficacy in viral inhibition of the disease. Natural substances such as herbs and mushrooms have previously demonstrated both great antiviral and anti-inflammatory activity. Thus, the possibilities of natural substances as effective treatments against COVID-19 may seem promising. One of the potential candidates against the SARS-CoV-2 virus may be Inonotus obliquus (IO), also known as chaga mushroom. IO commonly grows in Asia, Europe and North America and is widely used as a raw material in various medical conditions. In this review, we have evaluated the most effective herbs and mushrooms, in terms of the antiviral and anti-inflammatory effects which have been assessed in laboratory conditions.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Biological Products/therapeutic use , Coronavirus Infections/drug therapy , Fungi/chemistry , Magnoliopsida/chemistry , Plants, Medicinal/chemistry , Pneumonia, Viral/drug therapy , Agaricales/chemistry , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Basidiomycota/chemistry , Betacoronavirus , Biological Products/pharmacology , Chlorella/chemistry , Coronavirus Infections/virology , Humans , Pandemics , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/virology
9.
Methods Mol Biol ; 2203: 1-29, 2020.
Article in English | MEDLINE | ID: covidwho-728129

ABSTRACT

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. CoVs cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs, and upper respiratory tract and kidney disease in chickens to lethal human respiratory infections. Most recently, the novel coronavirus, SARS-CoV-2, which was first identified in Wuhan, China in December 2019, is the cause of a catastrophic pandemic, COVID-19, with more than 8 million infections diagnosed worldwide by mid-June 2020. Here we provide a brief introduction to CoVs discussing their replication, pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which are relevant for understanding COVID-19.


Subject(s)
Animal Diseases/virology , Betacoronavirus/physiology , Chickens/virology , Coronavirus Infections/virology , Coronavirus/physiology , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/virology , Animal Diseases/diagnosis , Animal Diseases/epidemiology , Animal Diseases/prevention & control , Animals , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Cattle , Coronavirus/genetics , Coronavirus/pathogenicity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Middle East Respiratory Syndrome Coronavirus/physiology , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , SARS Virus/genetics , SARS Virus/pathogenicity , SARS Virus/physiology , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/prevention & control , Spike Glycoprotein, Coronavirus/genetics , Swine , Virion , Virus Replication
10.
Clin Infect Dis ; 71(15): 858-860, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-719208

ABSTRACT

During major epidemic outbreaks, demand for healthcare workers (HCWs) grows even as the extreme pressures they face cause declining availability. We draw on Taiwan's severe acute respiratory syndrome (SARS) experience to argue that a modified form of traffic control bundling (TCB) protects HCW safety and by extension strengthens overall coronavirus disease 2019 (COVID-19) epidemic control.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology , Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Disease Outbreaks , Health Personnel , Humans , Pandemics , Personal Protective Equipment/virology , Pneumonia, Viral/virology , Taiwan/epidemiology
11.
PLoS Pathog ; 16(8): e1008643, 2020 08.
Article in English | MEDLINE | ID: covidwho-712942

ABSTRACT

The current state of much of the Wuhan pneumonia virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies and requires unimpeded access to data, analysis tools, and computational infrastructure. Here, we show that community efforts in developing open analytical software tools over the past 10 years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all SARS-CoV-2 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Pneumonia, Viral/virology , Public Health , Severe Acute Respiratory Syndrome/virology , Data Analysis , Humans , Pandemics
12.
Viruses ; 12(8)2020 08 07.
Article in English | MEDLINE | ID: covidwho-712882

ABSTRACT

Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Animals , Clinical Trials as Topic , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Models, Animal , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/prevention & control , Severe Acute Respiratory Syndrome/virology , Vaccines, DNA/immunology , Viral Vaccines/administration & dosage
13.
J Infect Dis ; 222(7): 1086-1089, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-709281

ABSTRACT

The recent development and regulatory approval of a variety of serological assays indicating the presence of antibodies against severe acute respiratory syndrome coronavirus 2 has led to rapid and widespread implementation of seroprevalence studies. Accurate estimates of seroprevalence are needed to model transmission dynamics and estimate mortality rates. Furthermore, seroprevalence levels in a population help guide policy surrounding reopening efforts. The literature to date has focused heavily on issues surrounding the quality of seroprevalence tests and less on the sampling methods that ultimately drive the representativeness of resulting estimates. Seroprevalence studies based on convenience samples are being reported widely and extrapolated to larger populations for the estimation of total coronavirus disease 2019 (COVID-19) infections, comparisons of prevalence across geographic regions, and estimation of mortality rates. In this viewpoint, we discuss the pitfalls that can arise with the use of convenience samples and offer guidance for moving towards more representative and timely population estimates of COVID-19 seroprevalence.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Population Surveillance , Reproducibility of Results , Sampling Studies , Seroepidemiologic Studies , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology
14.
Zool Res ; 41(5): 503-516, 2020 Sep 18.
Article in English | MEDLINE | ID: covidwho-709116

ABSTRACT

As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.


Subject(s)
Aging/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Cytokines/immunology , Macaca mulatta/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Age Factors , Aging/metabolism , Animals , Betacoronavirus/physiology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Cytokines/metabolism , Inflammation/immunology , Inflammation/veterinary , Inflammation/virology , Lung/immunology , Lung/pathology , Lung/virology , Macaca mulatta/virology , Monkey Diseases/immunology , Monkey Diseases/virology , Pandemics/veterinary , Pneumonia, Viral/veterinary , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/veterinary , Severe Acute Respiratory Syndrome/virology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Viral Load/immunology , Viral Load/veterinary , Virus Replication/immunology
15.
Clin Immunol ; 219: 108555, 2020 10.
Article in English | MEDLINE | ID: covidwho-696063

ABSTRACT

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19.


Subject(s)
Acute Kidney Injury/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/pathogenicity , Complement Inactivating Agents/therapeutic use , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Pneumonia, Viral/immunology , Severe Acute Respiratory Syndrome/immunology , Acute Kidney Injury/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/virology , Adult , Betacoronavirus/immunology , Biomarkers/metabolism , Complement Activation/drug effects , Complement C4b/antagonists & inhibitors , Complement C5/antagonists & inhibitors , Complement Membrane Attack Complex/antagonists & inhibitors , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Immunity, Humoral/drug effects , Male , Mannose-Binding Protein-Associated Serine Proteases/genetics , Mannose-Binding Protein-Associated Serine Proteases/immunology , Middle Aged , Neutrophils/immunology , Neutrophils/pathology , Pandemics , Peptide Fragments/antagonists & inhibitors , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/virology
16.
Eur Rev Med Pharmacol Sci ; 24(14): 7834-7844, 2020 07.
Article in English | MEDLINE | ID: covidwho-693570

ABSTRACT

The pandemic threat of COVID-19 causes serious concern for people and world organizations. The effect of Coronavirus disease on the lifestyle and economic status of humans is undeniable, and all of the researchers (biologists, pharmacists, physicians, and chemists) can help decrease its destructive effects. The molecular docking approach can provide a fast prediction of the positive influence the targets on the COVID-19 outbreak. In this work, we choose resveratrol (RV) derivatives (22 cases) and two newly released coordinate structures for COVID-19 as receptors [Papain-like Protease of SARS CoV-2 (PBD ID: 6W9C) and 2019-nCoV RNA-dependent RNA Polymerase (PBD ID: 6M71)]. The results show that conformational isomerism is significant and useful parameter for docking results. A wide spectrum of interactions such as Van der Waals, conventional hydrogen bond, Pi-donor hydrogen bond, Pi-Cation, Pi-sigma, Pi-Pi stacked, Amide-Pi stacked and Pi-Alkyl is detected via docking of RV derivatives and COVID-19 receptors. The potential inhibition effect of RV-13 (-184.99 kj/mol), and RV-12 (-173.76 kj/mol) is achieved at maximum value for 6W9C and 6M71, respectively.


Subject(s)
Antiviral Agents/metabolism , Betacoronavirus/metabolism , Papain/metabolism , RNA Replicase/metabolism , Resveratrol/metabolism , SARS Virus/metabolism , Viral Nonstructural Proteins/metabolism , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Binding Sites , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Crystallography, X-Ray , Hydrogen Bonding , Molecular Docking Simulation , Pandemics , Papain/chemistry , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Protein Structure, Tertiary , RNA Replicase/chemistry , Resveratrol/chemistry , Resveratrol/therapeutic use , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/virology , Viral Nonstructural Proteins/chemistry
17.
Eur Rev Med Pharmacol Sci ; 24(14): 7880-7885, 2020 07.
Article in English | MEDLINE | ID: covidwho-693519

ABSTRACT

The coronavirus SARS-CoV-2 at the origin of COVID-19 shares more than 70% genetic similarity with SARS-CoV-1 that was at the origin of 2003 SARS. Infection-associated symptoms are very similar between SARS and COVID-19 diseases and are the same as community-acquired pneumonia symptoms. Antibiotics were empirically given to SARS patients in the early stages of the pathology whereas a different strategy has been decided in the management of COVID-19 pandemic with a worldwide shutdown. The cytokine storm, both identified in SARS and COVID-19 severe cases, is generated through inflammasome activation, which opens therapeutic perspectives to counteract the pathogenic inflammation. As corticoids have numerous side effects that limit their use, focusing on anti-inflammasome agents could represent a safer alternative for patients with severe COVID-19.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Adrenal Cortex Hormones/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Humans , Inflammasomes/chemistry , Inflammasomes/metabolism , Pandemics , Pneumonia, Viral/epidemiology , Purinergic P2X Receptor Antagonists/therapeutic use , Receptors, Purinergic P2X7/chemistry , Receptors, Purinergic P2X7/metabolism , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology
18.
Eur Rev Med Pharmacol Sci ; 24(14): 7816-7825, 2020 07.
Article in English | MEDLINE | ID: covidwho-693354

ABSTRACT

Currently, the outbreak and spread of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are increasing worldwide. Furthermore, it has been considered as a major challenge, which threatens human beings and affects all aspects of their life. Understanding the cellular and molecular pathophysiology of the disease is currently under the focus of investigations. Accordingly, this turns the human scientific community attention to find a solution for addressing the challenge. The development of vaccines and efficient therapeutic modality is critical. So, both primary and clinical scientists are not only trying to decipher the structure of SARS-CoV-2, but also attempting to understand the underlying molecular mechanisms that cause tissues and cell injuries. SARS-CoV and SARS-CoV2 are highly homologous and share a highly similar function and behavior patterns. Therefore, this might guide us toward decoding the molecular mechanisms that are behind the SARS-CoV2 pathologic effects. It is noteworthy to mention that, the undesired host immune reactions play important roles in the pathophysiology of the disease, and it also seems that, renin-angiotensin signaling (RAS) is a key contributor in this regard. In this review, we provided a vision, highlight as well as discussing on potential therapeutic targets that might be considered to address the COVID-19 challenge.


Subject(s)
Betacoronavirus/physiology , SARS Virus/physiology , Severe Acute Respiratory Syndrome/pathology , Basigin/metabolism , Betacoronavirus/isolation & purification , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Integrins/metabolism , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Renin-Angiotensin System , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/virology , Troponin I/metabolism
19.
Int J Mol Sci ; 21(12)2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-692289

ABSTRACT

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Pandemics/prevention & control , Pneumonia, Viral/virology , Animals , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Drug Design , Genes, Viral , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Molecular Epidemiology , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , SARS Virus/genetics , Severe Acute Respiratory Syndrome/virology , Viral Vaccines/genetics , Viral Vaccines/immunology
20.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-690841

ABSTRACT

Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there is also a plethora of animal coronaviruses which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and rapidly disappeared in May 2003. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a possible threat to humans, but its pandemic potential so far is minimal, as human-to-human transmission is ineffective. The end of 2019 brought us information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence, and the virus rapidly spread in 2020, causing an unprecedented pandemic. At present, studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for understanding of the biology and evolution of the virus. Here, we show that fully differentiated human airway epithelium cultures constitute an excellent model to study infection with the novel human coronavirus SARS-CoV-2. We observed efficient replication of the virus in the tissue, with maximal replication at 2 days postinfection. The virus replicated in ciliated cells and was released apically.IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged by the end of 2019 and rapidly spread in 2020. At present, it is of utmost importance to understand the biology of the virus, rapidly assess the treatment potential of existing drugs, and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on SARS-CoV-2.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Respiratory Mucosa/virology , Severe Acute Respiratory Syndrome/virology , Virus Replication , Animals , Cell Line , Cells, Cultured , Chlorocebus aethiops , Humans , Pandemics , Vero Cells
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