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1.
J Investig Med High Impact Case Rep ; 9: 23247096211013215, 2021.
Article in English | MEDLINE | ID: covidwho-1598539

ABSTRACT

Bronchopleural fistula (BPF) is associated with high morbidity if left untreated. Although rare, the frequency of BPF in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming recognized in medical literature. We present a case of a 64-year-old male with BPF with persistent air leak due to SARS-CoV-2 pneumonia treated with Spiration Valve System endobronchial valve (EBV). An EBV was placed in the right middle lobe with successful cessation of air leak. In conclusion, the use of EBVs for BPF with persistent air leaks in SARS-CoV-2 patients who are poor surgical candidates is effective and safe.


Subject(s)
Bronchial Fistula/surgery , Bronchoscopy , COVID-19/complications , Empyema, Pleural/surgery , Pleural Diseases/surgery , Surgical Instruments , Bronchial Fistula/etiology , Chest Tubes , Empyema, Pleural/etiology , Humans , Male , Middle Aged , Pleural Diseases/etiology , SARS-CoV-2 , Thoracostomy
2.
Signal Transduct Target Ther ; 6(1): 167, 2021 04 24.
Article in English | MEDLINE | ID: covidwho-1585891

ABSTRACT

The ongoing 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat. The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms. However, the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown. Here, we demonstrate that SARS-CoV-2 nucleocapsid (N) protein, the major structural protein of the virion, promotes the virus-triggered activation of NF-κB signaling. After binding to viral RNA, N protein robustly undergoes liquid-liquid phase separation (LLPS), which recruits TAK1 and IKK complex, the key kinases of NF-κB signaling, to enhance NF-κB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-κB activation. These results suggest that LLPS of N protein provides a platform to induce NF-κB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.


Subject(s)
COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , NF-kappa B/metabolism , RNA, Viral/metabolism , SARS-CoV-2/metabolism , Signal Transduction , A549 Cells , Acrylates/pharmacology , Animals , COVID-19/drug therapy , COVID-19/pathology , Chlorocebus aethiops , HEK293 Cells , HeLa Cells , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Phosphoproteins/metabolism , Vero Cells
3.
Front Vet Sci ; 7: 586637, 2020.
Article in English | MEDLINE | ID: covidwho-1574270

ABSTRACT

Coronavirus Disease 2019 (COVID-19) ranks third in terms of fatal coronavirus diseases threatening public health, coming after SARS-CoV (severe acute respiratory syndrome coronavirus), and MERS-CoV (Middle East respiratory syndrome coronavirus). SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) causes COVID-19. On January 30, 2020, the World Health Organization (WHO) announced that the current outbreak of COVID-19 is the sixth global health emergency. As of December 3, 2020, 64 million people worldwide have been affected by this malaise, and the global economy has experienced a loss of more than $1 trillion. SARS-CoV-2 is a positive-sense single-stranded RNA virus belonging to the Betacoronavirus genus. The high nucleotide sequence identity of SARS-CoV-2 with the BatCoV RaTG13 genome has indicated that bats could be the possible host of SARS-CoV-2. SARS-CoV-2 penetrates the host cell via binding its spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is similar to the mechanisms of SARS-CoV and MERS-CoV. COVID-19 can spread from person to person via respiratory droplets and airborne and contaminated fomites. Moreover, it poses a significant risk to smokers, the elderly, immunocompromised people, and those with preexisting comorbidities. Two main approaches are used to control viral infections, namely, vaccination, and biosecurity. Studies to analyze the antigenicity and immunogenicity of SARS-CoV-2 vaccine candidates are underway, and few vaccines may be available in the near future. In the current situation, the Human Biosecurity Emergency (HBE) may be the only way to cope effectively with the novel SARS-CoV-2 strain. Here, we summarize current knowledge on the origin of COVID-19 as well as its epidemiological relationship with humans and animals, genomic resemblance, immunopathogenesis, clinical-laboratory signs, diagnosis, control and prevention, and treatment. Moreover, we discuss the interventional effects of various nutrients on COVID-19 in detail. However, multiple possibilities are explored to fight COVID-19, and the greatest efforts targeted toward finding an effective vaccine in the near future. Furthermore, antioxidants, polyphenols, and flavonoids, both synthetic and natural, could play a crucial role in the fight against COVID-19.

4.
Burns ; 47(7): 1547-1555, 2021 11.
Article in English | MEDLINE | ID: covidwho-1575639

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has the potential to significantly impact burns patients both directly through infective complications of an immunocompromised cohort, and indirectly through disruption of care pathways and resource limitations. The pandemic presents new challenges that must be overcome to maintain patient safety; in particular, the potential increased risks of surgical intervention, anaesthesia and ventilation. This study comprehensively reviews the measures implemented to adapt referral pathways and mitigate the risk posed by COVID-19 during the height of the pandemic, within a large Burns Centre. METHODS: A prospective cohort study was designed to assess patients treated at the Burns Centre during the UK COVID-19 pandemic peak (April-May 2020), following implementation of new safety measures. All patients were analysed for 30-day mortality. In addition, a prospective controlled cohort study was undertaken on all inpatients and a random sample of outpatients with telephone follow-up at 30 days. These patients were divided into three groups (operative inpatients, non-operative inpatients, outpatients). COVID-19 related data collected included test results, contact with proven cases, isolation status and symptoms. The implemented departmental service COVID-19 safety adaptations are described. RESULTS: Of 323 patients treated at the Burns Centre during the study period, no 30-day COVID-19 related deaths occurred (0/323). Of the 80 patients analysed in the prospective controlled cohort section of the study, 51 underwent COVID-19 testing, 3.9% (2/51) were positive. Both cases were in the operative group, however in comparison to the non-operative and outpatient groups, there was no significant increase in COVID-19 incidence in operative patients. CONCLUSIONS: We found no COVID-19 related mortality during the study period. With appropriate precautions, burns patients were not exposed to an increased COVID-19 risk. Similarly, burns patients undergoing operative management were not at a significantly increased risk of contracting COVID-19 in comparison to non-operative groups.


Subject(s)
Burns , COVID-19 , Patient Safety , Reconstructive Surgical Procedures , Burns/epidemiology , Burns/surgery , COVID-19/epidemiology , COVID-19 Testing , Cohort Studies , England , Humans , Pandemics/prevention & control , Patient Satisfaction , Prospective Studies , SARS-CoV-2 , Treatment Outcome
5.
Int J Infect Dis ; 2021 Mar 29.
Article in English | MEDLINE | ID: covidwho-1575136

ABSTRACT

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4+ T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies.

6.
Front Vet Sci ; 8: 572012, 2021.
Article in English | MEDLINE | ID: covidwho-1574919

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused great harm to global public health, resulting in a large number of infections among the population. However, the epidemiology of coronavirus has not been fully understood, especially the mechanism of aerosol transmission. Many respiratory viruses can spread via contact and droplet transmission, but increasing epidemiological data have shown that viral aerosol is an essential transmission route of coronavirus and influenza virus due to its ability to spread rapidly and high infectiousness. Aerosols have the characteristics of small particle size, long-time suspension and long-distance transmission, and easy access to the deep respiratory tract, leading to a high infection risk and posing a great threat to public health. In this review, the characteristics of viral aerosol generation, transmission, and infection as well as the current advances in the aerosol transmission of zoonotic coronavirus and influenza virus are summarized. The aim of the review is to strengthen the understanding of viral aerosol transmission and provide a scientific basis for the prevention and control of these diseases.

7.
Cochrane Database Syst Rev ; 10: CD013717, 2020 10 05.
Article in English | MEDLINE | ID: covidwho-1557155

ABSTRACT

BACKGROUND: In late 2019, first cases of coronavirus disease 2019, or COVID-19, caused by the novel coronavirus SARS-CoV-2, were reported in Wuhan, China. Subsequently COVID-19 spread rapidly around the world. To contain the ensuing pandemic, numerous countries have implemented control measures related to international travel, including border closures, partial travel restrictions, entry or exit screening, and quarantine of travellers. OBJECTIVES: To assess the effectiveness of travel-related control measures during the COVID-19 pandemic on infectious disease and screening-related outcomes. SEARCH METHODS: We searched MEDLINE, Embase and COVID-19-specific databases, including the WHO Global Database on COVID-19 Research, the Cochrane COVID-19 Study Register, and the CDC COVID-19 Research Database on 26 June 2020. We also conducted backward-citation searches with existing reviews. SELECTION CRITERIA: We considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across national borders during the COVID-19 pandemic. We also included studies concerned with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as indirect evidence. Primary outcomes were cases avoided, cases detected and a shift in epidemic development due to the measures. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. DATA COLLECTION AND ANALYSIS: One review author screened titles and abstracts; all excluded abstracts were screened in duplicate. Two review authors independently screened full texts. One review author extracted data, assessed risk of bias and appraised study quality. At least one additional review author checked for correctness of all data reported in the 'Risk of bias' assessment, quality appraisal and data synthesis. For assessing the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for observational studies concerned with screening, ROBINS-I for observational ecological studies and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed certainty of evidence with GRADE, and the review author team discussed ratings. MAIN RESULTS: We included 40 records reporting on 36 unique studies. We found 17 modelling studies, 7 observational screening studies and one observational ecological study on COVID-19, four modelling and six observational studies on SARS, and one modelling study on SARS and MERS, covering a variety of settings and epidemic stages. Most studies compared travel-related control measures against a counterfactual scenario in which the intervention measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of travel restrictions, or a combination of measures. There were concerns with the quality of many modelling studies and the risk of bias of observational studies. Many modelling studies used potentially inappropriate assumptions about the structure and input parameters of models, and failed to adequately assess uncertainty. Concerns with observational screening studies commonly related to the reference test and the flow of the screening process. Studies on COVID-19 Travel restrictions reducing cross-border travel Eleven studies employed models to simulate a reduction in travel volume; one observational ecological study assessed travel restrictions in response to the COVID-19 pandemic. Very low-certainty evidence from modelling studies suggests that when implemented at the beginning of the outbreak, cross-border travel restrictions may lead to a reduction in the number of new cases of between 26% to 90% (4 studies), the number of deaths (1 study), the time to outbreak of between 2 and 26 days (2 studies), the risk of outbreak of between 1% to 37% (2 studies), and the effective reproduction number (1 modelling and 1 observational ecological study). Low-certainty evidence from modelling studies suggests a reduction in the number of imported or exported cases of between 70% to 81% (5 studies), and in the growth acceleration of epidemic progression (1 study). Screening at borders with or without quarantine Evidence from three modelling studies of entry and exit symptom screening without quarantine suggests delays in the time to outbreak of between 1 to 183 days (very low-certainty evidence) and a detection rate of infected travellers of between 10% to 53% (low-certainty evidence). Six observational studies of entry and exit screening were conducted in specific settings such as evacuation flights and cruise ship outbreaks. Screening approaches varied but followed a similar structure, involving symptom screening of all individuals at departure or upon arrival, followed by quarantine, and different procedures for observation and PCR testing over a period of at least 14 days. The proportion of cases detected ranged from 0% to 91% (depending on the screening approach), and the positive predictive value ranged from 0% to 100% (very low-certainty evidence). The outcomes, however, should be interpreted in relation to both the screening approach used and the prevalence of infection among the travellers screened; for example, symptom-based screening alone generally performed worse than a combination of symptom-based and PCR screening with subsequent observation during quarantine. Quarantine of travellers Evidence from one modelling study simulating a 14-day quarantine suggests a reduction in the number of cases seeded by imported cases; larger reductions were seen with increasing levels of quarantine compliance ranging from 277 to 19 cases with rates of compliance modelled between 70% to 100% (very low-certainty evidence). AUTHORS' CONCLUSIONS: With much of the evidence deriving from modelling studies, notably for travel restrictions reducing cross-border travel and quarantine of travellers, there is a lack of 'real-life' evidence for many of these measures. The certainty of the evidence for most travel-related control measures is very low and the true effects may be substantially different from those reported here. Nevertheless, some travel-related control measures during the COVID-19 pandemic may have a positive impact on infectious disease outcomes. Broadly, travel restrictions may limit the spread of disease across national borders. Entry and exit symptom screening measures on their own are not likely to be effective in detecting a meaningful proportion of cases to prevent seeding new cases within the protected region; combined with subsequent quarantine, observation and PCR testing, the effectiveness is likely to improve. There was insufficient evidence to draw firm conclusions about the effectiveness of travel-related quarantine on its own. Some of the included studies suggest that effects are likely to depend on factors such as the stage of the epidemic, the interconnectedness of countries, local measures undertaken to contain community transmission, and the extent of implementation and adherence.


Subject(s)
COVID-19/prevention & control , Pandemics/prevention & control , SARS-CoV-2 , Travel-Related Illness , COVID-19/epidemiology , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/prevention & control , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Models, Theoretical , Observational Studies as Topic , Quarantine , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/prevention & control
8.
Glob Heart ; 16(1): 22, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1557646

ABSTRACT

Background: The emergence of novel coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase, and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions facilitated by international travel, leading to a pandemic. To guide effective control and interventions, primary data is required urgently, globally, including from low- and middle-income countries where documentation of cardiovascular manifestations and risk factors in people hospitalized with COVID-19 is limited. Objectives: This study aims to describe the cardiovascular manifestations and cardiovascular risk factors in patients hospitalized with COVID-19. Methods: We propose to conduct an observational cohort study involving 5000 patients recruited from hospitals in low-, middle- and high-income countries. Eligible adult COVID-19 patients will be recruited from the participating hospitals and followed-up until 30 days post admission. The outcomes will be reported at discharge and includes the need of ICU admission, need of ventilator, death (with cause), major adverse cardiovascular events, neurological outcomes, acute renal failure, and pulmonary outcomes. Conclusion: Given the enormous burden posed by COVID-19 and the associated severe prognostic implication of CVD involvement, this study will provide useful insights on the risk factors for severe disease, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients particularly from low and middle income countries from where the data remain scant.


Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/virology , Global Health , Observational Studies as Topic/methods , Cohort Studies , Hospitalization , Humans , Multicenter Studies as Topic , Pandemics , Prognosis , Risk Factors
9.
Pain Rep ; 6(1): e893, 2021.
Article in English | MEDLINE | ID: covidwho-1550636

ABSTRACT

Pain is a common symptom accompanying the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nonspecific discomfort such as sore throat and body ache are frequent. Parainfectious pain such as headache, myalgia, or neuropathic pain has also been reported. The latter seems to be associated with an autoimmune response or an affection of the peripheral neuromuscular system or the central nervous system because of the viral infection. Furthermore, chronic pain can be a complication of intensive care unit treatment due to COVID-19 itself (such as intensive care-acquired weakness) or of secondary diseases associated with the SARS-CoV-2 infection, including Guillain-Barré syndrome, polyneuritis, critical illness polyneuropathy, or central pain following cerebrovascular events. Data on long-lasting painful symptoms after clinically manifest COVID-19 and their consequences are lacking. In addition, preexisting chronic pain may be exacerbated by limited and disrupted health care and the psychological burden of the COVID-19 pandemic. Medical providers should be vigilant on pain during and after COVID-19.

10.
Clin J Am Soc Nephrol ; 16(11): 1755-1765, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526737

ABSTRACT

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.


Subject(s)
COVID-19/virology , Kidney Diseases/virology , Kidney/virology , SARS-CoV-2/pathogenicity , Animals , Biopsy , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Testing , Host-Pathogen Interactions , Humans , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
11.
Front Pharmacol ; 12: 652335, 2021.
Article in English | MEDLINE | ID: covidwho-1526785

ABSTRACT

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has a disastrous effect on mankind due to the contagious and rapid nature of its spread. Although vaccines for SARS-CoV-2 have been successfully developed, the proven, effective, and specific therapeutic molecules are yet to be identified for the treatment. The repurposing of existing drugs and recognition of new medicines are continuously in progress. Efforts are being made to single out plant-based novel therapeutic compounds. As a result, some of these biomolecules are in their testing phase. During these efforts, the whole-genome sequencing of SARS-CoV-2 has given the direction to explore the omics systems and approaches to overcome this unprecedented health challenge globally. Genome, proteome, and metagenome sequence analyses have helped identify virus nature, thereby assisting in understanding the molecular mechanism, structural understanding, and disease propagation. The multi-omics approaches offer various tools and strategies for identifying potential therapeutic biomolecules for COVID-19 and exploring the plants producing biomolecules that can be used as biopharmaceutical products. This review explores the available multi-omics approaches and their scope to investigate the therapeutic promises of plant-based biomolecules in treating SARS-CoV-2 infection.

12.
IEEE Rev Biomed Eng ; 14: 16-29, 2021.
Article in English | MEDLINE | ID: covidwho-1501334

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly around the world, resulting in a massive death toll. Lung infection or pneumonia is the common complication of COVID-19, and imaging techniques, especially computed tomography (CT), have played an important role in diagnosis and treatment assessment of the disease. Herein, we review the imaging characteristics and computing models that have been applied for the management of COVID-19. CT, positron emission tomography - CT (PET/CT), lung ultrasound, and magnetic resonance imaging (MRI) have been used for detection, treatment, and follow-up. The quantitative analysis of imaging data using artificial intelligence (AI) is also explored. Our findings indicate that typical imaging characteristics and their changes can play crucial roles in the detection and management of COVID-19. In addition, AI or other quantitative image analysis methods are urgently needed to maximize the value of imaging in the management of COVID-19.


Subject(s)
COVID-19/diagnosis , Artificial Intelligence , COVID-19/diagnostic imaging , Humans , Lung/diagnostic imaging , Lung/virology , Positron Emission Tomography Computed Tomography/methods , SARS-CoV-2/pathogenicity , Tomography, X-Ray Computed/methods , Ultrasonography/methods
13.
Clin Infect Dis ; 73(9): e2952-e2959, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501018

ABSTRACT

BACKGROUND: The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by reverse-transcription polymerase chain reaction (PCR) does not necessarily indicate shedding of infective virions. There are limited data on the correlation between the isolation of SARS-CoV-2, which likely indicates infectivity, and PCR. METHODS: A total of 195 patients with Coronavirus disease 2019 were tested (outpatients, n = 178; inpatients, n = 12; and critically unwell patients admitted to the intensive care unit [ICU] patients, n = 5). SARS-CoV-2 PCR-positive samples were cultured in Vero C1008 cells and inspected daily for cytopathic effect (CPE). SARS-CoV-2-induced CPE was confirmed by PCR of culture supernatant. Where no CPE was observed, PCR was performed on day 4 to confirm absence of virus replication. The cycle thresholds (Cts) of the day 4 PCR (Ctculture) and the PCR of the original clinical sample (Ctsample) were compared, and positive cultures were defined where Ctsample - Ctculture was ≥3. RESULTS: Of 234 samples collected, 228 (97%) were from the upper respiratory tract. SARS-CoV-2 was isolated from 56 (24%), including in 28 of 181 (15%), 19 of 42 (45%), and 9 of 11 samples (82%) collected from outpatients, inpatients, and ICU patients, respectively. All 56 samples had Ctsample ≤32; CPE was observed in 46 (20%). The mean duration from symptom onset to culture positivity was 4.5 days (range, 0-18). SARS-CoV-2 was significantly more likely to be isolated from samples collected from inpatients (P < .001) and ICU patients (P < .0001) compared with outpatients, and in samples with lower Ctsample. CONCLUSIONS: SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.


Subject(s)
COVID-19 , Animals , Chlorocebus aethiops , Critical Care , Humans , Immunologic Tests , SARS-CoV-2 , Vero Cells
14.
J Steroid Biochem Mol Biol ; 212: 105939, 2021 09.
Article in English | MEDLINE | ID: covidwho-1492339

ABSTRACT

7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/etiology , Ketocholesterols/blood , Animals , Biomarkers/blood , COVID-19/blood , COVID-19/drug therapy , Humans , Ketocholesterols/metabolism
15.
J Virol ; 95(16): e0061721, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1486509

ABSTRACT

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.


Subject(s)
Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Gene Expression , Host-Pathogen Interactions/genetics , Humans , Kinetics , Molecular Dynamics Simulation , Phenylalanine/chemistry , Phenylalanine/metabolism , Phylogeny , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS-CoV-2/classification , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Valine/chemistry , Valine/metabolism , Virulence , Virus Attachment
16.
Phytother Res ; 35(10): 5384-5396, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1479438

ABSTRACT

The current pandemic responsible for the crippling of the health care system is caused by the novel SARS-CoV-2 in 2019 and leading to coronavirus disease 2019 (COVID-19). The virus enters into humans by attachment of its Spike protein (S) to the ACE receptor present on the lung epithelial cell surface followed by cleavage of S protein by the cellular transmembrane serine protease (TMPRSS2). After entry, the SARS-CoV-2 RNA genome is released into the cytosol, where it highjacks host replication machinery for viral replication, assemblage, as well as the release of new viral particles. The major drug targets that have been identified for SARS-CoV-2 through host-virus interaction studies include 3CLpro, PLpro, RNA-dependent RNA polymerase, and S proteins. Several reports of natural compounds along with synthetic products have displayed promising results and some of them are Tripterygium wilfordii, Pudilan Xiaoyan Oral Liquid, Saponin derivates, Artemisia annua, Glycyrrhiza glabra L., Jinhua Qinggan granules, Xuebijing, and Propolis. This review attempts to disclose the natural products identified as anti-SARS-CoV-2 based on in silico prediction and the effect of a variety of phytochemicals either alone and/or in combination with conventional treatments along with their possible molecular mechanisms involved for both prevention and treatment of the SARS-CoV-2 disease.


Subject(s)
Antiviral Agents , Biological Products , COVID-19 , Drugs, Chinese Herbal , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Humans , Phytochemicals/pharmacology
17.
Viral Immunol ; 34(6): 416-420, 2021.
Article in English | MEDLINE | ID: covidwho-1475758

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected millions of individuals in the world. However, the long-term effect of SARS-CoV-2 on the organs of recovered patients remains unclear. This study is to evaluate the impact of SARS-CoV-2 on the spleen and T lymphocytes. Seventy-six patients recovered from COVID-19, including 66 cases of moderate pneumonia and 10 cases of severe pneumonia were enrolled in the observation group. The control group consisted of 55 age-matched healthy subjects. The thickness and length of spleen were measured by using B-ultrasound and the levels of T lymphocytes were detected by flow cytometry. Results showed that the mean length of spleen in the observation group was 89.57 ± 11.49 mm, which was significantly reduced compared with that in the control group (103.82 ± 11.29 mm, p < 0.001). The mean thicknesses of spleen between observation group and control group were 29.97 ± 4.04 mm and 32.45 ± 4.49 mm, respectively, and the difference was significant (p < 0.001). However, no significant difference was observed in the size of spleen between common pneumonia and severe pneumonia (p > 0.05). In addition, the decreased count of T lymphocyte was observed in part of recovered patients. The counts of T suppressor lymphocytes in patients with severe pneumonia were significantly decreased compared with those with moderate pneumonia (p = 0.005). Therefore, these data indicate that SARS-CoV-2 infection affects the size of spleen and T lymphocytes.


Subject(s)
COVID-19/immunology , SARS-CoV-2 , Spleen/pathology , T-Lymphocytes/immunology , Adult , Aged , Female , Humans , Lymphocyte Count , Male , Middle Aged , Young Adult
18.
Antioxid Redox Signal ; 35(14): 1207-1225, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1475726

ABSTRACT

Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 [TLR4] pathway and NLR family pyrin domain containing 3 [NLRP3] inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.


Subject(s)
Acetylcysteine/metabolism , COVID-19/metabolism , Hydrogen Sulfide/metabolism , Humans , Oxidation-Reduction
19.
Rev Rhum Ed Fr ; 88(5): 377-381, 2021 Oct.
Article in French | MEDLINE | ID: covidwho-1447100

ABSTRACT

Objectif: Cette étude a pour objectif de déterminer la prévalence du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) 2019 (COVID-19) chez des patients adultes traités par biothérapies ou inhibiteurs des JAK pour des rhumatismes inflammatoires chroniques, en particulier des arthrites inflammatoires chroniques. Méthodes: Pour cela, une étude basée sur la population, dans la province d'Udine (466 700 habitants d'âge > 15 ans, région du Frioul-Vénétie-Julienne, Italie) a été planifiée. Le critère principal de jugement était la prévalence du COVID-19 durant les deux premiers mois de l'épidémie. Tous les patients de notre province atteints de maladies rhumatismales et traités par biothérapies ou inhibiteurs des JAK au cours des 6 mois précédents ont été inclus (n = 1051). Résultats: Du 29 février au 25 avril 2020, 4 patients adultes (4/1051, 3,8/1000, IC 95 % 1,5-9,7/1000) ont été testés positifs au COVID-19 par RT-PCR et écouvillon. Au total, 47/1051 patients (4,5 %) ont été soumis au test COVID-19 par RT-PCR durant la même période, en raison de symptômes compatibles avec le COVID-19 pour 15 d'entre eux. Dans la population générale, la prévalence était de 937 cas/466700 (2/1000, IC 95 % 1,9-2,1/1000, valeur p = 0,33, test du Chi2), et 20 179/466 700 (4,3 %) prélèvements COVID-19 sur écouvillon ont été effectués. Conclusion: Le risque de COVID-19 chez les patients atteints de maladies rhumatismales et traités par biothérapies ou inhibiteurs des JAK n'apparaît pas différent de celui observé dans la population générale. Les patients doivent être encouragés à poursuivre en toute sécurité leur traitement et à respecter les mesures de prévention et de protection contre le COVID-19.

20.
Biomol NMR Assign ; 15(2): 335-340, 2021 10.
Article in English | MEDLINE | ID: covidwho-1442184

ABSTRACT

The SARS-CoV-2 virus is the cause of the respiratory disease COVID-19. As of today, therapeutic interventions in severe COVID-19 cases are still not available as no effective therapeutics have been developed so far. Despite the ongoing development of a number of effective vaccines, therapeutics to fight the disease once it has been contracted will still be required. Promising targets for the development of antiviral agents against SARS-CoV-2 can be found in the viral RNA genome. The 5'- and 3'-genomic ends of the 30 kb SCoV-2 genome are highly conserved among Betacoronaviruses and contain structured RNA elements involved in the translation and replication of the viral genome. The 40 nucleotides (nt) long highly conserved stem-loop 4 (5_SL4) is located within the 5'-untranslated region (5'-UTR) important for viral replication. 5_SL4 features an extended stem structure disrupted by several pyrimidine mismatches and is capped by a pentaloop. Here, we report extensive 1H, 13C, 15N and 31P resonance assignments of 5_SL4 as the basis for in-depth structural and ligand screening studies by solution NMR spectroscopy.


Subject(s)
5' Untranslated Regions , Nuclear Magnetic Resonance, Biomolecular , SARS-CoV-2/genetics , Inverted Repeat Sequences/genetics
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