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1.
Int J Mol Sci ; 21(14)2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-1934087

ABSTRACT

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30-40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways.


Subject(s)
Acute Lung Injury/metabolism , Deubiquitinating Enzymes/metabolism , Respiratory Distress Syndrome/metabolism , Animals , Humans , Pneumonia/metabolism , Signal Transduction/physiology , Ubiquitin/metabolism , Ubiquitination/physiology
2.
J Ayurveda Integr Med ; 13(1): 100424, 2022.
Article in English | MEDLINE | ID: covidwho-1838955

ABSTRACT

For centuries, traditional medicines of Ayurveda have been in use to manage infectious and non-infectious diseases. The key embodiment of traditional medicines is the holistic system of approach in the management of human diseases. SARS-CoV-2 (COVID-19) infection is an ongoing pandemic, which has emerged as the major health threat worldwide and is causing significant stress, morbidity and mortality. Studies from the individuals with SARS-CoV-2 infection have shown significant immune dysregulation and cytokine overproduction. Neutrophilia and neutrophil to lymphocyte ratio has been correlated to poor outcome due to the disease. Neutrophils, component of innate immune system, upon stimulation expel DNA along with histones and granular proteins to form extracellular traps (NETs). Although, these DNA lattices possess beneficial activity in trapping and eliminating pathogens, NETs may also cause adverse effects by inducing immunothrombosis and tissue damage in diseases including Type 2 Diabetes and atherosclerosis. Tissues of SARS-CoV-2 infected subjects showed microthrombi with neutrophil-platelet infiltration and serum showed elevated NETs components, suggesting large involvement and uncontrolled activation of neutrophils leading to pathogenesis and associated organ damage. Hence, traditional Ayurvedic herbs exhibiting anti-inflammatory and antioxidant properties may act in a manner that might prove beneficial in targeting over-functioning of neutrophils and there by promoting normal immune homeostasis. In the present manuscript, we have reviewed and discussed pathological importance of NETs formation in SARS-CoV-2 infections and discuss how various Ayurvedic herbs can be explored to modulate neutrophil function and inhibit NETs formation in the context of a) anti-microbial activity to enhance neutrophil function, b) immunomodulatory effects to maintain neutrophil mediated immune homeostasis and c) to inhibit NETs mediated thrombosis.

3.
Chin Med J (Engl) ; 134(13): 1522-1534, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1769417

ABSTRACT

ABSTRACT: Respiratory viruses are major human pathogens that cause approximately 200 million pneumonia cases annually and induce various comorbidities with chronic obstructive pulmonary disease (COPD), resulting in significant health concerns and economic burdens. Clinical manifestations in respiratory viral infections and inflammations vary from asymptomatic, mild, to severe, depending on host immune cell responses to pathogens and interactions with airway epithelia. We critically review the activation, effector, and regulation of T cells in respiratory virus infections and chronic inflammations associated with COPD. Crosstalk among T cells, innate immune cells, and airway epithelial cells is discussed as essential parts of pathogenesis and protection in viral infections and COPD. We emphasize the specificity of peptide antigens and the functional heterogeneity of conventional CD4+ and CD8+ T cells to shed some light on potential cellular and molecular candidates for the future development of therapeutics and intervention against respiratory viral infections and inflammations.


Subject(s)
Pneumonia , Pulmonary Disease, Chronic Obstructive , Respiratory Tract Infections , Virus Diseases , Viruses , CD8-Positive T-Lymphocytes , Humans
4.
J Clin Med ; 10(1)2020 Dec 30.
Article in English | MEDLINE | ID: covidwho-1753519

ABSTRACT

Candida species are common global opportunistic pathogens that could repeatedly and chronically cause oral mucosa infection and create an inflammatory environment, leading to organ dysfunction. Oral Candida infections may cause temporary or permanent damage to salivary glands, resulting in the destruction of acinar cells and the formation of scar tissue. Restricted function of the salivary glands leads to discomfort and diseases of the oral mucosa, such as dry mouth and associated infection. This narrative review attempts to summarize the anatomy and function of salivary glands, the associations between Candida and saliva, the effects of Candida infection on salivary glands, and the treatment strategies. Overall, clinicians should proactively manage Candida infections by educating patients on oral hygiene management for vulnerable populations, conducting frequent checks for a timely diagnosis, and providing an effective treatment plan.

5.
Emerg Microbes Infect ; 10(1): 578-588, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1490460

ABSTRACT

Mycobacterium tuberculosis (M. tuberculosis) is the pathogen which causes tuberculosis (TB), a significant human public health threat. Co-infection of M. tuberculosis and the human immunodeficiency virus (HIV), emergence of drug resistant M. tuberculosis, and failure to develop highly effective TB vaccines have limited control of the TB epidemic. Trained immunity is an enhanced innate immune response which functions independently of the adaptive/acquired immune system and responds non-specifically to reinfection with invading agents. Recently, several studies have found trained immunity has the capability to control and eliminate M. tuberculosis infection. Over the past decades, however, the consensus was adaptive immunity is the only protective mechanism by which hosts inhibit M. tuberculosis growth. Furthermore, autophagy plays an essential role in the development of trained immunity. Further investigation of trained immunity, M. tuberculosis infection, and the role of autophagy in this process provide new possibilities for vaccine development. In this review, we present the general characteristics of trained immunity and autophagy. We additionally summarize several examples where initiation of trained immunity contributes to the prevention of M. tuberculosis infection and propose future directions for research in this area.


Subject(s)
Autophagy , Immunity, Innate , Mycobacterium tuberculosis/immunology , Tuberculosis Vaccines/immunology , Tuberculosis/immunology , Tuberculosis/prevention & control , Adaptive Immunity , Animals , Humans , Immunologic Memory , Vaccination
6.
J Virol ; 95(15): e0046321, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1486505

ABSTRACT

The OC43 coronavirus is a human pathogen that usually causes only the common cold. One of its key enzymes, similar to other coronaviruses, is the 2'-O-RNA methyltransferase (MTase), which is essential for viral RNA stability and expression. Here, we report the crystal structure of the 2'-O-RNA MTase in a complex with the pan-methyltransferase inhibitor sinefungin solved at 2.2-Å resolution. The structure reveals an overall fold consistent with the fold observed in other coronaviral MTases. The major differences are in the conformation of the C terminus of the nsp16 subunit and an additional helix in the N terminus of the nsp10 subunits. The structural analysis also revealed very high conservation of the S-adenosyl methionine (SAM) binding pocket, suggesting that the SAM pocket is a suitable spot for the design of antivirals effective against all human coronaviruses. IMPORTANCE Some coronaviruses are dangerous pathogens, while some cause only common colds. The reasons are not understood, although the spike proteins probably play an important role. However, to understand the coronaviral biology in sufficient detail, we need to compare the key enzymes from different coronaviruses. We solved the crystal structure of 2'-O-RNA methyltransferase of the OC43 coronavirus, a virus that usually causes mild colds. The structure revealed some differences in the overall fold but also revealed that the SAM binding site is conserved, suggesting that development of antivirals against multiple coronaviruses is feasible.


Subject(s)
Betacoronavirus/enzymology , Methyltransferases/chemistry , Viral Proteins/chemistry , Betacoronavirus/genetics , Binding Sites , Crystallography, X-Ray , Methyltransferases/genetics , Protein Conformation, alpha-Helical , Viral Proteins/genetics
7.
Curr Pharm Des ; 27(32): 3444-3453, 2021.
Article in English | MEDLINE | ID: covidwho-1435740

ABSTRACT

BACKGROUND: Viruses are known as the major causative agents for infectious diseases globally. The coronaviruses are one of the serious pathogens to cause serious diseases in humans. Recently identified SARSCoV- 2 from Wuhan City, China, has emerged as a serious threat to human health and caused a global pandemic. Bats have been confirmed as a primary source of infection. The vaccination of the human population and animals serving as a potential reservoir is a straightforward strategy to control the transmission of any pathogen to humans. Natural products from many herbal plants are well known to have novel antiviral properties and evaluated against various viral diseases. There are many alkaloids that have shown to be effective against coronaviruses. METHODS: Recently, the antiviral efficacy of natural alkaloids known as Homoharringtonine (HTT) and Emetine has been evaluated and provided promising results against coronaviruses, including SARS-CoVs. These alkaloids may be very useful and can be used as antivirals against SARS-CoV-2 because they have already been reported to inhibit the replication of SASRS-CoV and other viruses in cell lines. CONCLUSION: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.


Subject(s)
Alkaloids , Biological Products , COVID-19 , Alkaloids/pharmacology , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biological Products/pharmacology , Emetine , Homoharringtonine , Humans , SARS-CoV-2
8.
Transbound Emerg Dis ; 68(5): 2722-2732, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1411004

ABSTRACT

African Swine Fever Virus (ASFV) is a highly contagious pathogen that causes disease in pigs, commonly characterized by acute haemorrhagic fever. Prior to August 2018, African Swine Fever (ASF) had not been reported in Asia, but has since spread throughout China, Mongolia, Korea, Vietnam, Laos, Cambodia, Myanmar, the Philippines, Hong Kong, Indonesia, Timor-Leste and Papua New Guinea. Using data collated from reports of confirmed cases, we applied spatio-temporal analysis to describe ASFV spread throughout Asia during its early phase-from 1 August 2018 (reported start date) to 31 December 2019-to provide an overview and comparative analysis. Analysis revealed a propagating epidemic of ASFV throughout Asia, with peaks corresponding to increased reports from China, Vietnam and Laos. Two clusters of reported outbreaks were found. During the epidemic, ASFV primarily spread from the North-East to the South-East: A larger, secondary cluster in the North-East represented earlier reports, while the smaller, primary cluster in the South-East was characterized by later reports. Significant differences in country-specific epidemics, morbidity, mortality and unit types were discovered. The initial number of outbreaks and enterprise size are likely predictors of the speed of spread and the effectiveness of ASFV stamping out procedures. Biosecurity methods, wild boar populations and the transportation of pigs and movement of infected fomites are discussed as likely risk factors for facilitating ASFV spread across Asia.


Subject(s)
African Swine Fever Virus , African Swine Fever , Swine Diseases , African Swine Fever/epidemiology , Animals , Disease Outbreaks/veterinary , Hong Kong , Sus scrofa , Swine , Swine Diseases/epidemiology
9.
Eur Phys J Plus ; 136(3): 319, 2021.
Article in English | MEDLINE | ID: covidwho-1388540

ABSTRACT

Infectious diseases afflict human beings since ancient times. We can classify the infectious disease in two principal types: the emerging diseases, that are caused by new pathogens, and the re-emerging diseases, due to a new spread of a known pathogen. Both types can then be subdivided in natural, accidental or intentional spreads. The risk associated to infectious diseases strongly increased in the last decades, especially because of the globalisation, which leads to a denser and more efficient link between nations, involving that a local infectious may easily spread worldwide, such as the SARS-CoV-2 in 2019-2020. The development of new methods to predict the spread of diseases is crucial. However, sometimes the variables are too many that classical algorithms fail in the prediction. Aim of this work is to investigate the use of an ensemble of recurrent neural networks for disease prediction, using real flu's data to train and develop an instrument with the capability to determine the future flues. Two different types of study have been conducted. The first study investigates the influence of the neural network architecture, and it has been performed using 12 seasons to train the model and 3 seasons to test it. The second test aims to investigate the number of seasons needed to have a good prediction for future ones. The results demonstrated that this approach could ensure very high performances also with simple architectures. The ensemble approach allows to have information about the uncertainty of the prediction, allowing also to take countermeasures as a function of that value. In the future, the use of this approach may be applied to many other types of disease.

10.
Clin Infect Dis ; 73(Suppl 1): S110-S117, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1364763

ABSTRACT

BACKGROUND: Respiratory tract infections are common, often seasonal, and caused by multiple pathogens. We assessed whether seasonal respiratory illness patterns changed during the COVID-19 pandemic. METHODS: We categorized emergency department (ED) visits reported to the National Syndromic Surveillance Program according to chief complaints and diagnosis codes, excluding visits with diagnosed SARS-CoV-2 infections. For each week during 1 March 2020 through 26 December 2020 ("pandemic period"), we compared the proportion of ED visits in each respiratory category with the proportion of visits in that category during the corresponding weeks of 2017-2019 ("pre-pandemic period"). We analyzed positivity of respiratory viral tests from 2 independent clinical laboratories. RESULTS: During March 2020, cough, shortness of breath, and influenza-like illness accounted for twice as many ED visits compared with the pre-pandemic period. During the last 4 months of 2020, all respiratory conditions, except shortness of breath, accounted for a smaller proportion of ED visits than during the pre-pandemic period. Percent positivity for influenza virus, respiratory syncytial virus, human parainfluenza virus, adenoviruses, and human metapneumovirus was lower in 2020 than 2019. Although test volume decreased, percent positivity was higher for rhinovirus/enterovirus during the final weeks of 2020 compared with 2019, with ED visits similar to the pre-pandemic period. CONCLUSIONS: Broad reductions in respiratory test positivity and respiratory ED visits (excluding COVID-19) occurred during 2020. Interventions for mitigating spread of SARS-CoV-2 likely also reduced transmission of other pathogens. Timely surveillance is needed to understand community health threats, particularly when current trends deviate from seasonal norms.


Subject(s)
COVID-19 , Virus Diseases , Emergency Service, Hospital , Humans , Pandemics , SARS-CoV-2 , Seasons , United States/epidemiology , Virus Diseases/epidemiology
11.
Biomass Convers Biorefin ; : 1-18, 2021 May 27.
Article in English | MEDLINE | ID: covidwho-1250946

ABSTRACT

Emergence of "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" causing "COVID-19" or "coronavirus disease 19" as pandemic has got worldwide attention towards hygiene as the first line of defense for the infection control. It is first line of defense not only from COVID-19 but also from other infectious diseases caused by deadly pathogens such as cholera, hepatitis, tuberculosis, polio, etc. Absence of any particular vaccine or treatment let World Health Organization (WHO) recommend to the public to maintain social distancing along with regularly washing their hands with soap, sanitize their hands (where washing is not possible), and disinfect their belongings and buildings to avoid the infection. Out of various formulations available in the market, WHO has recommended alcohol-based hand sanitizers, which mainly comprise of ethanol, isopropyl alcohols, and hydrogen peroxides in different combinations due to their high potential to kill the broad range of pathogens including bacterial, viral, fungal, helminthes, etc. Therefore, alcohol-based sanitizers are in high demand since centuries to prevent infection from pathogenic diseases. Ethanol is the most common and popular alcohol in terms of vanishing wide range of pathogens, convenient to use and its production. Ethanol is produced worldwide and is used in various sectors, e.g., beauty and cosmetics, food and beverages, and as the most demanding gasoline additive. The present review is focused on the ethanol production in India, its diversified applications emphasizing hand sanitizers with discussions on formulation of sanitizer and disinfectants, and viability of lignocellulosic and food grain-based ethanol. The review article also emphasizes on the technological details of 1G and 2G ethanol production, their associated challenges, and inputs for the improved ethanol yields so as to strengthen the supply chain of ethanol in India, and making "Atmanirbhar Bharat" (Self-reliant India) campaign of Indian government successfully viable.

12.
Int J Infect Dis ; 107: 179-181, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1300799

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the QIAstat-Dx® Respiratory SARS-CoV-2 Panel (QIAstat-SARS-CoV-2), which is a closed, fully automated, multiplex polymerase chain reaction (PCR) assay that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 21 other pathogens that cause respiratory disease. METHODS: Nasopharyngeal swabs from patients with or suspected of having coronavirus disease 2019 were collected and tested at Bichat-Claude Bernard Hospital, Paris, France. Using the World Health Organisation-approved real-time-PCR assay developed by the Charité Institute of Virology as the reference, positive percent agreement (PPA) and negative percent agreement (NPA) were calculated. RESULTS: In total, 189 negative and 88 positive samples were analyzed. QIAstat-SARS-CoV-2 had an NPA of 90.48% (95% confidence interval (CI), 85.37%, 94.26%) and a PPA of 94.32% (95% CI, 87.24%, 98.13%). Co-infections were detected by QIAstat-SARS-CoV-2 in 4/277 specimens. The methods exhibited comparable failure rates (23/307 [7.5%] vs. 6/298 [2.0%] for QIAstat-SARS-CoV-2 and reference methods, respectively). The turnaround time was shorter for QIAstat-SARS-CoV-2 compared with the reference method (difference in mean -14:30 h [standard error, 0:03:23; 95% CI, -14:37, -14:24]; P < 0.001). CONCLUSIONS: QIAstat-SARS-CoV-2 shows good agreement with the reference assay, providing faster and accurate results for detecting SARS-CoV-2.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Multiplex Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Nasopharynx/virology , Retrospective Studies , Young Adult
13.
Am J Epidemiol ; 190(7): 1396-1405, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1290657

ABSTRACT

Comparison of coronavirus disease 2019 (COVID-19) case numbers over time and between locations is complicated by limits to virological testing to confirm severe acute respiratory syndrome coronavirus 2 infection. The proportion of tested individuals who have tested positive (test-positive proportion, TPP) can potentially be used to inform trends in incidence. We propose a model for testing in a population experiencing an epidemic of COVID-19 and derive an expression for TPP in terms of well-defined parameters related to testing and presence of other pathogens causing COVID-19-like symptoms. In the absence of dramatic shifts of testing practices in time or between locations, the TPP is positively correlated with the incidence of infection. We show that the proportion of tested individuals who present COVID-19-like symptoms encodes information similar to the TPP but has different relationships with the testing parameters, and can thus provide additional information regarding dynamic changes in TPP and incidence. Finally, we compare data on confirmed cases and TPP from US states up to October 2020. We conjecture why states might have higher or lower TPP than average. Collection of symptom status and age/risk category of tested individuals can increase the utility of TPP in assessing the state of the pandemic in different locations and times.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , Models, Theoretical , Population Surveillance/methods , Humans , Incidence , Pandemics , SARS-CoV-2
14.
Neurol Ther ; 10(2): 523-537, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1274996

ABSTRACT

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system that typically develops within 4 weeks after infection. In addition to conventional infectious diseases with which we are familiar, emerging infectious diseases, such as Zika virus infection and coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have also been suggested to be associated with GBS. GBS is mainly categorized into a demyelinating subtype known as acute inflammatory demyelinating polyneuropathy (AIDP) and an axonal subtype known as acute motor axonal neuropathy (AMAN). Most patients who develop GBS after Zika virus infection or COVID-19 have AIDP. The concept of molecular mimicry between pathogens and human peripheral nerve components was established through studies of AMAN with anti-ganglioside GM1 antibodies occurring after Campylobacter jejuni infection. Although such mimicry between specific pathogens and myelin or Schwann cell components has not been clearly demonstrated in AIDP, a similarity of Zika virus and SARS-CoV-2 proteins to human proteins has been suggested. With the development of global commerce and travel, emerging infectious diseases will continue to threaten public health. From this viewpoint, the development of vaccines and antiviral drugs is important to prepare for and control emerging infectious diseases. Although a decrease in the number of patients after the 2015-2016 Zika epidemic increased the difficulty in conducting phase 3 trials for Zika virus vaccines, the efficacy and safety of new vaccines have recently been demonstrated for COVID-19. In general, vaccines can decrease the risk of infectious disease by stimulating the immune system, and discussions regarding an increased risk of autoimmune disorders, such as GBS, have been ongoing for many years. However, the risk of GBS is not considered a legitimate reason to limit the administration of currently available vaccines, as only a trivial association or no association with GBS has been demonstrated.

15.
Clin Microbiol Infect ; 27(12): 1772-1776, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1260699

ABSTRACT

BACKGROUND: A wide range of bacterial infections occur in coronavirus disease 2019 (COVID-19) patients, particularly in those with severe coronaviral disease. Some of these are community-acquired co-infections. OBJECTIVE: To review recent data that indicate the occurrence of hospital-onset bacterial infections, including with antibiotic-resistant isolates, in COVID-19 patients. SOURCES: Using PubMed, the literature was searched using terms including: 'COVID-19'; 'SARS-CoV-2'; 'bacterial infection'; 'healthcare-associated infection'; 'antibiotic resistance'; 'antimicrobial resistance'; 'multi-drug resistance'; 'Streptococcus'; 'Staphylococcus'; 'Pseudomonas'; 'Escherichia'; 'Klebsiella'; 'Enterococcus'; 'Acinetobacter'; 'Haemophilus'; 'MRSA'; 'VRE'; 'ESBL'; 'NDM-CRE'; 'CR-Ab'; 'VRSA'; 'MDR'. CONTENT: There is a growing number of reports of bacterial infections acquired by patients with severe COVID-19 after hospital admission. Antibiotic-resistant pathogens found to cause healthcare-associated infections (HAIs) in COVID-19 patients include methicillin-resistant Staphylococcus aureus, New Delhi metallo-ß-lactamase-producing carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, extended-spectrum ß-lactamase Klebsiella pneumoniae and vancomycin-resistant enterococci. COVID-19 has impacted bacterial HAIs in a number of ways with an increase in the incidence of New Delhi metallo-ß-lactamase-producing carbapenem-resistant Enterobacterales and carbapenem-resistant A. baumannii reported at some hospital sites compared with before the pandemic. Recommended guidelines for antimicrobial stewardship in COVID-19 patient treatment are discussed regarding minimization of empiric broad-spectrum antibiotic use. Other studies have reported a decrease in methicillin-resistant S. aureus and vancomycin-resistant enterococci cases, which has been attributed to enhanced infection prevention and control practices introduced to minimize intra-hospital spread of COVID-19. IMPLICATIONS: Poorer outcomes have been observed in hospitalized COVID-19 patients with an antibiotic-resistant infection. Although heightened IPC measures have been accompanied by a reduction in some HAIs at specific sites, in other situations, COVID-19 has been associated with an increase in bacterial HAI incidence. Further research is needed to define the cost-benefit relationship of maintaining COVID-19-related infection prevention and control protocols beyond the pandemic to reduce the burden of HAIs. In addition, the longer-term impact of high usage of certain broad-spectrum antibiotics during the COVID-19 pandemic requires evaluation.


Subject(s)
Bacterial Infections , COVID-19 , Community-Acquired Infections , Cross Infection , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , COVID-19/epidemiology , Carbapenems , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Cross Infection/drug therapy , Cross Infection/epidemiology , Delivery of Health Care , Drug Resistance, Bacterial , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Pandemics
16.
BMC Infect Dis ; 21(1): 524, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1259187

ABSTRACT

BACKGROUND: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults. CASE PRESENTATION: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed. CONCLUSION: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.


Subject(s)
Common Cold/diagnosis , Coronavirus 229E, Human , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Aged , Anti-Bacterial Agents/therapeutic use , Bronchoalveolar Lavage Fluid/virology , Common Cold/complications , Common Cold/virology , Coronavirus Infections/complications , Diabetes Mellitus , Healthcare-Associated Pneumonia/complications , Healthcare-Associated Pneumonia/drug therapy , High-Throughput Nucleotide Sequencing , Humans , Male , Pneumonia, Viral/drug therapy
17.
Lancet Microbe ; 2(8): e354-e365, 2021 08.
Article in English | MEDLINE | ID: covidwho-1253810

ABSTRACT

BACKGROUND: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. METHODS: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. FINDINGS: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59-84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. INTERPRETATION: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.


Subject(s)
Anti-Infective Agents , COVID-19 , Coinfection , Respiratory Tract Infections , Aged , Aged, 80 and over , COVID-19/epidemiology , Coinfection/drug therapy , Female , Humans , Male , Middle Aged , Pandemics , Prospective Studies , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , United Kingdom/epidemiology , World Health Organization
18.
Mol Med ; 27(1): 54, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249543

ABSTRACT

While vaccines traditionally have been designed and used for protection against infection or disease caused by one specific pathogen, there are known off-target effects from vaccines that can impact infection from unrelated pathogens. The best-known non-specific effects from an unrelated or heterologous vaccine are from the use of the Bacillus Calmette-Guérin (BCG) vaccine, mediated partly through trained immunity. Other vaccines have similar heterologous effects. This review covers molecular mechanisms behind the heterologous effects, and the potential use of heterologous vaccination in the current COVID-19 pandemic. We then discuss novel pandemic response strategies based on rapidly deployed, widespread heterologous vaccination to boost population-level immunity for initial, partial protection against infection and/or clinical disease, while specific vaccines are developed.


Subject(s)
BCG Vaccine/immunology , COVID-19/prevention & control , Pandemics , Vaccines/immunology , BCG Vaccine/therapeutic use , COVID-19/immunology , COVID-19/virology , Humans , Immunity, Heterologous/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Vaccines/therapeutic use
19.
Lancet Digit Health ; 3(6): e360-e370, 2021 06.
Article in English | MEDLINE | ID: covidwho-1240696

ABSTRACT

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. METHODS: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. FINDINGS: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded. INTERPRETATION: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. FUNDING: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).


Subject(s)
Bacterial Infections/epidemiology , COVID-19 , Respiratory Tract Infections/epidemiology , Bacterial Infections/transmission , COVID-19/prevention & control , Haemophilus influenzae , Humans , Incidence , Interrupted Time Series Analysis , Neisseria meningitidis , Population Surveillance , Prospective Studies , Public Health Practice , Streptococcus agalactiae , Streptococcus pneumoniae
20.
Molecules ; 26(10)2021 May 18.
Article in English | MEDLINE | ID: covidwho-1234780

ABSTRACT

COVID-19 represents a new potentially life-threatening illness caused by severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 pathogen. In 2021, new variants of the virus with multiple key mutations have emerged, such as B.1.1.7, B.1.351, P.1 and B.1.617, and are threatening to render available vaccines or potential drugs ineffective. In this regard, we highlight 3CLpro, the main viral protease, as a valuable therapeutic target that possesses no mutations in the described pandemically relevant variants. 3CLpro could therefore provide trans-variant effectiveness that is supported by structural studies and possesses readily available biological evaluation experiments. With this in mind, we performed a high throughput virtual screening experiment using CmDock and the "In-Stock" chemical library to prepare prioritisation lists of compounds for further studies. We coupled the virtual screening experiment to a machine learning-supported classification and activity regression study to bring maximal enrichment and available structural data on known 3CLpro inhibitors to the prepared focused libraries. All virtual screening hits are classified according to 3CLpro inhibitor, viral cysteine protease or remaining chemical space based on the calculated set of 208 chemical descriptors. Last but not least, we analysed if the current set of 3CLpro inhibitors could be used in activity prediction and observed that the field of 3CLpro inhibitors is drastically under-represented compared to the chemical space of viral cysteine protease inhibitors. We postulate that this methodology of 3CLpro inhibitor library preparation and compound prioritisation far surpass the selection of compounds from available commercial "corona focused libraries".


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases , Cysteine Proteinase Inhibitors/chemistry , SARS-CoV-2/enzymology , Small Molecule Libraries , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Humans
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