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1.
Int J Mol Sci ; 23(2)2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1624942

ABSTRACT

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb), resulted in almost 1.4 million deaths in 2019, and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes into close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic, innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb-host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional, with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay shows that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows a lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status, determined by factors such as age, might play an important role in determining infection outcome.


Subject(s)
Bacterial Capsules/genetics , Bacterial Capsules/metabolism , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/metabolism , Adolescent , Adult , Age Factors , Aged , Bronchoalveolar Lavage Fluid , Cellular Structures , Female , Gene Expression Regulation, Bacterial , Humans , Lipopolysaccharides/biosynthesis , Lipopolysaccharides/genetics , Male , Mannosides/biosynthesis , Mannosides/genetics , Mannosyltransferases/biosynthesis , Mannosyltransferases/genetics , Middle Aged , Young Adult
2.
J Med Case Rep ; 15(1): 621, 2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1582015

ABSTRACT

BACKGROUND: The coronavirus disease 2019 pandemic is predicted to have a net negative effect on tuberculosis control, with an estimated excess of 6.3 million tuberculosis cases and 1.4 million deaths by 2025. Programmatic issues such as the lockdown of tuberculosis services affect all patients, while biosocial factors have a differential impact on an individual's risk for tuberculosis or adverse tuberculosis outcomes. CASE PRESENTATION: We report three Hispanic cases of incident tuberculosis (two males, 43 and 44 years old; one female, 49 years old) after resolution of coronavirus disease episodes. Coincidentally, all cases shared a common risk factor: a chronic history poorly controlled diabetes. CONCLUSIONS: Our findings alert to the threat posed by the synergy between coronavirus disease and diabetes, on tuberculosis reactivation. In medium- to high-risk settings for tuberculosis, we recommend implementation of routine screening for latent tuberculosis infection in these cases, and preventive tuberculosis treatment in those who are positive.


Subject(s)
COVID-19 , Diabetes Mellitus , Tuberculosis , Adult , Communicable Disease Control , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Tuberculosis/complications , Tuberculosis/diagnosis , Tuberculosis/drug therapy
3.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294071

ABSTRACT

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis ( M . tb ), resulted in almost 1.4 million deaths in 2019 and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M . tb comes in close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M . tb upon contact, defining subsequent M . tb -host cell interactions and infection outcomes in vitro and in vivo . We also demonstrated that ALF from 60+ year old elders (E-ALF) vs . healthy 18- to 45-year-old adults (A-ALF) is dysfunctional with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay demonstrates that M . tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M . tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M . tb exposure to E-ALF shows lesser transcriptional response, with most of the M . tb genes unchanged or downregulated. Overall, this study indicates that M . tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status determined by factors such as age might play an important role in determining infection outcome.

4.
One Health ; 12: 100221, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1062535

ABSTRACT

Approximately a year into the COVID-19 pandemic caused by the SARS-CoV-2 virus, many countries have seen additional "waves" of infections, especially in the temperate northern hemisphere. Other vulnerable regions, such as South Africa and several parts of South America have also seen cases rise, further impacting local economies and livelihoods. Despite substantial research efforts to date, it remains unresolved as to whether COVID-19 transmission has the same sensitivity to climate observed for other common respiratory viruses such as seasonal influenza. Here, we look for empirical evidence of seasonality using a robust estimation framework. For 359 large cities across the world, we estimated the basic reproduction number (R0) using logistic growth curves fitted to cumulative case data. We then assess evidence for association with climatic variables through ordinary least squares (OLS) regression. We find evidence of seasonality, with lower R0 within cities experiencing greater surface radiation (coefficient = -0.005, p < 0.001), after adjusting for city-level variation in demographic and disease control factors. Additionally, we find association between R0 and temperature during the early phase of the epidemic in China. However, climatic variables had much weaker explanatory power compared to socioeconomic and disease control factors. Rates of transmission and health burden of the continuing pandemic will be ultimately determined by population factors and disease control policies.

5.
Nat Commun ; 11(1): 6122, 2020 11 30.
Article in English | MEDLINE | ID: covidwho-952011

ABSTRACT

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Disease Models, Animal , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Brain/immunology , Brain/pathology , Brain/virology , COVID-19/immunology , COVID-19/pathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Disease Susceptibility , Genetic Predisposition to Disease , Keratin-18/genetics , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Mortality , Promoter Regions, Genetic/genetics , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , Respiratory Mucosa/virology , Virus Diseases/immunology , Virus Diseases/pathology
6.
International Small Business Journal-Researching Entrepreneurship ; 38(6):504-514, 2020.
Article in English | Web of Science | ID: covidwho-841312

ABSTRACT

How did the great financial crisis (GFC) of 2008-2010 impact on R&D and innovation in the United Kingdom and internationally? What can we learn about the likely innovation effects of the COVID-19 crisis on small and medium enterprises (SME) innovation? Numerous international studies suggest the strong procyclicality of R&D and innovation investments in firms: investment rises in recovery and falls sharply in times of crisis. This procyclicality is driven in firms by both internal financial resources or slack and varying market incentives for innovation. Cash constraints, in particular, may impact most strongly on R&D and innovation investments by smaller firms. In the United Kingdom, the proportion of innovating firms fell by around a third during the GFC and took around four to six years to recover. Recovery was also uneven - notably weaker in some sectors and regions. The COVID-19 crisis seems likely to leave many firms financially weaker, with the most significant impacts on the willingness or ability of SMEs to sustain R&D and innovation. Where firms are able to sustain these investments, however, the evidence from the GFC suggests that they will lead to better survival chances, stronger growth and higher profitability. Some additional financial support for innovation has been announced by the UK government. Whether this will be sufficient to sustain SME levels of innovative activity, however, remains to be seen.

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