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  • Open Access English
    Authors: 
    Narayan Prasad; Mansi Bhatt; Sanjay K. Agarwal; H.S. Kohli; Natarajan Gopalakrishnan; Edwin Fernando; Manisha Sahay; Mohan Rajapurkar; Arpita Roy Chowdhary; Manish Rathi; +13 more
    Publisher: Elsevier BV

    Introduction The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. Methods We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. Results The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. Conclusion Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

  • Open Access English
    Authors: 
    Lisa M. Raven; Ann McCormack; Jerry R. Greenfield;
    Publisher: Oxford University Press
  • Open Access English
    Authors: 
    Bernard David Naughton; Ebru Akgul;
    Publisher: SAGE Publishing

    The entry of falsified and substandard medicines into the legitimate pharmaceutical supply chain has negative impacts on healthcare systems, patient safety, and patient access to medicine. The COVID-19 pandemic has highlighted the importance of access to safe medicine through legitimate pharmaceutical supply chains and the willingness of criminals to target medical products such as PPE (personal protective equipment) and COVID-19 treatments. In this article, we analyse data from the United Kingdom (UK) national medicine alert and recall database to identify and understand recent cases of substandard and falsified medicine in the UK’s healthcare systems. Using the UK as a case study, we describe that national drug alert and recall data are useful in their current form to record and understand cases of substandard and falsified medicines in the supply chain. However, if regulatory agencies published further data, these drug recall databases may be useful to support longitudinal and international comparative medicine quality studies. We suggest that regulatory agencies publish the number of affected medicine packs in each recalled batch, as part of the recall process. This will help policy makers, practitioners, and researchers to better understand, monitor and compare the quality of medicines within legitimate supply chains.

  • Open Access English
    Authors: 
    Arvind Rajamani; Ashwin Subramaniam; Kiran Shekar; Jumana Haji; Jinghang Luo; Shailesh Bihari; Wai Tat Wong; Navya Gullapalli; Markus Renner; Claudia Maria Alcancia; +2 more
    Country: Australia

    Abstract Background There has been a surge in coronavirus disease 2019 admissions to intensive care units (ICUs) in Asia-Pacific countries. Because ICU healthcare workers are exposed to aerosol-generating procedures, ensuring optimal personal protective equipment (PPE) preparedness is important. Objective The aim of the study was to evaluate PPE preparedness across ICUs in six Asia-Pacific countries during the initial phase of the coronavirus disease 2019 pandemic, which is defined by the World Health Organization as guideline adherence, training healthcare workers, procuring stocks, and responding appropriately to suspected cases. Methods A cross-sectional Web-based survey was circulated to 633 level II/III ICUs of Australia, New Zealand (NZ), Singapore, Hong Kong (HK), India, and the Philippines. Findings Two hundred sixty-three intensivists responded, representing 231 individual ICUs eligible for analysis. Response rates were 68–100% in all countries except India, where it was 24%. Ninety-seven percent of ICUs either conformed to or exceeded World Health Organization recommendations for PPE practice. Fifty-nine percent ICUs used airborne precautions irrespective of aerosol generation procedures. There were variations in negative-pressure room use (highest in HK/Singapore), training (best in NZ), and PPE stock awareness (best in HK/Singapore/NZ). High-flow nasal oxygenation and noninvasive ventilation were not options in most HK (66.7% and 83.3%, respectively) and Singapore ICUs (50% and 80%, respectively), but were considered in other countries to a greater extent. Thirty-eight percent ICUs reported not having specialised airway teams. Showering and “buddy systems” were underused. Clinical waste disposal training was suboptimal (38%). Conclusions Many ICUs in the Asia-Pacific reported suboptimal PPE preparedness in several domains, particularly related to PPE training, practice, and stock awareness, which requires remediation. Adoption of low-cost approaches such as buddy systems should be encouraged. The complete avoidance of high-flow nasal oxygenation reported by several intensivists needs reconsideration. Consideration must be given to standardise PPE guidelines to minimise practice variations. Urgent research to evaluate PPE preparedness and severe acute respiratory syndrome coronavirus 2 transmission is required.

  • Open Access English
    Authors: 
    Kariem El-Boghdadly; Danny J.N. Wong; Ruth Owen; Mark D. Neuman; Stuart J. Pocock; J. B. Carlisle; C. Johnstone; P. Andruszkiewicz; Paul A. Baker; Bruce M Biccard; +13 more
    Publisher: Wiley
    Country: United Kingdom

    Summary Healthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID‐19. Information on tracheal intubation episodes, personal protective equipment use, and subsequent provider health status was collected via self‐reporting. The primary endpoint was the incidence of laboratory‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure‐related factors, and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow‐up of 32 (18–48 [0–116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1%, and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in females, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID‐19 subsequently reported a COVID‐19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID‐19 transmission.

  • Open Access English
    Authors: 
    Morris, Andrew Conway; Tong, Allison;
    Country: Australia

    Coronavirus disease 2019 (COVID-19), the disease arising from the beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented a major challenge to health-care systems and societies across the world. Although previous highly pathogenic coronaviruses have emerged, namely severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, neither had the spread nor the persistence to result in large clinical trials of drug therapy. Much of our therapeutic knowledge in these viruses was therefore informed by inference from observational, in vitro, and experimental model studies. As a result, when SARS-CoV-2 emerged with a noted high morbidity and mortality, initial therapeutic drug treatment was often empiric. There are currently over 4400 trials concerning COVID-19 registered on the World Health Organization international clinical trials registry, and while not all these are interventional therapeutic trials, this illustrates the desire of the international clinical-scientific community to develop systematic and evidence-based approaches for the management of this major threat. This chapter discusses the broad strategies of therapeutic pharmacological approaches suggested, namely antiviral therapy, antiinflammatories, and immunomodulatory. Nonpharmacological approaches are also to be discussed. Then, it reviews the approaches to trials and trial design, the development and use of core outcome sets, and regulation of trials in pandemic settings. It reviews the publication and preprint availability of completed trials before discussing the ethics of empiric treatment outside the context of trials.

  • Publication . Article . 2020
    Open Access English
    Authors: 
    Susan Kenny;
    Publisher: Oxford University Press
  • Open Access English
    Authors: 
    Rachel P. Rosovsky; Kristen M. Sanfilippo; Tzu-Fei Wang; Sandeep K. Rajan; Surbhi Shah; Karlyn Martin; Fionnuala Ní Áinle; Menno V. Huisman; Beverley J. Hunt; Susan R. Kahn; +4 more
    Publisher: Wiley
    Country: Netherlands

    Abstract Background Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID‐19) is unknown due to limited published data in this population. Objectives We aimed to assess current global practice and experience in management of COVID‐19–associated coagulopathy to identify information to guide prospective and randomized studies. Methods Physicians were queried about their current approach to prophylaxis, diagnosis, and treatment of VTE in patients with COVID‐19 using an online survey tool distributed through multiple international organizations between April 10 and 14, 2020. Results Five hundred fifteen physicians from 41 countries responded. The majority of respondents (78%) recommended prophylactic anticoagulation for all hospitalized patients with COVID‐19, with most recommending use of low‐molecular‐weight heparin or unfractionated heparin. Significant practice variation was found regarding the need for dose escalation of anticoagulation outside the setting of confirmed or suspected VTE. Respondents reported the use of bedside testing when unable to perform standard diagnostic imaging for diagnosis of VTE. Two hundred ninety‐one respondents reported observing thrombotic complications in their patients, with 64% noting that the complication was pulmonary embolism. Of the 44% of respondents who estimated incidence of thrombosis in patients with COVID‐19 in their hospital, estimates ranged widely from 1% to 50%. One hundred seventy‐four respondents noted bleeding complications (34% minor bleeding, 14% clinically relevant nonmajor bleeding, and 12% major bleeding). Conclusion Well‐designed epidemiologic studies are urgently needed to understand the incidence and risk factors of VTE and bleeding complications in patients with COVID‐19. Randomized clinical trials addressing use of anticoagulation are also needed.

  • Open Access English
    Authors: 
    Patrick Hassett; Gerard F. Curley; Maya Contreras; Claire Masterson; Brendan D. Higgins; Timothy O'Brien; James Devaney; Daniel O'Toole; John G. Laffey;
    Publisher: Springer-Verlag
    Project: EC | HA-NFKB-VILI (207777)

    Purpose Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of superoxide dismutase (EC-SOD) to reduce the severity of endotoxin-induced lung injury. Methods Animals were randomly allocated to undergo intratracheal instillation of (1) surfactant alone (vehicle); (2) adeno-associated virus (AAV) vectors containing a null transgene (AAV-null); and (3) adeno-associated virus vectors containing the EC-SOD transgene (AAV-EC-SOD) and endotoxin was subsequently administered intratracheally. Two additional groups were randomized to receive (1) vehicle or (2) AAV-EC-SOD, and to undergo sham (vehicle) injury. The severity of the lung injury was assessed in all animals 24 h later. Results Endotoxin produced a severe lung injury compared to sham injury. The AAV vector encoding EC-SOD increased lung EC-SOD concentrations, and enhanced the antioxidant capacity of the lung. EC-SOD overexpression decreased the severity of endotoxin-induced ALI, reducing the decrement in systemic oxygenation and lung compliance, decreasing lung permeability and decreasing histologic injury. EC-SOD attenuated pulmonary inflammation, decreased bronchoalveolar lavage neutrophil counts, and reduced interleukin-6 and CINC-1 concentrations. The AAV vector itself did not contribute to inflammation or to lung injury. Conclusions Pulmonary overexpression of EC-SOD protects the lung against endotoxin-induced ALI. Electronic supplementary material The online version of this article (doi:10.1007/s00134-011-2309-y) contains supplementary material, which is available to authorized users.

  • Open Access English
    Authors: 
    Luke A. J. O'Neill; Mihai G. Netea;
    Publisher: Springer Science and Business Media LLC
    Country: Netherlands
    Project: EC | TRAIN-OLD (833247), EC | Metabinnate (834370)

    Bacillus Calmette–Guérin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19. Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.

Advanced search in Research products
Research products
arrow_drop_down
Searching FieldsTerms
Any field
arrow_drop_down
includes
arrow_drop_down
Include:
The following results are related to COVID-19. Are you interested to view more results? Visit OpenAIRE - Explore.
7,040 Research products, page 1 of 704
  • Open Access English
    Authors: 
    Narayan Prasad; Mansi Bhatt; Sanjay K. Agarwal; H.S. Kohli; Natarajan Gopalakrishnan; Edwin Fernando; Manisha Sahay; Mohan Rajapurkar; Arpita Roy Chowdhary; Manish Rathi; +13 more
    Publisher: Elsevier BV

    Introduction The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. Methods We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. Results The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. Conclusion Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

  • Open Access English
    Authors: 
    Lisa M. Raven; Ann McCormack; Jerry R. Greenfield;
    Publisher: Oxford University Press
  • Open Access English
    Authors: 
    Bernard David Naughton; Ebru Akgul;
    Publisher: SAGE Publishing

    The entry of falsified and substandard medicines into the legitimate pharmaceutical supply chain has negative impacts on healthcare systems, patient safety, and patient access to medicine. The COVID-19 pandemic has highlighted the importance of access to safe medicine through legitimate pharmaceutical supply chains and the willingness of criminals to target medical products such as PPE (personal protective equipment) and COVID-19 treatments. In this article, we analyse data from the United Kingdom (UK) national medicine alert and recall database to identify and understand recent cases of substandard and falsified medicine in the UK’s healthcare systems. Using the UK as a case study, we describe that national drug alert and recall data are useful in their current form to record and understand cases of substandard and falsified medicines in the supply chain. However, if regulatory agencies published further data, these drug recall databases may be useful to support longitudinal and international comparative medicine quality studies. We suggest that regulatory agencies publish the number of affected medicine packs in each recalled batch, as part of the recall process. This will help policy makers, practitioners, and researchers to better understand, monitor and compare the quality of medicines within legitimate supply chains.

  • Open Access English
    Authors: 
    Arvind Rajamani; Ashwin Subramaniam; Kiran Shekar; Jumana Haji; Jinghang Luo; Shailesh Bihari; Wai Tat Wong; Navya Gullapalli; Markus Renner; Claudia Maria Alcancia; +2 more
    Country: Australia

    Abstract Background There has been a surge in coronavirus disease 2019 admissions to intensive care units (ICUs) in Asia-Pacific countries. Because ICU healthcare workers are exposed to aerosol-generating procedures, ensuring optimal personal protective equipment (PPE) preparedness is important. Objective The aim of the study was to evaluate PPE preparedness across ICUs in six Asia-Pacific countries during the initial phase of the coronavirus disease 2019 pandemic, which is defined by the World Health Organization as guideline adherence, training healthcare workers, procuring stocks, and responding appropriately to suspected cases. Methods A cross-sectional Web-based survey was circulated to 633 level II/III ICUs of Australia, New Zealand (NZ), Singapore, Hong Kong (HK), India, and the Philippines. Findings Two hundred sixty-three intensivists responded, representing 231 individual ICUs eligible for analysis. Response rates were 68–100% in all countries except India, where it was 24%. Ninety-seven percent of ICUs either conformed to or exceeded World Health Organization recommendations for PPE practice. Fifty-nine percent ICUs used airborne precautions irrespective of aerosol generation procedures. There were variations in negative-pressure room use (highest in HK/Singapore), training (best in NZ), and PPE stock awareness (best in HK/Singapore/NZ). High-flow nasal oxygenation and noninvasive ventilation were not options in most HK (66.7% and 83.3%, respectively) and Singapore ICUs (50% and 80%, respectively), but were considered in other countries to a greater extent. Thirty-eight percent ICUs reported not having specialised airway teams. Showering and “buddy systems” were underused. Clinical waste disposal training was suboptimal (38%). Conclusions Many ICUs in the Asia-Pacific reported suboptimal PPE preparedness in several domains, particularly related to PPE training, practice, and stock awareness, which requires remediation. Adoption of low-cost approaches such as buddy systems should be encouraged. The complete avoidance of high-flow nasal oxygenation reported by several intensivists needs reconsideration. Consideration must be given to standardise PPE guidelines to minimise practice variations. Urgent research to evaluate PPE preparedness and severe acute respiratory syndrome coronavirus 2 transmission is required.

  • Open Access English
    Authors: 
    Kariem El-Boghdadly; Danny J.N. Wong; Ruth Owen; Mark D. Neuman; Stuart J. Pocock; J. B. Carlisle; C. Johnstone; P. Andruszkiewicz; Paul A. Baker; Bruce M Biccard; +13 more
    Publisher: Wiley
    Country: United Kingdom

    Summary Healthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID‐19. Information on tracheal intubation episodes, personal protective equipment use, and subsequent provider health status was collected via self‐reporting. The primary endpoint was the incidence of laboratory‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure‐related factors, and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow‐up of 32 (18–48 [0–116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1%, and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in females, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID‐19 subsequently reported a COVID‐19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID‐19 transmission.

  • Open Access English
    Authors: 
    Morris, Andrew Conway; Tong, Allison;
    Country: Australia

    Coronavirus disease 2019 (COVID-19), the disease arising from the beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented a major challenge to health-care systems and societies across the world. Although previous highly pathogenic coronaviruses have emerged, namely severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, neither had the spread nor the persistence to result in large clinical trials of drug therapy. Much of our therapeutic knowledge in these viruses was therefore informed by inference from observational, in vitro, and experimental model studies. As a result, when SARS-CoV-2 emerged with a noted high morbidity and mortality, initial therapeutic drug treatment was often empiric. There are currently over 4400 trials concerning COVID-19 registered on the World Health Organization international clinical trials registry, and while not all these are interventional therapeutic trials, this illustrates the desire of the international clinical-scientific community to develop systematic and evidence-based approaches for the management of this major threat. This chapter discusses the broad strategies of therapeutic pharmacological approaches suggested, namely antiviral therapy, antiinflammatories, and immunomodulatory. Nonpharmacological approaches are also to be discussed. Then, it reviews the approaches to trials and trial design, the development and use of core outcome sets, and regulation of trials in pandemic settings. It reviews the publication and preprint availability of completed trials before discussing the ethics of empiric treatment outside the context of trials.

  • Publication . Article . 2020
    Open Access English
    Authors: 
    Susan Kenny;
    Publisher: Oxford University Press
  • Open Access English
    Authors: 
    Rachel P. Rosovsky; Kristen M. Sanfilippo; Tzu-Fei Wang; Sandeep K. Rajan; Surbhi Shah; Karlyn Martin; Fionnuala Ní Áinle; Menno V. Huisman; Beverley J. Hunt; Susan R. Kahn; +4 more
    Publisher: Wiley
    Country: Netherlands

    Abstract Background Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID‐19) is unknown due to limited published data in this population. Objectives We aimed to assess current global practice and experience in management of COVID‐19–associated coagulopathy to identify information to guide prospective and randomized studies. Methods Physicians were queried about their current approach to prophylaxis, diagnosis, and treatment of VTE in patients with COVID‐19 using an online survey tool distributed through multiple international organizations between April 10 and 14, 2020. Results Five hundred fifteen physicians from 41 countries responded. The majority of respondents (78%) recommended prophylactic anticoagulation for all hospitalized patients with COVID‐19, with most recommending use of low‐molecular‐weight heparin or unfractionated heparin. Significant practice variation was found regarding the need for dose escalation of anticoagulation outside the setting of confirmed or suspected VTE. Respondents reported the use of bedside testing when unable to perform standard diagnostic imaging for diagnosis of VTE. Two hundred ninety‐one respondents reported observing thrombotic complications in their patients, with 64% noting that the complication was pulmonary embolism. Of the 44% of respondents who estimated incidence of thrombosis in patients with COVID‐19 in their hospital, estimates ranged widely from 1% to 50%. One hundred seventy‐four respondents noted bleeding complications (34% minor bleeding, 14% clinically relevant nonmajor bleeding, and 12% major bleeding). Conclusion Well‐designed epidemiologic studies are urgently needed to understand the incidence and risk factors of VTE and bleeding complications in patients with COVID‐19. Randomized clinical trials addressing use of anticoagulation are also needed.

  • Open Access English
    Authors: 
    Patrick Hassett; Gerard F. Curley; Maya Contreras; Claire Masterson; Brendan D. Higgins; Timothy O'Brien; James Devaney; Daniel O'Toole; John G. Laffey;
    Publisher: Springer-Verlag
    Project: EC | HA-NFKB-VILI (207777)

    Purpose Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of superoxide dismutase (EC-SOD) to reduce the severity of endotoxin-induced lung injury. Methods Animals were randomly allocated to undergo intratracheal instillation of (1) surfactant alone (vehicle); (2) adeno-associated virus (AAV) vectors containing a null transgene (AAV-null); and (3) adeno-associated virus vectors containing the EC-SOD transgene (AAV-EC-SOD) and endotoxin was subsequently administered intratracheally. Two additional groups were randomized to receive (1) vehicle or (2) AAV-EC-SOD, and to undergo sham (vehicle) injury. The severity of the lung injury was assessed in all animals 24 h later. Results Endotoxin produced a severe lung injury compared to sham injury. The AAV vector encoding EC-SOD increased lung EC-SOD concentrations, and enhanced the antioxidant capacity of the lung. EC-SOD overexpression decreased the severity of endotoxin-induced ALI, reducing the decrement in systemic oxygenation and lung compliance, decreasing lung permeability and decreasing histologic injury. EC-SOD attenuated pulmonary inflammation, decreased bronchoalveolar lavage neutrophil counts, and reduced interleukin-6 and CINC-1 concentrations. The AAV vector itself did not contribute to inflammation or to lung injury. Conclusions Pulmonary overexpression of EC-SOD protects the lung against endotoxin-induced ALI. Electronic supplementary material The online version of this article (doi:10.1007/s00134-011-2309-y) contains supplementary material, which is available to authorized users.

  • Open Access English
    Authors: 
    Luke A. J. O'Neill; Mihai G. Netea;
    Publisher: Springer Science and Business Media LLC
    Country: Netherlands
    Project: EC | TRAIN-OLD (833247), EC | Metabinnate (834370)

    Bacillus Calmette–Guérin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19. Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.