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1.
Clin Exp Immunol ; 202(2): 162-192, 2020 11.
Article in English | MEDLINE | ID: mdl-32935331

ABSTRACT

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled-up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/immunology , Humans , Pneumonia, Viral/immunology , SARS-CoV-2 , Vaccination
2.
Colorectal Dis ; 22(1): 86-94, 2020 01.
Article in English | MEDLINE | ID: mdl-31344300

ABSTRACT

BACKGROUND: Despite implementation of enhanced recovery after surgery (ERAS) and laparoscopic techniques, postoperative ileus (POI) remains frequent after colorectal surgery, impacting the patient, their recovery and health-care resources. Presently there are no tests that reliably predict or enable early POI diagnosis. Volatile organic compounds (VC) are products of human and microbiota cellular metabolism and we hypothesised that a detectable alteration occurs in POI. METHOD: This was a prospective observational study of patients undergoing laparoscopic colorectal resection within an established ERAS programme. Standardized end-expiratory breath sampling was performed on the morning of surgery and on the first three postoperative mornings. The concentrations of VCs commonly found in intestinal gas were analysed using selected ion flow tube mass spectrometry and GastroCH4 ECK®. Feasibility data, bowel preparation, postoperative oral intake, POI and 30-day morbidity were recorded. RESULTS: Of the 75 potentially eligible patients, 58 (77%) agreed to participate. Per-protocol breath sampling was successfully completed in 94%. There were no analytical failures. Baseline and postoperative concentrations of VCs were broadly comparable and were not altered by bowel preparation or postoperative oral intake. POI developed in 14 (29%) patients. Preoperative ammonia concentration was higher in patients who developed POI [830 parts per billion (ppb) vs 510 ppb, P = 0.027]. There was an increase in the concentration of acetic acid detected on day 2 in patients who developed POI (99 ppb vs 171 ppb, P = 0.021). CONCLUSION: Repeated VC breath sampling and analysis is feasible in the perioperative setting. An elevated ammonia concentration on the morning of surgery may be a potential predictor of POI.


Subject(s)
Breath Tests/methods , Colectomy/adverse effects , Intestinal Pseudo-Obstruction/etiology , Postoperative Complications/etiology , Volatile Organic Compounds/analysis , Aged , Ammonia/analysis , Colectomy/methods , Colectomy/rehabilitation , Enhanced Recovery After Surgery , Feasibility Studies , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Laparoscopy/rehabilitation , Male , Middle Aged , Perioperative Period , Predictive Value of Tests , Proctectomy/adverse effects , Proctectomy/methods , Proctectomy/rehabilitation , Prospective Studies , Risk Assessment/methods , Risk Factors
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