ABSTRACT
Introduction: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in-vitro activity against SARS-CoV-2. This clinical trial was designed to investigate the efficacy of carrageenan nasal and throat sprays in reducing the rate and severity of COVID-19 infection. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Methods: and analysis: A single centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water) or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks.Primary outcome: Acquisition of COVID-19 infection as confirmed by positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Hypothesis: That carrageenan spray will reduce SARS-CoV-2 attachment to the naso- and oropharyngeal mucosal epithelial cells thus reducing the effective viral infective dose preventing COVID19 infection and reducing disease severity where infection is not prevented. Ethics and dissemination : Ethics approval was obtained from Research Ethics Committee 6 South Wales (REC Reference 20/WA/0298; IRAS 283187) on the 18 th November 2020. The results will be submitted for publication in a peer-reviewed journal. Trial registration number: NCT04590365; registered on ClinicalTrials.gov (NCT04590365) on the 19 th October 2020.
Subject(s)
COVID-19 , Oropharyngeal NeoplasmsABSTRACT
ObjectivesTo confirm the incidence of perioperative SARS-CoV-2 infection and associated mortality after surgery. Design and settingAnalysis of routine electronic health record data from National Health Service (NHS) hospitals in England. MethodsWe extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between 1st January 2020 and 31st October 2020. The exposure was SARS-CoV-2 infection defined by ICD-10 codes. The primary outcome measure was 90-day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson co-morbidity index, index of multiple deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals. ResultsWe identified 1,972,153 patients undergoing surgery of whom 11,940 (0.6%) had SARS-CoV-2. In total, 19,100 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 2,618/11,940 [21.9%] vs No SARS-CoV-2: 16,482/1,960,213 [0.8%]; OR: 5.8 [5.5 - 6.1]; p<0.001). Amongst patients undergoing elective surgery 1,030/1,374,985 (0.1%) had SARS-CoV-2 of whom 83/1,030 (8.1%) died, compared with 1,092/1,373,955 (0.1%) patients without SARS-CoV-2 (OR: 29.0 [22.5 -37.3]; p<0.001). Amongst patients undergoing emergency surgery 9,742/437,891 (2.2%) patients had SARS-CoV-2, of whom 2,466/9,742 (25.3%) died compared with 14,817/428,149 (3.5%) patients without SARS-CoV-2 (OR: 5.7 [5.4 - 6.0]; p<0.001). ConclusionsThe low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIHigh mortality rates have been reported amongst surgical patients who develop COVID-19 but we dont know how this compares to the concurrent surgical population unaffected by COVID-19. C_LIO_LIStrict infection prevention and control procedures have substantially reduced the capacity of surgical treatment pathways in many hospitals. C_LIO_LIThe very large backlog in delayed and cancelled surgical procedures is a growing public health concern. C_LI What this study addsO_LIFewer than 1 in 100 surgical patients are affected by COVID-19 in the English National Health Service. C_LIO_LIElective surgical patients who do develop COVID-19 are 30 times more likely to die while in hospital. C_LIO_LIInfection prevention and control procedures in NHS surgical pathways are highly effective but cannot be safely relaxed. C_LI
Subject(s)
COVID-19ABSTRACT
BackgroundThe response to COVID-19 has required cancellation of all but the most urgent surgeries, including many cancer operations. We estimated the number of cancelled surgical procedures in the National Health Service (NHS) in England due to COVID-19 and how this deficit would change over time once elective surgery was reintroduced. MethodsModelling study using Hospital Episode Statistics (HES) data from 2014 to 2019. Using NHS England definitions, surgical procedures were grouped into four classes of urgency. We calculated time-weighted average numbers of surgical procedures from 1st March 2020 and extrapolated to 28th February 2021 informed by activity in previous years. We estimated the procedure deficit using multiple conservative assumptions and then modelled the reintroduction of elective surgery between 1st June 2020 and 28th February 2021, estimating the resources required to achieve this. Costs of surgery were calculated using NHS reference costs. Estimates are reported with 95% confidence intervals. Findings4,547,534 (3,318,195 - 6,250,771) patients with pooled mean age of 53.5 years were expected to undergo surgery in the NHS in England between 1st March 2020 and 28th February 2021. Due to COVID-19, 749,248 (513,565 - 1,077,448) surgical procedures were cancelled by 31st May 2020. As current guidelines require a gradual reintroduction of elective surgery, this deficit will increase further and 2,270,178 (1,453,057 - 3,363,472) patients will be awaiting surgery by 28th February 2021. The cost of these delayed procedures is {pound}4,688,318,443 ({pound}2,726,364,240 - {pound}7,070,166,056). However, the safe delivery of surgery during the pandemic will require substantial extra resources including personal protective equipment and universal preoperative screening, leading to additional costs of {pound}606,252,901 ({pound}521,159,931 - {pound}730,720,808). InterpretationReintroduction of elective surgery during the pandemic response in NHS England will be associated with substantial treatment delays for many patients, and a large increase in treatment costs. FundingNIHR (DRF-2018-11-ST2-062) to AJF.