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14th September 2021
An analysis of all COVID-19-related deaths in England between the 2nd of January and July 2021, has been published by the Office for National Statistics (ONS). The data include a breakdown of all recorded deaths analysed by vaccination status. Clearly, a certain number of both infections and deaths among those who have been vaccinated, referred to as breakthrough infections, are likely to occur simply because the COVID-19 vaccines have been administered to many millions of people and none can be considered as 100 per cent effective.
The risk of becoming infected with COVID-19 is, according to the ONS infection survey, highest within the first 21 days after receipt of the primer vaccine dose. The bulletin from the ONS examines deaths in relation to vaccination status and uses age-standardised mortality rates, which adjusts for differences in the population age distribution.
There were a total of 640 deaths in those who had received two COVID-19 vaccines; 182 within 21 days of their second vaccine dose and 458, 21 days after their second dose. Together, both groups represent 1.2% of all COVID-19 related deaths although only 0.8% (458/51,281) of all deaths occurred 21 days after the second vaccine dose. In other words, less than 1% of all COVID-19 related deaths occurred in those who were fully vaccinated. However, it is worth noting that the more infectious delta variant only became the dominant strain, according to the ONS, since the end of May 2021 and hopefully future bulletins will report upon any associated mortality changes.
In cases where the date of infection was known, among those who had received two vaccinations, 47.5% became infected 14 or more days after the second dose, leading to 256 deaths.
Characteristics of individuals with breakthrough deaths
Among the 256 deaths occurring 14 or more days after infection, linked data, which provides demographic and clinical information was available for 252 individuals. The information showed that the average age of death among these fully vaccinated individuals was 84 years. Nearly two-thirds (61.1%) were male and 76.6% were described as clinically vulnerable and 13.1% of deaths occurred among immunocompromised patients.
The latest set of ONS data clearly shows that COVID-19 related deaths are significantly reduced due to vaccination but also serves as a reminder that deaths will still occur, especially among the clinically vulnerable and immunocompromised, highlighting the need for booster doses.
27th July 2021
Patients hospitalised with COVID-19 experience a wide range of organ system complications including cardiac problems such as arrhythmias and myocarditis. Due to its widespread availability and potential for bedside use, echocardiographic information captured through transthoracic echocardiography (TTE), has become recognised as the preferred first-line imaging modality for patients with either known or suspected cardiac problems. Nevertheless, advice from the European Association of Cardiovascular Imaging (EACVI) is that cardiac imaging should only be performed where appropriate and only if it is likely to substantially change patient management or be lifesaving. Whether echocardiographic data can help with risk stratification in patients hospitalised with COVID-19 has been poorly explored. Thus, a team from the Department of Medicine and Surgery, University of Salerno, Italy, sought to determine whether echocardiographic parameters were associated with in-hospital mortality among those with COVID-19. They undertook a retrospective observational study among consecutive patients admitted to hospital with confirmed COVID-19 infection at seven Italian centres between March and April 2020. All patients underwent TTE within 48 hours of admission and the need for TTE was confirmed as being clinically appropriate by a consultant cardiologist. All patient demographics (age, gender, weight and height) clinical (i.e., co-morbidities, current therapies), laboratory and echocardiographic data were collected and stored electronically. Echocardiographic data included an evaluation of left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV). Left ventricular function was assessed by determination of left ventricular ejection fraction (LVEF) and the parameter used to assess global right ventricular function was tricuspid annular plane systolic excursion (TAPSE). The clinical course of patients was also recorded including the proportion who developed acute respiratory distress syndrome (ARDS).
A total of 1401 patients were hospitalised with COVID-19 and of whom, 226 (16.1%) underwent echocardiographic testing with TTE. Among this smaller cohort, the mean age was 68.9 years (62.4% male) and the majority (61.1%) had hypertension. In addition, 36 and 13 patients had previously undergone percutaneous coronary interventions and coronary artery bypass grafting respectively. Overall, 68 patients within this cohort died in hospital among whom, ARDS was more common (83.3% vs 31%, p <0.001). In those who died in hospital, there was a lower mean LVEF (47.6% vs 55.5%, death vs survivors, p < 0.001) and a lower TAPSE (17.5 vs 21.7, p < 0.001). Using regression analysis and after adjustment for various factors, amongst patients who experienced in-hospital mortality, reduced LVEF was independently associated with in-hospital mortality (relative risk, RR = 0.93, 95% CI 0.89–0.97, p < 0.001), as was reduced TAPSE (RR = 0.80, 95% CI 0.72–0.88) and the development of ARDS (RR = 3.05).
In discussing these findings, the authors highlighted how the risk of mortality was increased among patients with ARDS and the echocardiographic parameters TAPSE < 17 and an LVEF <50%. They suggested that TTE was useful for risk stratification in COVID-19 patients but recognised the limitation of not having TTE data prior to hospitalisation. The authors concluded that while their study has suggested an important relationship between echocardiographic parameters and in-hospital mortality, further studies were necessary to confirm these findings.
Silverio A et al. Clinical conditions and echocardiographic parameters associated with mortality in COVID-19. Eur J Clin Invest 2021
28th May 2021
Infection with COVID-19 has been found to be associated with raised levels of systemic inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and other cytokines. In addition, data have revealed how engagement of protein platforms (inflammasomes) and in particular, the nucleotide binding domain-like pyrin domain 3 (NLRP3) inflammasome, is strongly associated with disease severity.
The anti-inflammatory gout drug, colchicine, is known to inhibit the NLRP3 inflammasome and may therefore be of value in the treatment of patients hospitalised with COVID-19. The randomised evaluation of COVID-19 therapy (RECOVERY) trial aims to evaluate a number of therapeutic options for the management of hospitalised patients infected with COVID-19. The RECOVERY group have investigated several different treatments and recently examined the use of colchicine. For the present trial, patients were randomised 1:1 to usual care or usual care plus colchicine at a dose of 1mg after randomisation, followed by 500mcg 12 hours later and then 500mcg twice daily (orally or via nasogastric tube) for 10 days or until discharged from hospital. However, although patients were randomised, this was an open label trial, hence both treating clinicians and patients were not masked to treatment allocation although the study steering group and investigated were masked to outcome data during the trial. The primary outcome was all-cause mortality and assessed at 28 days post-randomisation. Secondary outcomes included time to hospital discharge and the need for invasive mechanical ventilation.
A total of 5610 patients with a mean age of 63.4 years (31% female) and of predominately (77%) White ethnicity, were randomised to colchicine and 5730 to usual care. The median duration of treatment with colchicine was 6 days and use of all other treatments was similar between the two groups. The proportion of patients allocated to colchicine who achieved the primary outcome was not different to placebo (21%) and the median time to hospital discharge was 10 days and again, similar between the two groups. Moreover, an equal number of patients progressed to invasive mechanical ventilation (70%).
In discussing these findings, the authors commented on how the use of colchicine had no impact on mortality, duration of hospitalisation or the need for mechanical ventilation. Additionally, this effect was evidence across all ages, ethnic groups and irrespective of symptom duration prior to randomisation. They also speculated that the anti-inflammatory properties of colchicine were either inadequate or did not sufficiently target the pathways induced by COVID-19 and concluded that the drug was of no benefit to those hospitalised with COVID-19.
RECOVERY Collaborative Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. MedRxiv 2021