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Take a look at a selection of our recent media coverage:

Remdesivir use in COVID-19 patients requiring ventilator support confers no advantage over standard care

12th April 2022

A study found that remdesivir use among COVID-19 patients in need of ventilator support offers no advantage over standard care

Remdesivir use among patients hospitalised with COVID-19 requiring ventilator or oxygen support did not improve clinical outcomes after 15 days compared with standard care. This was the conclusion of a European, multi-centre, open label, randomised, controlled trial.

Remdesivir is a pro-drug that is converted into a nucleoside analog and incorporated by the RNA-dependent RNA polymerase of COVID-19 into the growing RNA product before RNA synthesis stalls. The drug was approved by the EMA in June 2020 for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. Moreover, early data on remdesivir was encouraging and in a study of over 1000 patients, those randomised to remdesivir use had a median recovery time of 10 days compared with 15 days in those who received placebo. In contrast, however, the World Health Organization (WHO) Solidarity Trial, concluded that remdesivir, along with hydroxychloroquine, lopinavir and interferon regimens, had little or no effect on hospitalised patients with COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. 

With such conflicting results, the European team undertook the DisCoVeRy trial and which was designed to evaluate the safety and efficacy of possible therapeutic agents in hospitalised adult patients diagnosed with COVID-19. Recruited patients were adults hospitalised with COVID-19 who presented with either evidence of rales/crackles on examination and a SpO2 < 94% on room air or had a requirement for supplemental oxygen, high flow oxygen devices, non-invasive ventilation and/or mechanical ventilation. Patients were randomised 1:1 to either remdesivir use (200 mg on day 1 followed by a 100 mg 1-hour infusion once daily for 10 days) or standard care, which included the use of corticosteroids and anticoagulants. The primary outcome was the patient’s clinical status at day 15 as recorded on the 7-point ordinal WHO scale. The scale, which represents increasingly severe disease, ranges from 1 represented those not hospitalised and with no limitation on activities, through 5 (hospitalised on non-invasive ventilation or high flow oxygen) and 6 (hospitalised on invasive mechanical ventilation or extracorporeal membrane oxygenation) and 7 (dead). Several secondary outcomes were also used including in-hospital mortality and 28-day mortality.

Remdesivir use and clinical outcomes

A total of 857 participants with a median age of 64 years (69.5% male) were randomised to remdesivir (420) or standard care and, at randomisation, 39.4% of individuals had severe COVID-19.

Overall, 73.6% of participants had at least one co-morbidity with the most frequent being obesity (34.1%), cardiac disease (28%) and diabetes (27%).

At day 15, a similar proportion of those assigned to remdesivir and standard care were categorised as 1 on the WHO scale (14.8% vs 17%, remdesivir vs standard care) and a similar proportion had died (5% vs 6%). Overall, there was no significant difference between those assigned to remdesivir use or standard care (odds ratio, OR = 1.02, 95% CI 0.62 – 1.70, p = 0.93). Additionally, there were no significant differences in the distribution of the 7-point scale at day 29 (OR = 1.11, 95% CI 0.87 – 1.43, p = 0.40).

Furthermore, there were no significant differences for each of the secondary outcomes or subgroup analyses according to age, sex, duration of symptoms prior to randomisation or in the level of detectable viral loads at each sampling time.

The authors therefore concluded that the remdesivir use had no impact on clinical outcomes compared with standard care at either day 15 or day 29.

Citation
Ader F et al. Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial MedRxiv 2022

Prone positioning of no value in non-critically ill patients with COVID-19

4th April 2022

Prone positioning can reduce respiratory failure risk but it is unclear whether this approach helps non-critically ill patients with COVID-19

The use of prone positioning (PP) in non-critically ill patients hospitalised with COVID-19 does not improve outcomes according to the results of a large, pragmatic trial by researchers from the Division of General Internal Medicine, Sinai Health, Toronto, Canada.

Prone positioning involves lying a patient face down onto their anterior chest and abdomen to take advantage of physiologic changes that can result in improved oxygenation through decreased ventilation/perfusion mismatch and potentially, decreased lung injury. Among patients with COVID-19, pneumonia is the most common reason for admission to hospital and severe pneumonia can result in acute hypoxic respiratory failure necessitating supplemental oxygen therapy or respiratory support with mechanical ventilation. Acute respiratory distress syndrome (ARDS) can be precipitated by a pneumonia and for patients with severe ARDS, there is a strong recommendation to use prone positioning for more than 12 hours per day. Some evidence from a meta-trial has suggested that awake prone positioning of patients with hypoxaemic respiratory failure caused by COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. This led the authors to concluded that their results support the routine use of awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. However, whether this approach would benefit less severely ill patients, i.e., lead to a reduced risk of death or respiratory failure remains to be determined and was the subject of the present study by the Canadian team.

The trial recruited patients hospitalised with COVID-19 who required supplemental oxygen and who were independently able to adopt PP. Patients were randomised 1:1 to proning or standard of care, i.e., where there was no instruction to adopt a prone position. All participants were then followed until discharge from hospital or death or for 30 days. Among those randomised to PP, it was recommended that this position was used four times a day (2 hours per session) and participants were also asked to sleep overnight in this position. The primary outcome was a composite of in-hospital death, mechanical ventilation or worsening respiratory failure which was defined as the need for at least 60% fraction of inspired oxygen for more than 24 hours.

Prone positioning and outcomes

A total of 248 individuals with a median age of 56 years (36% female) were included in the analysis. Overall co-morbidities were hypertension (40%), diabetes (27%) and COPD or asthma (11%). The median time spent in PP during the first 72 hours was 6 hours and 0 hours in the control group.

The median time until the primary outcome was one day and occurred in 14% of those assigned to either group (odds ratio, OR = 0.92, 95% CI 0.44 – 1.92). There were also no differences in subgroup analyses based on age, or when stratified by baseline hypoxia.

The authors concluded that the use of prone positioning among hypoxic patients with COVID-19 did not improve clinical outcomes. However, they added that the wide confidence intervals precluded definitely ruling out benefit or harm.

Citation
Fralick M et al. Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE) BMJ 2022

Empagliflozin effective for patients hospitalised with acute heart failure

14th March 2022

Empagliflozin given to patients with acute de novo and decompensated heart failure upon admission to hospital improves clinical outcomes

Empagliflozin administered to patients once hospitalised with either de novo or decompensated heart failure leads to a clinically significant benefit over the next 90 days. This was the finding of a randomised trial by researchers from the University of Groningen Department of Cardiology, Groningen, The Netherlands.

Among patients with type 2 diabetes, sodium–glucose cotransporter 2 inhibitors such as empagliflozin, have been shown to reduce the risk of hospitalisation for heart failure and the risk of serious adverse renal events. Although an anti-diabetic agent and based on several recent clinical trials, empagliflozin is now also indicated for the treatment of symptomatic chronic heart failure with a reduced ejection fraction.

However, whether the drug would still provide a clinical benefit to patients if given to those already admitted to hospital with heart failure is unknown. For the present study, the Dutch researchers were interested in exploring whether empagliflozin would be clinically advantageous for patients, not only hospitalisation with heart failure but also on reducing worsening heart failure events (HFEs) and on the improvement of symptoms. They performed the Oral EMPagliflozin 10 mg Compared to Placebo, Initiated in Patients Hospitalised for acUte Heart faiLure (de Novo or Decompensated Chronic HF) Who Have Been StabilisEd or EMPULSE trial.

Included patients were those who had a primary diagnosis of acute de novo or decompensated chronic heart failure, irrespective of left ventricular ejection fraction. Individuals were randomised 1:1 to empagliflozin 10 mg or placebo and this occurred after at least 24 hours but no later than 5 days after admission, as early as possible after stabilisation and while still in hospital. The primary outcome of the study was the clinical benefit at 90 days, which was defined as a composite outcome of time to all-cause death, the number of HFEs, the time to the first HFE and a 5- point or greater difference in change from baseline in Kansas City Cardiomyopathy Questionnaire KCCQ after 90 days of treatment. The KCCQ is patient-reported outcome instrument that provides a measure of symptoms and physical limitations associated with heart failure. Assessments were based on the win ratio, which offers greater statistical power to detect and quantify a treatment difference by using all available information contained in the component outcomes.

Empagliflozin and clinical outcomes

A total of 530 patients with a median age of 71 years (34% women) were randomised to active treatment or placebo, within a median of 3 days after admission to hospital. The proportion of patients with diabetes ranged from 46.8% to 43.8%.

Overall, 33 (6.2%) of all patients died, 11 in the empagliflozin group and there were 67 patients assigned to empagliflozin who experienced at least one HFE. The adjusted mean change in KCCQ total score from baseline to 90 days was 36.2 in the empagliflozin group and 31.7 in the placebo arm. More patients taking empagliflozin had a clinical benefit compared to placebo (stratified win ratio = 1.36, 95% CI 1.09 – 1.68, p = 0.0054). This benefit was observed irrespective of the ejection fraction and for both de novo and decompensated heart failure in the presence or absence of diabetes.

The authors concluded that initiating empagliflozin as a component of usual clinical care for patients hospitalised with acute heart failure led to clinically meaningful benefits.

Citation
Voors AA et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022

Vitamin D-deficient patients 14-times more likely to get severe COVID-19

7th February 2022

Vitamin D-deficient patients are more likely to get severe COVID-19 and die compared with those with sufficient levels of the vitamin

Vitamin D-deficient individuals have been shown to be much more likely to experience severe COVID-19 and die in comparison to those with normal or sufficient levels of the vitamin. This was an important finding by researchers from the Department of Otolaryngology, Head and Neck Surgery, Galilee Medical Center, Israel.

Previous research has shown how vitamin D has a protective effect against respiratory tract infections when taken as a once daily dosage. Moreover, a 2021 systematic review which included 46 randomised controlled trials with 48,488 individuals, re-affirmed the benefits of daily supplementation with 400 –1000 IU of vitamin D for reducing the risk of acute respiratory tract infections compared with placebo. Several studies undertaken during the COVID-19 pandemic have suggested that a vitamin D deficient status was associated with increased COVID-19 risk. Furthermore, other data has shown how the vitamin D level is markedly low in severe COVID-19 patients although this was measured once in hospital. However, what is less clear, is the extent to which pre-infection or baseline vitamin D levels, impact on the clinical outcomes once patients become infected with COVID-19.

For the present study, the Israeli team set out to determine whether COVID-19 disease severity correlated with patient’s most recent vitamin D levels as documented in their medical records. They undertook a retrospective study of hospitalised, adult patients with a PCR-confirmed COVID-19 infection. The team defined COVID-19 disease severity at the point of highest severity. For instance, if a patient was admitted with mild disease and which subsequently deteriorated, this would be categorised as a critical illness. They used the most recent medical record for vitamin D status and then categorised patients as vitamin D deficient (< 20 ng/ml), insufficient (20 – 29.9 ng/ml), adequate (30 – 39.9 ng/ml) and high-normal (40 ng/ml). They used multivariable analysis to examine the relationship between vitamin D status and COVID-19 disease severity.

Vitamin D deficient status and COVID-19 severity

A total of 253 individuals with a mean age of 63.3 years (56.9% female) were included in the analysis. Among the cohort, 52.5% were vitamin D-deficient, 14.2% had levels between 20 and 30ng/ml and 15.8% had a level of 40ng/ml or above.

Mortality from COVID-19 occurred in 2.3% of those with adequate vitamin D levels and 25.6% of individuals who were vitamin D deficient (p < 0.001). When stratifying COVID-19 disease severity with vitamin D status, among those with the lowest vitamin D levels, a higher proportion (87.4%) developed severe or critical COVID-19 compared to mild to moderate disease, 34.3% (p < 0.001). In regression analysis, patients with vitamin D deficiency compared to those with high-normal levels (40 ng/ml) were 14 times more likely to develop severe or critical illness (odds ratio, OR = 14, 95% CI 4 – 51, p < 0.001). Overall, when comparing pre-hospital vitamin D levels with COVID-19 disease severity, there was a clear inverse relationship such that as vitamin D levels reduced, COVID-19 disease severity increased.

Further analysis revealed that age was an independent risk factor for more severe disease and the strongest correlation between vitamin D status and COVID-19 severity occurred in those aged 50 years and over (r = – 0.74, p < 0.001). However, this correlation was still significant among those under 50 years of age (r = -0.66, p < 0.001).

The authors described how early on in the current pandemic, there was much debate on the role of vitamin D in protecting against COVID-19. They suggested that their study provided further evidence of how vitamin D deficient patients were at a much higher risk of more severe COVID-19 infection and called for further studies to investigate if and when vitamin D supplementing in those who are deficient, impacts on COVID-19-related outcomes.

Citation
Dror AA et al. Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness PloS One 2022

Neurological manifestations seen in nearly half of children with COVID-19 and MIS-C

26th January 2022

Neurological manifestations have been found in nearly half of children hospitalised with COVID-19 or MIS-C according to a global study

A neurological manifestation has been found in 44% of children who had been hospitalised with either COVID-19 or multisystem inflammatory syndrome (MIS-C) according to researchers from the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID). This multinational research collaborative initiative was established in April 2020 and designed to collect information on the prevalence and outcomes of neurological manifestations associated with both acute infection with COVID-19 and those with MIS-C and the equivalent adult condition.

Among adults with COVID-19, neurological problems are common and in one study, 82% of patients reported experiencing such problems. In contrast, a study of 27 children with COVID-19 MISC-C, found that only four, previously healthy children, had new-onset neurological symptoms including encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. However, all four children were admitted to an intensive care unit.

The evidence of neurological manifestations in children to date is based on small samples. As a result, for the present study, the team made use of the GCS-NeuroCOVID) database and searched for children (i.e., those aged under 18 years of age) hospitalised with COVID-19 related condition which was either confirmed through testing or based on the presence of recognised clinical symptoms. The diagnosis of MIS-C was based on the Centers for Disease Control and Prevention (CDC) guidance. The primary outcome of the study was the frequency and type of neurological manifestations both overall, and due to COVID-19 and MIS-C.

Neurological manifestations identified

A total of 1,493 children with a median age of 8 (47% female) were included in the analysis, of whom 86% had COVID-19 and the remainder MIS-C.

Children with a pre-existing medical condition were more likely to become infected with COVID-19 than MIS-C (p < 0.001) although children with MIS-C were more likely to be admitted to intensive care units (69% vs 29%).

Overall, 44% of the whole cohort (40% of those with COVID-19 and 66% of those with MIS-C) had at least one neurological manifestation. The most common findings were headache (16% vs 47%, COVID-19 vs MIS-C) and acute encephalopathy (15% vs 22%) and for both conditions, this difference was statistically significant (p < 0.05). Other manifestations included seizures (8%), anosmia (4%) and ageusia (3.6%). Children with neurological manifestations were also more likely to require admission to ICU (51% vs 22%, p < 0.001).

Using regression analysis, the researchers identified that for the whole cohort, several factors including older age (adjusted odds ratio, aOR = 1.20, 95% CI 1.07 – 1.13), MIS-C (aOR = 2.16), neurologic (aOR = 3.48) and a pre-existing metabolic condition (aOR = 1.65) were all significantly (p < 0.05) associated with the presence of neurological manifestations.

Commenting on these results, the authors noted how the frequency of observed neurological manifestations in the cohort was fortunately much lower than that reported in adults, which was 80%. They concluded that neurological symptoms were a common problem in children hospitalised with COVID-19 and that the presence of such symptoms was much more likely in older children and those with pre-existing neurological and metabolic conditions.

Citation

Fink EL et al. Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C Pediatr Neurol 2022

Inhaled unfractionated heparin improves oxygenation in patients with COVID-19

24th January 2022

Inhaled unfractionated heparin appears safe and leads to an improvement in oxygenation among patients hospitalised with COVID-19

Inhaled unfractionated heparin can be safely used in hospitalised patients with COVID-19 and improves oxygenation according to a retrospective analysis by researchers from Saint George Hospital, Intensive Care Unit, Sydney, Australia.

There is a strong rational for the use of inhaled unfractionated heparin (IUH) in the treatment of patients with COVID-19, given the evidence that heparin blocks spike protein binding and/or infection by pseudo-typed virus and authentic COVID-19. Moreover, in a preliminary and pre-pandemic study, the use of IUH in patients with or at risk of acute respiratory distress syndrome, the drug was was well tolerated and there was less progression of lung injury and an earlier return home.

For the present study, the Australian team recruited hospitalised patients infected with COVID-19 and who had shown clinical deterioration despite standard of care and offered them treatment with IUH. The drug was nebulised and given at a dose of 5000IU every 8 hours or initially at 10,000 IU every four hours and if tolerated increased to 25,000 IU every six hours. The outcomes of interest were activated partial thromboplastin time (APTT) and the highest level achieved during treatment. Efficacy outcomes were oxygenation which was assessed by the ratio of oxygen saturation to the fraction of inspired oxygen (S/F ratio).

Findings

A total of 98 patients with an average age of 66 years (52% male) were enrolled in the study, 79 of whom were intubated and the median time from COVID-19 symptom onset to use of IUH was 6.7 days for non-intubated patients compared to 8 days among intubated patients.

In 3 patients on UFH, APTT levels did not significantly increase from a baseline of 72 to a peak of 84 seconds (p = 0.17).

The S/F ratio decreased by an average of 9.2 units each day prior to IUH, suggesting a deterioration of oxygenation although after commencement of therapy, this began to increase compared to baseline in all patients and for each of the doses used (p < 0.001) with intubated patients showing the greatest improvement.

In discussing these results, the authors noted that the use of IUH was associated with improved oxygenation. However, an important caveat was that the study did not have a control group and that IUH was administered at different doses and durations, together with the fact that COVID-19 severity was also not uniform. Nevertheless, they argued that this heterogeneity was a potential advantage, demonstrating that the use of IUH was safe across the COVID-19 disease spectrum. While based on a case series, the authors added that there are several ongoing trials examining the value of IUH in patients hospitalised with COVID-19 and which should report in the future.

Citation

van Haren FMP et al. Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID‐19: A multicentre case series of 98 patients Br J Clin Pharmacol 2022

Higher dexamethasone dose of no benefit in critically ill COVID-19 patients

28th October 2021

Doubling the dose of dexamethasone dose in COVID-19 patients hospitalised with severe hypoxia had no effect on 28-day mortality.

Increasing the dexamethasone dose from 6 mg to 12 mg/day in hospitalised patients with COVID-19 and severe hypoxia, has no effect on overall mortality. This was the conclusion of a randomised trial undertaken by researchers from the COVID STEROID 2 Trial group, Department of Intensive Care, Rigshospitalet, Copenhagen, Denmark. The value of dexamethasone in hospitalised patients with COVID-19 was shown in an open-label trial published in February 2021, which found that dexamethasone 6mg/daily for 10 days, resulted in a lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen. Guidance from the World Health Organisation also recommends a dexamethasone dose of 6 mg/daily either orally or intravenously.

Whether a higher dexamethasone dose would be more beneficial to those with severe COVID-19 is uncertain. However, some evidence suggests that in patients with acute respiratory distress syndrome (which can be induced by infection with the virus) initial dexamethasone doses of 20 mg for five days, could reduce the duration of mechanical ventilation and overall mortality. Thus, the purpose of the COVID STEROID 2 trial was to evaluate the efficacy and safety of a higher dose of dexamethasone in hospitalised adult patients with COVID-19 and severe hypoxia. The researcher’s working hypothesis was that a higher dexamethasone dose would increase the number of days alive without life support. The study was conducted at 26 hospitals in four countries and included patients who required supplemental oxygen, and both non-invasive and invasive mechanical ventilation. Participants were randomised 1:1 to receive either 6 or 12 mg of dexamethasone daily as a bolus injection for up to 10 days after randomisation. Patients were assessed after 28 days with the primary outcome set as the number of days alive without life support (i.e., invasive mechanical ventilation, circulatory support or kidney replacement therapy) after 28 days. There were several secondary outcomes, including the number of days alive without life support at 90 days.

Findings

A total of 982 randomised patients were included in the final analysis with a median age of 65 years (31% female). The most common co-morbidities were diabetes (27% in the 12 mg dexamethasone group, 34% in the 6 mg group) and ischaemic heart disease or heart failure (14% in both groups). After 28 days, the median number of days alive without life support was 22 days in those with a dexamethasone dose of 12 mg and 20.5 days in the dexamethasone 6 mg group (adjusted mean difference, aMD  = 1.3 days, p = 0.07). The 28-day mortality was 27.1% and 32.3% (dexamethasone 12 mg vs 6 mg). Similarly after 90 days the corresponding number of days was 84 and 80 days (dexamethasone 12 mg vs 6 mg) and this difference was not statistically significant.

The authors concluded that doubling the dexamethasone dose did not improve the number of days alive but suggested that they trial might have been underpowered to identify a significant difference.

Citation

The COVID STEROID 2 Trial Group. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomised Trial. JAMA 2021

Molnupiravir halved risk of hospitalisation for patients with COVID-19

6th October 2021

Molnupiravir, an investigational anti-viral agent, has been shown to reduce hospitalisation in patients with COVID-19.

According to an interim analysis, Merck and Ridgeback’s investigational anti-viral drug, molnupiravir (MPV), halved the risk of hospitalisation in patients with mild-to-moderate COVID-19. MPV is a pro-drug that is incorporated by RNA polymerase into COVID-19 and which has been shown in preliminary studies, to reduce nasopharyngeal COVID-19 infectious virus and viral RNA.

The results come from the Phase III MOVe-OUT trial, designed to evaluate the safety, tolerability and efficacy of MPV in non-hospitalised patients with COVID-19. Enrolled patients had laboratory-confirmed mild-to-moderate COVID-19 and with an onset of symptoms within 5 days of study randomisation. In addition, all patients were required to have at least one risk factor associated with poor disease outcome. A second trial, examined the value of MPV in hospitalised patients although this was halted after it became apparent that molnupiravir was unlikely to demonstrate a clinical benefit in hospitalised patients.

MOVe-OUT is evaluating molnupiravir at a dose of 800mg twice daily and while the results are yet to be published, the interim analysis seems positive. According a joint press release from the companies, 7.3% (28/385) of patients receiving MPV were either hospitalised or died through to Day 29 following randomisation (28/385), compared with 14.1% (53/377) of placebo-treated (p=0.0012). In addition, after 29 days, there were no deaths were reported in patients who received MPV compared to 8 deaths in the placebo arm.

The incidence of drug-related adverse events was shown to be comparable (12% and 11% MPV vs placebo). Fewer subjects discontinued study therapy due to an adverse event in the molnupiravir group (1.3%) compared to the placebo group (3.4%).

Merck plans to submit an application for Emergency Use Authorisation (EUA) to the FDA as soon as possible and plans to submit marketing applications to other regulatory bodies worldwide.

Source: Merck and Ridgeback press release, October 2021

Similar factors associated with COVID-19 severity in children and adults

21st September 2021

A US study has found that as with adults, the same clinical factors affect COVID-19 severity and hospitalisation in children and adolescents.

The available evidence clearly shows that infection with COVID-19 is disproportionately higher in adults compared with children. Nevertheless, emerging data suggests that in children infection with COVID-19 can induce multisystem inflammatory syndrome and lead to serious illness. While the pandemic has revealed how several clinical factors such as older age, various co-morbidities and ethnicity, are all associated with a higher level of COVID-19 severity, much less is known about which factors lead to more severe disease in children.

This lack of information prompted a group of US researchers from the Division of Hospital Medicine, Monroe Carell Jr, Children’s Hospital, Vanderbilt, Nashville, Tennessee, US, to undertake a retrospective cohort study across 45 US children’s hospitals to assess factors associated with COVID-19 severity in paediatric patients. The researchers included patients as young as 30 days old to 18 years of age, discharged from either an emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19. The researcher collected demographic data and information on the presence of any co-morbidities, particularly those which appeared to result in a worse prognosis among adults. The outcome of interest was COVID-19 severity which was categorised as mild (i.e., ED discharge), moderate (in-patient admission) and severe (intensive care (ICU) admission) and very severe (ICU admission with mechanical ventilation, shock or death). The results were analysed using regression analysis and presented as odds ratios adjusted for various factors including ethnicity and co-morbidities.

Findings
The study included 19,976 ED encounters of children with a median age of 6 years (51.2% male) with the most common ethnicities being Hispanic (48.8%) and non-Hispanic White (21.1%). In the majority of cases (79.9%) COVID-19 severity was mild (79.7%) and these individuals were discharged from the ED. However, among the 4063 (20.3%) patients who were hospitalised, the majority had moderate COVID-19 severity (79.3%) with 11.3% classed as severe and 9.4% as very severe. When compared with those who were discharged from the ED, the clinical factors associated with an increased odds of hospitalisation included obesity/type 2 diabetes (adjusted Odds ratio, aOR = 10.4, 95% CI 8.90 – 13.3), asthma (aOR = 1.40, 95% CI 1.3 – 1.60), cardiovascular disease (aOR = 5.0), an immunocompromised condition (aOR = 5.9) and pulmonary disease (aOR = 3.2). Only Black ethnicity impacted on the risk of hospitalisation compared to those of White ethnicity, (aOR = 1.52, 95% CI 1.20 – 1.93). With respect to age, compared to children aged 0 – 4 years, the risk of hospitalisation was lower among those aged 5 – 11 years (aOR = 0.50, 95% CI 0.45 – 56) and 12 – 17 years (aOR = 0.75, 95% CI 0.69 – 0.82). However, once hospitalised, the risk of higher COVID-19 severity increased in both groups: 5 – 11 group (aOR = 2.66) and 12 – 17 years (aOR = 2.09).
The authors concluded that while older children were at a lower risk of hospitalisation with COVID-19, once hospitalised, they appeared to be a higher risk of more severe disease. In addition, as with adults, similar co-morbidities were associated with a greater risk of hospitalisation and higher COVID-19 severity once admitted.

Citation
Antoon JW et al. Factors associated with COVID-19 disease severity in US children and adolescents. J Hosp Med 2021

Over 1 in 10 COVID-19 infections were hospital-acquired

16th August 2021

An analysis of COVID-19 infections during the first wave has revealed that just over 1 in 10 of these infections were hospital-acquired.

During the first wave of the COVID-19 pandemic there were a huge number of patients admitted to hospital. Ensuring minimal hospital-acquired infection was therefore of paramount importance, especially as earlier research with SARS and MERS had shown that human-to-human transmission occurred mainly within the healthcare setting. In a letter to the Lancet, a team from Lancaster Medical School, Lancaster University, UK, have examined the extent to which nosocomial, i.e., hospital-acquired, COVID-19 infections occurred during the first wave of the pandemic. The researchers used records contained in the International Severe Acute Respiratory Emerging Infection Consortium (ISARIC) and which has already reported on the clinical characteristics of 20,133 hospital in-patients during the initial phase of the pandemic. For the current analysis, the team examined records of patients enrolled in the UK arm of ISARIC and who had an onset of symptoms before the beginning of August 2020. In trying to determine whether patients were likely to have a hospital-acquired infection, the team considered both their admission date and the date of symptom onset. They used the recorded infection date for a patient and identified those who were admitted before infection, as likely candidates for a hospital-acquired infection.

Findings
The researchers estimated that there were 82,624 patients admitted to hospital before the beginning of August 2020 and found that 11.3% (95% CI 11.1 – 11.6) of these became infected with COVID-19 after admission to hospital. When restricting their analysis to the middle of May 2020, this proportion increased to 15.8% (95% CI 15.8 – 19.6). Using a more conservative estimate of symptom onset at least 14 days after hospital admission, the proportion reduced to 6.8%. An interesting additional finding was how there was marked heterogeneity between hospital trusts. For example, in cases where the trust provided both acute and general care, the incidence of infections was 9.7% (95% CI 9.4 – 9.9) whereas this was substantially higher in residential community care hospitals (61.9%, 95% CI 56.4 – 68) and in mental health hospitals (67.5%). The authors were unable to account for this extreme variation and called for an urgent investigation to identify and promote best practice for infection control.
In discussing these findings, they identified that a recognised limitation of the ISARIC dataset was that it was unable to identify patients infected during admission or those who were discharged before developing symptoms and who might have acquired their infection within the hospital. In other words, the authors felt that their overall estimate of the nosocomial infection rate is probably an underestimate. The concluded that with lessons learnt from the first wave coupled with the development of vaccines, NHS infection control policies should now be sufficiently robust to prevent the burden of hospital-acquired infections.

Citation
Read JM et al. Hospital-acquired SARS-CoV-2 infection in the UK’s first COVID-19 pandemic wave. Lancet 2021