Volume 2 - Issue 4
From the desk of the Editor-in-Chief
(1). Brown E et al. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet. 2.21;398(10296): P262-76
SGLT2 inhibitors and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose lowering therapies, with additional benefits of weight loss and blood pressure reduction.
Data from cardiovascular outcome trials have highlighted that these drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality.
Ongoing research using hard renal endpoints such as end stage kidney disease rather than surrogate markers might clarify the reno-protective benefits of both agents.
When used for glucose lowering, SGLT2 inhibitors are most effective if the estimated glomerular filtration rate is more than 60 ml per min per 1.73 m2 at initiation and should be avoided where there is a risk of diabetic ketoacidosis.
GLP-1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer and used with caution in patients with a history of pancreatitis of a known cause. These drugs are now second-line, or even arguably first-line, glucose lowering therapies in patients with cardio renal disease, irrespective of glycemic control.
If an SGLT2 inhibitor or GLP-1 receptor agonist is considered suitable in patients with type 2 diabetes, treatment should be prioritized according to existing evidence:
GLP-1 receptor agonists should be considered in patients at a high risk of, or with established, cardiovascular disease and SGLT2 inhibitors considered for patients with heart failure (with reduced ejection fraction) or chronic kidney disease (with or without established cardiovascular disease).
There is now compelling data on the benefits of these drugs for a range of other clinical indications even without type 2 diabetes, including for GLP-1 receptor agonists in patients with obesity and overweight with weight-related comorbidities.
(2). Gu X, Cao B. In-hospital complications associated with COVID-19. 2021;398(10296):P188-90
As the COVID-19 pandemic persists globally, an emerging challenge is the shift from acute infection to the burden of long-term consequences resulting from the disease. Although a consensus terminology has not yet been reached, the post-acute stage of COVID-19 is mostly defined as 3 or 4 weeks after symptom onset, and long or chronic COVID-19 is defined as symptoms and abnormalities persisting or presenting beyond 12 weeks. Most studies have focused on acute and subacute COVID-19, although evidence-based guidance for the management of long COVID-19 is limited. Comprehensively understanding the health effects of COVID-19 from its acute to chronic stages is important, not only for the preparation of further waves of the pandemic, but also for assessing the burden on health-care systems due to COVID-19 consequences.In The Lancet, Thomas Drake and colleagues report their prospective study of in-hospital complications of COVID-19 and the impact on clinical prognosis at discharge, initiated at the early stages of the pandemic.
73,197 adult patients were studied, of whom 44% were female and 73% were White, from 302 UK health-care facilities, with COVID-19 and admitted to hospital between Jan 4 and Aug 4, 2020. The study showed that among those admitted to hospital with COVID-19, a high proportion (49.7%) had at least one complication. The occurrence of complications was not only associated with a higher risk of mortality during hospitalization, but also reduced the ability of patients to self-care once discharged.
In most COVID-19 studies, mortality and respiratory support during hospitalization have been used as hard endpoints; however, in this study, the authors have shifted the attention and instead use multi-organ complications during hospitalization as the main endpoint. Furthermore, despite the mean age of this cohort being 71 years (SD 18), they also focused on younger patients in whom the case fatality rate was low but might suffer more from post-acute COVID-19.
Previous studies have mainly focused on patients with COVID-19 who are most susceptible to complications, such as older people (aged ≥ 50 years) and those with more comorbidities. Drake and colleagues' findings about risk factors of complications are consistent with previous results.
Their results show that the increasing risk of complications affecting a specific organ is positively associated with pre-existing comorbidities of the same organ, age, and gender for nearly all types of complications, except for gastrointestinal and liver complications. Further assessment of the association of complications with survival status and critical care shows both numbers and types of complications matter, with more complications associated with worse survival status, and complex respiratory and cardiovascular complications showing the strongest association with survival status.
Nevertheless, the relative effect of complications on survival status and quality of life among people of different age groups was not previously understood. One of the most notable findings in this study is that the relative risk of death is much higher in younger patients with complications when compared with those of the same age who did not suffer a complication, whereas in older patients, the relative impact of complications on mortality appears to be lower. Whether this difference in complications on mortality was statistically significant was not examined by the authors. This finding is independent of the presence and number of comorbidities and indicates that attention should also be paid to younger patients who are less likely to die during the acute phase but more likely to live longer with complications in the days after acute or subacute COVID-19.
By dissecting the effect of multi-organ complications of COVID-19 from different angles including age, gender, and comorbidity, the study provides inspiring ideas for long-term cohort studies by balancing attention between younger and older patients.
However, several questions need to be answered in future studies. First, this study only focused on in-hospital complications and its effect on survival status and ability of self-care at discharge. Therefore, the effects of complications on long-term consequences need to be assessed. Second, socioeconomics, race, and ethnicity are important considerations for long COVID-19. The authors described the proportions of complications among patients with different ethnicities and included deprivation as a confounding factor without further comprehensive evaluation. It would be interesting and informative to examine the data regarding socioeconomics and ethnicity as the authors have done for age, gender, and comorbidity. Finally, although the model construction was robust, residual confounding effects cannot be excluded. Some factors such as the sequential organ failure assessment score and D-dimer on admission, and the use of dexamethasone that were shown to be related to in-hospital mortality were not adjusted.
The public health effect of post-acute COVID-19 is substantial considering the large number of people infected by SARS-CoV-2 globally. In addition to delineating the diverse manifestation across the full clinical spectrum of post-acute COVID-19, the pathophysiological mechanisms attributable to post-acute COVID-19, especially long COVID-19, need to be further elucidated among people with different demographic and clinical characteristics. Furthermore, research on the effects of the serological features, together with immunological aberrations and inflammatory damage resulting from acute SARS-CoV-2 infection, on post-acute or long COVID-19 is needed.
(3). Burki T. The final frontier: health in space. Lancet. 2021;398(10296):199-200
The rise of space tourism and plans to send people to Mars are prompting new studies of the health effects of space flight.
Cephalad fluid shift is only really a problem if you leave the planet. There is around a litre and a half of fluid in the lower part of the human body, outside the circulation system, and gravity keeps it there. When humans enter microgravity, this fluid floats into the chest and head, in a syndrome astronauts call "puffy face, chicken legs". This syndrome is one of the first physiological changes that space travelers' experience. Fortunately, like nearly all the effects of microgravity (there is no such thing as zero gravity), cephalad fluid shift does not outlast one's time in space.
Most of the 560 or so humans who have gone into space have ventured no further than the International Space Station (ISS). In cosmic terms, that barely counts as space at all. The ISS is about 250 miles above the Earth's surface, close enough for the planet's magnetic field to offer substantial protection from the galactic cosmic rays and solar particle events that zip around beyond the Van Allen radiation belt. Astronauts who were part of the US Apollo missions that landed 12 people on the Moon from 1969 to 1972 talked of seeing flashes of light when they closed their eyes-most likely space radiation.
Five decades later, we are entering a new era of space travel. Elon Musk, Jeff Bezos, and Richard Branson-three billionaires-are exploring the possibilities of commercial space flights, though the first phase of space tourism will not extend further than low Earth orbit. China's missions to the Moon are well underway. It has already landed several lunar rovers, one of which returned to Earth late last year with 2 kg of Moon rock. A crewed space flight is likely to follow.
The National Aeronautics and Space Administration (NASA) intends to return humans to the Moon by 2024. The agency's lunar exploration programme will entail setting up a viable system for humans to live in deep space for a period of a few months. If it proves successful, NASA has its sights on a new frontier: landing human beings on Mars. The Red Planet lies, on average, 140 million miles away from Earth (the Moon is around 250,000 miles away). Traversing this kind of distance is a gargantuan task. Aside from wrestling with the formidable technical issues, researchers are looking closely into the hazards that space travel presents to human health.
Nick Caplan leads the Aerospace Medicine and Rehabilitation Laboratory at Northumbria University, Newcastle, UK. "Human beings have evolved to live, breathe, and perform movements in a gravity-loading environment", he explained. "In space, the body has to adapt to a completely different environment, where it is not subject to the same kind of forces, and so it de-conditions." For every month an astronaut spends in space, they lose 1-2% of their bone density, because their legs no longer hit the ground thousands of times a day. The loss does not seem to abate with time, which could prove problematic for those travelling long distances in space. "Astronauts tend to maintain their upper body muscles, because they are pulling themselves around the space station, but their legs and spinal muscles start to waste away", said Caplan. The ISS is equipped with a gym, including a treadmill, a bicycle, and a weightlifting machine, which helps astronauts to stay in shape, but back muscles require continual activity. "On Earth, you are using the spinal muscles at a very low level all day to stand up against gravity; you cannot make up for that with only a couple of hours of daily exercise", said Caplan.
The intensive reconditioning programmes that astronauts are put through when they return home mean that their fitness and strength are typically restored. There are indications that the microarchitecture of the bones remains altered, although drawing firm conclusions is difficult given the small sample size and lack of long-term follow-up. "When you are dealing with astronaut health, the evidence comes in the form of case studies", said Caplan. "So although each astronaut is studied in tremendous detail, you do not have the numbers for statistical validation."
The heart shrinks in space, because it is no longer required to pump blood upwards to the head. After spending 340 days on the ISS, Scott Kelly's heart was 27% smaller than when he set off for the station. Upon returning to Earth, without countermeasures, 25% of male astronauts and 80% of female astronauts find it difficult to maintain their blood pressure while standing up. NASA has designed a compression garment for use on the lower part of the body to alleviate the problem.
The exact cause of space flight-associated neuro-ocular syndrome has yet to be identified. The condition involves structural alterations to the eye and can affect the vision. The sensorimotor system is also disrupted in microgravity. When astronauts return to Earth, NASA has them attempt a tandem walk, which requires the astronaut to cross their arms, close their eyes, and walk in a straight line. Very few crew members manage to do it on their first day back; it can even be a struggle on the second day. Caplan has heard from astronauts who have stumbled into doorways after coming back from space. All of which has implications for the potential trip to Mars, during which the crew will be expected to exit the spacecraft, drive a rover, and set up the electricity supply.
Radiation is another concern. Aside from its carcinogenic properties, radiation causes sickness and poses threats to the cardiovascular and central nervous systems. In June, the US National Academies of Sciences, Engineering, and Medicine issued a report endorsing NASA's proposal to establish a limit of approximately 600 millisieverts (mSv) for radiation astronauts are exposed to over their career. 600 mSv equates to a 3% lifetime risk of death from radiation-induced cancer for a woman aged 35 years. This limit would represent a considerably stricter standard than those for the Canadian, European, and Russian space agencies, which have each set career dose limits of 1000 mSv.
Hedvig Hricak, a radiologist at Memorial Sloan Kettering Cancer Center, is chair of the committee convened to compile the National Academies report. "Space radiation is very different from radiation on Earth: much of it is unpredictable and its effects are not well understood", Hricak told The Lancet. "You have uncontrolled solar flares and galactic cosmic rays that are very high energy and full of heavy ions." The committee estimated that a trip to Mars could exceed the new standard by up to 150%. NASA is developing a waiver process.
Galactic cosmic rays are a complex mix of radiation. "It is only recently that we have been able to mimic galactic cosmic rays here on Earth", said Steve Platts, acting chief of the human research programme at NASA. "We are still working to understand them." Spacecraft are fitted with on-board shielding, but the weight of the material limits how much can be used, as does the potential for secondary radiation effects. "A lot of the damage that is done by radiation to the human body is mediated through reactive oxygen species and oxidative stress, so anti-oxidants are one possible mitigation; research on this is happening widely in terrestrial medicine", adds Platts.
NASA has identified about 30 health risks associated with space travel. The list includes radiation, but the agency does not consider it to be the greatest risk faced by space travellers. "The radiation dose that the crew receives at low Earth orbit is not all that large", points out Platts. "It is more of a threat when we talk about missions to the Moon and beyond, but even then radiation does not rise up to the highest level of risk that we track."
Platts is more concerned about the effects of isolation and confinement for those who undertake long-duration space expeditions. A return trip to Mars is expected to take three years. The crew cannot expect the regular staff turnover or intense support that they receive at the ISS. Thus far, only eight astronauts have spent more than 300 days in space in a single mission. When the astronauts do get to Mars, there will be a 20 min communication delay to Earth. They will have no escape from their fellow travellers. They will have to deal with any medical emergencies themselves. Moreover, they will have to become accustomed to dealing with psychological stressors that cannot be readily replicated in Earth-bound training.
However, those who are selected to travel to Mars will be heavily vetted and highly trained, with a keen eye on how well they can function with their fellow team members. Lighting within the spacecraft will be extremely important to help stabilise body rhythms. Menus will have to be carefully chosen. NASA is developing artificial intelligence systems that can interact with crew members and is doing short and long-term isolation studies on Earth. As with much of space exploration, a lot of uncertainty remains. "Viewed from Mars, Earth is just a dot", said Caplan. "We cannot predict how people will react to being unable to discern their home planet. No-one has ever been in that position before."
(4). Moses DA et al., Neuroprosthesis for decoding speech in a paralyzed person with anarthria. N Engl J Med. 2021; 385:217-27
Technology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent advancement over existing methods for assisted communication.
The researchers implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, they recorded 22 h of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. They used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity, and applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them.
They decoded sentences from the participant's cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, they detected 98% of the attempts by the participant to produce individual words, and classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period.
In a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model.
(5). Dougan M. Bamlanivimab plus etesevimab in mild or moderate COVID-19. N Engl J Med. 2021.
Patients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (COVID-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications.
In this phase 3 trial, the researchers randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate COVID-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within three days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as COVID-19-related hospitalization or death from any cause by day 29.
A total of 1035 patients underwent randomization and received an infusion of bamlanivimab-etesevimab or placebo. The mean (±SD) age of the patients was 53.8 ± 16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab-etesevimab group had a COVID-19â€“related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, -4.8 percentage points; 95% confidence interval [CI], -7.4 to -2.3; relative risk difference, 70%; P < 0.001). No deaths occurred in the bamlanivimab-etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as COVID-19-related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, -1.20; 95% CI, -1.46 to -0.94; P < 0.001).
Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of COVID-19â€“related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load
(6). Ting C et al. Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses. BMJ. 2021;374:n1537
To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins.
Design systematic review and meta-analysis
Data sources Studies were identified from previous systematic reviews and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials, up to August 2020.
Randomised controlled trials in adults without a history of cardiovascular disease that compared statins with non-statin controls or compared different types or dosages of statins were included.
Main outcome measures
Primary outcomes were common adverse events: self-reported muscle symptoms, clinically confirmed muscle disorders, liver dysfunction, renal insufficiency, diabetes, and eye conditions. Secondary outcomes included myocardial infarction, stroke, and death from cardiovascular disease as measures of efficacy.
A pairwise meta-analysis was conducted to calculate odds ratios and 95% confidence intervals for each outcome between statins and non-statin controls, and the absolute risk difference in the number of events per 10â€‰000 patients treated for a year was estimated. A network meta-analysis was performed to compare the adverse effects of different types of statins. An Emax model based meta-analysis was used to examine the dose-response relationships of the adverse effects of each statin.
Sixty-two trials were included, with 1,20,456 participants followed up for an average of 3.9 years. Statins were associated with an increased risk of self-reported muscle symptoms (21 trials, odds ratio 1.06 (95% confidence interval 1.01 to 1.13); absolute risk difference 15 (95% confidence interval 1 to 29)), liver dysfunction (21 trials, odds ratio 1.33 (1.12 to 1.58); absolute risk difference 8 (3 to 14)), renal insufficiency (eight trials, odds ratio 1.14 (1.01 to 1.28); absolute risk difference 12 (1 to 24)), and eye conditions (six trials, odds ratio 1.23 (1.04 to 1.47); absolute risk difference 14 (2 to 29)) but were not associated with clinically confirmed muscle disorders or diabetes. The increased risks did not outweigh the reduction in the risk of major cardiovascular events. Atorvastatin, lovastatin, and rosuvastatin were individually associated with some adverse events, but few significant differences were found between types of statins. An Emax dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive.
For primary prevention of cardiovascular disease, the risk of adverse events attributable to statins was low and did not outweigh their efficacy in preventing cardiovascular disease, suggesting that the benefit-to-harm balance of statins is generally favorable.
(7). Cashin AG et al. Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain: systematic review and meta-analysis. BMJ 2021;374:n1446
To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain.
Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021.
Systematic review and meta-analysis of randomized controlled trials.
Eligibility criteria for study selection
Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain.
Data extraction and synthesis
Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool. Outcomes included pain intensity (measured on a 0-100-point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event).
Forty nine trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference -7.7, 95% confidence interval-12.1 to-3.3) but not a reduction in disability (-3.3, -7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias.
Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty.
(8). McKinnon C. Glioblastoma: clinical presentation, diagnosis, and management. BMJ 2021;374:n1560
Early symptoms of brain tumors in adults are non-specific, and patients may present multiple times to primary care services before they are referred for investigation. Look for symptoms of raised intracranial pressure (such as headaches exacerbated by lying down, triggered by the Valsalva manoeuvre, or associated with vomiting or visual disturbance), combinations of symptoms (such as headache plus cognitive impairment, headache plus weakness, headache plus personality change), and symptoms that progress over time. New onset focal or generalized seizures in adulthood also warrant investigation for a brain tumor.
In patients with symptoms or signs suggestive of a brain tumor, arrange urgent magnetic resonance imaging of the head with and without contrast through a rapid access "suspected cancer" pathway, when available. In patients with suspicion of raised intracranial pressure, arrange a same day clinical assessment and contrast enhanced computed tomography of the head.
Glioblastoma is the most common primary brain cancer. Standard treatment includes maximal safe resection followed by concomitant radiotherapy and temozolomide chemotherapy and then adjuvant temozolomide. Disease progression is expected in all cases and consideration of further treatment should take into account the patient's performance status, tumour size, tumour location, and time since first treatment.
Key supportive medications may include corticosteroids for vasogenic oedema and antiepileptic medication if seizures occur.
Because of the incurable and rapidly progressive nature of glioblastoma, close collaboration between multidisciplinary teams in tertiary care hospitals and primary care services is recommended. Early involvement of general practitioners and specialist community palliative care teams can assist patients and caregivers with advance care planning as well as management of symptoms, physical and cognitive impairment, communication difficulties, and the innate uncertainties about disease progression.
Glioblastoma is the most common primary brain cancer in adults. Despite surgical resection, chemotherapy, and radiotherapy, median survival after diagnosis is only 14-16 months.
(9). John BV et al. Association of BNT162b2 mRNA and mRNA-1273 vaccines with COVID-19 infection and hospitalization among patients with cirrhosis. JAMA Intern Med. 2021;13:e214325
Are COVID-19 mRNA vaccines associated with decrease in COVID-19 infections and death in a real-world setting among patients with cirrhosis of the liver?
In this retrospective cohort study of US veterans with cirrhosis that compared 20,037 patients who received either a Pfizer BNT162b2 mRNA or a Moderna mRNA-1273 COVID-19 vaccine with 20,037 propensity score matched controls, receipt of 1 dose of either vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% reduction in hospitalization of death due to COVID-19 infection after 28 days.
This cohort study found that mRNA vaccines against COVID-19 were associated with reduced COVID-19 infections in individuals with cirrhosis, despite hyporesponsiveness to other vaccines.
Two mRNA-based vaccines against coronavirus disease 2019 (COVID-19) were found to be highly efficacious in phase 3 clinical trials in the US. However, patients with chronic illnesses, including cirrhosis, were excluded from clinical trials. Patients with cirrhosis have immune dysregulation that is associated with vaccine hyporesponsiveness.
To study the association of receipt of the Pfizer BNT162b2 mRNA or the Moderna mRNA-1273 vaccines in patients with cirrhosis compared with a propensity-matched control group of patients at similar risk of infection and severe disease from COVID-19.
Design, setting, and participants
Authors performed a retrospective cohort study of patients with cirrhosis who received at least 1 dose of a COVID-19 mRNA vaccine at the Veterans Health Administration. Patients who received at least 1 dose of the vaccine (n = 20 037) were propensity matched with 20,037 controls to assess the associations of vaccination with new COVID-19 infection and COVID-19 hospitalization and death.
Receipt of at least one dose of the BNT162b2 mRNA or the mRNA-1273 vaccines between December 18, 2020, and March 17, 2021.
Main outcomes and measures
COVID-19 infection as documented by a positive result for COVID-19 by polymerase chain reaction, hospitalization, and death due to COVID-19 infection.
The median (interquartile range) age of the vaccinated individuals in the study cohort was 69.1 (8.4) years and 19, 465 (97.2%) of the participants in each of the vaccinated and unvaccinated groups were male, consistent with a US veteran population. The mRNA-1273 vaccine was administered in 10,236 (51%) and the BNT162b2 mRNA in 9801 (49%) patients. Approximately 99.7% of patients who received the first dose of either vaccine with a follow-up of 42 days or more received a second dose. The number of COVID-19 infections in the vaccine recipients was similar to the control group in days 0 to 7, 7 to 14, 14 to 21, and 21 to 28 after the first dose. After 28 days, receipt of one dose of an mRNA vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% protection against hospitalization or death due to COVID-19 infection. The association of reduced COVID-19 infections after the first dose was lower among patients with decompensated (50.3%) compared with compensated cirrhosis (66.8%). Receipt of a second dose was associated with a 78.6% reduction in COVID-19 infections and 100% reduction in COVID-19â€“related hospitalization or death after seven days.
Conclusions and relevance
This cohort study of US veterans found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19-related hospitalization or death in patients with cirrhosis.
(10). Mahase E. COVID-19: vulnerable children aged 12-15 will be offered Pfizer vaccine, UK announces. BMJ 2021;20(374):n1841
Children aged 12-15 who are at increased risk of serious illness from infection with SARS-CoV-2 will be offered the Pfizer-BioNTech vaccine, the UK's Joint Committee on Vaccination and Immunisation (JCVI) has announced.
This will include children with severe neurodisabilities and those with underlying conditions that result in immunosuppression. The committee has also recommended that children aged 12-17 who live with an immunosuppressed person will also be offered the vaccine. This adds to the existing recommendation that at-risk young people aged 16-17 should be offered the vaccine.
The vaccine is not being recommended to children outside these groups, as the committee concluded that the "health benefits in this population are small, and the benefits to the wider population are highly uncertain."
The Pfizer vaccine is the only COVID-19 vaccine authorized for children (aged 12 and over) in the UK. Extremely rare reports of myocarditis and pericarditis have arisen after the Pfizer and Moderna vaccines were given to millions of younger adults.1
Penelope Toff, co-chair of the BMA's Public Health Medicine Committee, expressed concern that adolescents living in multigenerational households and communities, particularly in more deprived areas, had been excluded from this list of eligible children. She said it was "vital" that they were considered.
Lawrence Young, virologist and professor of molecular oncology at Warwick Medical School, said that the decision not to offer the vaccine to all children aged 12 and over was "worrying," especially as England was now "relying on vaccination and personal responsibility, as opposed to mandated restrictions."
COVID-19 restrictions in England were eased on 19 July despite new cases rising to 50,000 a day and experts warning that around half a million people could develop long COVID during this wave of infections. Young highlighted other countries-including many in the EU, as well as Singapore, Japan, the UAE, the US, Canada, and the Philippines-where all children aged 12 and over were to be offered the vaccine.3
Penny Ward, visiting professor in pharmaceutical medicine at King's College, London, expressed confusion at the list of conditions considered to put children at risk of severe illness, as many of the conditions listed for 16-18 years olds were not included in the age 12-15 list.
She said, "No clear explanation is given for this, and as a consequence one might imagine lengthy discussions in GP surgeries between parents of children with brittle diabetes and renal disease and their GP adviser. Perhaps JCVI might consider a fuller-preferably completely referenced-document for use by the folks at the sharp end of patient care."
When asked at a Science Media Centre briefing about vaccinating under 16 year olds who are pregnant, Adam Finn, JCVI member and a professor of paediatrics at the University of Bristol, said that it was a tricky decision but that the vaccine had not been recommended for this group.
He said, "We are now receiving increasing amounts of information that does indicate that pregnant women are not just similarly at risk, but actually probably an enhanced risk compared to other women of the same age. But balance of risk and benefit gets quite difficult when you get down into teenage pregnancies, because the risks of serious disease in teenagers get progressively lower as they get younger.
"So at the moment, pregnant under 16 year olds are not listed in our recommendations. But of course, that evidence will be kept under close review."
Responding to concerns around long COVID in children, Finn said that the current evidence suggested that the "likelihood of long-lasting symptoms in children having had the infection beyond one to two months is extremely low."
However, other health leaders, including Taiwan's former director general of health promotion administration, Shu-Ti Chiou, have highlighted studies in children which have reported surprisingly high levels of long COVID. One study of 129 children infected with the virus found that while only six were admitted to hospital, half of the children still reported at least one COVID-19 symptom six months post-infection.