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Damage to heart found in more than half of COVID-19 patients discharged from hospital

Around 50% of patients who have been hospitalized with severe COVID-19 and who show raised levels of a protein called troponin have damage to their hearts. The injury was detected by magnetic resonance imaging (MRI) scans at least a month after discharge, according to new findings.

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Around 50% of patients who have been hospitalized with severe COVID-19 and who show raised levels of a protein called troponin have damage to their hearts. The injury was detected by magnetic resonance imaging (MRI) scans at least a month after discharge, according to new findings published (Thursday) in the European Heart Journal [1].

Damage includes inflammation of the heart muscle (myocarditis), scarring or death of heart tissue (infarction), restricted blood supply to the heart (ischaemia) and combinations of all three.

The study of 148 patients from six acute hospitals in London is the largest study to date to investigate convalescing COVID-19 patients who had raised troponin levels indicating a possible problem with the heart.

Troponin is released into the blood when the heart muscle is injured. Raised levels can occur when an artery becomes blocked or there is inflammation of the heart. Many patients who are hospitalized with COVID-19 have raised troponin levels during the critical illness phase, when the body mounts an exaggerated immune response to the infection. Troponin levels were elevated in all the patients in this study who were then followed up with MRI scans of the heart after discharge in order to understand the causes and extent of the damage.

Professor Marianna Fontana, professor of cardiology at University College London (UK), who led the research together with Dr. Graham Cole, a consultant cardiologist at Imperial College London, said: “Raised troponin levels are associated with worse outcomes in COVID-19 patients. Patients with severe COVID-19 disease often have pre-existing heart-related health problems including diabetes, raised blood pressure and obesity. During severe COVID-19 infection, however, the heart may also be directly affected. Unpicking how the heart can become damaged is difficult, but MRI scans of the heart can identify different patterns of injury, which may enable us to make more accurate diagnoses and to target treatments more effectively.”

The researchers investigated COVID-19 patients discharged up until June 2020 from six hospitals across three NHS London trusts: Royal Free London NHS Foundation Trust, Imperial College Healthcare NHS Trust and University College London Hospital NHS Foundation Trust. Patients who had abnormal troponin levels were offered an MRI scan of the heart after discharge and were compared with those from a control group of patients who had not had COVID-19, as well as from 40 healthy volunteers.

“The recovering COVID-19 patients had been very ill; all required hospitalization and all had troponin elevation, with around one in three having been on a ventilator in the intensive care unit,” said Prof. Fontana.

“We found evidence of high rates of heart muscle injury that could be seen on the scans a month or two after discharge. Whilst some of this may have been pre-existing, MRI scanning shows that some were new, and likely caused by COVID-19. Importantly, the pattern of damage to the heart was variable, suggesting that the heart is at risk of different types of injury. While we detected only a small amount of ongoing injury, we saw injury to the heart that was present even when the heart’s pumping function was not impaired and might not have been picked up by other techniques. In the most severe cases, there are concerns that this injury may increase the risks of heart failure in the future, but more work is needed to investigate this further.”

The function of the heart’s left ventricle, the chamber that is responsible for pumping oxygenated blood to all parts of the body, was normal in 89% of the 148 patients but scarring or injury to the heart muscle was present in 80 patients (54%). The pattern of tissue scarring or injury originated from inflammation in 39 patients (26%), ischaemic heart disease, which includes infarction or ischaemia, in 32 patients (22%), or both in nine patients (6%). Twelve patients (8%) appeared to have ongoing heart inflammation.

Prof. Fontana said: “Injury relating to inflammation and scarring of the heart is common in COVID-19 patients with troponin elevation discharged from hospital, but is of limited extent and has little consequence for the heart’s function.

“These findings give us two opportunities: firstly, to find ways of preventing the injury in the first place, and from some of the patterns we have seen, blood clotting may be playing a role, for which we have potential treatments. Secondly, detecting the consequences of injury during convalescence may identify subjects who would benefit from specific supporting drug treatments to protect heart function over time.”

The findings of the study are limited by the nature of patient selection and included only those who survived a coronavirus infection that required hospital admission.

“The convalescent patients in this study had severe COVID-19 disease and our results say nothing about what happens to people who are not hospitalized with COVID, or those who are hospitalized but without elevated troponin. The findings indicate potential ways to identify patients at higher or lower risk and suggest potential strategies that may improve outcomes. More work is needed, and MRI scans of the heart have shown how useful it is in investigating patients with troponin elevation,” concluded Prof. Fontana.

The study is also the subject of a discussion between Prof. Fontana and Prof. Eike Nagel, at the Society for Cardiovascular Magnetic Resonance annual meeting on Friday 19 February, where it will be presented for the first time [2]. Prof. Nagel, director of the Centre for Cardiovascular Imaging at Deutsches Zentrum Für Herz-Kreislauf-Forschung (DZHK), Frankfurt, Germany, is the senior author on an earlier paper [3] that found ongoing heart problems in up to 78% of COVID-19 patients who were less sick and most of whom did not require admission to hospital.

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Notes:

[1] “Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance”, by Tushar Kotecha et al. European Heart Journal. doi:10.1093/eurheartj/ehab075

[2] Society for Cardiovascular Magnetic Resonance virtual scientific sessions 2021, 09.00-09.45 hrs Central Standard Time in USA (6 hours behind GMT): https://bit.ly/3oMn84t

[3] JAMA Cardiol. 2020;5(11):1265-1273. doi: 10.1001/jamacardio.2020.3557.

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COVID-19 infection in pregnancy not linked with still birth or baby death

However the research, from over 4,000 pregnant women with suspected or confirmed COVID-19, also found women who had a positive test were more likely to have a premature birth.

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COVID-19 infection in pregnancy is not associated with stillbirth or early neonatal death, according to a new study.

However the research, from over 4,000 pregnant women with suspected or confirmed COVID-19, also found women who had a positive test were more likely to have a premature birth.

The research, led by scientists from Imperial College London and published in the journal Ultrasound in Obstetrics and Gynecology, used data from the UK and the USA.

The study team looked at data from 4004 pregnant women who had suspected or confirmed COVID-19. Of these women, 1606 were from the UK, from a data registry called PAN-COVID, while 2398 were from the US, from the American Academy of Pediatrics SONPM data registry.

PAN-COVID was funded by the Medical Research Council, UK National Institute for Health Research and the NIHR Imperial Biomedical Research Centre.

All the women gave birth between January-August 2020.

The research found that no babies died from COVID-19 in the study. There was also no increase in risk of stillbirth or low birth weight.

However, both the UK and US data suggested a higher risk of pre-term birth (defined as birth before 37 weeks).

In the UK data, 12 per cent of women with suspected or confirmed COVID-19 had a pre-term delivery – 60 per cent higher than the national average rate of 7.5 per cent. In the US data, 15.7 per cent of women had a pre-term birth, 57 per cent higher than the US national average of 10 per cent.

The study team say part of this association may be due to doctors deciding to deliver the baby early due to concerns about the effect of COVID-19 infection on mother and baby. The rate of spontaneous pre-term birth was lower than expected.

Professor Christoph Lees, senior author of the study from Imperial’s Department of Metabolism, Digestion and Reproduction, said: “The finding that COVID-19 infection does not increase the risk of stillbirth or baby death is reassuring. However, a suspected or confirmed COVID-19 diagnosis was linked to a higher risk of preterm birth, and it isn’t entirely clear why.”

Dr Ed Mullins, co-author from Imperial’s Department of Metabolism, Digestion and Reproduction, added: “This study supports the prioritisation of vaccination for women who are pregnant or who plan to become pregnant, and existing measures that protect women in pregnancy from infection, in order to reduce pre-term birth.”

The proportion of babies born to mothers with confirmed COVID-19, and who subsequently tested positive for the SARS-CoV-2 virus (which causes COVID-19) was 2 per cent in the UK study, and 1.8 per cent in the US study.

The majority of women in the study had no pre-existing conditions such as diabetes or a respiratory condition such as asthma.

In the UK study eight of the women died, while four women died in the US study.

The study team say that although these death rates are higher than expected for women giving birth, they are similar to the expected death rates seen among adults with a confirmed COVID-19 infection. This suggests that women in pregnancy are not at a higher risk of death from COVID-19 than non-pregnant women.

Among women in the UK arm of the study, 66.5 per cent were European or North American, 1.9 per cent were Middle Eastern, 1.1 per cent were North African, 4.2 per cent were African south of the Sahara or Caribbean, 7.5 per cent were from the Indian subcontinent, and 9.2 per cent were South East Asian. Among the US arm of the study 37 per cent were white, 25 per cent were Black or African, 4.1 per cent were Asian, 0.4 per cent were American Indian or Alaska Native American.

Professor Fiona Watt, Executive Chair of Medical Research Council, which helped fund the study, said: “It is obviously critical to understand how COVID-19 affects different groups of people. We’re proud to have funded the present study in which, for the past year, researchers have monitored the health of a substantial number of pregnant women and their babies. The study’s findings, that there is no increased risk of stillbirth and early neonatal death in women who contracted COVID-19 while pregnant, are reassuring. However, the study highlights the need for more research to determine if, or how, COVID-19 affects maternal outcomes or premature birth.”

The American Academy of Pediatrics SONPM data registry was led by Professor Mark Hudak.

The Centre for Trials Research at Cardiff University was responsible for building the online database, data management and the statistical analyses. Julia Townson, Senior Research Fellow and co-author from Cardiff University said: “I am delighted that the Centre for Trials Research at Cardiff University has been able to collaborate with Imperial College London on this important research. It has been a mammoth undertaking by the team, requiring a rapid build of the database and web page, as well as cleaning and analysing the data.”

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TB vaccine may protect newborns against other infectious diseases

Infants who had been vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. Protection from BCG didn’t seem to be against one specific type of infection, but for all types, such as common colds, chest infections, and skin infections.

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The tuberculosis (TB) vaccine Bacillus Calmette-Guerin (BCG) could protect newborns against a variety of common infections, such as upper respiratory tract infections, chest infections and diarrhoea, according to a new study in The Lancet Infectious Diseases.

The research is the first of its kind to rigorously investigate the full range of illnesses BCG could protect infants against. It suggests that vaccinating all babies on the day of birth with BCG could reduce neonatal infections and death in areas with high infectious disease rates, potentially saving thousands of lives a year. The results also increase the possibility that the vaccine might be used to protect children and adults against COVID-19 and other new infectious diseases.

Led by the London School of Hygiene & Tropical Medicine (LSHTM) through the MRC/UVRI & LSHTM Uganda Research Unit, and funded by the Wellcome Trust, the study involved a randomized control trial of 560 newborns in Uganda, who were monitored for a range of illnesses.

After six weeks, infection rates from any disease were 25% lower in the group who received the vaccine at birth, compared to the group that had not yet received the vaccination. Particularly vulnerable groups such as low birth weight babies, and boys, seemed to be protected the most. Importantly, BCG appeared to protect against mild, moderate and severe types of infections.

Sarah Prentice, lead author from LSHTM, said: “Nearly a million babies die every year of common infections so we urgently need better ways to protect them. Our research suggests that ensuring that BCG is given at birth could make a big difference in low income countries, potentially saving many lives.”

In the study, healthy Ugandan infants were randomly assigned to receive BCG at birth or at six weeks of age. The infants were followed-up by doctors, blinded to the intervention, for 10 weeks to look for episodes of any type of illness or infection.

The research team then compared how often infants in the two groups presented to doctors with infections of any kind, except TB, to see whether having BCG made a difference. They also took blood samples from both groups, to look at differences in their innate immune system, the body’s first line of defence against infections.

Infants who had been vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. Protection from BCG didn’t seem to be against one specific type of infection, but for all types, such as common colds, chest infections, and skin infections.

After the group receiving BCG at six weeks had been vaccinated, there was no difference in the rates of infection between the two groups – the delayed group’s immunity ‘caught-up’ once they’d received BCG.

Hazel Dockrell, Professor of Immunology at LSHTM and one of the co-authors of the study, adds: “It’s very exciting to think that BCG vaccination might help keep newborns safe against other dangerous infections, in addition to providing protection against TB. Although BCG is recommended at birth in many countries, it is often delayed due to logistical difficulties. Ensuring that the vaccine is given on day one, in areas with high rates of infectious disease, could have a major impact on infections and deaths in the newborn period.”

The team can’t definitively say why BCG offered this additional non-specific protection, but the research showed evidence of changes in the innate immune system of vaccinated infants, which may suggest that BCG boosts the immune system to work better against any infection.

This has led the researchers to suggest that it could provide protection in the early stages of novel outbreaks, such as COVID-19 or Ebola, before specific vaccines have been developed.

Further studies are already underway to explore whether BCG could play a role in the response to COVID-19, with large trials involving health care workers and the elderly. The Director General of WHO Dr Tedros Ghebreyesus has co-authored an article expressing interest in the possible use of BCG for protection against COVID-19.

Dr Prentice said: “Since the findings show that BCG seems to offer wider protection against a range of infections, our study also raises hopes it might be useful in protecting the general population against COVID-19 and future pandemics – though we will need to see the results of other, more specific studies to know for sure.”

The researchers also believe it is worth investigating whether reintroduction of BCG in countries where it is no longer in routine use, such as the UK, is beneficial, not for its effects against TB, but to protect vulnerable infants in neonatal units against other infections.

The authors acknowledge limitations of their study. As it was relatively small, it was not possible to show an effect of BCG on numbers of deaths from infections in the study participants. Also, because the study was only conducted in Uganda, it cannot be certain that these extra, beneficial effects of BCG would be seen in other settings. However, previous studies conducted in West Africa have shown a reduction in neonatal deaths following BCG at birth, to a similar extent as the reduction in infection rates seen in this study.

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Partners’ company helps us stay connected during pandemic

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Living with a romantic partner helps people feel more socially connected during COVID-19, new research stated. But no other pandemic-era social dynamic carries notable benefits: not your kids, not kibitzing with your bestie on Facetime, and not your adorable-adoring pets.

“Research prior to the pandemic has long shown that partners are one of the strongest predictors of social connection and well-being,” said UCR researcher Karynna Okabe-Miyamoto, lead co-author of the study, published recently in the journal Plos One. “And our research during the current COVID-19 pandemic has shown the same. Living with a partner uniquely buffered declines in social connection during the early phases of the pandemic.” By April 2020, many workplaces and stores had been shuttered, and social distancing measures had been implemented. The social existence of many people was relegated to the four walls of their homes, and their families became their only social connections.

The effectiveness of social distancing in reducing virus transmission had been established even before COVID-19. Researchers were curious about how to protect psychological health when such measures are in place.

The first study was conducted in Canada and included 548 undergraduate students. The second was conducted in the United State and United Kingdom and included 336 participants.

In the studies, participants reported their perceived social connection before and during the pandemic. They were asked to rate statements such as “I felt close and connected with other people who are important to me” and “People are around me, but not with me.” They were also asked to declare their social distancing adherence and whether they travel outside of the home for work.

Looking at participants before and during the pandemic, the authors wrote that people living with a romantic partner were most likely to improve in social connection after social distancing measures.

But the size of one’s household during the pandemic made little difference in feelings of social connectedness. Nor did being in the company of one’s children, or one’s pets. Working outside the home did nothing to help people feel socially connected, nor did video calls with friends and family.

“Living with a partner – but not how many people or who else one lives with – appeared to confer benefit during these uncertain and unprecedented times,” the authors wrote.

Researchers wrote the finding is consistent with past research that affirms romantic relationships lead to a greater sense of wellbeing and feeling connected. “In part,” the authors wrote, “because happier people are more likely to find partners.”

The researchers say policy makers should consider measures that place a priority on maintaining social connection, balanced against transmission risk.

In addition to Okabe-Miyamoto, who is a UCR graduate student, authors include UCR psychology professor Sonja Lyubomirsky and student researcher Dunigan Folk and social psychologist Elizabeth Dunn, both of University of British Columbia. The article in Plos One is titled “Changes in social connection during COVID-19 social distancing: It’s not (household) size that matters; it’s who you’re with.”

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