Category: COVID

SA Research Shedding Light on Role of Microclots in Long COVID

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Professor Resia Pretorius sounds rushed when Spotlight first tracks her down by phone at Heathrow Airport outside London. She is about to board a plane to South Africa after attending a conference, meetings, and symposia in the United Kingdom, all with the purpose of unravelling the complexity of long COVID and how to treat it.

There is no global consensus among researchers and clinicians on a definition for long COVID, there is no adequate diagnostic test for the debilitating condition, and the causes of patients progressing to long COVID are, at this stage, theoretical.

However, Pretorius who heads the Department of Physiological Science at the University of Stellenbosch remains upbeat. Her research group is the first to have reported evidence of inflammatory microclots in blood samples from individuals with long COVID, potentially solving an important piece of the long COVID puzzle.

She says scientific collaboration is intensifying to find answers to long COVID which affects 43% or 100 million people globally post-infection, according to a meta-analysis and systematic review.

Later speaking from Stellenbosch, Pretorius describes herself as a “lab person” who has been trying to find the cause of long COVID since 2020. “I have always been passionate about research. Now, I am working with clinicians and researchers in the UK, the USA, and other parts of the world. I am too worried to miss anything so I am at all of these meetings. There are 40 to 50 researchers globally who talk to each other regularly. We are going to crack this I know. We just have to.”

Causes of long COVID

As explained in a recent article in the journal Science, there are three leading theories scientists are pursuing in an attempt to decipher the effects of post-COVID-19 infection – which leads to an array of symptoms, including shortness of breath, fatigue, headaches, palpitations, and impairments in mental health and cognition or brain fog.

One theory is that SARS-CoV-2 stubbornly persists in the body, even after the acute infection passes. Studies have shown that the virus lingers in a wide range of body sites, especially in the nerves and other tissues.

Another theory based on blood samples from COVID-19 patients reveals an immune system in disarray even eight months after first testing positive. The body’s cells do not appear to recover.

Images of micro clots as seen under an electron microscope
Images of micro clots as seen under an electron microscope. PHOTO: Supplied

The third, an area in which Pretorius has distinguished herself internationally, is that COVID-19 is not only a lung disease but significantly affects the vascular (blood flow) and coagulation (blood clotting) systems of the body.

A recent study published in the Cardiovascular Diabetology journal, conducted by Pretorius and colleagues, found that there is significant microclot formation in the blood of both acute COVID-19 and long COVID patients. A microclot is a blood clot that can only be seen through a microscope.

Pretorius explains that in a healthy person clots may form, for example, when you cut yourself. The main clotting protein is a molecule called fibrinogen. “When you’re healthy, it’s in solution. And then when you cut yourself, collagen is exposed, and a little gel called fibrin prevents you from bleeding out. In healthy individuals, the clots are then broken down by a process called fibrinolysis.

Blood samples from patients with long COVID have revealed high levels of various inflammatory molecules trapped in the microclots including fibrinogen and Alpha-2 antiplasmin – a molecule that prevents the breakdown of microclots.

The persistent blood clots essentially result in cells not getting enough oxygen in the tissues to sustain bodily functions. This, Pretorius says, may be central to numerous debilitating symptoms.

In healthy individuals, the body’s plasmin-antiplasmin system maintains a fine balance between blood clotting to prevent blood loss after an injury and fibrinolysis which prevents blood clots from forming.

With high levels of alpha(2)-antiplasmin in the blood of acute COVID-19 patients and individuals suffering from long COVID, the body’s ability to break down the clots is significantly undermined. The blood circulation becomes clogged up.

Microclots are generally not found in people who do not have long COVID. Pretorius says you can find them in some other conditions, such as diabetes, “but the difference is the number and the extreme presence of the clots with long COVID, that’s what’s making the difference,” she says.

Insoluble clots

Another difference is that the clots in long COVID are insoluble. When Pretorius tried to dissolve these clots using an enzyme called trypsin in her laboratory, they would not dissolve. They are resistant to fibrinolysis.

Initially, Pretorius was looking at acute COVID-19 infection. We received blood samples from ICU patients and we made blood smears and looked at them under a scanning electron microscope that can enlarge a sample hundreds of thousands of times. We then added a fluorescent dye or marker called Thioflavin T which lights up when there are misfolded proteins. This happens when, for example, the spike protein binds to the soluble fibrinogen molecule making it insoluble.

The SARS-CoV-2 virus is known to bind to ACE2 receptors and TMPRSS receptors which are found on platelets (blood cells that help with clotting). They are also found on the endothelium (the inner-most lining of the blood vessels). By binding to the platelets and the endothelium, the virus sets off a torrent of clotting causing vascular damage.

Pretorius says in early 2021, “I got a report from Harvard collaborators and others to say that patients do not fully recover post-infection and they referred to this as long COVID.

“I said let’s get the samples. We looked at the blood samples and lo and behold we found the clots and they were fully persistent. I was not surprised to find the clots in long COVID because I knew with acute COVID many people were dying because of clots in the lungs and shortness of breath. But, I did not know the extent to which they were present in long COVID.”

“When we did proteomics analysis on the sample, when we looked at the different molecules in the blood, I could not dissolve the sample with typical enzymes. I used a massively abrasive enzyme called Trypsin which dissolves any possible protein. But it could not dissolve these cells. The resilience of these clots, that they simply don’t get dissolved, surprised me,” Pretorius says.

Pretorius recalls that in 2020, several South African clinicians alerted others to COVID-19 not being a typical viral pneumonia but suggested it was also a vascular disease. “At that stage, it was massively controversial with many dismissing this idea saying it’s a virus that affects the lungs and that’s it,” she says.

Pretorius says this was despite papers published overseas in 2020 that concluded COVID-19 was also a vascular disease. “It was made controversial in South Africa but it is now widely accepted that COVID-19 also affects clotting as well as the body’s vasculature (network of blood vessels).”

Pretorius says, “Although the microclot is a theory, it encompasses all of the other suggested causes of long COVID because the spike protein itself can trigger microclots. We have submitted a paper, looking at many more blood samples, where we found inflammatory molecules trapped inside the blood clots which do not break down. We also found antibodies so the theories about immune abnormalities, persistent virus, and microclots are intertwined. All of these can cause organ damage. So if you look at it from a systems biology approach, all of these are valid.”

Many are told that their symptoms are possibly psychological, all in their head, and they are told to get some rest and to stop stressing. Meanwhile, the patients are very ill

Diagnostics

Pretorius says there are no general pathology tests readily available to diagnose people with long COVID.

“People that are desperately ill – bedridden or in wheelchairs – are often given generalised blood tests. They are told that their pathology test results are within normal to healthy ranges. Many are told that their symptoms are possibly psychological, all in their head, and they are told to get some rest and to stop stressing. Meanwhile, the patients are very ill,” she says.

Pretorius says the main reason the traditional laboratory tests do not pick up any of the inflammatory molecules is that they are trapped inside the insoluble microclots. A typical pathology test looks at the soluble content of the blood, so if the molecules are trapped they will be missed.

“We patented a long COVID test which is just a simple microscopy test that is a useable diagnostic method to see if microclots are present,” Pretorius says.

Microscopy methods are not readily available at pathology laboratories. However, Pretorius says, “We have crowd-funded and received funding from the Polybio Research Foundation in America to buy a flow cytometer for our blood lab to develop a flow cytometry method that can be used in the typical pathology labs. So we hope to have a diagnostic that will be readily available in a couple of months.”

Treatment

Pretorius says colleagues in the United Kingdom have already designed two randomised controlled trials to independently test both coagulation therapy (CLOTT-UK) and Apheresis (CLOTT-Apheresis trial ) in which microclots and inflammatory molecules are filtered out in a dialysis-type treatment. These trials will study whether anticoagulants and Apheresis give long-lasting relief of symptoms. These trials are being planned and researchers are waiting for ethics approval.

In addition, colleagues from the University of Sheffield Hallam and from the University of Manchester have independently set up microclot testing in their labs and they are planning to publish their UK cohort results soon. They are also correlating long COVID severity to microclot presence, says Pretorius.

“It’s been quite a ride. Seeing the devastation of long COVID, I realise why I decided not to be a clinician… handling and hearing all the issues is just so sad,” says Pretorius.

But, she remains determined to help “crack” long COVID.

Republished from Spotlight under a Creative Commons 4.0 licence.

Source: Spotlight

SARS-CoV-2 Variants are Evolving to Evade Human Interferons

SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Researchers have investigated how antiviral proteins called interferons interact with SARS-CoV-2. The study, published in PNAS, focuses on how the innate immune system defends against this coronavirus, which appears to be adapting to evade this interferon response.

The study was the result of a collaborative effort, including the laboratories of Mario Santiago, PhD, associate professor of medicine and Eric Poeschla, MD, professor of medicine, both at the University of Colorado School of Medicine.

While the adaptive arm of the immune system robustly deals with infection by generating antibodies and T cells, the innate arm forms an earlier, first line of defence by recognising conserved molecular patterns in pathogens.

“SARS-CoV-2 just recently crossed the species barrier into humans and continues to adapt to its new host,” said Prof Poeschla. “Much attention has deservedly focused on the virus’s serial evasions of neutralising antibodies. The virus seems to be adapting to evade innate responses as well.”

The type I Interferon system is a major player in antiviral defence against all kinds of viruses. Virus-infected cells release type I interferons (IFN-α/β), which warn the body of the intrusion. Secreted interferons cause susceptible cells to express powerful antiviral mechanisms to limit viral growth and spread. The interferon pathway could significantly reduce the levels of virus initially produced by an infected individual.

“They are clinically viable therapeutic agents that have been studied for viruses like HIV-1 for years,” explained Prof Santiago. “Here we looked at up to 17 different human interferons and found that some interferons, such as IFNalpha8, more strongly inhibited SARS-CoV-2. Importantly, later variants of the virus have developed significant resistance to their antiviral effects. For example, substantially more interferon would be needed to inhibit the omicron variant than the strains isolated during the earliest days of the pandemic.”

The data suggests that COVID clinical trials on interferons, dozens of which are listed in clinicaltrials.gov, may need to be interpreted based on which variants were circulating when the study was conducted. Researchers say that future work to decipher which of SARS-CoV-2’s multitude of proteins might be evolving to confer interferon resistance may contribute in that direction.

Source: University of Colorado Anschutz Medical Campus

COVID Experience may Have Changed Doctors’ Willingness to Resuscitate

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The pandemic may have changed doctors’ end of life decision-making, making them more willing to not resuscitate very sick and/or frail patients and raising the ICU transfer threshold, suggest the results of a snapshot survey of UK doctors published in the Journal of Medical Ethics.

Views on euthanasia and physician-assisted dying remain unchanged however, with around a third of respondents still strongly opposed to these policies.

The COVID pandemic transformed many aspects of clinical medicine, including end-of-life care, prompted by thousands more patients than usual requiring it, the researchers said. 

Because of this, they wanted to find out if the pandemic significantly changed the way in which doctors make end-of-life decisions, specifically in respect of ‘Do Not Attempt Cardio-Pulmonary Resuscitation’ (DNACPR) and treatment escalation to ICU.

These aspects of end-of-life care were chosen because of the controversy surrounding DNACPR decisions, in part prompted by an increase in cardiac arrests associated with COVID infections, and concerns about ICU capacity strained by the pandemic. 

The researchers also wanted to know if the pandemic had changed doctors’ views on euthanasia and physician assisted suicide as surveys on these issues by the British Medical Association (BMA) and the Royal Colleges of Physicians and General Practitioners had been carried out before it started.

The online survey was open to doctors of all grades and specialties between May and August 2021, when hospital admissions for COVID in the UK were relatively low.

In all, 231 responses were received: 15 from foundation year 1 junior doctors (6.5%); 146 from senior junior doctors (SHOs) (63%); 42 from hospital specialty trainees or equivalent (18%); 24 from consultants or GPs (10.5%); and 4 others (2%).

In respect of DNACPR, which refers to the decision not to attempt to restart a patient’s heart when it or breathing stops, over half the respondents were more willing to do this than they had been previously.

When the responses were weighted to represent the different medical grades in the NHS national workforce, the results were: ‘significantly less’ 0%; ‘somewhat less’ 2%; ‘same or unsure’ 35%; ‘somewhat more’ 41.5%; ‘significantly more’ 13%; and ‘not applicable’ 8.5%.

When asked about the contributory factors, the most frequently cited were: ‘likely futility of CPR’ (88% pre-pandemic, 91% now): co-existing conditions (89% both pre-pandemic and now): and patient wishes (83.5% pre-pandemic, 80.5% now). Advance care plans and ‘quality of life’ after resuscitation also received large vote-share.

The number of respondents who stated that ‘patient age’ was a major factor informing their decision increased from 50.5% pre-pandemic to around 60%. And the proportion who cited a patient’s frailty rose by 15% from 58% pre-pandemic to 73%. 

But the biggest change in vote-share was ‘resource limitation’, which increased by 20%, from 2.5% to 22.5%. 

When asked whether the thresholds for escalating patients to intensive care or providing palliative care had changed, the largest vote-share was the ‘same or unsure’: 46% (weighted) for referral; 64.5% (weighted) for palliative care.

But a substantial minority said that now they had a higher threshold for referral to intensive care (22.5% weighted) and a lower threshold for palliation (18.5% weighted).

When it came to the legalisation of euthanasia and physician assisted suicide, the responses showed that the pandemic has led to marginal, but not statistically significant, changes of opinion.

Nearly half (48%) were strongly or somewhat opposed to the legalisation of euthanasia, 20% were neutral or unsure, and around a third were somewhat or strongly in favour before the pandemic. These proportions changed to 47%, 18%, and 35%, respectively. 

But a substantial minority said that now they had a higher threshold for referral to intensive care (22.5% weighted) and a lower threshold for palliation (18.5% weighted).

When it came to the legalisation of euthanasia and physician-assisted suicide, there was no statistically significant change in opinion.

Nearly half (48%) were strongly or somewhat opposed to the legalisation of euthanasia, 20% were neutral or unsure, and around a third were somewhat or strongly in favour before the pandemic. These proportions changed to 47%, 18%, and 35%, respectively. 

Similarly, just over half (51%) said they had strongly or somewhat opposed the legalisation of physician assisted suicide, 24% had been neutral or unsure, and 25% had been somewhat or strongly in favour.  These proportions changed to 52%, 22%, and 26%, respectively. 

The impetus to make more patients DNACPR, prompted by pressures of the pandemic, persisted among many clinicians even when COVID hospital cases returned to low levels, the researchers noted. The factors informing it were compatible with regulatory (GMC) ethical guidance, with the exception of limited resources.

“At the start of the pandemic, the BMA advised clinicians that in the event of NHS resources becoming unable to meet demand, resource allocation decisions should follow a utilitarian ethic.

“However, what is clear from our results is that for a significant proportion of clinicians, resource limitation continued to factor into clinical decision making even when pressures on NHS resources had returned to near-normal levels,” they wrote.

The survey results also suggest that the pandemic has helped clinicians gain a greater understanding of the risks, burdens, and limitations of intensive care and had further educated them in the early recognition of dying patients, and the value of early palliative care, they added. 

“What is yet to be determined is whether these changes will now stay the same indefinitely, revert back to pre-pandemic practices, or evolve even further,” they conclude.

Source: EurekAlert!

Increase in Cardiovascular Disease Diagnoses after COVID

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A new study published in PLOS One found that COVID infection is associated with a nearly six-fold increase in cardiovascular disease (CVD) diagnoses over 12 months after the infection. 

The study analysed of UK electronic health records, comparing the risks of new diabetes mellitus (DM) and CVD diagnoses in the 12 months after infection. Researchers matched a cohort of 428 650 COVID patients matched to controls.

There was an 80% increased risk of DM diagnosis in the first month after COVID infection, a trend that has been echoed in previous studies, although those studies’ results seem to indicate a temporary form of the disease resulting from the acute stress of viral infection.

The findings showed that the largest increases were in pulmonary embolism (Relative Risk [RR] 11.51) and in atrial arrhythmias (RR 6.44). New CVD diagnoses rose five weeks after infection and incidence declined within 12 weeks to a year and returned to baseline or showed a net decrease. Increased risk for new DM diagnoses remained elevated by 27% for up to 12 weeks. 

“It’s definitely reassuring that over the longer timeframe, cardiovascular disease and diabetes risk does seem to return to baseline levels,” study author Emma Rezel-Potts, PhD, told The Guardian. “But we do have to be cautious in the acute period with cardiovascular disease and take note that the risk of diabetes seems to be elevated for several months, so that could be a good opportunity for risk prevention.” 

She also stressed that the findings could be explained by many factors. For example, the COVID patients in the study were more likely to be overweight and had more underlying health problems compared to uninfected controls, predisposing them to DM and CVD. Additionally, some may have had underlying conditions which were discovered when they were treated for COVID.

Source: The Guardian

Menstrual Changes after COVID Vaccine

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A new analysis of offers the most comprehensive assessment so far of menstrual changes experienced by pre- and post-menopausal individuals in the first two weeks after being vaccinated against COVID. Published in the journal Science Advances, the study adds to the growing body of evidence that significant numbers of people experience this unexpected side effect.

“Menstruating and formerly menstruating people began sharing that they experienced unexpected bleeding after being administered a COVID vaccine in early 2021,” the scientists who led the study wrote. Because vaccine trials typically do not ask about menstrual cycles or bleeding, this side effect was largely ignored or dismissed.

Early reports about post-vaccination menstrual changes were largely brushed aside, said Kathryn Clancy, a professor of anthropology who led the research with Katharine Lee, another anthropology professor. Some clinicians said it was unclear how a vaccine could trigger such changes.

However, it is known that other vaccines – including those for typhoid, Hepatitis B and HPV – are sometimes associated with changes in menstruation, Prof Clancy said. The changes are more likely to be associated with an increase in immune-related inflammatory pathways, as opposed to any hormonal changes.

“We suspect that for most people the changes associated with COVID vaccination are short-term, and we encourage anyone who is worried to contact their doctor for further care,” Lee said. “We want to reiterate that getting the vaccine is one of the best ways to prevent getting very sick with COVID, and we know that having COVID itself can lead not only to changes in periods, but also hospitalisation, long COVID and death.”

The researchers used a survey to query people about their experiences after vaccination. Launched in April 2021, the survey asked for demographic and other information but focused on respondents’ reproductive history and experiences regarding menstrual bleeding. The team downloaded the data from the surveys on June 29, 2021. Only those who had not been diagnosed with COVID were included in the analysis, as COVID itself is sometimes associated with menstrual changes. Data from people aged 45–55 years was excluded to avoid the confounding of effect menstrual changes associated with perimenopause.

“We focused our analysis on those who regularly menstruate and those who do not currently menstruate but have in the past,” Prof Clancy said. “The latter group included postmenopausal individuals and those on hormonal therapies that suppress menstruation, for whom bleeding is especially surprising.”

A statistical analysis revealed that 42.1% of menstruating survey respondents reported a heavier menstrual flow after receiving the COVID-19 vaccine. Some experienced this in the first seven days but many others saw changes 8–14 days after vaccination. Roughly the same proportion, 43.6%, reported no alteration of their menstrual flow after the vaccine, and a smaller percentage, 14.3%, saw a mix of no change or lighter flow, the researchers report.

Because the study relied on self-reported experiences logged more than 14 days after vaccination, it cannot establish causality or be seen as predictive of people in the general population, Lee said. But it can point to potential associations between a person’s reproductive history, hormonal status, demographics and changes in menstruation following COVID vaccination.

For example, the analysis revealed that respondents who had experienced a pregnancy were most likely to report heavier bleeding after vaccination, with a slight increase among those who had not given birth. A majority of non-menstruating premenopausal respondents on hormonal treatment experienced breakthrough bleeding after receiving the vaccine. This side effect was common in respondents using long-acting reversible contraception and 38.5% of those undergoing gender-affirming hormone treatments reported this side effect.

Those who were older, and those who experienced fever or fatigue as a side effect of vaccination were also more likely than other groups to report heavier menstrual flow after vaccination. White respondents were slightly less likely to report heavier menstrual flow.

Those who had experienced endometriosis, menorrhagia, fibroids or other reproductive problems also were more likely to report a heavier menstrual flow post-vaccination, the team found. The largest single increase was in those who have been pregnant without a delivery.

While the uptick in menstrual flow for some people may be transitory and quickly resolve, unexpected changes in menstruation can still cause concern, Prof Lee said.

“Unexpected breakthrough bleeding is one of the early signs of some cancers in post-menopausal people and in those who use gender-affirming hormones, so experiencing it can make people worry and require expensive and invasive cancer-screening procedures,” Prof Lee said.

“This screening is very important so we can catch cancers early,” Prof Clancy said. “For diagnostic purposes, it would be helpful to know whether there are other causes for the bleeding.”

“We’d love to see future vaccine testing protocols incorporate questions about menstruation that go beyond screening for pregnancy,” Prof Lee said. “Menstruation is a regular process that responds to all kinds of immune and energetic stressors, and people notice changes to their bleeding patterns, yet we don’t tend to talk about it publicly.”

Source: University of Illinois at Urbana-Champaign

Activities That Changed During the Pandemic – and Didn’t Change Back

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A new analysis describes how people in the UK shifted the amount of time they spent on various activities over various stages of pandemic restrictions and shifted to online versus in-person settings. The findings were published in the open-access journal PLOS ONE.

When the COVID pandemic began, the U.K. joined many countries in introducing restrictions on people’s movement and social activities to mitigate viral spread. A growing body of research reveals how such restrictions have affected people’s lifestyles worldwide. This study examined how UK residents’ habits changed over time as different restrictions were implemented and lifted.

The researchers conducted six online surveys of UK residents between April 2020 and July 2021 and were ultimately able to follow 203 people who responded to multiple surveys. The surveys included questions about 16 different types of activities respondents participated in during different phases of the pandemic, such as journalling, shopping, and getting active, and whether they participated online or in person.

Statistical analysis of the responses showed that the biggest changes in terms of amount of time spent – as well as the biggest changes in online versus in-person participation – occurred for cultural activities, spending time with others, and travelling. Changes were most pronounced in March to June 2020, corresponding with the first lockdown period, when participation in all 16 activities decreased. The biggest shift from in-person to online participation occurred from March to October 2020, which included the first lockdown followed by relaxation of restrictions.

Cultural activities, such as going to museums, and group activities were the two categories that fell the most, and did not recover to pre-pandemic levels when UK restrictions were lifted on July 19, 2021. During the restrictions, participation was mostly online in these activities. Spending time with family was among the most robust, and remained mostly in-person, though supplemented by online interaction.

These findings could help policymakers understand the impact of their pandemic restrictions. In the future, the researchers plan to investigate how demographic factors, such as age and employment, may have affected the results, as well as long-term mental health implications of the lifestyle changes.

Professor Patty Kostova, leader of the study, added: “This longitudinal research study illustrated citizens’ resilience throughout the stages of the pandemic.”

Lan Li adds: “This longitudinal study determines the frequency and way of people doing activities from Spring 2020 to Summer 2021 during different phases of the COVID pandemic in the UK. The findings provide an invaluable insight into understanding how people in the UK changed their lifestyle, including what activities they do, and how they accessed those activities in light of the COVID pandemic and related public health policy implemented to address the pandemic.”

Source: ScienceDaily

SA Study Finds no Increased Severity in Omicron BA.4 and BA.5 Infections

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South African researchers have found that, compared to Omicron BA.1 and earlier infections, those caused by Omicron BA.4 and BA.5 do not have an increased risk of hospitalisation for severe disease or death.

The study, which appears online in the medRxiv server, aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

In their study, the researchers included public sector patients aged 20 years or older with laboratory-confirmed COVID between 1 and 21 May 2022 (for the BA.4/BA.5 wave) and equivalent prior wave periods. They compared the risk for death and severe hospitalisation/death (all within 21 days of diagnosis), adjusting for for demographics, comorbidities, admission pressure, vaccination and prior infection.

Comparing 3793 patients from the BA.4/BA.5 wave and 190 836 patients from previous waves the risk of severe hospitalisation or death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12). Both Omicron waves had a lower risk of severe outcomes than previous waves. They also found that both prior infection (aHR 0.29) and vaccination (aHR 0.17; 0.40 for boosted vs no vaccine) were protective.

Overall, the researchers found that COVID disease severity was similar for the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, which were both strongly protective.

Nitrous Oxide Safe and Effective Therapy for Severe COVID in Pregnancy

Pregnant with ultrasound image
Source: Pixabay

High dose inhaled nitric oxide gas (iNO) is a safe and effective respiratory therapy for pregnant women hospitalised with severe COVID pneumonia, resulting in faster weaning from oxygen and shorter hospital stay, according to a study published in Obstetrics & Gynecology. Massachusetts General Hospital (MGH) researchers reported that the addition of twice-daily nitric oxide to standard of care oxygen therapy decreased the respiratory rate of pregnant women with low oxygenation levels of the blood without causing any side effects.

“To date, very few respiratory treatments to complement supplemental oxygenation in COVID pregnant patients have been tested,” explained the study’s senior author, Lorenzo Berra, MD. “Investigators from all four medical centers that participated in our study agreed that administration of high dose nitric oxide through a snug-fitting mask has enormous potential as a new therapeutic strategy for pregnant patients with COVID.”

Pneumonia triggered by COVID is particularly threatening to pregnant women since it may quickly progress to hypoxaemia, requiring hospitalisation and cardiopulmonary support. “Compared to non-pregnant female patients with COVID, pregnant women are three times more likely to need intensive care unit admission, mechanical ventilation, or advanced life support, and four times more likely to die,” noted lead author Carlo Valsecchi, MD. “They also face a greater risk of obstetric complications such as preeclampsia, preterm delivery, and stillbirth.”

Nitric oxide is a therapeutic gas that was initially approved by the U.S. Food and Drug Administration in 1999 for inhalation treatment of intubated and mechanically ventilated newborns with hypoxic respiratory failure. With MGH driving many early studies, iNO in high concentrations was also shown to be effective as an antimicrobial in reducing viral replication of SARS-CoV-1 and, more recently, SARS CoV-2. During the first wave of COVID, MGH treated six non-intubated pregnant patients with iNO at high doses of up to 200 parts per million (ppm). Favourable outcomes with iNO led MGH clinicians to offer this treatment to other pregnant patients, and motivated the present study.

Researchers and clinicians from multiple departments in four hospitals – including critical care medicine, respiratory care, and maternal foetal medicine – studied 71 pregnant patients with severe COVID pneumonia admitted to these hospitals, 20 of whom received iNO200 twice daily. The study found that iNO therapy at this dosage, when compared to standard of care alone, resulted in reductions in the need for supplemental oxygen and in hospital and ICU lengths of stay. No adverse events related to the intervention were reported in either mothers or their babies.

“Being able to wean patients from respiratory support quicker could have other profound implications, including reducing stress on women and their families, lowering the risk of hospital-acquired infections, and relieving the burden on the health care system,” noted Dr Berra. “Above all, our study supports the safety of high dose nitric oxide in the pregnant population, and we hope more physicians will consider incorporating it into carefully monitored treatment regimens.”

Source: Massachusetts General Hospital

Employees’ Rights: What Does The Law Say about COVID Vaccination?

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In the past year, the Commission for Conciliation, Mediation and Arbitration (CCMA) has delivered several arbitration awards which have upheld the dismissals of employees who refused to get vaccinated against COVID.

But a recent award has created some confusion about whether this is still allowed and under what circumstances.

On 22 June, CCMA Commissioner Richard Byrne found that it was unfair and unconstitutional for Baroque Medical, which supplies and sells medical equipment, to retrench Kgomotso Tshatshu for refusing to get a Covid vaccination. The company was ordered to pay her 12 months’ salary as compensation (the maximum allowed).

But this contradicts an earlier CCMA award by Commissioner Piet van Staden, delivered in May, who found that Baroque Medical was within its rights to retrench another employee, Cecilia Bessick, who had also refused to get a COVID vaccine.

These conflicting decisions may be understandable, because CCMA arbitration awards do not create binding legal precedent in the same way as court judgments. The most recent CCMA ruling therefore does not set a binding legal precedent that employees cannot be dismissed for refusing to get a COVID vaccine.

The Labour Court has also not yet delivered any binding judgment about whether an employer can fairly dismiss an employee who refuses to get a Covid vaccination. Until this occurs, it is likely the CCMA will continue to give conflicting decisions about whether employers can fairly dismiss employees who refuse to get a vaccine.

Below, we explain what the law currently says about whether an employee can be dismissed for refusing to get a COVID vaccine and under what circumstances.

Labour Relations Act

The Labour Relations Act (LRA) says that an employee can only be dismissed for these reasons: when they are guilty of misconduct; suffer from an incapacity, such as ill health or injury, which prevents them from performing their duties; have to be retrenched because of the economic, structural, technological or similar needs of their employer.

The LRA also requires an employer to follow a fair procedure before dismissing an employee. Usually, this would involve explaining to an employee why they could be dismissed if they refuse to get a Covid vaccine and give the employee an opportunity to explain why they should not be dismissed.

The LRA, however, does not explain whether an employee who refuses to get vaccinated can be dismissed for misconduct or incapacity. The LRA also does not explain whether an employee who refuses to get a Covid vaccine can be retrenched.

Occupational Health and Safety Act

But the Occupational Health and Safety Act does require employers to take all reasonable steps to provide their employees with a safe and healthy working environment. The act also requires employers to take reasonable steps to ensure other people who may be affected by their business activities (such as customers or suppliers) are not exposed to a hazard to their health or safety – such as Covid.

During March, the Minister of Labour issued a Code of Good Practice which explains the steps that an employer should take to manage Covid in their workplace and to comply with their legal duties to provide a safe and healthy working environment.

This code was enacted after a previous directive on managing Covid in the workplace was repealed after the State of Disaster came to an end.

Code of Good Practice

According to the new Code of Good Practice, every employer with at least 20 employees must conduct a “risk assessment” and must develop a COVID plan with the measures it will implement regarding vaccination of employees and when they should be fully vaccinated. When developing the plan, the employer must consult with any representative trade union in its workplace or an employee representative.

The risk assessment and plan, among other things, should identify employees who must be vaccinated and must notify them of their duty to get a vaccination.

The code also states employers can require employees to disclose their vaccination status and to produce a vaccine certificate in order to give effect to the code.

The code further states that employees can lawfully refuse work when there exists a serious risk that they may imminently be exposed to COVID in the workplace. Should this occur, the employer cannot take any action against that employee for refusing to work, such as later dismissing or suspending them from work.

There may be situations where a refusal by employees to work because other employees refuse to get vaccinated, could justify the dismissal of the employees who refuse to get a COVID vaccine. This is because the refusal of many employees to work could affect the ability of a company or business to operate. This could potentially justify retrenchment of employees who refuse to get a COVID vaccine.

However, should an employee refuse to get vaccinated, the code also says that the employer should take steps to reasonably accommodate them in a position that does not require them to be vaccinated. Should an employee produce a valid medical certificate, which provides legitimate reasons why they cannot be vaccinated, the employer can send that employee to another doctor at their own expense.

The code does recognise that it would be unfair to dismiss employees who cannot be vaccinated on valid medical grounds. But, the duty to accommodate employees who refuse to get vaccinated on other grounds would depend on whether an employer has another position available which does not require that employee to be vaccinated. Should the employer not have an alternative position which does not require the employee to be vaccinated, this could be a fair reason to dismiss them.

It is important to note that the code does state that it reflects the policy position of the Department of Labour and that it should be applied until any of its provisions are reversed by a court judgment. Until the Labour Court delivers a binding judgment on when employees can be dismissed for refusing to get a COVID vaccination, it would seem it would be best to follow the provisions of the code.

By Geoffrey Allsop

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Vaccine Acceptance is Increasing Around the World

Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

COVID vaccine acceptance across much of the world increased by 3.7% between 2020 and 2021, according to a new study published in Nature Communications.

In a June 2021 survey of over 23 000 individuals across 23 countries, the researchers found that 75.2% of respondents reported vaccine acceptance, up from 71.5% one year earlier.  

The study was carried out during a year of substantial but very unequal global COVID vaccine availability and acceptance, which required new assessments of the drivers of vaccine hesitancy and the characteristics of people not vaccinated.

Vaccine hesitancy was most consistently associated with concerns about vaccine safety and efficacy and mistrust in vaccine development. Other factors associated with vaccine hesitancy varied by country and included personal experience with COVID (eg, sickness or loss of a family member) and demographic characteristics (eg, gender, education, and income).

The authors also found that vaccine hesitancy was not associated with a country’s current COVID case burden and mortality. In June 2021, vaccine hesitancy was reported most frequently in Russia (48.4%), Nigeria (43%), and Poland (40.7%), and least often in China (2.4%), the UK (18.8%), and Canada (20.8%).

“In order to improve global vaccination rates, some countries may at present require people to present proof of vaccination to attend work, school, or indoor activities and events,” said CUNY SPH Senior Scholar Jeffrey Lazarus. “Our results found strong support among participants for requirements targeting international travellers, while support was weakest among participants for requirements for schoolchildren.”

Those who were vaccine-hesitant were also less likely to express support for vaccine mandates. “Importantly, however, recommendations by a doctor, or to a lesser extent by an employer, might have an impact on a respondent’s views on vaccination in some countries,” said CUNY SPH Dean Ayman El-Mohandes.

Although some countries are currently disengaging from evidence-based COVID control measures, the disease has by no means been controlled or ended as a public health threat. The authors note that for ongoing COVID vaccination campaigns to succeed in improving coverage going forward, substantial challenges remain. These include targeting those reporting lower vaccine confidence with evidence-based information campaigns and greatly expanding vaccine access in low- and middle-income countries.

The Role of Social Networks

The researchers also held a meeting to explore vaccine messaging. According to data presented from a European survey carried out by the Vaccine Confidence Project, the population group most exposed to social networks, ie people under 24, with secondary or university studies and living in urban areas, are the most reluctant to be vaccinated. Additionally, messages that call for vaccination as a “moral obligation” are strongly rejected compared to those that call for “protection,” which are more commonly well received.

As with previous studies, humour was shown to be one of the most effective ways to convey anti-vaccine messages. Therefore, participants in the meeting agreed on the need to disseminate the benefits of vaccines using this same tool, but without making fun of those who have mistaken beliefs about vaccines. In the face of misinformation, it is important to improve information on vaccination using simple language and channels that reach the population, such as social networks, the participants concluded.

Source: CUNY Graduate School of Public Health and Health Policy