Category: COVID

Brazil’s ICU Beds Full Amidst ‘Catastrophe’

Brazilian doctors say the situation is “well beyond chaos” even as the country’s COVID-sceptic president refuses to take decisive action against the pandemic.  

An article in The Guardian reports that Brazil is facing the worst medical crisis in its history, as researchers from its leading healthcare institute, Fiocruz, have said the country is entering into a “catastrophe”.

COVID intensive care units in virtually all of the country’s hospitals are either full or almost full, with Fiocruz warning that “The situation is absolutely critical.”

Ricardo Barros, Bolsonaro’s leader in the lower house said on Wednesday: “Our situation isn’t all that critical. Compared to other countries, it’s actually quite comfortable.” This was said on a day in which 2798 fatalities and a record 90 830 new cases were reported.

However, intensive care physicians interviewed by The Guardian tell a different story.

“Things are desperate,” said Dr Hermeto Paschoalick, the head of the critical care unit in the midwestern state of Mato Grosso do Sul, where ICUs are currently 93% full.

Things were worse elsewhere, especially in the state’s capital. “I was told yesterday that there’s a health clinic there with 20 ambulances parked outside. The patients are arriving from small towns in the interior and there’s nowhere to put them – so they just keep them in the ambulances,” said Dr Paschoalick.

Although most in his care were over 60s, Dr Paschoalick said there were young people as well. “Right now, I’ve got three people on ventilators including a 22-year-old woman and another who is 25. Both were pregnant when they arrived. One lost the baby, the other managed to give birth. Both are intubated and in a really bad state,” he said.

Many doctors are forced to choose which patients can receive a bed in ICU.

“People are going around saying Brazil is going to collapse,” said critical care doctor Pedro Carvalho at a university hospital in the riverside town of Petrolina. “But we’ve collapsed already – completely collapsed.” 

Brazil’s President Jair Bolsonaro meanwhile, shows no sign of changing his stance, claiming that there is a “war” against him. 

Source: The Guardian

A Tougher Spike Protein is Behind Transmissibility of Variants

Researchers at Boston Children’s Hospital have analysed the structure of the SARS-CoV-2 variants, and have found that a tougher spike protein is likely responsible for their greater transmissibility.

Using a cryo electron microscope, the researchers imaged the spike protein down to the atomic level and discovered that the D614G mutation (a substitution of in a single amino acid ‘letter’ in the spike protein’s genetic code) produced a sturdier spike protein.

In the original, wild-type SARS-CoV-2, the spike protein would latch onto a cell’s ACE2 receptor and then fold in on itself, allowing the virus’ outer membrane to more easily fuse with the cell’s surface. However, they were susceptible to folding early, rendering those spike proteins useless. Around half of a SARS-CoV-2’s spike proteins would be folded in this way. However, this also made the virus harder for the immune system to lock on to.

“Because the original spike protein would dissociate, it was not good enough to induce a strong neutralising antibody response,” said research leader Bing Chen, PhD  at Boston Children’s Hospital.

When Chen and colleagues imaged the mutated spike protein, fewer are folded early because the D614G mutation blocks the shape change. While the spike protein is sturdier, it comes at the cost of being able to attach less easily to the ACE2 receptor.

“Say the original virus has 100 spikes,” Dr Chen explained. “Because of the shape instability, you may have just 50 percent of them functional. In the G614 variants, you may have 90 percent that are functional, so even though they don’t bind as well, the chances are greater that you will have infection.”

Dr Chen proposed that vaccines currently being updated should be modified for this new spike protein mutation, which should also have the side benefit of making the vaccines more effective. 

Applying structural biology to the spike protein, the team had come up with a ‘decoy’ molecule that bound to the spike protein 200 times more strongly than to the body’s ACE2 receptors. This was shown to inhibit the virus in the culture, opening up the door to a new type of treatment. 

Source: Medical Xpress

Journal information: Jun Zhang et al. Structural impact on SARS-CoV-2 spike protein by D614G substitution, Science (2021). DOI: 10.1126/science.abf2303

New French COVID Variant Invisible to PCR Tests

French authorities have announced the detection of a variant of SARS-CoV-2 in the northwestern region of Brittany that has escaped detection by standard polymerase chain reaction (PCR) tests.

Real-time PCR tests are considered to be the current gold standard for detection of SARS-CoV-2, and currently take 4-6h to yield a result. PCR tests make millions to billions of copies of a small sample of DNA to create a larger sample for analysis.

Eight carriers of the variant were identified using genomic sequencing among a cluster of 79 cases in the town of Lannion in the Côtes d’Armor on March 13th.

In a statement on Monday, the French health ministry said that according to initial analyses, the new variant did not appear more transmissible or cause more severe disease. However, on Tuesday, authorities said that this variant was able to escape detection in PCR tests is raising concern.

Belgian virologist and interfederal COVID spokesperson Steven Van Gucht clarified the situation, in that about eight individuals presented with standard coronavirus symptoms, “but the tests remained negative.”

The World Health Organization has labelled this new French COVID variant a ‘variant under investigation’ (VUI), of which there are many thousands currently being monitored, as opposed to more serious variants like the South African B.1.351 variant which is more transmissible and is a ‘variant of concern’ (VOC).

However, just because this variant escaped the PCR tests being used in that area does not mean that it necessarily can escape all of them, as laboratories vary in the tests that they perform.

According to Gucht, tests differ in the different parts of the virus they look for, and also test for at least two to three. “Usually, a good test does not depend on detecting one specific part. So, if there is a mutation in one part of the virus, that signal may be lost, but there is usually a second or third signal that will be found,” explained Gucht.

French authorities are setting up systems to monitor the spread of this variant, and are also putting measures in place to contain it.

Source: News-Medical.Net

AstraZenaca Ineffective Against SA Variant in Early Trial

In a phase Ib/II trial, the AstraZeneca vaccine was ineffective against both the South African SARS-CoV-2 variant or the wild-type virus.

In this South African trial, the vaccine’s overall efficacy versus mild-to-moderate COVID was 21.9% and efficacy against the B.1.351 variant was 10.4%.

Participants’ median age was 30, about 56% were men, and 71% were black. Almost 20% of participants were obese, 42% were smokers, and about 3% of those had underlying hypertension or chronic respiratory conditions. All were HIV negative. The median time between doses was 28 days.

Overall, 19 of 750 in the vaccine group (2.5%) and 23 of 717 in the placebo group (3.2%) developed mild-to-moderate COVID. 

In regard to the secondary outcome of testing effectiveness against the B.1.351 variant, the authors note that “the trial was powered for the primary objective of a vaccine efficacy of at least 60% in preventing COVID-19 of any severity, regardless of variants.”

Exploratory analyses found about 33.5% efficacy against COVID of any severity more than 14 days after the first dose. No cases of severe COVID were reported among the participants, but with the groups’ demographics, especially their relatively young age, it was unlikely that severe COVID would be observed in such a small trial.

Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit at Wits, said in a press release that the AstraZeneca results “threw a curveball” after the initial “euphoria” over the effectiveness of the first COVID vaccines. He nevertheless stressed that the AstraZeneca vaccine was still important in preventing hospitals being overrun with COVID patients.

Despite the disappointing results, Prof Madhi said these findings “need to be made in the context of ongoing global spread and community transmission of the B.1.351 variant”.

Source: MedPage Today

Journal information: Madhi SA, et al “Efficacy of the ChAdOx1 nCOV-19 Covid-19 vaccine against the B.1.351 variant” N Engl J Med 2021; DOI: 10.1056/NEJM2102214.

WHO and Health Experts Back AstraZeneca Vaccine

Woman receiving an injection in the upper arm. Photo by Gustavo Fring from Pexels.

Although a number of EU countries have halted the use of the AstraZeneca vaccine, the company along with a number of health experts insist that it is safe.

AstraZeneca said in a statement on Monday that there were 15 deep vein thrombosis (DVT) events and 22 pulmonary embolism (PE) cases among 17 million people in the EU and UK who have received at least one AstraZeneca vaccine dose.    

“This is much lower than would be expected to occur naturally in a general population of this size and is similar across other licensed COVID-19 vaccines,” the pharmaceutical company said.

The company pointed out that in the clinical trials, “even though the number of thrombotic events was small, these were lower in the vaccinated group. There has also been no evidence of increased bleeding in over 60 000 participants enrolled.”

The European Medicines Agency (EMA) reiterated that there is no indication that the vaccine was responsible for these adverse events. The organisation is currently reviewing the vaccine, and more information is expected in its monthly safety report due during the week. They are currently scheduled to meet on Tuesday.

There are however concerns that slowing the pace of vaccinations will result in more lives lost and fuel vaccine hesitancy.

“I do worry that some people will not be able to differentiate between an unrelated or coincidental VTE [venous thromboembolism] occurrence (due to DVT/PE being so common in the general population) and a causative relationship,” Stephan Moll, MD, of the division of haematology at the University of North Carolina at Chapel Hill, said to MedPage Today.

WHO chief scientist Soumya Swaminathan, MD, noted that it has happened before: Norway early on raised concerns about deaths among the elderly getting vaccinated, but then clarified it was only the expected rate of death.

She pointed out that of the 300 million-odd doses of all COVID vaccines administered globally, not one death has been documented as having been caused by vaccination, “We do not want people to panic. We would for the time being recommend that countries continue vaccinating with AstraZeneca.”

Canada, meanwhile, has said that it will continue to use the AstraZeneca vaccine. The company is likely to seek emergency use authorisation from the United States for its jab when it clears its Stage III clinical trials in that country.

“This does not necessarily mean these events are linked to vaccination, but it’s routine practice to investigate them,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus at a press briefing Monday. “It shows that the surveillance system works and effective controls are in place.”

Source: MedPage Today

Have COVID Restrictions Eroded The Right to Dissent?

Image by Niek Verlaan from Pixabay

An article in The Guardian explores how the COVID pandemic and its restrictions have also may have caused an erosion in the institutions of democracy around the world.

On Saturday, a vigil at Clapham Common in the UK for Sarah Everard, a woman believed to have been murdered by a police officer, was broken up by police in a heavy-handed manner which drew widespread criticism.
Defending the Metropolitan police’s handling of the situation, assistant commissioner Helen Ball argued the force had to act “because of the overriding need to protect people’s safety” from COVID. In 2020, Black Lives Matter protestors were criticised for their actions in the first waves of the pandemic, but their actions did not cause a spike in infections. Indeed, the protests may have helped deter the spread of COVID due to their deterring people from going to restaurants and other forms of social gatherings.

While the Clapham Common event was not on the same scale, it is possible that even very large and boisterous protests are not ‘super-spreader’ events. And, according to the human rights organisation Liberty, they can be performed safely. For example a socially distanced rally was held in Tel Aviv in April last year against the Israeli prime minister, Benjamin Netanyahu, where thousands of people,   each in their own space, separated by two metres, were able to shout and wave banners.

“Protest is the lifeblood of a healthy democracy, and it’s critical that we can all stand up to those in power, and make our voices heard,” said Lana Adamou, a lawyer at Liberty. “Safe, socially distanced demonstrations are perfectly possible, and it is the duty of the police to facilitate them, not block them. The current restrictions should be interpreted compatibly with our rights enshrined in the Human Rights Act.”

However a report published by Carnegie Europe in January observed that human rights are being eroded in the name of public health, with many governments using the pandemic as a pretext to crack down on dissent.

“While governments have claimed that they were imposing measures to tackle the pandemic, these measures often have been contradictory and have excessively restricted the right to peaceful assembly,” the report said, saying that while economic activities were enabled, large protests were still prohibited. In Sweden large groups were allowed to congregate in restaurants and at sporting events, but public gatherings and protests involving more than eight people were banned. It also noted that police used tactics such as kettling, a controversial tactic where police corral protestors into tight groups before arresting them, which can increase the spread of infection.

These restrictions have forced some campaigners to become creative in their protests. In the Netherlands, climate activists filled a square in front of the Dutch parliament in the Hague with 1000 shoes from all over the country. In Croatia, a civil society movement staged balcony protests against the governance of the mayor of Zagreb.

What campaigners in some countries will be asking is whether or not the pandemic has eroded the right to dissent, and to what extent will mass public protests be allowed to return once the COVID threat has passed.

Source: The Guardian

COVID Vaccination in Immunosuppressed Patients Produces Weak Response

An article by Dorry Segev, MD, PhD for MedPage Today reveals poor results for COVID vaccination in immunosuppressed patients, with concerning implications. 

Dr Segev professor of surgery and epidemiology and associate vice chair of surgery at Johns Hopkins University School of Medicine and Bloomberg School of Public Health.

Dr Segev and colleagues launched a national study of vaccine immune responses in immunosuppressed solid organ transplant recipients. Among 436 COVID-naïve participants who received their first mRNA vaccine dose, only 17% of them mounted detectable antibodies to SARS-CoV-2.  The researchers also found that those taking anti-metabolites (eg, mycophenolate or azathioprine) were less likely to develop antibody responses, with 8.75% with detectable antibody found in those taking anti-metabolites versus 41.4% in those not taking them.

“Naturally, we were disappointed to see these findings, as we were hoping to be able to tell our immunosuppressed patients that the vaccines seemed to work well for them. Given this observation, the CDC should update their new guidelines for vaccinated individuals to warn immunosuppressed people that they still may be susceptible to COVID-19 after vaccination,
Dr Segev wrote. 

The current CDC guidelines are worded in a way that suggests vaccination translates into immunity, Dr Segev pointed out, but the study demonstrates that for most transplant recipients, as well as other immunosuppressed patients that the vaccine does not automatically confer immunity. This could also be a concern for the some 37.9 million people around the world living with HIV, although the effects of achieving viral suppression with antiretroviral therapy have so far not been well investigated in relation to COVID. Vaccine trials so far have not had sufficient numbers of participants living with HIV to draw any conclusions.

Notably, their previous research did show that rates of COVID infection and mortality were not greater for immunosuppressed transplant patients. 
Dr Segev noted that there are some implications for immunosuppressed patients; firstly, that they should at the very least receive the second dose of their vaccination (the current research is only on the effects of the first dose), and secondly, immunosuppressed patients should be aware that they may not necessarily be immunised after receiving a vaccination. They should speak to their provider about an antibody test to determine if the immunisation has been achieved.

The researchers are continuing to investigate other aspects of immune response besides antibodies, such as T and B cells, and are also looking at other vulnerable populations.

Source: MedPage Today

‘3 Feet’ Social Distancing Rule Being Considered by US

Data that suggest a ‘three feet’ social distancing rule is under consideration, according to Dr Anthony Fauci, the foremost infectious disease expert in the US.

To control COVID transmission, the World Health Organization recommends social distancing at one metre (3.3 feet), and a three feet distance used in some schools in the US is based on this. When asked about the new report on a CNN programme on Sunday, Dr Fauci agreed the data appeared to indicate that three feet is sufficient.   

While the Centers for Disease Control and Prevention do not currently recommend a rule change, Dr Fauci said that the report is being reviewed by them.

“What the CDC wants to do is accumulate data, and when data shows ability to be three feet, they will act accordingly,” Dr Fauci said, adding that its director, Dr Rochelle Walensky, was aware of the new research, with the CDC also conducting its own studies. “I don’t want to get ahead of official guidelines,” he added.

The researchers, who controlled for community rates of coronavirus in their analysis, concluded that lower physical distancing policies can safely be adopted in school settings, as long as other measures like universal masking are in place.

The study compared COVID infection rates among staff and students across 242 school districts in the state of Massachusetts, and found that schools with a three feet social distancing rule did not have a significantly different rate of transmission compared to those with the standard six feet rule.

However, there is a limitation to COVID monitoring in school-aged populations. While children may be infected as readily from COVID, they are less likely to develop illness from COVID, and so they are also less likely to get tested.

Source: NY Times

Netherlands and Ireland Suspend AstraZeneca Vaccine Over Blood Clots

In the wake of reports from Norway of blood clots in people shortly after receiving the AstraZeneca vaccine, the Netherlands and Ireland have suspended its use.

The Dutch Health ministry on Sunday said that there was still no evidence of a direct link between the vaccine and possible adverse effects from Norway and Denmark, and there were no reported cases in the Netherlands.

“We can’t allow any doubts about the vaccine,” Dutch health minister Hugo de Jonge said. “We have to make sure everything is right, so it is wise to pause for now.”

Earlier on Sunday Ireland’s deputy chief medical officer, Dr Ronan Glynn, said that deployment of the AstraZeneca vaccine, which makes up 20% of the country’s 570 000 doses given so far, should be “temporarily deferred” with immediate effect as recommended by the country’s National Immunisation Advisory Committee (NIAC). However, he emphasised that there was no proof that blood clots had been caused by the vaccine.

The first blood clots were reported in Austria, and prompted a wave of concern, with Denmark suspending the AstraZeneca vaccine, along with the north of Italy. These latest cases in Norway resulted in three hospitalisations and one death.

The Norwegian Medicines Agency said the four people who had the AstraZeneca injection all had reduced numbers of blood platelets. It added: “People under the age of 50 who have received the AstraZeneca vaccine and feel increasingly unwell more than three days after vaccination, and who notice larger or smaller blue spots in the skin (skin haemorrhages) must consult a doctor or out-of-hours medical service as soon as possible.

“Similar incidents have been reported in other European countries, and the European Medicines Agency (EMA) is considering whether there may be an association with the coronavirus vaccines. So far, no conclusion has been reached.”

Professor Karina Butler, head of NIAC, said it was acting out of an abundance of caution but wanted a better understanding of this unanticipated cluster of “very serious” clotting events in younger people.

There were similarities to other cases reported elsewhere in Europe, she added. It was necessary to know “was there a possibility of a relationship with the vaccine, something which was rare but very serious and could have significant outcomes”, she said to Virgin Media News.

The agency did not yet know whether more blood clots were happening than expected in the population generally. “But they do seem to have clustered together at a level and in younger people – I mean less than 65 – where we wouldn’t necessarily have expected them to happen and thus the question was should we just pause until we get that information, because above all we want to maintain confidence in the vaccine programme so that people can feel that what they are getting is safe, that any serious safety signal is being thoroughly investigated,” she said. 

In a statement, Dr Glynn said: “It has not been concluded that there is any link between the Covid-19 vaccine AstraZeneca and these cases. However, acting on the precautionary principle, and pending receipt of further information, the NIAC has recommended the temporary deferral of the Covid-19 vaccine AstraZeneca vaccination programme in Ireland.”

Source: The Guardian

Bat Coronavirus 94.5% Similar to SARS-CoV-2 Found

Researchers in China and Australia have reported the discovery of novel bat coronaviruses with a similarity of up to 94.5% to SARS-CoV-2. 

This finding further illuminates the diversity and complex evolutionary history of these viruses. A pre-print version of the research paper is available on the bioRxiv server.

Now, Weifeng Shi from Shandong First Medical University & Shandong Academy of Medical Sciences in Taian, China and colleagues have conducted a meta-transcriptomic analysis of samples collected from 23 bat species in Yunnan province in China during 2019 and 2020.  

Using a combination of genome sequencing and sampling studies, researchers identified a number of SARS-CoV-2-related coronaviruses in wildlife species that together pointed to underestimation of the phylogenetic and genomic diversity of coronaviruses.

“Our study highlights both the remarkable diversity of bat viruses at the local scale and that relatives of SARS-CoV-2 and SARS-CoV circulate in wildlife species in a broad geographic region of Southeast Asia and southern China,” said the team.

Bats are hosts to a broad range of viruses that can infect humans, and four of the seven known human coronaviruses have zoonotic origins.  They are also host to many coronaviruses, but sometimes “intermediate” hosts such as dromedary camels (MERS-CoV) are involved in the jump to humans.

Retrospective genome sequencing and sampling studies identified a number of SARS-CoV-2-related coronaviruses in wildlife species. These included the RaTG13 virus, which is the closest known relative of SARS-CoV-2,  found in the Rhinolophus affinis bat. SARS-CoV-2-related viruses have also been identified in various other Rhinolophid bats across Asia.

“Collectively, these studies indicate that bats across a broad swathe of Asia harbour coronaviruses that are closely related to SARS-CoV-2 and that the phylogenetic and genomic diversity of these viruses has likely been underestimated,” said Shi and colleagues.

Notably, one of these novel bat coronaviruses – RpYN06 – exhibited 94.5% sequence identity to SARS-CoV-2 across the whole genome, with key similarities in certain genes. Low genopmic sequence identity in the spike gene made RpYN06 the second closest relative of SARS-CoV-2, next to RaTG13. This is far more similar than seen in other SARS-CoV-2-like viruses identified in wildlife species.

Indeed, while the other three SARS-CoV-2-related viruses identified here were almost identical in sequence, the spike protein sequences formed an independent lineage that was separated from known sarbecoviruses (a  viral subgenus or the coronaviruses that  includesSARS-CoV-2)   by a relatively long branch.

“Collectively, these results highlight the extremely high, and likely underestimated, genetic diversity of the sarbecovirus spike proteins, which likely reflects their adaptive flexibility,” wrote Shi and colleagues.

The researchers say studies have previously shown that host switching of coronaviruses among bats is a frequent occurrence.

Source: News-Medical.Net

Journal information: Shi W, et al. Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses. bioRxiv. 2021. doi: https://doi.org/10.1101/2021.03.08.434390