Tag: covid variants

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How The COVID Variant Was Discovered in South Africa

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The so-called South African variant was identified by an international team of researchers, including biomedical scientists from the University of California, Riverside. They explain the process behind discovering the variants, why they are so concerning, and what the future holds.

“The new COVID variants are the next new frontier,” said Adam Godzik, a professor of biomedical sciences in the UC Riverside School of Medicine. “Of these, the SA and Brazil strains are most worrying. They have mutations that make them resistant to antibodies we generate with existing vaccines. It is commonly believed we are in a tight race: Unless we vaccinate people quickly and squash the pandemic, new variants would dominate to the point that all our COVID vaccines would be ineffective.”

Prof Godzik and Arghavan Alisoltani-Dehkordi, a postdoctoral researcher who joined his lab two years ago, helped characterise the new SA variant by providing its spike protein structure using computer simulations.  

Dr Alisoltani-Dehkordi, who was a postdoctoral fellow at the University of Cape Town before she joined UCR, mentioned that research teams at the University of KwaZulu-Natal  and UCT discovered the new SARS-CoV-2 variant from samples collected between October 15 and November 25, 2020, in three provinces. By early November, this variant rapidly became the dominant variant in samples from two provinces. The researchers suggested that this may be due to increased transmissibility or immune escape.

“Each SARS-CoV-2 variant has specific mutations defining it,” Dr Alisoltani-Dehkordi said. “Professor Godzik and I used computer modeling to suggest possible structural and functional consequences of spike protein mutations in the SA lineage. Our analysis, confirmed also by several other research groups, shows that some of the mutations potentially result in a higher transmissibility of the virus and a weaker immune response.”

The SA variant has been detected in 40 countries, and is quite likely present in more still.

“This variant is probably spreading in areas where it has not been sequenced and is, therefore, not identifiable,” Prof Godzik said. “In the US, sequencing is still a slow process. In many parts of the country, including Riverside, we have no information whatsoever about variants.”

The SA variant prompted concern among scientists because its mutations allowed it to evade antibody protection, and potentially, vaccines. Indeed, the AstraZeneca vaccine rollout was halted in South Africa due to the low level of protection against this new variant.

“That’s when it received a high level of interest,” Prof Godzik said. “Subsequent research confirmed it is resistant to vaccines and is spreading. South Africa is doing a good job, however, at controlling the variant through quarantining and other measures.”

Common mutational signatures can be seen in each of the newly emerged SARS-CoV-2 variants of concern in the UK, SA, Brazil, and California. But each of these variants also has a unique set of mutations; for example, the SA and Brazil variants have two unique mutations on spike proteins K417N and E484K, respectively. But, as Prof Godzik explains, there is no single “SA variant”, rather a branch on an evolutionary tree. And viruses can acquire mutations and escape at any time.

Prof Godzik thinks COVID will become a permanent feature of our lives. “It takes six months to develop a flu vaccine,” he said. “Models predict the evolution of the flu virus and vaccines are produced before the variants show up. If the predictions are good, the vaccines work. If they miss, a heavy flu season follows. This is how COVID will likely behave. A lot of effort will be invested in predicting what will happen the following year, vaccines would then be updated, and people will need to get a booster shot.”

Source: University of Riverdale, California

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Bolsonaro Tells Brazilians to ‘Stop Whining’ About COVID

On By ModernMedia

Amidst a surge of COVID cases and deaths in Brazil that have brought its healthcare system to the brink of collapse, President Jair Bolsonaro has told its citizens to “stop whining”, saying that the country must balance economic concerns against controlling the pandemic.

According to Brazil’s health ministry, the country has suffered 260 000 deaths from the virus, the second highest in the world after the United States.

“Stop whining. How long are you going to keep crying about it?” Mr Bolsonaro said at an event. “How much longer will you stay at home and close everything? No one can stand it anymore. We regret the deaths, again, but we need a solution.”

In order to stave off further disaster, a number of local governments have started taking matters into their own hands by imposing their own curfews and other social distancing measures. 

São Paulo’s governor, João Doria, who has been particularly critical of Mr Bolsonaro’s response to the pandemic, called President Bolsonaro “a crazy guy” for attacking “governors and mayors who want to buy vaccines and help the country to end this pandemic”.

“How can we face the problem, seeing people die every day? The health system in Brazil is on the verge of collapse,” Mr Doria said.

This comes as a Duke University scientist, another Bolsonaro critic, warned of the danger of another quarter of a million deaths, and called for an immediate lockdown to help control the situation.

The situation is exacerbated by the emergence of the P.1 variant which emerged in Manaus, and has high transmissibility and the capability to evade immunity, having a 25% to 60% chance of reinfecting an immune individual.

Source: BBC News

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Scientist Issues Stark Warning on Brazil’s COVID Response

On By ModernMedia

If Brazil continues to let COVID rage unchecked, it risks deadly new variants emerging to threaten the global community, a Duke University neuroscientist in Brazil told The Guardian.

Miguel Nicolelis urged the international community to put pressure on the Brazilian government, which has made little effort to manage its COVID outbreak which has so far left a quarter of a million Brazilians dead. Brazil’s COVID deaths amount to one tenth of the world’s total.

“The world must vehemently speak out over the risks Brazil is posing to the fight against the pandemic,” said Nicolelis who has spent much of the lockdown in his São Paulo flat.

“What’s the point in sorting the pandemic out in Europe or the United States, if Brazil continues to be a breeding ground for this virus?”

He said: “It’s that if you allow the virus to proliferate at the levels it is currently proliferating here, you open the door to the occurrence of new mutations and the appearance of even more lethal variants.”

Manaus, the largest city in the Brazilian Amazon, has already seen the emergence of a deadly, highly transmissible variant, P1, six cases of which have been detected in the UK already. The new variant with its “unique constellation of mutations” may also evade immunity, scientists have warned.

“Brazil is an open-air laboratory for the virus to proliferate and eventually create more lethal mutations,” Nicolelis said. “This is about the world. It’s global.”

The warning comes as hospitals around Brazil are on the verge of collapse, with a record 1726 daily deaths recorded on Tuesday.

“We’ve now gone past 250 000 deaths, and my expectation is that if nothing is done we could have lost 500 000 people here in Brazil by next March. It’s a horrifying and tragic prospect, but at this point it’s perfectly possible,” he said.

Nicoleis puts the blame squarely upon Brazil’s far right President Jair Bolsonaro. “The policies that he is failing to put into practice jeopardise the fight against the pandemic in the entire planet.”

José Gomes Temporão, who was the health minister during the 2009 swine flu pandemic, said Bolsonaro and others would have to be held accountable for their poor response.

“To this day, Brazil doesn’t have a national plan to combat COVID,” Temporão complained, criticising Bolsonaro’s failure to secure sufficient vaccines for Brazil. 

“I don’t think there is any other leader who is so obtuse, so backward, who has such a mistaken and warped vision of reality as the president of Brazil,” Temporão said. “History will condemn these people.”

Source: The Guardian

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Real-world Results for Pfizer Vaccine Match Trials

On By ModernMedia

Encouraging results have been reported from Israel, where the real-world efficacy of the Pfizer vaccine closely matches that seen in clinical trials.

Israel has engaged in the world’s most aggressive COVID immunisation schedule, with some 30% of its population vaccinated by late January with at least one dose.

Israeli health fund Clalit matched 600 000 vaccinated individuals to an equal number of unvaccinated individuals. Those who were vaccinated experienced a similar rate of positive COVID tests as was observed in clinical trial data, equating to a 94% effectiveness. Crucially, almost no severe cases of COVID were observed in vaccinated individuals. This pattern was also seen in the over-70s age group, which is generally underrepresented in trials.

Public health doctor Prof Hagai Levine said that high vaccination coverage of the most susceptible groups was key. However, he said that he could not give an answer as to what number needed to be vaccinated before containment measures could be eased. 

“We still don’t know what the impact is on transmission,” he said. But he added that “the vaccine is useful for personal protection”.

The greatest drop in cases was seen in the over 60s age group, and in areas which had been vaccinated, indicating that this was not the result of lockdown. However, many people still remain unvaccinated, resulting in tens of thousands of cases. Prof Segal noted that the fall in cases was not as rapid as had been hoped, due to the B.1.1.7 or UK strain becoming dominant in Israel.

“We still have to exit our lockdown very cautiously,” he warned, or else hospitalisations would spike again.

The fact that the same rate was observed in clinical trials is important news for other countries, which are watching to see the effects of Israel’s vaccination programme.

Source: BBC News

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Research Shows ‘UK Variant’ is up to 70% Deadlier

On By ModernMedia

A review of research on the COVID variant B.1.1.7, also known as ‘the UK variant’, has shown it to be 30% to 70% more deadly than the original wild-type COVID strain.

Concerns over the deadliness of B.1.1.7 were raised in January, when the UK government’s New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) presented initial findings suggesting that B.1.1.7 cases were deadlier than non-variant cases. After this, they released an updated report which is available online. The report makes the cases that the earlier linked community testing and mortality data were all based on the same datasets, and so had the same biases. However, the group explained that the new analysis was more valid.

“More recent analyses have added a wider range of data sets and been able to control for additional confounders, increasing confidence in the association of the [variant of concern] with increased disease severity,” the group wrote.  

London School of Hygiene & Tropical Medicine found a relative hazard of mortality within 28 days was 1.58 for variant-infected individuals, while Imperial College London used a case-control weighting method to find a case fatality ratio of 1.36 for variant cases. Public Health England  found a “death risk ratio” of 1.65 in matched cohort analysis for variant cases versus non-variant cases.

A number of other studies investigated the variant’s impact on hospitalisation. Public Health Scotland used S-gene target failure as a proxy for variant case detection. They found that S-gene target failure cases had a higher risk for hospitalisation than the S-gene positive cases.
Some studies did not support the higher fatality risk, such as the UK’s Office for National Statistics (ONS), which said that “the number of deaths are too low for reliable inference.”

A number of limitations were reported in the study, including potential bias in case ascertainment, representativeness, unmeasured confounders and secular trends. They also tried to control for nursing home status in hospital reports, but not all of these could be excluded.

“There are potential limitations in all datasets used but together these analyses indicate that it is likely that … B.1.1.7 is associated with an increased risk of [hospitalisation] and death compared to infection with non-[B.1.1.7] viruses,” the group concluded.

In mid-January, modelling by the CDC indicated that the UK variant would become the dominant strain in the United States by March. At the end of January, President Joe Biden had pledged to increase vaccinations to 1.5 million per day, a target which would still not be able to contain the spread of the variant.

Source: MedPage Today

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SARS-CoV-2 Mutation Evolved in Immunocompromised Patient

On By ModernMedia

The discovery of SARS-CoV-2 mutations evolving in an immunocompromised patient treated with convalescent plasma has been revealed by Ravindra Gupta, MD, PhD, of University of Cambridge in England, and team.

“We have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host,” the authors wrote.

Previous research has shown that immunosuppressed patients could serve as reservoirs for norovirus variants.

Although they did not claim the UK variant was created by that particular case, Gupta’s group speculated that the plasma therapy could have unleashed the resistant variants, and could do so in other immunosuppressed patients too.

They wrote that, in such patients, “the antibodies administered [in plasma] have little support from cytotoxic T cells, thereby reducing chances of clearance and theoretically raising the potential for escape mutations.” 

They cautioned that convalescent plasma use should be limited, and only with appropriate infection control in monitoring in immunosuppressed patients.

A man in his 70s, who had received immunotoxic chemotherapy to treat lymphoma eight years previously, was initially hospitalised in May with neutropenic sepsis, and, about a week later, tested positive for SARS-CoV-2. He was discharged later in May, but in late June was readmitted with cough and breathlessness.

His condition worsened and he received dexamethasone and two 10-day courses of remdesivir 5 days apart. On two days around July 20, convalescent plasma was administered; more remdesivir and convalescent plasma was administered about 4 weeks later. He died shortly afterward.

Gupta and team took viral samples from this patient on 23 occasions, and over the first 57 days, they observed little change in viral population upon treatment with remdesivir, but after the July round of convalescent plasma, a shift in viral genotype occurred.

Initially the patient’s viral serotype showed a mutation first reported in China. However, in late July, a variant was observed with two alterations in the spike protein, including the deletion seen in the B.1.1.7 variant. Testing showed a twofold reduced susceptibility to the antibodies in the convalescent plasma.

The team wrote that this sort of evolution is unlikely to emerge in immunocompetent patients. They cautioned against using convalescent plasma in severe COVID patients, and especially those who were immunosuppressed.

The study’s limitations included being only a single case, and samples were taken from the upper respiratory tract and not the lower respiratory tract. 
Given South Africa’s large HIV positive population, if viral evolution is driven by convalescent plasma in immunosuppressed patients, this raises questions for the country’s COVID strategy.

Source: MedPage Today

Journal information: Kemp SA, et al “SARS-CoV-2 evolution during treatment of chronic infection” Nature 2021; DOI: 10.1038/s41586-021-03291-y.

Categories : COVID Immune SystemTags :

New “Double Antibodies” can Treat COVID Variants

On By ModernMedia

A new generation of “double antibodies” has been developed which can protect against all SARS-CoV-2 variants, as well as inhibiting mutations against the antibodies.

These “bispecific”  antibodies were created by the Institute for Research in Biomedicine (IRB; Bellinzona, Switzerland), which is affiliated to the Università della Svizzera italiana (USI).

While traditional antibody-based immunisation is able to offer protection against SARS-CoV-2, there is still a need to protect against variants which may achieve “vaccine escape”, as well as inhibiting mutations which give rise to resistance, as with antibiotic resistance in bacteria.

The researchers overcame these difficulties by splicing together a pair of antibodies to make a “bispecific” antibody that simultaneously targets two viral sites. The bispecific antibody treatment has proved effective in mouse models, which maintained body weight when infected with SARS-CoV-2, compared to infected controls, which lost 20-30% body weight before humane euthanisation. The paper is available on the bioRxiv preprint server.

Study author Luca Varani of USI explained: “We exploited our knowledge of the molecular structure and biochemical traits of the virus to fuse together two human antibodies, obtaining a single bispecific molecule simultaneously attacking the virus in two independent sites critical for infectivity. Supercomputing simulations allowed us to refine and validate the bispecific antibody design, which was later produced and tested in the laboratory. Although the virus can mutate and escape from the attack of a single first-generation antibody, we have shown that it cannot do so against the double action of the bispecific.

“A single injection of the bispecific antibody provides instantaneous protection against the disease in pre-clinical trials. The antibody effectively reduces viral burden in the lungs and mitigates inflammation typical of COVID-19”, said Daniel Ruzek from the Czech Academy of Sciences who led the antibody pre-clinical testing.

The effectiveness of the bispecific antibodies holds promise for human clinical trials, with the prospect of being both an effective prevention and treatment of COVID.

Source: News-Medical.Net

Journal information: Gasparo, R D., et al. (2020) Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease. bioRxiv.doi.org/10.1101/2021.01.22.427567.

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SA Experts Confirm That COVID Variant is More Contagious

On By ModernMedia

A panel of South African experts confirmed on Monday that the SA strain of COVID is 50% more transmissible than previous strains.

Collecting data from the main infection clusters around the country, the experts came to the conclusion that while more contagious, the new variant is not more lethal. 

“There is no evidence the new COVID variant is more severe than the original variant,” said epidemiologist Professor Salim Abdool Karim, co-chair of the Ministry of Health’s scientific committee.

However, the SA healthy system has been strained by the sheer number of cases. Concerns over more transmissible variants have prompted the UK government to switch to administering the first dose of two-dose vaccines such as the one from Pfizer, and leaving an extended period before a second dose is administered, even though protection will wane over time.

Another panel member, Dr Waasila Jassat, said that although hospital admissions had increased, the overall death rate had not, supporting the case for the variant not being more lethal.

The spread of the variant in December prompted the government to reinstate its lockdown. It also resulted in many countries banning flights from South Africa in a bid to stem the variant. Prof Karim said that it was not yet known if current vaccines would protect against the SA variant, although studies were underway.

Another panel member, virologist Professor Alex Sigal stated: “The world has underestimated this virus.” He added that it was evolving and adapting to humans.

The experts also urged that it should not be referred to as the “South African variant”. The variant could have turned up anywhere in the world, and it was only thanks to the country’s excellent genomic surveillance that it was picked up at all, they said.

Source: Medical Xpress

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COVID Variants May Increase False Negative Results, FDA Warns

On By ModernMedia

The UK variant of the SARS-CoV-2 virus, known as B.1.1.7 could affect the accuracy of certain molecular COVID tests, causing increased false negative results, the US Food and Drug Administration (FDA) has warned.

A false negative from the UK variant could happen if the variant’s mutation happened to be in a part of the virus’ genome that was assessed by that test. However, genetic tests that target multiple parts of the virus genome are less likely to be affected by the new variants, the FDA advises.

Although the possibility of false negative results are to be expected from almost all tests, the effect of the COVID variants could impact the ability to properly monitor the disease, as well as complicating diagnosis.  

The FDA issued an alert on Friday, saying that they monitor tests which have received an Emergency Use Authorisation (EUA). They highlight three tests as being affected, with potentially less sensitivity to the mutations:

  • Accula SARS-Cov-2 Test, from Mesa Biotech
  • TaqPath COVID-19 Combo Kit, from Thermo Fisher Scientific)
  • Linea COVID-19 Assay Kit, from Applied DNA Sciences

However, the warning for Accula test was a result of “an abundance of caution”, and the latter two assess multiple genetic targets, so they are not likely to be impacted. The FDA issued recommendations for the users of these devices.The FDA’s warning was prompted by computer simulations showing reduced efficacy in certain tests for the virus variant.

In their press release, the FDA did not specifically mention whether any tests may be affected by mutations in the South African virus variant.

Source: MedPage Today