Wednesday, August 18, 2021

Does the explosion of the delta variant mean we need a new COVID-19 vaccine?

The rapid spread of the delta variant of SARS-CoV-2 has put more patients in hospital beds and led to reinstatements of mask mandates in some cities and states. The variant, which is more transmissible than previous variants, also seems more able to cause breakthrough infections in vaccinated people.

Fortunately, vaccines are forming a bulwark against severe disease, hospitalization and death. But with the specter of delta and the potential for new variants to emerge, is it time for booster shots — or even a new COVID vaccine?

For now, public health experts say the far bigger emergency is getting first and second doses into people who haven't had a single shot. Most people don't need boosters to prevent severe illness, and it's not clear when or if they will. But companies are already looking into updating their vaccines for coronavirus mutations, and there is a good chance that third shots are coming soon for some people. Already, the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) have greenlighted booster shots for immunocompromised individuals.

"I think we're looking at an inevitable move toward boosters, at least in higher-risk people like those of advanced age and obviously the immunocompromised," said Dr. Eric Topol, a professor of molecular medicine at The Scripps Research Institute in California.

Vaccine developers are working on the question of whether future COVID-19 shots will need to be tweaked for the delta variant, or other new variants. For now though, initial evidence hints that boosters of the original vaccine should add protection against delta.

While all the COVID-19 vaccines in the U.S. are doing a fabulous job of preventing severe disease and death, it's clear that breakthrough infections are more common with this variant. Data on efficacy is still emerging, and efficacy is a moving target depending on a lot of factors. It's hard to make apples-to-apples comparisons between countries or hospital systems, said Jordi Ochando, an immunologist and cancer biologist at the Icahn School of Medicine at Mount Sinai. Different countries have different levels of vaccination, have used different vaccine mixes with different dose scheduling, and have different populations with different age stratification, comorbidities and levels of previous infection.

Still, synthesizing data from different countries suggests the mRNA vaccines by Pfizer-BioNTech and Moderna are probably up to 60% or as low as 50% protective against infection with delta, Topol wrote on Twitter. That's right on the border of efficacy at which the Food and Drug Administration would approve a new COVID-19 vaccine. The J&J vaccine is probably less protective against symptomatic illness than a two-dose mRNA vaccine, based on studies finding that it elicits lower levels of neutralizing antibodies (which block the virus from entering cells).

Data is now emerging that the J&J vaccine likely prevents severe disease from delta as well. Though people with symptomatic breakthrough infections can spread the delta variant, the vaccines do still seem to reduce the likelihood of transmission by making any infection that does occur shorter. A study conducted in Singapore found that viral load started at similar levels in vaccinated and unvaccinated individuals who were infected with delta, but it dropped much faster in vaccinated individuals, beginning a steeper decline around day 5 or 6 of illness. This could mean that vaccination shortens the infectious period. However, more confirmation is necessary to show whether the Singapore results will hold up. The discovery that vaccinated people can have viable virus in their noses if infected is what made the CDC reverse its recommendation that vaccinated people did not need to wear masks.

It's not clear exactly why delta can break through vaccine-induced protection more frequently, but there may be multiple factors at play. One is that the antibodies that the vaccine elicits may not bind to the virus variant as well. Delta appears to have spike mutation proteins that make original coronavirus antibodies a worse fit, according to research published in Nature in July. This means that previously infected and vaccinated people have antibodies that aren't quite as protective against delta as they were against the original or alpha variants, said Yiska Weisblum, a postdoctoral researcher in retrovirology at The Rockefeller University in New York.

Another possible reason for waning efficacy is that the immune system starts letting down its guard over time. This happens with the pertussis vaccine, which is why expectant parents and other adults who are going to be around unvaccinated newborns should get booster shots.

"Right now, the U.S. is the driver of the world delta wave, and we are the leading force of nurturing new variants, because it's out of control here."

Whether waning immunity is likely to be a problem for COVID-19 vaccines is currently a hot topic among researchers. Israeli health authorities say they've seen an increase in breakthrough infections in people immunized in January versus March and are concerned about an uptick in more severe breakthrough cases in those 60 and older, according to Haaretz.

Data from an Israeli HMO published on the preprint server medRxiv before peer review found that 2% of people who requested a PCR test for any reason post-vaccination received a positive result. People vaccinated more than 146 days before being tested were twice as likely to experience a breakthrough infection. The vast majority of the cases in the study were delta. It's difficult to track waning immunity because you need to revisit the same group of people over time, tracking their infection status, Scripps' Topol told Live Science. That kind of data hasn't really emerged yet. But Topol said he's transitioned from skepticism over waning immunity to belief that it is occurring.

"It does look like there is a substantial interaction with delta finding people who are several months out from when they got fully vaccinated," Topol said. "It's a double hit. If you were six months out, and there is no delta, you're probably fine. The problem is this interaction."


COVID: 90% of patients treated with new Israeli drug discharged in 5 days

Some 93% of 90 coronavirus serious patients treated in several Greek hospitals with a new drug developed by a team at Tel Aviv’s Sourasky Medical Center as part of the Phase II trial of the treatment were discharged in five days or fewer.

The Phase II trial confirmed the results of Phase I, which was conducted in Israel last winter and saw 29 out of 30 patients in moderate to serious condition recover within days.

“The main goal of this study was to verify that the drug is safe,” Prof. Nadir Arber said. “To this day we have not registered any significant side effect in any patient from both groups.”

The trial was conducted in Athens because Israel did not have enough relevant patients. The principal investigator was Greece’s coronavirus commissioner, Prof. Sotiris Tsiodras.

Arber and his team, including Dr. Shiran Shapira, developed the drug based on a molecule that the professor has been studying for 25 years called CD24, which is naturally present in the body.
“It is important to remember that 19 out of 20 COVID-19 patients do not need any therapy,” Arber said. “After a window of five to
12 days, some 5% of the patients start to deteriorate.”

The main cause of the clinical deterioration is an over activation of the immune system, also known as a cytokine storm. In case of COVID-19 patients, the system starts attacking healthy cells in the lungs.

“This is exactly the problem that our drug targets,” he said.
CD24 is a small protein that is anchored to the membrane of the cells and it serves many functions including regulating the mechanism responsible for the cytokine storm.

Arber stressed that their treatment, EXO-CD24, does not affect the immune system as a whole, but only targets this specific mechanism, helping find again its correct balance.

“This is precision medicine,” he said. “We are very happy that we have found a tool to tackle the physiology of the disease.”
“Steroids for example shut down the entire immune system,” he further explained. “We are balancing the part responsible for the cytokine storms using the endogenous mechanism of the body, meaning tools offered by the body itself.”

Arber noted that another breakthrough element of this treatment is its delivery. “We are employing exosomes, very small vesicles derived from the membrane of the cells which are responsible for the exchange of information between them,” he said. “By managing to deliver them exactly where they are needed, we avoid many side effects,” he added.

The team is now ready to launch the last phase of the study.
“As promising as the findings of the first phases of a treatment can be, no one can be sure of anything until results are compared to the ones of patients who receive a placebo,” he said.

Some 155 coronavirus patients will take part in the study. Two-thirds of them will be administered the drug, and one-third a placebo.

The study will be conducted in Israel and it might be also carried out in other places if the number of patients in the country will not suffice.

“We hope to complete it by the end of the year,” Arber said.
If the results are confirmed, he vowed that the treatment can be made available relatively quickly and at a low cost.

“In addition, a success could pave the wave to treat many other diseases,” he concluded.




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