With this series, we aim to remind our readers that while COVID-19 causes great sorrow and loss around the world, the resulting global emergency has also meant that scientists are working at an unprecedented pace. They are making progress that is easy to overlook among the worrying numbers of new cases and deaths.
Two recent MNT articles COVID-19: 5 reasons to be cautiously hopeful and COVID-19: Physical distancing, drug trials offer hope looked at the latest developments in potential treatments, vaccines, and the outcomes of infection control measures during the pandemic.
We continue our series with this third Special Feature, which continues to monitor progress in the areas mentioned above.
Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.
We focus on a vaccine that some researchers believe may be available by the fall and round up expert opinions on this promising development. We also cover an app-based social tracing system that could help create ‘intelligent’ physical distancing instead of national lockdowns.
We previously reported that the World Health Organization (WHO) have launched a global megatrial that involves testing four potential treatments for COVID-19. Remdesivir, initially developed to treat Ebola, was one of those four potential treatments.
Now, scientists from the University of Alberta in Edmonton, Canada, say that remdesivir is showing promise in in vitro experiments.
The same team had previously demonstrated that remdesivir effectively combatted another coronavirus, MERS-CoV. It did so by blocking polymerases, which are enzymes that allow the virus to replicate.
Study co-author Prof. Matthias Götte explains, “If you target the polymerase, the virus cannot spread, so it’s a very logical target for treatment.”
He continues to report the results of the team’s new experiments: “We obtained almost identical results as we reported previously with MERS, so we see that remdesivir is a very potent inhibitor for coronavirus polymerases.”
Prof. Götte goes on to explain, “These coronavirus polymerases are sloppy, and they get fooled, so the inhibitor gets incorporated many times, and the virus can no longer replicate.”
Still, the author cautions, “We’ve got to be patient and wait for the results of the randomized clinical trials.”
Another hopeful finding comes from researchers from Cornell University in Ithaca, NY. These scientists also started their research efforts by drawing parallels with other coronaviruses, such as SARS-CoV and MERS-CoV.
Namely, they looked at the spike protein that coronaviruses have and zoomed in further on the “fusion peptides” — these are short-chain amino acids that the spike proteins contain.
“What’s really interesting about SARS-CoV and MERS-CoV, and this new virus, SARS-CoV-2, is this particular part of the protein, the fusion peptide, is almost exactly the same in those three viruses,” explains study co-author Prof. Susan Daniel.
The new study found that calcium ions enable fusion peptides to help coronaviruses penetrate healthy cells through a process called membrane fusion. This offers a potential target for a new antiviral treatment.
The team has already secured funding to start developing an antibody that could stop this process by targeting SARS-CoV-2’s fusion peptide.
“Blocking the fusion step is significant because the fusion machinery doesn’t evolve and change as fast as other parts of the protein do. It’s been built to do a particular thing, which is to merge these two membranes together. So if you can develop antiviral strategies to reduce that efficiency, you could have potentially very broadly-acting treatments.”
– Prof. Susan Daniel
Sarah Gilbert, a professor of vaccinology at Oxford University’s Jenner Institute in the United Kingdom, and her team may soon be closing in on a vaccine for SARS-CoV-2.
The approach “uses a harmless chimpanzee virus to carry the fragment of SARS-CoV-2 that is required for immunity,” explains Ian Jones, Professor of virology at the University of Reading, U.K.
Colin Butter, an associate professor of bioveterinary science at the University of Lincoln in the UK, explains: “Professor Gilbert’s team […] have made a recombinant vaccine against the SARS-CoV-2 virus by taking a virus that is entirely harmless to humans, the Chimp Adenovirus designated ChAdOx1, and inserting into it the spike protein gene from the [new] coronavirus.”
Prof. Gilbert believes that the vaccine will be available for general use by the fall, which could prevent a potential second wave of the new coronavirus.
“That is just about possible if everything goes perfectly,” Prof. Gilbert told The Times in an interview. The researchers are set to put the new vaccine into human trials in the next 2 weeks.
The researcher explains that during the pandemic, scientists can fast-track the process through which the vaccine reaches the population by doing many of the necessary steps in parallel.
“First, there is the need to manufacture the vaccine for clinical studies under tightly controlled conditions, certified and qualified — we need ethical approval and regulatory approval. Then, the clinical trial can start with 500 people in phase I.”
“This is always in healthy adults aged about 18 to 55, and usually the primary read-out from a phase 1 study is safety,” Prof. Gilbert explains. “Then we can do phase 2, looking at a wider age range; in this case, we are going to increase the age range, 55 to 70 plus. We are looking at safety in the older age group, [and] we expect to see weaker immune responses.”
The researcher explains that she and her team plan to spread their studies across different countries so that they can reduce the time it takes to test the vaccine.
“[I]t’s vital we go fast before a high proportion [of the population] become infected. But it also means we are going to need to do studies in different countries because the amount of virus transmission is affected by the lockdowns.”
The vaccine could get approval “under emergency use legislation,” meaning that “in an emergency situation, if the regulators agree, it’s possible to use a vaccine earlier than in normal circumstances,” Prof. Gilbert adds.
It is worth noting that other experts have expressed concern over Prof. Gilbert’s estimates.
Prof. David Salisbury, for example, says, “[I]t is not just the availability of the first dose that we need to focus on. We need to know by when there will be sufficient doses to protect all of the at-risk population, probably with two doses, and that means industrial-scale manufacturing that governments do not have.”
The approach in itself, however, is viable, and the research group benefits from a lot of credibility in the scientific community. The approach “has been extensively tested in other situations, so there is indeed a good chance it will work as designed,” says Prof. Jones.
“The [research] group has a long history of success in this area,” adds Dr. Butter. “On the basis of this prior experience, it would be reasonable to assume that the vaccine would induce antibody and cellular immune responses, both of which may be important in controlling the virus in an individual.”
“Any final roll-out will almost certainly need a level of manufacturing the [U.K.] does not readily have, so transfer to and liaison with an external manufacturer may also need to be tackled. But the roadmap is clear, let’s hope they get there.”
– Prof. Ian Jones
Tissue plasminogen activator (tPA) is a drug designed and approved to prevent blood clots in people who have had a stroke, pulmonary embolism, or heart attack.
Now, a new trial to test its benefits for relieving acute respiratory distress syndrome (ARDS) in people with COVID-19 is underway.
TPA acts as an anticoagulant. This means it prevents blood clotting by breaking down fibrin. Fibrin can form plugs in the airways and contributes to small clots in the blood vessels of the lungs.
In patients with COVID-19, these small microfibrin plugs in the air sacs lead to ARDS. As a result, these patients require ventilators to be able to breathe.
“We’re hearing anecdotally that a subset of patients with COVID-19-induced ARDS are clotting abnormally around their catheters and [intravenous] lines,” explains Dr. Michael B. Yaffe, Ph.D., an acute care surgeon at the Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA.
Dr. Yaffe is also the senior author of the study that proposed repurposing tPA to treat COVID-19 complications.
“We suspect these patients with aggressive clotting will show the most benefit from tPA treatment, and this new clinical trial will reveal whether that’s the case,” says Dr. Yaffe.
The scientists have started to recruit some of the COVID-19 patients admitted to the BIDMC for the trial. The team also hopes to find biomarkers that can help identify patients who are most likely to benefit from the treatment.
“If effective and safe for the treatment of ARDS in patients with COVID-19, tPA could save lives by reducing recovery time and freeing up more ventilators for other patients in need.”
– Christopher D. Barrett, clinical trial investigator
Another finding that may help relieve the pressure on public health systems is a mobile app-based contact tracing system.
The authors of the new project explain that such a system could help reduce the rate at which the virus spreads while also mitigating some harmful effects of a full national lockdown.
Dr. David Bonsall — senior researcher at Oxford University’s Nuffield Department of Medicine, clinician at Oxford’s John Radcliffe Hospital both in the UK, and co-lead of the project — explains how the system works.
He says, “The mobile app concept we’ve mathematically modeled is simple and doesn’t need to track your location. It uses a low energy version of Bluetooth to log a memory of all the app users with whom you have come into close proximity over the last few days.”
“If you then [contract the virus], these people are alerted instantly and anonymously and advised to go home and self-isolate. If app users decide to share additional data, they could support health services to identify trends and target interventions to reach those most in need.”
The findings could pave the way for “intelligent [physical] distancing,” avoiding the social and economic effects of full lockdowns.
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