This week brings more interesting COVID-19 updates. The evolving landscape of vaccines and treatments is growing increasingly complicated. If you have questions, feel free to write us here. Also if you were forwarded this newsletter and would like to join the email list to receive it weekly, you may register here.
This week we learned that Johnson and Johnson paused their phase 3 vaccine trial because of an “unexplained illness” in a participant. This is a good reminder of the safety protocols put in place for any phase 3 trial. Pauses are normal and occur each time there is an illness or serious side effect in a participant that is not expected. During the pause, researchers collect more information about the patient and monitor the illness while trying to determine if it is caused by the vaccine. Typically, that information is not made public until the end of the trial when all the data is published. A similar pause occurred last month for Astra Zeneca’s vaccine after a patient illness in the U.K.
Also this week, the drug manufacturer Pfizer announced that it received approval from the FDA to expand its phase 3 vaccine trial to include children age 12 years and older. In Sept. Pfizer received approval to expand testing to adolescents 16 years and older. This represents a move toward answering the question about vaccine safety in children. It is a positive first step.
2) Antibody Treatment
The National Institute of Health (NIH) paused Eli Lilly’s phase 3 trial of a monoclonal antibody therapy for COVID-19. This drug is similar to the experimental therapy made by Regeneron that the President received recently. The drug consists of cloned neutralizing antibodies. The Eli Lilly trial is sponsored by the NIH, who recommended the pause after a pre-set difference was achieved between the testing and placebo groups. This means there was a measurable difference in safety between the two groups. In this scenario, a pause is taken while the data and safety monitoring board reviews the information. Their duty is to determine if the drug is causing harm. As part of a standard phase 3 trial, the patients, researchers, and sponsors are blinded, meaning they do not know which group received the medication or the placebo. This blinding will continue until the review process is complete. As of this moment, we do not know any more details about the differences between the two groups. Enrolled patients will continue to be monitored while new patient enrollment is suspended.
Eli Lilly is also running multiple simultaneous trials of this medication in different types of patients. The drug is being tested in non-hospitalized patients with a recent diagnosis of COVID-19, and those at risk who have not been infected yet. The data and safety monitoring board is allowing those trials to continue.
3) Remdesivir and the W.H.O.
The World Health Organization released its SOLIDARITY trial results on Oct 15th. This multinational trial conducted in 405 hospitals across 30 countries was designed to test Remdesivir, Hydroxychloroquine, Lopinavir and Interferon-β1a in patients hospitalized with COVID-19. Patients received one or more of these treatments and the trial concluded that none of these medications resulted in any significant benefit. Remdesivir is another one of the experimental medications given to the President recently, and also given to many patients throughout the U.S. based on emergency authorization by the FDA. These results come after the recent publication of a Remdesivir trial by the manufacturer Gilead, showing an improvement in time to recovery. Though it may seem confusing to have contradicting trials, this is a very common scenario in medical research. It is typical for therapies to go through numerous trials in increasing population sizes and under multiple conditions before a final conclusion is made about the benefits. Trials are structured to test medications in specific scenarios and it can take years of study and numerous investigations before we know the exact circumstances and population that benefit from a drug. In this case, the WHO trial was large and robust casting some doubt about the manufacturer sponsored trial published earlier. More study will follow, but for the time being it seems unlikely this drug is making a significant difference in those hospitalized with COVID-19.
4) Re-infection with COVID-19
The U.S. had its first published case of reinfection with COVID-19. The patient is a 25 year old male in Washoe County, Nevada. He became infected with a mild COVID-19 illness on April 18, 2020 with a confirmed positive test. He had two subsequent negative tests in May 2020 and then became ill and tested positive once again on June 5, 2020. Investigation of the virus strains from both positive tests showed the virus had mutated and the patient’s symptoms were significantly worse the second time. The case report concludes “All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2.” Though this is the first case in the U.S. there have been multiple other cases reported internationally. The important things to take away from these cases are that reinfection is rare but possible and that precautions are still necessary even after recovery.
5) New York Travel Restrictions
New York State has added more U.S. States to its travel advisory list. Ohio, Michigan, and Virginia join the growing list of locations from which a traveler must quarantine. The same states have been added to the travel advisory lists for New Jersey and Connecticut. Interestingly, Connecticut does allow for travelers to terminate quarantine early or bypass it completely if they have a negative COVID test 72 hours prior to or anytime after arrival. It is not clear why Connecticut has chosen to allow this exclusion but it is important to remember that testing does not end quarantine early in the CDC, NY, or NJ guidelines. The purpose of quarantine is to determine if someone develops symptoms within 14 days of an exposure. A negative test is unable to predict if symptoms will develop in the future. A test can only tell us if someone is infected and shedding virus at the time of the testing. There may be insufficient virus levels to cause symptoms or be detectable, and a negative test in this scenario can be misleading.
We have also had a few questions about travelers visiting residents in NY, NJ, and CN. The mandatory quarantine applies to the visitors and not to the residents being visited. Visitors are expected to isolate for 14 days and monitor for symptoms. Those people who have visitors staying with them should take extra precautions during this time frame but may continue to attend school, go to work, and go about their daily routine.
6) The Great Barrington Declaration
The White House is reported to have “embraced” the Great Barrington Declaration. This declaration, authored by three physicians, was released to the public on Oct 5th. The point of the declaration can be summed up in three quotes:
“We know that vulnerability to death from COVID-19 is more than a thousand-fold higher in the old and infirm than the young. Indeed, for children, COVID-19 is less dangerous than many other harms…”
“The most compassionate approach that balances the risks and benefits of reaching herd immunity, is to allow those who are at minimal risk of death to live their lives normally to build up immunity to the virus through natural infection, while better protecting those who are at highest risk. “
“Adopting measures to protect the vulnerable should be the central aim of public health responses to COVID-19. “
The declaration calls for the lifting of restrictive measures on the young and those with less risk in order to allow for the development of herd immunity. We have discussed herd immunity in previous newsletters, but this is the point at which a sufficient number of people in the population are immune because they have recovered, and the disease is unable to spread through the population anymore. To date, estimates have suggested it would require from 50-80% (1,2)of the population to become immune to stop the spread of COVID-19. Recent publications have suggested that even in the hardest hit areas, like New York City, there is at best 20% immunity.
The declaration does describe a careful approach to protecting those at risk but it is important to note that a higher number of people infected in the community poses a higher threat to those at risk. The declaration does make some good suggestions like advocating for high accuracy testing in nursing homes, staffing nursing homes with people that are immune, and providing community resources like home grocery delivery to keep those at risk safe at home. We found it to be an interesting read. There are also almost 3 hours of accompanying video of the authors answering questions from the press.
Some of the suggestions describes the approach Sweden has taken. It is an interesting case study in pandemic response. You can read more about Sweden and the details of their response here. At a time when the country is struggling from economic uncertainty and people are becoming fatigued, there are certainly good suggestion here to consider. However, the answer is not simple. The important aspects of such a plan (ie. the details) are not included in this declaration. It would be interesting to read more about the implementation of such a method in the U.S. We will keep you informed of any more information from this group when it is released.
More about herd immunity:
- “Herd Immunity” is Not an Answer to a Pandemic
- Scientific consensus on the COVID-19 pandemic: we need to act now
- It is bad science to say covid-19 infections will create herd immunity
- Herd immunity – Association of Professionals in Infection Control and Epidemiology
- What is Herd Immunity and How Can We Achieve It With COVID-19?