Research support for COVID-19 therapies
COVID-19 has radically changed the world and affected all of our lives. While the magnitude of this health crisis may seem overwhelming, we all have a part to play. Scientists around the world are studying SARS-CoV-2 (the virus causing COVID-19) to rapidly develop treatments and vaccines. The Parsemus Foundation is helping to support research that focuses on simple, inexpensive therapies that may prove to greatly limit the impact of the virus while the well-funded search for a vaccine continues. The information provided here is quickly evolving as we learn more — so check back for updates!
Trained innate immunity
In a few words: Live attenuated vaccines may provide protection from sepsis caused by COVID-19
Prior to COVID-19, several groups of researchers around the globe had been independently studying the impact of vaccines on overall health. They found that children who had received live, attenuated vaccines had significant positive health outcomes (beyond protection from the specific disease) including reduced mortality and hospitalization due to unrelated infections. Live attenuated vaccines (LAVs) include oral polio, MMR (measles, mumps, rubella) and BCG (bacterial tuberculosis). It turns out that this type of vaccine can train the body to mount a better immune response to all sorts of biological threats. This “non-specific trained innate immunity” occurs through the interaction of the live microbes in the vaccine with our own immune system. (Further info on adaptive vs. innate immune response).
Drs. Paul Fidel (Louisiana State University) and Mairi Noverr (Tulane University) are studying LAVs in several models. They propose that these vaccines train leukocyte precursors in the bone marrow to function more effectively against infections. One of their recent projects in mice reported that vaccination with a live attenuated fungal strain induced “trained innate” protection against lethal polymicrobial sepsis. The protection was related to long-lived myeloid-derived suppressor cells (MDSCs), reported to inhibit sepsis and mortality in several animal species. In other words, challenging an animal with a weak infectious agent inspired its bone marrow to make broadly protective substances that lasted months.
Death from COVID-19 infection is usually from sepsis, in which the body mounts a hyper-immune response that causes organs to malfunction. If LAVs can increase suppressor cells that stop sepsis, could a simple vaccine help us to reduce the impact of COVID-19? Mortality is much lower in children than older adults. One hypothesis is that children have fewer ACE2 receptors. But could it be possible that common childhood vaccinations are also helping protect youngsters from the serious health outcomes?
The Parsemus Foundation provided funding to Dr. Fidel and colleagues so that they could initiate a controlled, randomized clinical trial in healthcare workers and first responders in New Orleans. They are measuring the level of suppressor cells in participants who received the MMR vaccine versus placebo, as well as monitoring them for COVID-19 infection to see if the vaccination helps train their immune system to fight it. For more information on Drs. Fidel and Noverr’s research, check out this webinar.
There are other LAVs that may have help to fight COVID-19. BCG vaccination against tuberculosis is being tested in randomized clinical trials in healthcare workers in several countries, and the oral polio vaccine has been suggested as another option. We are excited to see all of these angles pursued. However, neither vaccine is used in the US and the limited supply of BCG is needed to save infants’ lives in at-risk countries, which may make MMR more useful to fight a global pandemic. Supporting evidence can be found in a recent prospective observational study from Mexico City that reported a reduction in severity of COVID-19 infection for individuals who had recently received the MMR vaccine (see details here English or Spanish). A recent Washington Post article highlighted the potential importance of childhood vaccines to battle COVID-19. It cites a study by Mayo Clinic physicians that reported seven types of vaccines given up to five years ago were associated with having a lower rate of infection with the new coronavirus.
The idea is catching on! Following Parsemus Foundation’s support, Dr. Fidel received a $300,000 FAST Grant to expand the MMR clinical study. And a new study of the impact of MMR on COVID-19 infection is planning to enroll 30,000 health care workers worldwide. If Dr. Fidel’s and other scientists’ hypotheses are right, receiving a simple MMR vaccine could save lives!
Blood sugar and COVID-19 infection
In a few words: Controlling glucose levels may reduce severe COVID-19 outcomes
Individuals with diabetes are at higher risk of severe illness from COVID-19 infection. Can tighter control over blood glucose levels make a difference to patients? A recent publication by an Italian team led by Raffaele Marfella provided evidence that COVID-19 patients with hyperglycemia who were treated with insulin infusion had a lower risk of severe disease than patients without insulin infusion. And scientists in China, France and the US reported that patients with the virus and pre-existing Type 2 diabetes had better outcomes if they had improved glycemic control or were on diabetes medication (metformin), and worse outcomes with uncontrolled hyperglycemia.
Metformin, a common medication for people with type II diabetes or prediabetes, and its potential ability to help the body deal with a COVID-19 infection is of particular interest. Scientists have long called for more clinical research on metformin. It may have antiviral action and is an inexpensive medication. Metformin has been used for years off-label to treat other metabolic conditions like obesity, cardiovascular disease, and high blood pressure – the same risk factors for poor outcomes after COVID-19 infection. Researcher Nir Barzilai, of the Institute for Aging Research at the Albert Einstein College of Medicine, is one of the strongest proponents of studying metformin as an inexpensive (<$5/month), widely available medication to ward off the diseases of aging.
Metformin lowers blood sugar and inflammation by activating an enzyme called AMPK. This activity also appears to reduce angiotensin-converting enzyme 2 (or ACE2) which serves as a gateway for COVID-19 to enter and infect cells. Thus, the way metformin works to control blood sugar might also help to control coronavirus infection (see this article in Everyday Health). But randomized controlled studies are needed to know if the survival benefits observed are due to metformin or some other factors. With the battle against COVID-19 upon us, it is time to better understand the impacts of metformin.
Researchers from the University of Minnesota, under the leadership of Drs. Christopher J. Tignanelli and Carolyn Bramante, are planning a multi-center randomized controlled study to investigate the use of metformin for prevention and treatment of SARS-CoV-2. The Parsemus Foundation has provided the seed funding for this project and is seeking larger funders to initiate this important clinical trial. Please contact us at firstname.lastname@example.org for more details.