COVID-19

COVID-19 virus

Project Summary

Along with an effective vaccine against COVID-19, a number of near-term therapies may reduce the impact of the virus around the world. Two good candidates for safe, available treatment that appear to reduce the impact of COVID-19: live attenuated vaccines like MMR (measles, mumps, rubella) and the well-known diabetes medication metformin.
  • COVID-19 has spread around the world causing high mortality and suffering, as well as significant economic impacts.
  • Over 1 million people worldwide have died of the virus, with the United States having the highest number of deaths and infections.
  • Research on a vaccine against SARS-CoV-2 is ongoing, but widespread vaccination will likely take significant time even after regulatory approvals.
  • Treatments are needed now to battle the COVID-19 virus, to prevent or reduce the impact of infection.
  • The Parsemus Foundation is supporting simple, inexpensive therapies for COVID-19 using vaccines and medication that are already available and proven safe.
  • Observational data provide good support for the use of live attenuated vaccines (like MMR) and the diabetes medication metformin to battle COVID-19. Clinical studies are planned or underway to confirm the efficacy of these therapies prior to widespread use.

Project Topics

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!

Scanning electron image of SARS-CoV-2 Virus. Credit: NIAID

Trained innate immunity with live attenuated vaccines

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 for months.

Death from COVID-19 infection is usually due to 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 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 systems to fight it. For more information on Drs. Fidel and Noverr’s research, check out this webinar.

Other LAVs may 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 U.S., 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 that seven types of vaccines administered up to five years ago were associated with having a lower rate of infection with the new coronavirus.

The idea is catching on! Following the 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!

Metformin, blood sugar and COVID-19 infection

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 U.S. 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.

Of particular interest is the potential ability of Metformin, a common medication for people with type II diabetes or prediabetes, to help the body deal with a COVID-19 infection. Scientists have long called for more clinical research on metformin. This inexpensive (<$5/month) medication may have antiviral action. 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 a 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.

Take Action

Additional funding is needed to expand the study on the use of MMR vaccination to reduce the impact of COVID-19 to nursing home environments. The clinical study on metformin’s ability to prevent or treat COVID-19 is pending funding. Please contact us at info@parsemus.org for more details and how you can help to support these important research projects.

Live Attenuated Vaccines

  • Benn CS, Fisker AB, Whittle HC, Aaby P. (2016). Revaccination with live attenuated vaccines confer additional beneficial nonspecific effects on overall survival: A review. EBioMedicine 10:312-7. (free full text)
  • Chumakov K, Benn CS, Aaby P, et al. (2020). Can existing live vaccines prevent COVID-19? Science 368(6496): 1187-1188. (free full text)
  • Esher SK, Fidel PL, Noverr MC. (2019). Candida/Staphylococcal polymicrobial intra-abdominal infection: Pathogenesis and perspectives for a novel form of trained innate immunity. J Fungi 5(2): 37. (free full text)
  • Fidel PL, Noverr MC (2020). Could an unrelated live attenuated vaccine serve as a preventive measure to dampen septic inflammation associated with COVID-19 infection? mBio Jun 2020, 11 (3) e00907-20. (free full text)
  • Larenas‐Linnemann DE, Rodríguez‐Monroy F. (2020). Thirty‐six COVID‐19 cases preventively vaccinated with mumps‐measles‐rubella vaccine: All mild course. Allergy 07 September 2020. (free full text)

Metformin

  • Bode B, Garrett V, Messler J, et al. (2020). Glycemic characteristics and clinical outcomes of COVID-19 patients hospitalized in the United States. J Diabetes Sci Technol 14(4):813-821. (free full text)
  • Bramante C, Ingraham N, Murray T, et al. (2020 preprint). Observational study of metformin and risk of mortality in patients hospitalized with Covid-19. MedRxIV June 28, 2020. (abstract)
  • Bramante C, Tignanelli CJ, Dutta N, et al. (2020 preprint). Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19. MedRxIV  Sept 2, 2020. (abstract)
  • Sardu C, D’Onofrio N, Balestrieri ML, et al. (2020). Outcomes in patients with hyperglycemia affected by Covid-19: Can we do more on glycemic control? Diabetes Care 43(7): 1408–1415. (free full text)
  • Zhu L, She Z, Cheng X, et al. (2020).  Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes. Cell Metabolism 31, 1068–1077. (free full text)

Human Health News