COVID-19

COVID-19 virus

Project Summary

Along with effective vaccines against COVID-19, a number of near-term therapies may reduce the impact of the virus around the world. Promising candidates for safe, available treatment that appear to reduce the impact of COVID-19: the existing medications metformin and fluvoxamine. Live attenuated vaccines like MMR (measles, mumps, rubella) may also help prevent or treat sepsis related to COVID-19 infection. Other “repurposed” medications are also being studied. If you are recently COVID-positive, you can sign up for a clinical trial of fluvoxamine

  • COVID-19 has spread around the world causing high mortality and suffering, as well as significant economic impacts.
  • Over 4 million people worldwide have died of the virus, with the United States having the highest number of deaths and infections.
  • Vaccines against SARS-CoV-2 have been approved, but widespread vaccination will likely take significant time.
  • Treatments are needed now to battle the COVID-19 virus, to prevent or reduce the impact of infection.
  • The Parsemus Foundation is supporting the use of 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), the diabetes medication metformin, and the antidepressant fluvoxamine to battle COVID-19. Clinical studies are underway to confirm the efficacy of these therapies prior to widespread use.
  • A number of other candidates to treat COVID infection are available. 

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. Even as vaccines start to rollout in many countries, it will be months or years before enough people are vaccinated to end the pandemic. More research on therapies is critically needed. The information provided here is quickly evolving as we learn more — so check back for updates! For scientific publications, media coverage, and information on enrolling in clinical trials – see Additional Resources below.

Structure of the SARS-CoV-2 coronavirus molecule

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. 

Researchers from the University of Minnesota, under the leadership of Drs. Carolyn Bramante and Christopher J. Tignanelli, have launched 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 clinical trial participants are actively being enrolled.

Fluvoxamine reduced COVID-19 hospitalizations in preliminary studies

Fluvoxamine is an existing medication that has shown great promise for treatment of COVID-19 infection. It is an SSRI (selective serotonin reuptake inhibitor) antidepressant that is commonly prescribed for obsessive-compulsive disorder. This medication’s ability to fight inflammation and block activation of platelets likely reduce the incidence of sepsis and blood clots that are common features of severe COVID-19 infection. 

Results from a randomized, placebo-controlled study of fluvoxamine was reported by researchers from Washington University. In 152 adult outpatients with symptomatic COVID-19, those treated with fluvoxamine had a lower likelihood of worsening symptoms over 15 days than the control group. Additional real-world experience supports the use of fluvoxamine. In an outbreak of COVID-19 at the Golden Gates Field Racetrack, physicians offered fluvoxamine to the 113 individuals testing positive. In total, 65 persons opted for fluvoxamine, and 48 opted for observation alone with no therapy. None of the patients selecting fluvoxamine were hospitalized and all recovered, while six of those not taking the medication (or 12.5%) were hospitalized, many had lingering symptoms, and one died. 

While some physicians may offer existing medications like fluvoxamine off-label to COVID-19 patients, data are needed from larger, randomized, controlled clinical trials to obtain emergency use authorization in the United States. A number of clinical trials are available. The University of Minnesota COVID OUT metformin clinical trial has added evaluation fluvoxamine and ivermectin. These trials are for individuals recently diagnosed with COVID-19. The Together Trial is an international clinical study evaluating fluvoxamine, metformin, and ivermectin.

For reviews of data on fluvoxamine, check out these sites: Encycla, COVID-19 Early Treatment Fund.

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 often 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.  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. 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.

UPDATE: Despite the promise of the MMR vaccine to reduce the health consequences of COVID-19, the LSU clinical trial did not enroll enough participants to test whether MMR could prevent the COVID-19 virus. But this study, along with an international Gates Foundation clinical trial, will add to our understanding of live attenuated vaccines.

Other potential therapies

A number of safe, inexpensive medicines that are already on the market could provide treatment options for COVID-19. Clinical trials are underway to evaluate the impact of these repurposed drugs on the coronavirus. However, funding for research on therapies for COVID-19 is only a fraction of the funding that has been available for vaccine development and there is no centralized process for enrolling patients in trials. These challenges have hampered scientists in completing large randomized, controlled clinical studies. Yet, therapies have the potential to save the lives of hundreds of thousands of people and keep most out of the hospitals. 

Fortunately, these issues are gaining more media attention (see Additional Resources below), and private funders (like the Parsemus Foundation) are stepping up to get clinical trials started. There is also a call for off-label use of some medications on a case-by-case basis, especially when the risk is very low and the potential benefit to treat COVID is high.

These other medications are being studied as therapies for COVID-19 infection:

  • Ivermectin – an anti-parasitic medication
  • Nitazoxanide – an anti-parasitic medication
  • Colchicine – an anti-inflammatory used for gout
  • Famotidine – an over-the-counter histamine-2 blocker used to treat heartburn

Take Action

  • Stay up to date on new developments in the effort to prevent or treat COVID-19 infections. Sign up for our Human Health Newsletter for updates (scroll to the bottom of the page).
  • If you are recently COVID-positive, you can sign up for a clinical trial of fluvoxamine.
  • To help support the clinical trials on the use of metformin, fluvoxamine or ivermectin to prevent or treat COVID-19, please contact us at info@parsemus.org for more details.

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)

Fluvoxamine

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)

Media coverage

  • Harris J. Continuing the fight against COVID-19. University of Minnesota Foundation Summer 2021.
  • Landhuis E. Scientists Seek Covid Treatment Answers in Cheap, Older Drugs. California Healthline Mar 26, 2021.
  • Stone S. New COVID-19 treatment trial is first to include pregnant women. ABC Denver Mar 31, 2021.
  • Raddatz K. U Of M Medical School studies whether diabetes drug is effective against COVID. CBS Minnesota Mar 19, 2021.
  • Kabani M. COVID-19 research points to repurposed drugs. 60 Minutes Mar 7, 2021.
  • Snowbeck C. University of Minnesota to expand study of whether common diabetes drug could treat COVID. Star Tribune Mar 2, 2021.
  • Gupta S, Kane A. Everything old is new again: Repurposing drugs to treat Covid-19. CNN Feb 27, 2021.
  • Walters K. MMR vaccine shows some COVID-19 protection. HCPlive Feb 26, 2021.
  • Sukhatme V, Sukhatem V. A call to action: Immediate deployment 0f select repurposed drugs for COVID-19 outpatient treatment. HealthAffairs Feb 9, 2021.
  • McMaster University. New study to test drugs for early COVID-19 infection. EurekAlert Feb 9, 2021.
  • Emanuel E, Bright R, Gounder C, Borio L, Osterholm M, Gawande A. Opinion: Vaccines alone won’t solve the pandemic. Here are 3 other things we must do. Washington Post Feb 5, 2021.
  • Landhuis, E. The antidepressant fluvoxamine could keep mild COVID-19 from worsening. Science News Feb. 1, 2021.
  • Klausner J. Existing drugs could help treat covid-19. How do we know when to use them? Washington Post Jan 27, 2021.
  • Al-Agba N. What if I can’t get the COVID-19 vaccine right now? KitSap Sun Dec 26, 2020.
  • Rapaport L. Metformin linked with lower risk of death from COVID-19 in people with Type 2 diabetes. Everyday Health Jun 9, 2020.

Clinical trials 

  • University of Minnesota  Evaluating ivermectin, metformin, and fluvoxamine for outpatient Covid treatment in the United States 
  • ACTIV-6 National Institutes of Health evaluating existing medications 

Human Health News