Alpha-lipoic acid (ALA) has been demonstrated to reduce ADAM17 activity which could reduce host cell susceptibility to a SARS-CoV-2 infection.  Insulin therapy used in treating diabetes mellitus has also been shown to reduce ADAM17 activation.  Together, these treatments may have a synergistic effect in their ability to reduce ADAM17 activity and may have a stronger, more protective effect in diabetic COVID-19 patients than treating them with ALA alone.  

Michigan State University

Alpha-lipoic acid (ALA) is a drug that is currently used to treat diabetic polyneuropathy.  It increases insulin signalling sensitivity, functions as an antioxidant, and inhibits NF-kB activity.  Additionally, ALA has been demonstrated to have anti-viral properties.  Its ability to reduce NF-kB activity, increase intracellular glutathione concentrations, chelating metal ions, and restoring antioxidant levels have all been shown to have protective effects against different viruses.  ALA may be specifically useful in treating or preventing COVID-19 because of its ability to prevent ACE2 upregulation by inhibiting ADAM17, increasing intracellular pH by activating sodium/potassium pumps, and increasing the amount of intracellular antioxidants to bolster the host cell's defense mechanism.  

Using Alpha-Lipoic Acid (ALA) to Treat or Prevent COVID-19

Cure, E., & Cure, M. C. (2020). Alpha-lipoic acid may protect patients with diabetes against COVID-19 infection. Medical Hypotheses, 110185.
https://www.sciencedirect.com/science/article/pii/S0306987720310604?casa_token=Q4ATHQoHhWUAAAAA:CBkMfamaSgvWCDxvhZOPzwcnfIWZXdqCdHXlGFWAW5WQkqtqhKmEasZEVJLmDsrexTcJ1yU2mQ
doi: 10.1016/j.mehy.2020.110185

Alpha-lipoic acid may protect patients with diabetes against COVID-19 infection

A Combination Therapy of Alpha-Lipoic Acid (ALA) and Insulin May Have a Synergistic Effect in Diabetic COVID-19 Patients

17 critically ill patients from Wuhan, China were recruited from February - March 2020.  They participated in a randomized, single-blind, group sequential, active-controlled trial to tests the effects of alpha-lipoic acid (ALA) could ameliorate inflammation, reduce reactive oxygen species (ROS), and improve organ function in COVID-19.  Patients in the treatment group were given 1200 mg/d intravenous ALA once daily on top of their existing treatment, and they were given ALA treatment for 7 additional days beyond standard medical care.  After 30 days, the all-cause mortality rate in the control group was 77.8% (7/9) whereas it was 37.5% (3/8) in the treatment group.  While a decrease was observed, the results were not significant (p=0.09) due to a limited sample size.

Alpha-Lipoic Acid (ALA) May Improve the 30 Day Survival Rate of Critically Ill COVID-19 Patients

17 critically ill patients from Wuhan, China were recruited from February - March 2020. They participated in a randomized, single-blind, group sequential, active-controlled trial to tests the effects of alpha-lipoic acid (ALA) could ameliorate inflammation, reduce reactive oxygen species (ROS), and improve organ function in COVID-19. Patients in the treatment group were given 1200 mg/d intravenous ALA once daily on top of their existing treatment, and they were given ALA treatment for 7 additional days beyond standard medical care.  Patient organ function was assessed using the Sequential Organ Failure Estimate (SOFA) score.  After 7 days of ALA treatment, the control group's SOFA score increased by 1.7 points (4.3-6.0) whereas the treatment group's score increased by 0.2 points (3.8-4.0).  These results were not significant (p=0.36) due to a limited sample size.  

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