In partnership with CATO SMS, JanOne is currently preparing an investigator-initiated IND package for the FDA, which it expects to submit in the coming month. If cleared to proceed by the FDA, clinical management of any ensuing research trials could start quickly and be conducted by Dr. Amol Soin, JanOne’s chief medical officer. By mitigating severe organ and tissue damage, JAN101 can potentially have a significant impact on the long-term health of these patients
COVID-19, a mild to severe contagious infectious disease caused by a novel coronavirus, has everyone’s attention. As we continue to learn more about the virus, it is abundantly clear that the majority of Covid-related deaths result from acute respiratory distress syndrome (ARDS) and severe lung inflammation. When coupled with patients who have existing underlying medical conditions such as chronic lung disease, heart conditions, diabetes, kidney and liver disease and thrombosis (clotting), a common thread is beginning to emerge. In addition, immune weakening diseases, particularly those that compromise the lining of blood vessels, have further captured the attention of researchers and the medical community alike.
As more data has been collected, we believe a clearer picture is emerging that indicates the COVID-19 respiratory virus may not be the trigger for a respiratory disease. Rather, it may be a respiratory virus that reveals itself as a vascular disease. A handful of researchers are finding ways to decrease the risk of acute cardiovascular disease, which could very well be the answer.
According to a recent study in the New England Journal of Medicine, tissue analysis showed that infection with SARS-CoV-2, the virus that causes COVID-19, caused severe damage to the endothelial cells that line blood vessels and triggered widespread blood clotting.(1) In simple terms, the barrier between the blood vessels and tissue that controls blood flow is severely compromised. This in turn restricts and damages the patient’s vascular system, inhibiting the ability for blood cells to carry oxygen to the lungs, compounded by the inability of the vessels within the lungs to produce enough oxygen to sustain human life.
While the New England Journal of Medicine study only included seven Covid patients, if the findings prove to be a common consequence of Covid infection, an entirely new treatment may materialize. Rather than treating COVID-19 as a respiratory condition, success may be achieved with treating the underlying vascular tissue damage caused by the attack of Covid on endothelial cells. The result may mitigate ARDS and lung inflammation, dampen the severity of the disease and provide hope for better recovery compared to current treatments.
Before COVID-19, it was examined that sodium nitrite could serve as a potentially safe and well-tolerated treatment for cardiovascular – and related – disease(s). In 2016, the National Heart, Lung, and Blood Institute (NHLBI) assembled a workshop to identify approaches to address how best to study nitrite exposures into ongoing studies of cardiovascular epidemiology. Sodium nitrite gives the body a potent signaling molecule – called nitric oxide – that targets blood vessels allowing them to expand and increase blood flow. Since nitric oxide decreases in production as we age, added sodium nitrite can improve blood vessels and feasibly reduce the further risk of cardiovascular disease.(2) According to NHLBI, nitric oxide has been identified as an important biologically active molecule in the late 1980s as the elusive “endothelium‐derived relaxation factor.”
Caught in the eye of a “cyto-storm”
How does COVID-19 change from a relatively mild case to a severe case that infiltrates the lungs, leading to ARDS, pneumonia and fluid build-up? The answer lies in the body’s immune response to new flu variants, including the novel coronavirus. When the virus expresses itself, one hypothesis is that the body produces an overabundance of cytokines (immune cells that cause systemic inflammation), which were believed to be the major cause of death in the Spanish Flu and Swine Flu, and now COVID-19.
Known as a “Cytokine storm”, the mass flood of these immune molecules may result in the shutdown of the bodies organs, leading to death. Cytokines are highly destructive to endothelial blood cells further proving the link between vascular disease.(3) Once a Cytokine storm begins, the consequences can be fatal.
Breathing new life into COVID-19 treatment
If we are to assume that COVID-19 is a vascular disease, a sodium nitrite compound currently in clinical trials may prove to be a beneficial treatment. Sodium nitrite has recently demonstrated positive results on vascular conditions such as Peripheral Artery Disease (PAD), diabetic neuropathy and even vascular decline associated with normal aging. In preclinical and clinical studies, sodium nitrite has shown promise repairing and restoring vascular function with minimal adverse events. In addition, in an aged mice study, nitrite administration has been shown to reduce the production of inflammatory cytokines and thrombosis (blockages).
Since the pervasive distribution of any safe vaccine candidate may not be a reality until the end of 2021, a sodium nitrite-based treatment may offer a safe and immediate solution for treating the vascular and organ problems associated with Covid infections. High risk patients and those with complex medical conditions could potentially see improvement in pulmonary function and endothelial cell health. This treatment could be a gamechanger for mitigating COVID-19 complications, including the long-term prevention of subsequent organ damage.
There are currently ongoing studies to confirm that COVID-19 may be a vascular disease that ultimately impedes respiratory function. As respiratory damage and restricted oxygen levels are the primary culprits for Covid mortality rates, it is also what has led researchers down the path of a novel approach for using sodium nitrite that may just clear the air for Covid-19 patients.
By Tony Giordano, PhD, Chief Scientific Officer at JanOne and Amol Soin, MD, Chief Medical Officer at JanOne. The referenced New England Journal of Medicine article was led by Steven Mentzer, HMS professor of surgery, at Brigham and Women’s Hospital. Also referenced was an article titled “Cytokine Storm: The Sudden Crash in Patients with COVID-19” by Dr. Randy Crone, Cytokine storm expert at the University of Alabama Birmingham. Members of JanOne’s scientific advisory board also hold current positions at Brigham and Women’s Hospital and University of Alabama, Birmingham.
- Ackermann, Maximilian, et al. “Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.” New England Journal of Medicine, vol. 383, no. 2, 2020, pp. 120–128., doi:10.1056/nejmoa2015432.
- Devan, Allison E., et al. “Effects of Sodium Nitrite Supplementation on Vascular Function and Related Small Metabolite Signatures in Middle-Aged and Older Adults.” Journal of Applied Physiology, vol. 120, no. 4, 2016, pp. 416–425., doi:10.1152/japplphysiol.00879.2015.
- Patterson CC, Smith AE, Yarnell JW, Rumley A, Ben-Shlomo Y, Lowe GD. The associations of interleukin-6 (IL-6) and downstream inflammatory markers with risk of cardiovascular disease: The caerphilly study. Atherosclerosis. 2010;209(2):551–557. [PubMed] [Google Scholar]