The Chinese are releasing preliminary data/results with their experience. They have demonstrated that ARDS, as I have mentioned before, which is Acute Respiratory Distress Syndrome, is a huge problem that results from contracting coronavirus infection.
Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020.
Exposures Confirmed COVID-19 pneumonia.
Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed.
Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72).
Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.
ARDS is Acute Lung Injury.
We have a drug that treats ARDS and is safe in humans and has been tested with solid data in animals...just look at the news release from Algernon
The decision to file with the U.S. FDA, was made after a recent independent study found that Ifenprodil significantly reduced Acute Lung Injury and improved survivability in an animal study with Asian H5N1 infected mice by 40%. Asian H5N1 is the most lethal form of influenza known to date with an over 50% mortality rate. The drug was also previously shown in a separate study to prolong survival under anoxic (low oxygen) conditions, as might occur in patients with severely impaired lung function.
Ifenprodil H5N1 Animal Study Background:
A genome wide RNAi interference approach to identify genes that aid in the recovery of cell viability after H5N1 infection, lead to the identification of the NMDA receptor antagonist Ifenprodil, which when tested in an animal model of H5N1 infection showed:
Markedly decreased leukocyte infiltration and lung injury scores in effected lungs Significantly ameliorated edema infected mouse lung tissue Significantly improved the survival of H5N1 infected mice by 40%
“This is a very important step for the Company as we move forward on our strong belief, based on the data, that NP-120 (Ifenprodil) may be an effective treatment for coronavirus (COVID-19),” said Christopher J. Moreau, CEO of Algernon Pharmaceuticals. “I would like to thank the entire Algernon team for all of the hard work and dedication this past week that went into preparing our pre-IND application. We will update the market shortly on the direction we receive from the U.S. FDA and based on circumstances, we are hoping for an expedited response.”
About NP-120 (Ifenprodil)
NP-120 (Ifenprodil) is an N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist specifically targeting the NMDA-type subunit 2B (Glu2NB). Ifenprodil also exhibits agonist activity for the Sigma-1 receptor, a chaperone protein up-regulated during endoplasmic reticulum stress. Although the anti-fibrotic activity of Ifenprodil in IPF is not known, recent studies have suggested a link between both receptors and pathways associated with fibrosis.
Glutamate (Glu) is the main excitatory neurotransmitter which acts on glutamate receptors in the central nervous system (CNS) but overactivation of these receptors can cause several damages to neural cells including death. Recent studies show that the glutamate agonist N-methyl-d-aspartate (NMDA) can trigger acute lung injury (ALI). ALI is a direct and indirect injury to alveolar epithelial cells and capillary endothelial cell, causing diffuse pulmonary interstitial and alveolar edema and acute hypoxic respiration failure. ALI is characterized by reduced lung volume and compliance, and imbalance of the ventilation/perfusion ratio, inducing hypoxemia and respiratory distress and its severe stage (oxygen index <200) known as acute respiratory distress syndrome (ARDS). (1) Furthermore, pathological findings show that 64% of ARDS patients may have pulmonary fibrosis during convalescence (2).
NP-120 (Ifenprodil) was initially developed by Sanofi in the 1970’s in the French and Japanese markets for the treatment of circulatory disorders. The drug is genericized and sold in Japan and South Korea and is used to treat certain neurological conditions.
