COVID-19 Drugs: Yale Study Shows That Janus Kinase-Inhibitors And Type I Interferon Reduces Mortality Risk in COVID-19 Patients
: With global death rates now reaching more than 754,000 (168,000 just in America alone) and the official infected cases at more than 22 million, medical researchers are desperate to find drugs and treatment protocols that can at help reduce mortality rates. To date there is no real effective drugs that can really treat COVID-19 effectively (remdesivir ‘s efficacy is now being questioned extensively and there are no real antivirals that have been approved to date to treat COVID-19). There is a concerted effort by the pharma giants, American social media platforms, American media and American health authorities to suppress all research studies on cheaper repurposed drugs, supplements and herbs to treat COVID-19 due to issues of greed and profit.
The world is now seeing a new surge of COVID-19 infections literally in every country including those that were initially deemed as having managed the COVID-19 crisis well. This is just a prelude to the actual wave that will start around year end to coincide with the cooler seasons and the start of the typical flu seasons and many experts are already forecasting an unprecedented scenario while many common people especially Americans are either living in denial or are claiming that they are ‘tired’ of the current COVID-19 crisis. Even scary are that some authorities, businesses and common people are believing that the COVID-19 crisis is nearing its end while it reality the COVID-19 crisis is expected to last for another 3 to 5 years with increasing severity in all aspects.
Medical researchers are desperately trying to discover new treatment protocols to improve the outcome in severe COVID-19 cases. However, most attempts have been unsuccessful.
A new research by scientists from Yale University offers some new hopes as it reports that the use of two drug categories, namely, JAK inhibitors and Type I interferons (IFNs), is associated with a dramatic improvement in mortality in COVID-19.
JAKs or Janus-kinases are transmembrane proteins that are required for and increase the intensity of signals from growth factors and cytokines to host cells.
It has been found that inhibitors of these proteins helps to reduce the level of inflammation by bringing down the cytokine levels. Each of these drugs targets a specific JAK, such as baricitinib and ruxolitinib, which inhibit JAK1 and JAK2, respectively.
According to Yale researchers, their use in severe COVID-19 is obvious, therefore.
These drugs have already been used off-label in conditions mediated by excessive cytokine release. The current study seeks to establish the utility of these drugs in severe COVID-19, therefore, in a larger population.
The research findings of the Yale Study are currently published on a preprint server but are currently undergoing peer-review. https://www.medrxiv.org/content/10.1101/2020.08.10.20172189v1
The research looked at the effect of JAK inhibition used in five studies, including just over 170 patients, on outcomes like mortality, ICU admission, the need for mechanical ventilation, the need for acute respiratory distress syndrome (ARDS), and discharge within 14 days. The researche
rs found that these drugs produced a dramatic reduction in the odds of dying of COVID-19 by 88%, compared to standard treatment.
Significantly the odds of requiring ICU admission fell by 95% in a group of 125 patients on JAK-inhibitor treatment.
Another drug of interest was Type I IFN-α/β which are protein signaling molecules secreted by infected cells.
These interferons promote a state of antiviral resistance in other cells in the proximity and also enhance the production of cytokines. The most potent antivirals are type I and type III IFNs, with their effects being mediated via the JAK/STAT pathway. This leads to the activation of many genes called the interferon-stimulated genes (ISGs) that prevent viral replication at several checkpoints.
S it is known that receptors for type I IFNs are distributed extensively, they have a broad range of antiviral activity by inhibiting viral replication both directly and indirectly through multiple mechanisms.
They have been known as being useful in treating viral hepatitis as well as SARS and MERS, previous outbreaks of coronavirus disease.
Past smaller studies have shown benefit from the use of type I IFNs along with antivirals, but the current study aims to review the effects in a larger population, which will also show the impact of these drugs on the outcome of COVID-19. And in another analysis of the same number of patients, the odds of being discharged at 14 days were almost 23 times higher.
The detailed meta-analysis conducted over three sets of studies, including 990, 454, and 1480 patients on type I interferon therapy, showed that type I IFN therapy did improve the odds of discharge by 90% while reducing the odds of mortality by 80%.
But it should be noted that this therapy did not reduce the need for ICU admission or mechanical ventilation. The odds of severe or critical disease were also similar to those in patients on standard care.
Interestingly, a combined Type I interferon therapy as well JAK inhibitors offer a twin approach, limiting early viral replication to reduce the severity of the disease, while reducing the extent of inflammation to a level that reduces harm to the host.
Importantly, this is the first systematic review that looks at the outcome of treatment with these drugs in patients with COVID-19.
The observed strong association observed between these drugs and the drastic fall in mortality and ICU admission odds would indicate the need for further investigation into the potential benefit of these therapies in improving the clinical outcome in patients with COVID-19.
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