181 CMAAO CORONA FACTS and MYTH Human Challenge
Dr K Aggarwal
With inputs from Dr Monica Vasudev
1047: Human Challenge Trials for COVID-19 Vaccine and the Risk?
Human challenge trials for the COVID-19 vaccine —volunteering to be given an unproven vaccine, then being exposed to the virus on purpose instead of waiting to be exposed and for infection to occur naturally in the community.
The goal is to speed vaccine development. More than 32,000 people from the United States and 139 other countries have already signed up with an online registry, 1Day Sooner.
The trials could effectively deliver a vaccine and end the pandemic more quickly, but the unknowns about this novel coronavirus, the lack of an effective treatment for COVID-19, and the accelerated pace of the research give pause, because the extra risk could come at a high cost: the health, or potentially the life, of the volunteers.
These trials can be faster than conventional field trials, partly because fewer participants must be exposed to provide early estimates of efficacy and safety; if one vaccine doesn't work, researchers can move on to other candidates. In challenge trials, volunteers receive the vaccine candidate or a placebo, just as participants in traditional trials do. After waiting a period for the vaccine to take effect, the volunteers are exposed to the virus.
Whereas traditional vaccine trials may enroll 30,000 participants in phase 3 studies and have results in 6 months, challenge trials may need only about 150 participants and have results in 6 weeks. In addition, the studies can compare multiple vaccine candidates at once; the most promising are selected to move on to larger studies.
Can a volunteer really give informed consent when there are so many unknowns about COVID-19? Clinicians say they would communicate the pros and cons should one of their patients ask about joining up.
In the past 50 years, the WHO says, ''challenge studies have been performed safely in tens of thousands of consenting adult volunteers under the oversight of research ethics committees." The studies have helped to speed development of vaccines against cholera and typhoid and to evaluate immune protection against influenza.
Shaving even 1 day off vaccine development time could save 7120 lives, according to estimates by experts.
Reducing development time by 3 months would save more than a half million lives, estimated, assuming that one sixth of the world would acquire COVID-19 annually and that a vaccine would prevent 0.2% of those people from dying.
Study participants may be high-risk individuals who volunteer because they believe that these first vaccine attempts could prevent them from contracting COVID-19, a belief of the "prevention misconception."
Guidance On Glycemia in Dexamethasone-Treated COVID-19
New guidance from the UK National Diabetes COVID-19 Response Group
Triple insult of dexamethasone-induced impaired glucose metabolism, COVID-19-induced insulin resistance, and COVID-19 impaired insulin production.
August 2 in Diabetic Medicine
Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, showed that dexamethasone reduced deaths in patients with COVID-19 on ventilators or receiving oxygen therapy.
The advice is not intended for critical care units but can be adapted for that use.
The dose used in RECOVERY — 6 mg daily for 10 days — is five- to sixfold greater than the therapeutic glucocorticoid replacement dose.
High glucocorticoid doses can exacerbate hyperglycemia in people with established diabetes, unmask undiagnosed diabetes, precipitate hyperglycemia or new-onset diabetes, and can also cause hyperglycemic hyperosmolar state (HHS).
The guidance recommend a target glucose of 108-180 mg/dL and up to 216 mg/dL is "acceptable."
Use of once- or twice-daily NPH insulin is recommended for patients whose glucose has risen above 216 in some cases with the addition of a long-acting analog.
The guidance says that patients already taking premixed insulin formulations can continue using them while increasing the dose by 20% to 40%.
Given the risk of hypoglycemia associated with those formulations, many experts say they would switch those patients to NPH during the time that they're on dexamethasone.