I mentioned last week that our winter respiratory virus season was picking up, and it seems to be doing so with a vengeance in many US locales with 4 virus categories circulating simultaneously. We continue to deal with 2 respiratory enterovirus groups, rhino/enteroviruses and respiratory syncytial viruses (RSV), for which we have no good therapies or preventive measures, other than a monthly monoclonal antibody preventive therapy for RSV in high-risk infants. (Help is on the way for RSV, both for a longer lasting monoclonal antibody preventive as well as immunization for pregnant women to help pass on immunity to their newborns.) The best preventive therapy is good ol' handwashing and avoiding contact with ill individuals.
For the other 2 viruses, COVID-19 and influenza, we do have excellent antiviral preventive methods and treatments. Everyone eligible (essentially everyone over 6 months of age) should receive recommended vaccines for both. Clinicians should be well-versed in antiviral treatments for both viruses.
It could be a rough road ahead since most infants have never seen these common viruses, other than SARS-CoV-2, so their immune systems are seeing a lot of new things.
This week I'm highlighting aspects of the pandemic that were lost, especially early on, hoping we make fewer mistakes in the future.
Ethics and Empathy
This week's New England Journal of Medicine had an interesting Perspective piece on ethics and global health. It used COVID-19 as the example, but the sentiments apply to all of healthcare. It's a relatively quick read (and doesn't require a journal subscription!) that I recommend to everyone, including the lay public. The main focus is on an ethical approach to global health during pandemics to hit the right balance of assistance to those in need. I was struck personally by the mention of medical providers receiving priority, such as for covid vaccines, in a pandemic. I certainly recall a degree of guilt getting my vaccine before others at higher risk and also worrying that my wife had to wait a bit longer for hers. Of course the justification, objectively correct, is that keeping healthcare providers safe ultimately helps save more lives than just those of vaccine recipients.
I've also been pained by a seeming demise of empathic feelings in general during the pandemic. For example, many people have made decisions about their personal vaccinations without regard to the benefit their immunity would give to immunocompromised and other high-risk people in their communities. Part of this, I suspect, is an example of Abraham Maslow's hierarchies of needs. With the fear and loss of control we all felt during the pandemic, it's only natural to revert to lower levels on Maslow's hierarchy, i.e. concern for personal safety and physiologic needs (food, sleep, health). I'm hopeful we can see a return to empathy playing a stronger role in all of our behaviors.
Ivermectin, Medical Uncertainty, and Clinician Judgment
You would almost need to be living under a rock the past couple years not to be aware of the ivermectin/covid kerfuffle. We never had any credible evidence that ivermectin was beneficial for treating or preventing COVID-19 disease, but it ended up being a political football. I can state unequivocally that a politician is the last person I would want making personal medical choices for me.
However, what was lost in these political wars was the fact that absence of evidence of benefit is very different from evidence of absence of benefit. The former statement just means that we don't know if a treatment works, usually because the necessary studies haven't been done. The latter indicates that those studies were done and they showed no benefit. Ivermectin is an approved drug for several uses, but not covid. However, every clinician I know uses medications for "off-label" situations. This is perfectly legal and often results because there is little incentive for pharmaceutical companies to pay for more studies of an already approved drug - the company won't be able to recoup their costs of the newer studies which often involve diseases much less common than what was studied for original FDA approval.
A few folks raised interest in ivermectin use in covid, and some clinicians started using it. Unfortunately, a backlash against this developed, perhaps based more in political and cultural wars than in science. This led to threats of some clinicians losing hospital privileges and/or medical licenses for prescribing ivermectin for covid. Stepping back, it would almost be like me losing my medical license for prescribing a common antibiotic for a premature infant, just because it wasn't approved for use in that population. (That actually continues to be the case; FDA and NIH have created an entire system to prioritize and fund studies of approved drugs that were never studied adequately in certain pediatric populations.)
With ivermectin for covid, I think we have finally crossed into the "evidence of absence" category with the long-awaited publication of a new study on top of others with different populations also showing evidence of absence. The study itself is a randomized, double-blind, placebo-controlled platform trial of treatments for covid. It is part of the ACTIV-6 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) study platform. The study itself can get a little dense, so I'm going to split up the discussion for 2 groups.
For Clinicians
You are all probably familiar with most of the study design terms mentioned above, with the possible exception of "platform trial" which is really interesting. Briefly, this mechanism allows for comparison of multiple different treatments, including placebo, for the same condition. Doing so requires different statistical considerations, which is where it gets pretty complicated, but in general I believe it's a brilliant approach to use in a pandemic situation.
The findings were pretty clear for this patient population, namely those at least 30 years of age with mild to moderate covid (at least 2 symptoms of acute infection present for less than 7 days) who did not require hospitalization. The enrollment took place during periods of delta and omicron presence in the community, meaning it is about as relevant as we can get to our current situation. 817 participants received ivermectin and 774 received placebo, again in a double-blind fashion. The main endpoint was time to sustained recovery (3 consecutive days without symptoms); also monitored were 7 secondary outcomes. Bottom line after wading through all the statistics: no benefit. Along with other studies of ivermectin, I think we can put to rest any use of this drug for covid. Of course, we don't have any studies in children, but in my opinion the biology of the disease in children would not justify a clinical trial in younger patients.
Plain Language Summary
When medical researchers want to determine if a treatment works for a specific disease, they generally set up a series of studies to determine if the treatment is both safe and effective in that situation. Ultimately, they want to test the treatment in a group of individuals with the disease, and they want to make sure that what they observe in these individuals truly reflects the impact of the treatment, rather than other factors or just occurring by coincidence.
The best way to achieve this is to perform a randomized, double-blind, placebo-controlled study. What does all that mean? It's all about trying to eliminate bias, or confounding factors, that might lead to false study conclusions. Randomization means that whether a participant receives the actual treatment or just a placebo (inactive or no treatment) is determined by a fancy coin toss. Blinding means that the participant (and the researcher monitoring the participant if it is a double-blind trial) doesn't know which they are receiving. Randomization and blinding help prevent false conclusions that might happen, such as the participant being more likely to notice an upset stomach if they know they are receiving the real treatment.
With this study, and others preceding it, I think we can drop the issue of using ivermectin for COVID-19. We have much better treatments and preventive measures already available.
As we enter a new phase of the pandemic and, I hope, a transition to an endemic era where we learn to live with SARS-CoV-2, let's try to get back to a time when our society was a little less panicked and volatile.
I once was lost but now I'm found/Was blind but now I see.