Back Back
COVID-19 Prevention
The Evolution of COVID-19 Prevention

Released: August 08, 2024

Expiration: August 07, 2025

Deepali Kumar
Deepali Kumar, MD, MSc, FRCP(C), FAST
Erin K. McCreary
Erin K. McCreary, PharmD, BCIDP
Marcus Pereira
Marcus Pereira, MD, MPH, FAST
Activity Information

Activity

Progress
1
Course Completed
Key Takeaways
  • In theory, it makes sense to wait at least 14 days after the COVID-19 vaccine before administering a COVID-19 monoclonal antibody.
  • There is some in vitro evidence that the monoclonal antibody pemivibart neutralizes the new FLiRT variants.

The following is a recap of key questions asked by healthcare professionals during a program featuring Deepali Kumar, MD, MSc, FRCP(C), FAST; Erin K. McCreary, PharmD, BCIDP; and Marcus Pereira, MD, MPH, FAST, discussing the latest advances in COVID-19 prevention.

Does molnupiravir promote viral mutation, particularly among transplant patients?

Deepali Kumar, MD, MSc, FRCP(C), FAST:
Yes, molnupiravir acts on the RNA dependent RNA polymerase of the SARS-CoV-2 virus and induces mutations in the virus. This is its mechanism of action: By increasing the frequency of mutations in the viral genome, molnupiravir causes an “error catastrophe” for the virus, thereby inhibiting viral replication.

Transplant patients often have higher SARS-CoV-2 viral loads than the general population, and they can shed virus for longer periods of time. Therefore, in theory, mutant viruses could be transmissible for longer in transplant patients. However, that phenomenon has not been demonstrated at a practical level.

Would overuse of monoclonal antibodies contribute to the evolution of resistant viral variants?

Deepali Kumar, MD, MSc, FRCP(C), FAST:
No. In general, use of monoclonal antibodies does not promote evolution of resistant viral variants.

The SARS-CoV-2 virus is mutating all the time as it replicates, so the more viral replication occurs, the more mutations that virus accumulates. Viral replication drives viral evolution. Overall, the contribution of monoclonal antibodies to that process is very small.

In fact, by using monoclonals as prevention or treatment, we actually stop viral replication and prevent further viral mutation. In the big picture, I do not think that evolution of antibody-resistant variants is a reason to avoid using them. 

Are the new monoclonal antibodies effective against the FLiRT variants in terms of preventing infection?

Erin K. McCreary, PharmD, BCIDP:
There is some evidence that the new antibodies neutralize the FLiRT variants. On June 14, 2024, the makers of pemivibart issued a press release stating, “Pseudovirus in vitro neutralization data show continued neutralizing activity of VYD222 (pemivibart) against the KP.1.1 FLiRT and KP.3 SARS-CoV-2 variants.”

However, we know that in vitro test results do not always directly translate to in vivo efficacy. So, I think every antibody needs to be studied in clinical trials. Ideally, we would have robust clinical outcomes data to guide decision-making, but I would not avoid giving pemivibart to patients who may need it just because we do not have that data yet. I would err on the side of giving it to them, as long as it is safe.

What is the short-term and long-term safety of preventive monoclonal antibodies in immunocompromised patients?

Erin K. McCreary, PharmD, BCIDP:
There are not much data available regarding long-term effects of the monoclonal antibodies. There are many confounding factors, including COVID-19 infection itself. To study this, investigators would need to recruit a very large population of people, ideally limited to those who never got COVID-19 after infusion with monoclonal antibodies, and monitor them to see if they experience any phenomena that could be correlated to their previous monoclonal antibody infusion. Realistically, I am not sure that would be possible.

However, anecdotally, I have not observed any long-term issues in my patients. Even immediate infusion reactions were rare.

In my clinic, the only time we ever saw a safety signal was with bebtelovimab, which was formulated as an IV push or a rapid administration instead of an infusion. When we first started giving that drug, we observed more infusion reactions, particularly among pregnant people. To mitigate this, we did extensive counseling on letting the drug come to room temperature and then injecting that drug into a flowing saline infusion rather than directly. That seemed to mitigate the infusion reactions.

Otherwise, I found monoclonal antibodies were a dream to work with: safe and highly effective. Patients loved them as well.

For which patient populations are preventive monoclonal antibodies most appropriate?

Deepali Kumar, MD, MSc, FRCP(C), FAST:
There are very few safety concerns with monoclonal antibodies, so I would recommend them for people who would derive the greatest benefit from them or those who are at greatest risk of severe COVID-19 infection: immunocompromised individuals, including recent transplant recipients, and patients in the older age group or with multiple comorbidities.

How long should people wait between getting vaccinated for COVID-19 and using preventive antibodies, and vice versa?

Erin K. McCreary, PharmD, BCIDP:
Currently, there are no specific recommendations regarding the timing between COVID-19 vaccination and pemivibart administration. However, based on prior recommendations for tixagevimab/cilgavimab, I would advise that, for any new monoclonal antibody:

  1. Patients can receive a preventive antibody a minimum of 14 days after the COVID-19 vaccine.
  2. Patients can receive a COVID-19 vaccine at any time after receiving a preventive antibody.
  3. If patients have recently had a COVID-19 infection, they can receive a preventive antibody once they are fully recovered from COVID-19 and no longer considered contagious.

Marcus Pereira, MD, MPH, FAST:
I agree. The idea is that you should give 2 weeks for the vaccine to work because you do not want to neutralize the vaccine with monoclonal antibodies.

However, I do not think that that was based on solid evidence, but rather on avoiding theoretical risks. The best course of action is to be pragmatic for your patients and their individual best interests.

How would you counsel an unvaccinated patient who is on the transplant list with alcohol-related liver disease and who has had COVID-19 twice but is still hesitant to be vaccinated?

Marcus Pereira, MD, MPH, FAST:
This is a difficult one. First and foremost, I think we should understand that it is quite human to be scared of vaccines, and we should not dismiss that sentiment. If someone does not feel comfortable with the vaccine, we should try to understand why and guide them through it.

I would tell this patient that I am glad that they did okay with the first 2 episodes of COVID-19. However, a cirrhotic liver puts people at enormous risk of severe COVID-19 disease, and SARS-CoV-2 infection does not grant lasting immunity. There is no guarantee of a positive outcome if they get COVID-19 this fall or winter.

I find that it is also helpful to discuss the different types of vaccines. If patients are hesitant to receive an mRNA vaccine, there is a vaccine that is protein based. Patients often become more receptive to vaccination when they learn that may have already received vaccines using this same technology.

Your Thoughts?

How likely are you to recommend preventive monoclonal antibodies to your patients at high risk of severe COVID-19? Leave a comment to join the discussion!