COVID-19 Boosters: New MMWR Report Explores Waning Immunity

As many states are relaxing restrictions and seemingly sending the message the pandemic is over, the Centers for Disease Control and Prevention has published concerning data in the latest Morbidity and Mortality Weekly Report (MMWR) on the waning of immunity produced by COVID-19 boosters after 4 months. These data confirm a New England Journal of Medicine report that cited a 6.3-fold decrease in neutralization of the Omicron variant 6 months after a booster was given.

The MMWR report analyzed clinical data on vaccine efficacy during the Omicron surge. The research found vaccine efficacy in the prevention of visits to urgent treatment centers and emergency rooms fell from 87% at 2 months, to 66% at 4 months, to 31% at ≥ 5 months. Prevention of hospitalizations fell from 91% at 2 months to 78% at 4 months. Data on the prevention of hospitalization after 4 months are not yet available.

A fourth booster is currently recommended for those 18 years of age or older by Israel’s vaccine advisory panel. A number of other countries, including the United States and United Kingdom, recommend a fourth dose for immunosuppressed individuals. Although data are limited, antibodies increased comparable to the third dose, but may not be high enough to protect against infections.

Those who have had previous infections are also not necessarily immune to Omicron. The UK Health Security Agency reports that 9.5% of all Omicron infections are reinfections. The Imperial College of London reported that natural immunity from a previous infection had an efficacy of only 19% in the prevention of a symptomatic reinfection by the Omicron variant. However, this is better than a 2-dose AstraZeneca and Pfizer/BioNTech vaccine, which had an efficacy of a 0% to 20% in the prevention of symptomatic disease. But unlike an infection, individual can receive boosters for a vaccination. The efficacy then jumps from 55% to 80% against Omicron.
 
If an individual has had a previous infection, they should receive a vaccination. Two recent articles in the New England Journal of Medicine report that vaccination after infection produces a significant and meaningful increase in immunity. The first study by Ariel Hammerman, et al., found that vaccination after COVID-19 infection produced a more than 4-fold decrease in Delta variant reinfections. And that even a single dosage of the Pfizer vaccine produced a significant decrease in the rate of reinfections.
 
The second study by Victoria Hall, et al., evaluated the durability of protection during the Delta surge. Those who were vaccinated with the Pfizer/BioNTech vaccine alone had waning immunity, with an effectiveness in the prevention of infections of 51% at a median of 201 days. In those who had a previous infection, there was an 86% less chance of reinfection up to 1 year after the primary infection. After the first year, the protection against infection had considerable waning and was reduced to 69%. However, those who had a primary infection and were then vaccinated had protection of 90%. And “waning of protection was not observed from more than 1 year after primary infection or more than 6 months after vaccination.” Of importance is that both of these studies were conducted during the Delta surge and the results may not be applicable for Omicron.
 
The large Omicron peak in morbidity and mortality that the United States has endured is because of Omicron’s high infectivity and its ability to avoid many of the monoclonal antibody products, leaving only a few effective medications that are in extremely short supply.
 
The good news is that there are exciting new medications and vaccines in the pipeline that represent a quantum leap in how we approach the treatment of Omicron.

Pfizer and Moderna have both announced they are planning to have an Omicron variant-specific vaccine available by late spring.
 
Multiple companies and research organizations have developed biological products that are able to target areas of the spike protein which are common to most SARS-CoV-2 variants. Presumably, this is the target that, if changed, could result in the virus having difficulty attaching to the ACE-2 receptor. Two monoclonal antibodies are currently effective against Omicron, along with other types of SARS-CoV-2 variants. These monoclonal antibodies are produced by GSK and Eli Lilly. Both are in very short supply but should be on the market soon.
 
A WHO Variant of Concern, the Stealth Omicron (BA.2), may pose even new challenges and has been reported to be more severe and infectious than Omicron (BA.1). In addition, it is being initially reported that it may “largely” escape current vaccines and could be resistant to many monoclonal antibody products, including the GSK antibody, sotrovimab. However, a vaccination booster appears to restore immunity with a 74% protection against illness.

The Walter Reed Army Institute of Research is testing a pan-coronavirus vaccine that can carry up to 24 different spike proteins needed for coronavirus attachment. The Duke Human Vaccine Institute is also working on a pan-coronavirus vaccine. Duke’s vaccine works by eliciting an antibody, DH-1047, which was found to neutralize both SARS-CoV-1 (the virus behind the deadly 2003 SARS epidemic) and SARS-CoV-2 (the virus that causes COVID-19). This antibody targets a part of the virus that appears not to change and is needed for cellular binding. Both SARS-CoV-1 and SARS-CoV-2 use the ACE-2 receptor for viral entry.

So, what needs to be done? For now, keep your immunity as high as possible by becoming vaccinated and obtaining the recommended boosters, along with following public health advice. Even variants from animal hosts will probably not be able to defeat some of these new products. For now, get a booster and then plan to obtain the Omicron-specific vaccine when it becomes available later in the spring. Then, if either the Army or Duke vaccines are successful, plan on obtaining a pan-coronavirus vaccine. At that point, hopefully, the pandemic will all but come to an end, and we will only be dealing with sporadic infections that occur in those who are immunosuppressed or not updated on their vaccination status.