COVID vaccines: Are you ‘primed’ for the best outcome?

As I rolled over in my sweat-drenched sheets, head throbbing, eyes heavy and feeling nauseated, I could pinpoint every aching muscle in my body. The combination of symptoms was all too familiar. Though drastically less severe, it was eerily similar to being sick from COVID-19 roughly a year prior. This time, however, my symptoms occurred after receiving the vaccine the day before. Several fellow health care workers had reported parallel experiences following their vaccinations — some after their first dose and others after their second. 

The scientist in me wondered whether these reactions might be related to preexisting, yet unchecked, COVID-19 antibody levels. As I lay there unable to sleep, in what was likely a fever-induced delirium, it dawned on me that, for certain groups, there might be a smarter way to get vaccinated.

Infection from any organism, including COVID-19, activates several different arms of the immune system, some in more robust ways than others. This underlying activation due to infection or exposure, in synergy with a vaccination, could lead to overstimulation of the immune response. This might explain the symptoms that not only I had, but also many frontline colleagues. We represent a group with high rates of COVID-19 antibodies (known as seroprevalence) even prior to becoming vaccinated. 

Given known hesitation in certain populations to receive the novel vaccinations, an adverse reaction of any kind might deter large numbers of individuals from receiving the shot. For high-risk, vulnerable groups, emerging data suggest that seroprevalence of COVID-19 infection is likely higher than tested and reported. Therefore, a natural question arises of whether there may be a smarter way to administer the vaccines in high seroprevalent groups. An intentional, well-planned approach to avoid eliciting adverse immune responses and still achieve herd immunity could accomplish the dual goals of vaccinating those at greatest risk for severe COVID-19 outcomes and ending mass suffering, both medical and economic, related to the virus. 

COVID-19 vaccines are being administered, offering hope and opening the possibility of an eventual return to some semblance of normal. With the daunting tasks of vaccine production, distribution and administration, as well as the need to overcome a multitude of barriers like vaccine hesitancy, there could be additional ways to refine processes in order to assure that mass vaccination systems are as smart and specific as possible. 

To date, the most widely available and approved vaccines in the U.S. rely on messenger RNA (mRNA) technology and are administered in two doses. With logistical, storage and compliance concerns, consideration of alternative methods might be in order for effective, efficient vaccination of the greater populace.

Current trends point toward an overall decline in new active COVID-19 cases. This shift is attributable to a combination of several factors: stricter mask-wearing and hygiene practices, social distancing, vaccination efforts, natural immunity or high rates of seroprevalence in those who already have been exposed, infected and recovered. 

For the nearly 30 million Americans who have, as of this writing, already been exposed, infected and recovered from COVID-19, resulting in an immune system that may carry some level of antibody protection or “COVID primed,” should an alternative dosing regimen such as a single dose of vaccine be utilized? This is of particular interest in light of the Johnson & Johnson vaccine, recently approved for emergency use by the U.S. Food and Drug Administration. 

The data indicate that the one-shot Johnson & Johnson vaccine is 66 percent effective for preventing moderate to severe cases of COVID-19 worldwide (higher in the U.S. alone) — an acceptable level of efficacy when compared to the yearly influenza vaccine. Nonetheless, the vaccine is already being labeled as an “inferior” inoculation. The BioNTec Pfizer vaccine was found to have less efficacy after only a single dose yet increased to almost 95 percent with a second shot. Would this also be the case with a second dose of the Johnson & Johnson vaccine? Would the efficacy rate increase with a two-dose regime? Moreover, in a “COVID-primed” individual or those from a high seroprevalence population, would a single shot be sufficient to elicit robust and appropriate levels of immunity, given the presence of preexisting, underlying immunity?

In other words, should a one-dose vs. two-dose regimen depend more on the individual being vaccinated, rather than the particular vaccine type itself? Similarly, should the decision regarding which vaccine to administer depend upon who is being vaccinated — the “COVID-primed” or the “COVID-naïve” individual? 

These questions have many implications, including the possibility of the preferential use of the Johnson & Johnson vaccine in “COVID-primed” or high seroprevalent groups. A more deliberate approach could liberate additional mRNA vaccine doses for those who are “COVID-naive” and who, therefore, would need an initial robust response to the vaccine. Furthermore, and most importantly, while we scramble to manufacture, procure and distribute finite numbers of vaccine vials, smarter and more targeted administration could help expedite the utilization of vaccines. 

A closer look at the level of protection obtained by a single shot vaccine regimen for those who are “COVID-primed” is needed. Rigorous, effective and efficient antibody prescreening tools to identify these individuals would be required as well. Every precious dose counts. Now is the time to refine systems, implement the smartest approaches possible, avoid potential adverse reactions to vaccination, and best disperse limited supplies. Addressing these outstanding questions in order to hone and improve the process of distribution and administration is ever more important given the imperative to vaccinate the world’s population. After all, global immunity is the only way to reach the goals of preventing further devastating outcomes, containing spread and striving for normalcy. 

Dara E. Udo, M.D., M.P.H., is urgent and immediate care physician at Westchester Medical Group, White Plains (N.Y.) Hospital, and Greenwich (Conn.) Hospital.

Jacki Hart, M.D., director of the Bassuk Center in Needham, Mass., and Mark C. Poznansky, M.D., Ph.D., director of the Vaccine and Immunotherapy Center at Massachusetts General Hospital, contributed to this column.