Opinion: Alternative Vaccine Strategy To Reduce COVID-19 Morbidity, Mortality

Population immunity is required in order to beat COVID-19. According to an opinion piece by Michael Criqui and Robert M. Kaplan on NPR, a quicker end to the pandemic requires two policy changes: delaying inoculation of those with prior COVID-19 infections, and temporarily widening the interval between the vaccine doses.

While some health professionals may disagree, this alternative strategy could slow the severe morbidity and mortality associated with COVID-19.

Should People With Prior COVID-19 Be Immunized?

Among nearly 100 million confirmed COVID-19 cases worldwide, there are only 39 (0.00004%) documented reinfections. Harvey et al reported on 3.2 million subjects, 11.6% with a positive antibody test and 88.3% with a negative antibody test, who were followed at 30-day intervals. They found that positive antibodies persisted and were associated with a 90% reduced risk for SARS-CoV-2 over 90 days in comparison to antibody negative subjects. Lumley et al similarly showed a 90% reduced risk in 112,541 healthcare workers in the UK. In the latter study, among the 1177 workers who were seropositive at baseline, only 2 became PCR positive, and both remained asymptomatic.

These findings suggest it is safe to delay vaccinations for those with prior infection.

When Should The Booster Doses Be Given?

The Biden administration hopes to administer 100 million doses during their first 100 days in office (ending April 30, 2021). The second component of the alternative strategy is to use the available doses to double the number of individuals exposed to the vaccine in the near-term.

The data in both the Pfizer and Moderna trials indicate full vaccine efficacy beginning 10-14 days after the first dose. The phase 1 studies of these two mRNA-based vaccines show the antibody response to a single dose is similar to convalescent plasma, and natural infection shows prolonged immunity. Proponents of strict adherence to the two dose schedule point to estimates that the first dose is only about 50% effective for preventing COVID-19 infections. But these analyses include the 14-day post-inoculation period before neutralizing antibodies are fully established. In fact, the Moderna trial showed that the first dose was 94% effective for the interval 15-30 days after the first injection, exactly the same efficacy as for the period following the second dose.

An Alternative COVID-19-Vaccine-Rollout Strategy Would Save Lives

With the alternative strategy, each person would receive a second dose 90 days after the first. To model the potential harms and benefits, the two assumed that about 3 million doses were distributed each week in the US in the beginning of 2021 and distribution will increase by an average of 500,000 doses each week before reaching a plateau of about 10 million doses/week by June.

Thereafter, manufacturing would be able to adjust to meet demand. Using data from the IHME model, they estimated there will be an average of 200,000 cases of COVID-19 per day during this time period. The two-dose strategy would immunize 50 million persons with two doses. However, since current projections indicate 5 million of these persons will have had prior COVID, only 45 million could benefit.

Based on an average of 200,000 cases of COVID-19 per day, X .95% vaccine efficacy = 2.63 million people would avoid COVID-19 with this strategy through April. Their alternative strategy would immunize 100 million persons with one dose, excluding persons with prior COVID-19. With this strategy, 5.85 million people could avoid COVID-19 and in theory an additional 3.22 million people would avoid infection compared to the standard strategy.

In the US approximately 15% of COVID-19 patients are hospitalized and 1.7% die from the disease. Thus, the alternative strategy could prevent 480,000 hospitalized cases and 54,400 deaths by April 30.

Risks and Benefits

Not Immunizing People With Previous Infections

Approximately 40 million people in the US will have experienced a confirmed case of COVID-19 prior to May 1. Vaccine supply remains very limited and postponing the two doses of the vaccine for previously infected people could free up 80 million doses. The previously infected could be vaccinated later if deemed medically appropriate.

Delaying The Second Dose Until 90 Days After The First

Criqui and Kaplan are concerned that so little attention has been devoted to the consequences of not enacting this strategy. Yes, there could be an immunity risk from prolonging the dosing interval. However, data from the AstraZeneca trial suggest delaying the second dose results in more rather than less durability of the immune response.

Considering limited vaccine availability, the two believe their strategy would be both more successful and more ethical. Their bottom-line concern is this: considering limited vaccine availability, in the short term there is little benefit from vaccinating either people with a prior infection or those who have already had a first dose. Using the limited supply for these two groups would cause harm by depriving fully vulnerable persons of needed protection.