Our model shows that all individuals with a negative preboarding test can be released with a negative post-arrival test, with both tests achieving sensitivity ≥ 90% and specificity ≥ 97%, even when incidence rate reaches 0.1 and Rt is 4. The rapid tests can be implemented easily and quickly, which will allow the travelers to depart the airport within 30 minutes if tested negative.
In Table 1, 2, and 3, we assumed Rt < 3 in countries with strict restriction policies in place, with empirical evidence that Rt was 2.55 (2.26, 2.86) in South Africa in November 2021 when Omicron dominated.20 For countries that prefer less restrictions, the tables provide Rt of 10 as the upper limit, when we believe governments will need to put some restrictions in place to flatten the curve. In addition, we modeled Table 1 and Table 2 with ten times the adjusted BIR of WHO approved vaccines (20 times the BIR from clinical trials) to account for waning effects of the vaccines and variants of concern. When Omicron dominated in the United States, the peak daily case rate in New York State was 254.5 per 100,000 in fully vaccinated people and 2023 per 100,000 in unvaccinated people.21 Accordingly, the BIR is estimated to be 0.0025 in fully vaccinated people and the incidence rate is 0.0202 in unvaccinated people. Therefore, Table 1, 2, and 3 are still valid with Omicron being the dominant variant.
There are caveats to our study. First, we suggest that partially vaccinated individuals should be treated as unvaccinated individuals since the BIRs for partially vaccinated individuals differ greatly in the first three weeks after the first dose.22 Second, governments can use Fig. 1 to extrapolate testing and quarantine strategies for the vaccines that we did not list in the tables. For example, the clinical trial BIR of Sputnik V is 0.001069 and the adjusted BIR accounting for asymptomatic infections is 0.002138.23 Policymakers can refer to incidence rate, which is BIR for vaccinated people, of 0.05 in Fig. 1 as a conservative estimate when they are formulating policies for travelers vaccinated with Sputnik V (ten times adjusted BIR is 0.02138, accounting for waning vaccine efficacy). Third, travelers vaccinated with mixed vaccines can follow the general policy of fully vaccinated travelers or the policy for the least effective vaccine they received. For example, studies have shown a dose of AstraZeneca followed by an mRNA vaccine creates antibody responses higher than two doses of AstraZeneca;24 as such, the AstraZeneca branch of our Table 2 may provide an overestimation for expected transmission and can be used in these travelers who have received these mix and match vaccines.
If we account for known waning immunity of the vaccines, the decision tree (Table 2) could still be valid for Pfizer, Moderna, Janssen, and AstraZeneca up to six months after the second dose. The BIR of people fully vaccinated with Pfizer after six months is 0.0035 in Israel,25 less than ten times the adjusted BIR (0.0097) modeled for Pfizer in Table 2. Even though Moderna, Janssen, and AstraZeneca have not reported BIR six months after second dose, when compared to Pfizer, studies of these vaccines have shown slower decline rate of vaccine effectiveness five to six months after the second dose.26 However, Sinovac, Sinopharm, Novavax, and Covaxin have not reported their rates of waning efficacy after six months. Once their efficacies are known, policies targeting these vaccines may need to be adjusted (Fig. 1).
Boosters are important in mitigating the waning effects of vaccines and can provide additional protection. For example, travelers vaccinated with three doses of Pfizer or AstraZeneca have vaccine efficacies above 93%, similar or better than the original clinical trials with Pfizer and AstraZeneca.27 Also, booster vaccines can result in antibody levels higher than the original two doses, e.g., Moderna showed higher neutralization titers 28 days post booster compared to 28 days post second dose,28 and the seroconversion rates of neutralizing antibodies towards COVID-19 variants were higher in people vaccinated with three doses of Sinovac compared to two doses.29 Furthermore, early data on antibody levels suggest that boosters may further protect against Omicron.29,30 With preliminary data suggesting that three doses of Pfizer produce an immune response against Omicron similar to that of two doses against earlier variants, governments may consider a three-shot requirement for travelers to qualify as fully vaccinated.
Our model is flexible and can be adapted to real-life situations. For example, when in doubt, governments can invalidate the preboarding test – not considering the information provided by the negative preboarding test at all – and refer to the “Unvalidated” rows in Table 1, 2, and 3.
Finally, the data from the randomized controlled clinical trials we based on may not be identical to the real-world data (Table 2). For example, Sinovac and Sinopharm reported lower BIR compared to AstraZeneca in published clinical trials; however, their effectiveness is less certain because they provided lower antibody responses compared to AstraZeneca and severe outbreaks were seen in countries mainly vaccinated with the two vaccines despite rollout success.31 Real world BIRs are needed to provide additional evidence for decision making.