Abstract

BACKGROUND

Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission.

METHODS

We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2–infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination.

RESULTS

Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In vaccinated index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination.

CONCLUSIONS

Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission.

Discussion

We found that both the BNT162b2 and ChAdOx1 nCoV-19 vaccines were associated with reduced onward transmission of SARS-CoV-2 from index patients who became infected despite vaccination. However, in index patients who were vaccinated with BNT162b2 and probably in those who were vaccinated with ChAdOx1 nCoV-19, reductions in transmission of the delta variant were smaller than reductions in transmission of the alpha variant. In population-based studies, vaccines have continued to provide protection against infection with the delta variant, but to a lesser degree than against infection with the alpha variant.⁸ Therefore, the delta variant eroded vaccine-associated protection against transmission both by making infection more common and by increasing transmission from infected vaccinated persons.

Vaccines have been hypothesized to reduce onward transmission by reducing viral loads.^14,15 In our study, vaccination was associated with higher Ct values (lower viral loads) of the alpha variant and, to a smaller extent, with higher Ct values of the delta variant. Higher Ct values were associated with less transmission (Figure 4B). However, we found that differences in Ct values at diagnosis in the index patient accounted for only 7 to 23% of the effect of vaccination, with most of the effect of vaccination probably occurring through other mechanisms. This finding indicates that Ct values measured in diagnostic testing are not necessarily a surrogate for the effect of vaccination on transmission. Ct values at diagnosis are probably imperfectly representative of viral loads at transmission, despite the relationship observed between Ct values and transmission, because viral loads are dynamic over time.²² Vaccination may also act by facilitating faster clearance of viable infectious virions,^17,18 but they may leave damaged ineffective virions behind that still contain PCR-detectable RNA. Studies of this possibility and of how antigen assays perform after vaccination could lead to improvement in diagnostic tests after vaccination.

We found differences between vaccines that may have reflected their differing mechanisms of action. Index patients who were vaccinated with BNT162b2 had contacts who were less likely to have positive PCR tests for the delta variant than those of index patients who had received ChAdOx1 nCoV-19. There was potentially insufficient power to resolve differences between the vaccines with respect to the alpha variant because relatively few persons who were vaccinated twice became infected before the delta variant became the dominant lineage. The incidences of infections with the alpha variant and those with the delta variant were also lower among contacts vaccinated twice with BNT162b2 than among those vaccinated twice with ChAdOx1 nCoV-19.

Protection against onward transmission waned during the 3-month period after the second vaccination. Some protection against the alpha variant remained, but much of the protection against onward transmission of the delta variant was lost, particularly with ChAdOx1 nCoV-19. Waning of protective behaviors may explain some of the change, because the use of measures such as social distancing and mask wearing in vaccinated persons may have decreased. However, reductions in antibody levels²³ and vaccine effectiveness⁸ over time provide support for the importance of biologic explanations. In addition, some of the observed decline in protection may be attributed to a longer period since vaccination in persons who were vaccinated early; these persons may have been clinically vulnerable, with immune systems that were weaker than those of persons who were vaccinated more recently.

Contacts were also more likely to test positive as the time since their second vaccination increased. Although contacts who received BNT162b2 had increased protection throughout the 3-month period after the second vaccination, this protection waned faster with BNT162b2 than with ChAdOx1 nCoV-19, as was also seen with new infections in a representative survey in the United Kingdom.⁸

Our study has several limitations. In order to minimize bias introduced by differences in testing behavior arising for multiple reasons, including the vaccination status of contacts, we included only contacts who had undergone PCR testing. Therefore, we cannot estimate secondary attack rates according to the vaccination status of patients and contacts, and the absolute protective effects of vaccination on transmission may be underestimated because vaccine-protected, uninfected contacts may not have sought testing. Our approach is also unlikely to eliminate bias, particularly if test-seeking behavior is related to perceived vaccine efficacy, given the nonspecificity of many symptoms of Covid-19.²⁴

Some contacts may have been infected by a source other than the identified “index patient”; this would attenuate associations between index-patient–related variables, including vaccination status, and the outcome. To minimize this effect, we restricted our study to contacts who had undergone testing 1 to 10 days after testing in an index patient, with very similar findings when the analysis was restricted to 2 to 7 days. Better data on symptom onset and the timing of exposures between patients and contacts could improve estimates.

In addition, we did not have sufficient data to account for previous infection status, which is also imperfectly ascertained in national testing programs. Increasing immunity arising from previous infection in the unvaccinated comparator group potentially reduces estimates of vaccine effectiveness over time; however, with adjustment for calendar time, previous infection can be allowed for at a population level, along with changes in test-seeking behavior and the incidence of other infections that cause symptoms that are similar to those of Covid-19.²⁵

We used S-gene target failure and time, rather than sequencing, as a proxy to distinguish infection with the alpha variant from that with the delta variant; thus, some low-viral-load delta variant infections with S-gene target failure may have been misclassified as alpha variant infections. However, we restricted the time period of our data set to minimize this effect. We considered all PCR tests in contacts, including results of assays without an S-gene target, so we could not assess the concordance of patient–contact S-gene target failure as evidence supporting transmission.

Finally, we did not have data to adjust for coexisting conditions in clinically vulnerable persons or for health care workers. Both of these groups were vaccinated earlier in the Covid-19 pandemic and were more likely to have had shorter dosing intervals than those who were vaccinated later. This lack of adjustment may have affected the findings, particularly on waning of vaccine protection over time and differences according to vaccine type; it also precluded analysis of the effect of the dosing interval.⁸

The delta variant has spread globally and caused resurgences of infection even in areas with high vaccination coverage. Increased onward transmission from persons who become infected despite vaccination is probably an important reason for this spread. Booster vaccination campaigns that are being considered and implemented²⁶ may help to control transmission as well as prevent infections.

Supported by the U.K. Government Department of Health and Social Care; the National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with Public Health England (NIHR200915); and the NIHR Biomedical Research Centre, Oxford. Dr. Eyre is a Robertson Foundation Fellow and an NIHR Oxford Biomedical Research Centre Senior Fellow; and Dr. Walker is an NIHR Senior Investigator.

The views expressed in this article are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health, or Public Health England.

Source: NEJM