The effect of vaccination-induced immunity on viral loads of the SARS-CoV-2 variant Omicron

In a recent study published in Nature Communicationresearchers analyzed nationwide vaccination data and cycle cut-off data from four laboratories in Israel that perform quantitative reverse transcription polymerase chain reaction (qRT-PCR) testing of respiratory syndrome coronavirus severe acute 2 (SARS-CoV-2) to determine the effect of vaccination-induced immunity on viral loads of the SARS-CoV-2 Omicron variant.

Study: Viral load dynamics of SARS-CoV-2 Delta and Omicron variants after multiple vaccine doses and prior infection. Image Credit: MedMoMedia/Shutterstock

Background

Vaccine efficacy testing typically involves measuring neutralizing antibody titers and examining the protective effects of immune responses against infection and severe symptoms. Viral transmissibility determined by viral load is often overlooked. However, viral load has important implications for public health initiatives. Cycle cut-off values ​​from qRT-PCR assays, which are negatively correlated with viral load, can be used to determine viral variant transmissibility and infectivity.

Despite full vaccination and booster regimens among much of the population, Israel has seen a resurgence of the SARS-CoV-2 Omicron variant, prompting the administration of a fourth booster dose to healthcare workers, the elderly population and those at high risk. However, while studies have examined the impact of vaccination-induced immunity on Delta variant viral loads, the efficacy of vaccines in reducing Omicron variant viral loads remains unexplored.

About the study

In the current study, researchers conducted a retrospective analysis using vaccination data and positive SARS-CoV-2 PCR test records, including cycle cutoff values ​​from four major Israeli laboratories in the Organization. of maintaining health. Multiple positive tests for the same individual over a 90-day period were considered a single infection.

Demographic information was combined with encrypted PCR test results and vaccination data to provide each patient’s vaccination status, cycle cutoff, age and gender. Patients were then grouped by vaccination status at infection event, with vaccination status at infection defined as unvaccinated, two doses with infection within 10–39, 40–69, or more than 70 days after second dose, three doses with infection within 10-39, 40-69 or more than 70 days after third dose, four doses and unvaccinated with prior SARS-CoV-2 infection.

The follow-up period was also divided according to the dominant variant of SARS-CoV-2, with the period from June 15 to December 1, 2021 being the period of dominance of the Delta variant, and from December 28, 2021 to January 29, 2022, being the period of Omicron dominance.

Multivariate linear regression analysis was performed for cycle cutoffs with vaccination status, age, gender, calendar time, and laboratory used as covariates. The analysis was also conducted separately for PCR assays that amplified the SARS-CoV-2 nucleocapsid gene and those that measured the envelope gene.

Results

The results indicated that while the vaccines reduced viral loads of the Omicron variant in the short term, the effect of the vaccine on cycle thresholds was not long lasting. In contrast, immunity induced by previous SARS-CoV-2 infections declined less slowly.

During Delta variant dominance, two doses of vaccine produced a three-fold decrease in viral loads compared to unvaccinated patients, but efficacy of the second dose declined by day 70, with cycle threshold values ​​of patients with two doses being the same as those of unvaccinated patients. The first booster dose (third vaccine) showed a similar trend, with cycle thresholds being high in the short term but decreasing by day 70.

Cycle cutoff values ​​for PCR testing during the Omicron period increased in response to a recent third dose of vaccine, but were not significantly different for unvaccinated, two-dose, and late three-dose patients. The results indicated that the effect of vaccination-induced immunity was weaker for the Omicron variant than for the Delta variant.

The analysis was conducted separately for elderly patients who received the fourth dose of vaccine. The results revealed an increase in cycle threshold values ​​for these patients, with values ​​comparable to those of patients who had already been infected with SARS-CoV-2 and significantly higher than those of unvaccinated patients. The fourth dose was found to be effective in the short term in reducing viral load.

conclusion

In summary, the study compared vaccination status to the cycle threshold values ​​of positive SARS-CoV-2 PCR tests of patients who had an infection during the dominance of the Delta and Omicron variants.

The results indicated that the immune effect of the vaccine on viral loads decreased by day 70 for the primary and booster doses. In comparison, immunity induced by previous SARS-CoV-2 infections waned much more slowly. A fourth booster dose showed significant protective effects and a reduction in viral load, with cycle threshold values ​​comparable to those of patients with previous infections.

While vaccinations have been extremely effective in reducing morbidity and mortality, the waning effect on reducing virus transmissibility necessitates a reassessment of vaccination campaigns.

Journal reference:

  • Woodbridge, Y. et al. (2022) “Viral load dynamics of SARS-CoV-2 Delta and Omicron variants after multiple vaccine doses and prior infection”, Nature Communication13(1). do I: 10.1038/s41467-022-33096-0.

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