In a recent study published in Nature Communications, researchers analyzed nationwide vaccination data and cycle threshold value data from four laboratories in Israel that conduct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quantitative reverse transcription polymerase chain reaction (qRT-PCR) tests to determine the effect of vaccination-induced immunity on the viral loads of the SARS-CoV-2 Omicron variant.
Vaccine efficacy testing generally involves measuring the neutralizing antibody titers and examining the protective effects of the immune responses against infection and severe symptoms. The transmissibility of the virus determined by the viral load is often overlooked. However, the viral load has important implications for public health initiatives. The cycle threshold values of qRT-PCR tests, which are negatively correlated to the viral load, can be used to determine the transmissibility and infectiousness of the viral variant.
Despite complete vaccination and booster regimens among a large portion of the population, Israel experienced a resurgence of the SARS-CoV-2 Omicron variant, prompting the administration of a fourth booster dose to healthcare workers, the elderly population, and high-risk individuals. However, while studies have examined the impact of vaccination-induced immunity on viral loads of the Delta variant, the efficacy of vaccines in reducing viral loads of the Omicron variant remains unexplored.
About the study
In the present study, the researchers conducted a retrospective analysis using vaccination data and records of positive SARS-CoV-2 PCR tests, including the cycle threshold values from four major Israeli Health Maintenance Organization laboratories. Multiple positive tests for the same individual within a span of 90 days 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 threshold value, age, and sex. The patients were then grouped according to the vaccination status during the infection event, with the vaccination status during infection being defined as unvaccinated, two doses with an infection within 10–39, 40–69, or more than 70 days after the second dose, three doses with an infection within 10–39, 40–69, or more than 70 days after the third dose, four doses, and unvaccinated with previous SARS-CoV-2 infection.
The follow-up period was also divided based on the dominant SARS-CoV-2 variant, with June 15 to December 1, 2021, being the period of dominance for the Delta variant, and December 28, 2021, to January 29, 2022, being the Omicron dominance period.
A multivariate linear regression analysis was conducted for the cycle threshold values with vaccination status, age, sex, calendar time, and laboratory used as covariates. The analysis was also conducted separately for PCR tests that amplified the SARS-CoV-2 nucleocapsid gene and those that measured the envelope gene.
The results reported that while vaccines reduced the viral loads of the Omicron variant in the short term, the effect of the vaccine on cycle threshold values was not long-lived. In contrast, the immunity induced by previous SARS-CoV-2 infections was seen to wane less slowly.
During the dominance of the Delta variant, two vaccine doses were seen to produce a threefold decrease in the viral loads as compared to unvaccinated patients, but the efficacy of the second dose was seen to wane by day 70, with cycle threshold values of patients with two doses being the same as those of unvaccinated patients. The first booster (third vaccine) dose showed a similar trend, with cycle threshold values being high in the short term but waning by day 70.
The cycle threshold values for PCR tests during the Omicron period were seen to increase in response to a recent third vaccine dose but were not significantly different for the unvaccinated, two-dose, and late three-dose group patients. The results indicated that the effect of the vaccination-induced immunity was lower for the Omicron variant than for the Delta variant.
The analysis was conducted separately for elderly patients who received the fourth vaccine dose. The results revealed an increase in cycle threshold values for these patients, with values comparable to those of patients with previous SARS-CoV-2 infections and significantly higher than those of unvaccinated patients. The fourth dose was considered effective in the short term for reducing the viral load.
To summarize, the study compared vaccination status with 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 waned by day 70 for the primary and booster doses. In comparison, the immunity induced by previous SARS-CoV-2 infections was seen to wane significantly slower. A fourth booster dose showed significant protective effects and a decrease in viral load, with cycle threshold values comparable to those for patients with previous infections.
While vaccinations have been tremendously effective in reducing morbidity and mortality, the waning effect on reducing the transmissibility of the virus necessitates a reassessment of vaccination campaigns.
- Woodbridge, Y. et al. (2022) "Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection", Nature Communications, 13(1). doi: 10.1038/s41467-022-33096-0.