Beyond their substantial protection of individual vaccinees, coronavirus disease 2019 (COVID-19) vaccines might reduce viral load in breakthrough infection and thereby further suppress onward transmission. In this analysis of a real-world dataset of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results after inoculation with the BNT162b2 messenger RNA vaccine, we found that the viral load was substantially reduced for infections occurring 12-37 d after the first dose of vaccine. These reduced viral loads hint at a potentially lower infectiousness, further contributing to vaccine effect on virus spread.The recently authorized BNT162b2 Coronavirus Disease 2019 (COVID-19) messenger RNA (mRNA) vaccine is approximately 95% efficient in preventing polymerase chain reaction (PCR)-confirmed symptomatic disease from 7 d after the second dose and also provides some early protection starting 12 d after the first dose 1,2 . As countries race to vaccinate a substantial portion of their populations in the coming months, it is hoped that the basic reproduction number of the virus will decrease. This effect can be achieved by reducing the number of susceptible people, as well as by reducing viral load and, thereby, viral shedding of post-vaccination infections, which might render them less infectious [3][4][5][6][7] . However, the effect of vaccination on viral load in COVID-19 post-vaccination infections is currently unknown 8 .As of February 11, 2021, Maccabi Healthcare Services (MHS) in Israel has vaccinated more than 1 million of its members as part of a national rapid rollout of the vaccine. MHS member SARS-CoV-2 tests are often carried out in the MHS central laboratory, which offers the opportunity to track post-vaccination infections. In this study, we retrospectively collected and analyzed the quantitative reverse transcription PCR (RT-qPCR) test measurements of three SARS-CoV-2 genes-E, N and RdRp (Allplex 2019-nCoV assay, Seegene)-from positive post-vaccination tests performed at the MHS central laboratory between December 21, 2020, and February 11, 2021 (n = 4,938 patients, study population; Table 1). The study period was characterized by high and steady rates of positive COVID-19 tests (Extended Data Fig. 1), indicating an ongoing epidemic wave.In an analysis of the infection cycle threshold (Ct) over time, we found that the mean viral load substantially decreased 12 d after vaccination with the first vaccine dose, coinciding with the known early onset of vaccine-mediated protection 1 . When we calculated the mean Ct for post-vaccination infections identified on each day

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Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we find that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increases by 2.7 [CI: 2.3-3.0] relative to unvaccinated in the first month post the booster dose, yet then decays to a difference of 1.3 [CI: 0.7-1.9] in the second month and becomes small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster’s effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus.

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we found that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increased by 2.7 [CI: 2.3-3.0] relative to unvaccinated in the first month post the booster dose, yet then decayed to a difference of 1.3 [CI: 0.7-1.9] in the second month and became small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster's effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus.

The BNT162b2 vaccine showed high real-life effectiveness both at preventing disease and in reducing viral loads of breakthrough infections, but coincidental with the rise of the Delta-variant SARS-CoV2, these protective effects have been decreasing, prompting a third, booster, vaccine inoculation. Here, analyzing viral loads of over 11,000 infections during the current wave in Israel, we find that even though this wave is dominated by the Delta-variant, breakthrough infections in recently vaccinated patients, still within 2 months post their second vaccine inoculation, do have lower viral loads compared to unvaccinated patients, with the extent of viral load reduction similar to pre-Delta breakthrough observations. Yet, this infectiousness protection starts diminishing for patients two months post vaccination and ultimately vanishes for patients 6 months or longer post vaccination. Encouragingly, we find that this diminishing vaccine effectiveness on breakthrough infection viral loads is restored following the booster vaccine. These results suggest that the vaccine is initially effective in reducing infectiousness of breakthrough infections even with the Delta variant, and that while this protectiveness effect declines with time it can be restored, at least temporarily, with a booster vaccine.

Background Routine testing for SARS-CoV-2 in the community is essential for guiding key epidemiological decisions from the quarantine of individual patients to enrolling regional and national preventive measures. Yet, the primary testing tool, the RT-qPCR based testing, is notoriously known for its low sensitivity, i.e. high risk of missed detection of carriers. Quantifying the false-negative rate (FNR) of the RT-qPCR test at the community settings and its dependence on patient demographic and disease progression is therefore key in designing and refining strategies for disease spread prevention. Methods Analyzing 843,917 test results of 521,696 patients, we identified false-negative (FN) and true-positive (TP) results as negative and positive results preceded by a COVID-19 diagnosis and followed by a later positive test. Regression analyses were used to determine associations of false-negative results with time of sampling after diagnosis, patient demographics and viral loads based on RT-qPCR Ct values of the next positive tests. Findings The overall FNR was 22.8%, which is consistent with previous studies. Yet, this rate was much lower at the first 5 days following diagnosis (10.7%) and only increased in later dates. Furthermore, the FNR was strongly associated with demographics, with odds ratio of 1.74 (95% CI: 1.58-1.9) for women over men and 2.54 (95% CI: 2.39-2.69) for a 20 versus a 50 year old patient. Finally, FNR was associated with viral loads (p-value 0.002), with a difference of 1.1 (95% CI: 0.60-1.57) between the average Ct of the N gene in a positive test following a false-negative compared to a positive test following a true-positive. Interpretation Our results show that in the first few days following diagnosis, when results are critical for quarantine decisions, RT-qPCR testing is more reliable than previously reported. Yet the reliability of the test result is reduced in later days as well as for women and younger patients, where the viral loads are typically lower. Funding This research was supported by the ISRAEL SCIENCE FOUNDATION (grant No. 3633/19) within the KillCorona-Curbing Coronavirus Research Program.

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