One of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual's protection but can reduce transmission.

No abstract

1Mutations fuel evolution and facilitate adaptation to novel environments. However, 2 characterizing the spectrum of mutations in a population is obscured by high error rates of next 3 generation sequencing. Here, we present AccuNGS, a novel in vivo sequencing approach that 4 detects variants as rare as 1:10,000. Applying it to 46 clinical samples taken from early infections 5 of the human-infecting viruses HIV, RSV and CMV, revealed large differences in within-host 6 genetic diversity among virus populations. Haplotype reconstruction revealed that increased 7 diversity was mostly driven by multiple transmitted/founder viruses in HIV and CMV samples. 8Conversely, we detected an abundance of defective virus genomes (DVGs) in RSV samples, 9including hyper-edited genomes, nonsense mutations and single point deletions. Higher 10 proportions of DVGs correlated with increased viral loads, suggesting increased cellular co-11 infection rates, which enable DVG persistence. AccuNGS establishes a general platform that 12 allows detecting DVGs, and in general, rare variants that drive evolution. 13 2016; Wang, et al. 2017); error reduction by overlapping paired reads in paired-end sequencing 46 (Chen-Harris, et al. 2013;Schirmer, et al. 2015;Preston, et al. 2016); and usage of improved 47 polymerases (Imashimizu, et al. 2013). However, most experimental methods described above 48 are designed for samples with high biomass and are inapplicable for sequencing of clinical 49 samples, where the biomass may be extremely low. Furthermore, these experimental protocols 50 may introduce their own artifacts to the sequencing process (Lou, et al. 2013; Brodin, et al. 51 2015). On the computational side, it has been suggested that well-established variant callers do 52 not perform well on clinical virus samples (McCrone and Lauring 2016). Here, we sought to 53 develop a simple and rapid approach that can tackle the problem of accurate sequencing of 54 clinical samples, and applied it to study the early stages of virus infection. 55We describe AccuNGS, a simple yet powerful approach for accurate population sequencing and 56 bioinformatics variant calling. We extensively optimize all stages of the method to ensure high 57 accuracy and maximal yield. We use AccuNGS to perform in-depth sequencing of 46 samples 58 from three different major human pathogenic viruses: human immunodeficiency virus (HIV), 59 respiratory syncytial virus (RSV), and cytomegalovirus (CMV), all sampled during the acute 60 infection stage. We compare the within-host genetic diversity among and within different virus 61 populations, and find patterns characteristic of each virus. We demonstrate the role of multiple 62 transmitted/founder viruses as major contributors to the genetic diversity in HIV and CMV. 63 Furthermore, we identify and quantify the impact of various host editing enzymes on the 64 mutational spectrum of viral genomes/populations in vivo. Intriguingly, we find that RSV 65 samples bear much higher levels of potentially defective virus genome (DVGs) ...