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

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.

Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020. This is a retrospective analysis of serological data, showing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli health care workers receiving BNT162b2. Sero-conversion occurred in 14 days in all study participants, with IgG levels peaking approximately 30 days after initiation of the vaccination series. A statistically significant difference was observed in IgG levels between subjects younger than 50 years and older participants, although in all cases, IgG levels were well above the level considered reactive by the test's manufacturer. The importance of this difference needs to be studied further, but a potential difference in vaccine efficacy and vaccine effect length could possibly be present between these two groups.

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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.

BACKGROUND Cytomegalovirus (CMV) is the most common intrauterine infection, leading to infant brain damage. Prognostic assessment of CMV-infected fetuses has remained an ongoing challenge in prenatal care, in the absence of established prenatal biomarkers of congenital CMV (cCMV) infection severity. We aimed to identify prognostic biomarkers of cCMV-related fetal brain injury. METHODS We performed global proteome analysis of mid-gestation amniotic fluid samples, comparing amniotic fluid of fetuses with severe cCMV with that of asymptomatic CMV-infected fetuses. The levels of selected differentially excreted proteins were further determined by specific immunoassays. RESULTS Using unbiased proteome analysis in a discovery cohort, we identified amniotic fluid proteins related to inflammation and neurological disease pathways, which demonstrated distinct abundance in fetuses with severe cCMV. Amniotic fluid levels of 2 of these proteins — the immunomodulatory proteins retinoic acid receptor responder 2 (chemerin) and galectin-3–binding protein (Gal-3BP) — were highly predictive of the severity of cCMV in an independent validation cohort, differentiating between fetuses with severe ( n = 17) and asymptomatic ( n = 26) cCMV, with 100%–93.8% positive predictive value, and 92.9%–92.6% negative predictive value (for chemerin and Gal-3BP, respectively). CONCLUSION Analysis of chemerin and Gal-3BP levels in mid-gestation amniotic fluids could be used in the clinical setting to profoundly improve the prognostic assessment of CMV-infected fetuses. FUNDING Israel Science Foundation (530/18 and IPMP 3432/19); Research Fund – Hadassah Medical Organization.

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Accurate subtyping of hepatitis C virus genotype 1 (HCV-1) remains clinically and epidemiologically relevant. The Abbott HCV Genotype Plus RUO (GT Plus ) assay, targeting the core region, was evaluated as a reflex test to resolve ambiguous HCV-1 results in a challenging sample collection. 198 HCV-1 specimens were analysed with GT Plus (38 specimens with and 160 without subtype assigned by the Abbott RealTi me Genotype II (GT II) assay targeting the 5’NC and NS5B regions). Sanger sequencing of the core and/or NS5B regions were performed in 127 specimens without subtype assignment by GT II, with “not detected” results by GT Plus , or with mixed genotypes/subtypes. The remaining GT Plus results were compared to LiPA 2.0 ( n = 45) or just to GT II results if concordant ( n = 26). GT Plus successfully assigned the subtype in 142/160 (88.8%) samples. “Not detected” results indicated other HCV-1 subtypes/genotypes or mismatches in the core region in subtype 1b. The subtyping concordance between GT Plus and either sequencing or LiPA was 98.6% (140/142). Therefore, combined use of GT II and GT Plus assays represents a reliable and simple approach which considerably reduced the number of ambiguous HCV-1 results and enabled a successful subtyping of 98.9% of all HCV-1 samples.