Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Is vitamin D binding protein a novel predictor of labour?

Vitamin D binding protein (VDBP) has previously been identified in the amniotic fluid and cervicovaginal fluid (CVF) of pregnant women. The biological functions of VDBP include acting as a carrier protein for vitamin D metabolites, the clearance of actin that is released during tissue injury and the augmentation of the pro-inflammatory response. This longitudinal observational study was conducted on 221 healthy pregnant women who spontaneously laboured and delivered either at term or preterm. Serial CVF samples were collected and VDBP was measured by ELISA. Binary logistic regression analysis was performed to assess the utility of VDBP as a predictor of labour. VDBP in the CVF did not change between 20 and 35 weeks' gestation. VDBP measured in-labour was significantly increased 4.2 to 7.4-fold compared to 4-7, 8-14 and 15-28 days before labour (P<0.05). VDBP concentration was 4.3-fold significantly higher at 0-3 days compared to 15-28 days pre-labour (P<0.05). The efficacy of VDBP to predict spontaneous labour onset within 3 days provided a positive and negative predictive value of 82.8% and 95.3% respectively (area under receiver operator characteristic curve  = 0.974). This longitudinal study of pregnant women suggests that VDBP in the CVF may be a useful predictor of labour

Efficacy of VDBP to predict spontaneous labour onset (N = 141 women; 392 samples).

<p>Efficacy of VDBP to predict spontaneous labour onset (N = 141 women; 392 samples).</p

ROC curves of VDBP to predict labour onset within 3, 7 and 14 days.

<p>Subjects who provided two or more samples were included in the analysis (N = 392), with the subject entered as a categorical factor in the model. Area under the curves were 0.974 at ≤3 days; 0.943 at ≤7 days; and 0.934 at ≤14 days prior to spontaneous labour onset. Optimal predictive utility was obtained at ≤3 days from spontaneous labour.</p

The effect of sexual intercourse and vaginal microbiology status on VDBP concentration.

<p>(A) Unprotected sexual intercourse within 48 h of CVF collection did not affect the VDBP concentration in women who delivered either term (<i>P</i> = 0.237) or preterm (<i>P</i> = 0.406, 2-way ANOVA). (B) The microbiology status of women with subsequent preterm or term labour did not affect the VDBP concentration. Within each labour group, VDBP was not significantly different between women with normal vaginal flora, Group B Streptococcus (GBS) colonisation, <i>Candida</i> spp. colonisation, <i>Ureaplasma</i> spp. colonisation, and women with mixed colonisation (Term: <i>P</i> = 0.478, Preterm: <i>P</i> = 0.557; 2-way ANOVA). The box and whisker plots represent the median and interquartile range with the 5^th and 95^th centile range. Outliers are represented by open circles.</p

Demographic and clinical data of participants in the study (N = 221 women).

<p><i>Values are presented as mean ± SD</i></p

Flow Diagram illustrating the pool of 221 women recruited in the two arms of the study.

<p>Eight subanalyses of VDBP expression in the CVF were performed and the number of samples utilised is indicated.</p

The VDBP concentration in the CVF significantly increased with advancing gestational age.

<p>The * indicates significance in the VDBP concentration in gestational groups ≤30–31 weeks' compared with CVF samples collected ≥36 weeks' gestation. The † indicates significance in VDBP concentration between samples collected at 36 and 37 weeks' gestation compared with samples collected at 40 and 41 weeks' gestation. Statistical significance was defined as <i>P</i><0.05 (2-way ANOVA). The box and whisker plots represent the median and interquartile range with the 5^th and 95^th centile range. Outliers are represented by open circles.</p

The comparison of VDBP concentration between singleton and twin pregnancies.

<p>VDBP was not significantly different between singleton and twin gestation in-labour (<i>P</i> = 1.000), 0–7 days (<i>P</i> = 0.997), 8–14 days (<i>P</i> = 1.000), 15–21 days (<i>P</i> = 0.750), 22–28 days (<i>P</i> = 0.999), and >28 days (<i>P</i> = 1.000) before labour onset (2-way ANOVA). The box and whisker plot represents the median and interquartile range with the 5^th and 95^th centile range. Outliers are represented by open circles.</p

The VDBP concentration in the CVF significantly increased with approaching spontaneous term labour onset.

<p>The * indicates a significant difference in VDBP concentration in the CVF between the in-labour group and groups ≥4 days from labour. The † indicates a significant difference between the 0–3 day group versus groups ≥15 days from labour onset. The ‡ indicates a significant difference between the 4–7 day group versus groups ≥15 days from labour onset. The § indicates a significant difference between the 8–14 day group versus groups ≥29 days from labour onset. The ¤ indicates a significant difference between the 15–28 day group versus groups ≥29 days from labour onset. Statistical significance was defined as <i>P</i><0.05 (2-way ANOVA). The box and whisker plots represent the median and interquartile range with the 5^th and 95^th centile range. Outliers are represented by open circles.</p