Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant

Abstract

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

Fig. 1. Summary of the epidemiology and early detection of the Delta SARS-CoV-2 variant in Guangdong.

a Time series of 167 laboratory-confirmed infections originating from the first index case on 21 May 2021. Daily numbers of new infections are shown in red and samples with high-quality sequences (coverage >95%) are shown in blue. b The Delta variant transmission in the Guangzhou outbreak. The transmission relationship between 126 sequenced cases was indicated with solid lines (high confidence) or the dash lines (unsure). The interactive version could be found at https://viz.vslashr.com/guangdongcdc/. c Estimate of the time interval between exposure and time of the first PCR + test in quarantined individuals. The curves show the best-fitting distributions of the interval durations for Delta variant cases (n = 46) and for A/B clade cases (n = 29). Bars show the histograms of estimated intervals durations (days). d Two-tailed Wilcoxon signed-rank test P values (P < 0.001), showing significant changes in Ct (Cycle threshold) values of the first PCR + test in quarantined individuals, for the Delta variant infections (n = 62) and for previous A/B clade strains infections (n = 63). Dots represent Ct values for RT-PCR of the ORF1ab gene. Box plots indicate the median (middle line), 25th and 75th percentiles (box) and minimum and maximum value (whiskers). e Schematic of the relation between the viral growth rate and the relative viral loads on the day viruses were first detected (Day 0). The viral load on Day 0 was measured. The horizontal dashed line in purple represents the detection threshold of RT-PCR testing; the dashed line in red represents the lower limit above which infectious viruses could be potentially isolated. f Temporal profile of serial Ct value from quarantined individuals. Longitudinal PCR testing was performed on quarantined individuals (N = 46, overall and stratified by symptom status. The detection limit was Ct = 40. The thick lines show the trend in viral load, using smoothing splines. We only included data from the first PCR + test to the first PCR- test during the infection; the few re-positive tests were excluded (Supplementary data 1).

Fig. 2. Viral phylogenies and transmission dynamics of the Guangzhou outbreak.

a A time-resolved phylogenetic tree was estimated using the NextStrain pipeline and includes (i) Guangdong sequences collected from local infections and imported cases, January 2020–June 2021, and (ii) reference sequences from different genetic lineages. The sequences from the Guangdong Delta variant outbreak (21 May 2021–18 June 2021) are highlighted with a red box. The changing frequencies of SARS-CoV-2 lineages (according to pangolin classification scheme, https://github.com/cov-lineages/pangolin) identified in Guangdong (most of which are imported) are shown in the lower panel. b Maximum likelihood tree of 126 sampled sequences of the Guangzhou outbreak. The sequence of the first index case (XG5137_GZ_2021/5/21) was used as the reference. SNV frequencies (%) across the virus genome (numbering according to the reference) are marked with colored dots (right hand panel).

Fig. 3. Transmission bottleneck size and transmissions of intra-host variants in the outbreak.

a Estimated bottleneck size in donor-recipient transmission pairs (n = 29) was calculated using the exact beta-binomial method. Bars show mean and 95%CI, calculated using the likelihood ratio test. b Minor iSNVs transmission resulted in the diversity of viral population. The pie charts show the frequency of iSNVs. Arrows show the direction of transmission for those pairs of cases for which this is known with high confidence.