Recent studies have indicated that the delta variant is associated with increased viral loads, implying enhanced infectivity of this variant3, 4, 5. Nevertheless, the limited size of datasets used in these studies as well as the different diagnostic methods could lead to bias and preliminary conclusions with regards to the viral load and infectivity that is associated with the delta variant. In this study we have compared the CT-values and viral load obtained from samples that were tested positive during the time periods during which the non-VOC, alpha and delta variants were dominant, as evidenced by genomic surveillance of SARS-CoV-2 in the South Limburg region of The Netherlands. It was found that samples that were tested positive since the delta variant became dominant contained significantly higher loads of SARS-CoV-2 compared to samples that were tested during which the non-VOC or alpha variant were dominant. Based on the standard curve used for conversion of CT values to viral loads (Figure S1A), it is estimated that samples harboring the delta variant contain about 4-fold higher loads of SARS-CoV-2 compared to samples harboring non-VOC or the alpha variant. These observations were confirmed using a subset of WGS-confirmed samples in which samples containing the delta variant harbored significantly higher loads of SARS-CoV-2 compared to their non-VOC (about 7-fold) or alpha variant (about 4-fold) counterparts. It has to be noted that the delta variant became dominant at the moment that > 60% of the population received at least one dose and > 35% of the total population was fully vaccinated in The Netherlands, leaving open the possibility that the observed differences in viral load might even be more pronounced in non-vaccinated individuals. Interestingly, when using WGS-confirmed data, which consists of samples < CT30, a significantly higher load was observed for samples harboring the alpha variant compared to the non-VOC variant. When performing the same analysis by only including samples < CT30 for non-WGS confirmed samples, there was also a moderate increased viral load observed for samples obtained during the period during which the alpha variant was dominant versus samples collected during the non-VOC period. Recently, it was reported that samples from people who are infected with the delta variant harbor up to 1000 times higher viral loads than people infected with the clade 19A/19B viruses4. We did not observe such differences compared to the non-VOC or alpha variant, neither in CT value, nor in estimated viral load. Nevertheless, it has to be noted that the former study4 comprised a much smaller dataset (62 samples harboring delta variant vs 63 samples harboring clade 19A/19B isolates) which was part of an outbreak, used a different RNA isolation method and PCR assay and compared the delta variant to a mixture of samples harboring nextstrain clade 19A/19B variants, which did not harbor the D614G mutation that enhances infectivity 9, 10, 11 and were much closer related to the original Wuhan strain than the non-VOC isolates in our study. One of the strengths of this study is the large dataset of samples of which the great majority was tested using the same or a highly comparable workflow (Figure S1). Furthermore, follow-up samples obtained from the same subject were filtered out of the dataset as much as possible, to avoid bias. Finally, extensive genomic surveillance in the region allowed us to accurately estimate the dominant period for each variant as WGS of a subset of samples confirmed the observed trends. Limitations of this study can be found in the fact that the available dataset of the delta variant is still limited in size compared to the other datasets and the fact that the non-VOC group consists of many different pangolin lineages.
In conclusion, our study shows that samples from individuals that are infected with the delta variant harbor about 4-fold higher loads of SARS-CoV-2 compared to individuals that are infected with non-VOC or the Alpha variant, which is significantly lower than previously reported4.