Signatures of rising SARS-CoV-2 Delta infections in New York

By Susha Cheriyedath, M.Sc.Reviewed by Benedette Cuffari, M.Sc.Dec 15 2021

In a recent study published on the medRxiv* preprint server, researchers determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic makeup in fully vaccinated individuals from New York University Langone Health (NYULH). The researchers also estimated the probability of breakthrough infections by the Delta variant as compared to other variants.

Study: Clinical and genomic signatures of rising SARS-CoV-2 Delta breakthrough infections in New York. Image Credit: Corona Borealis Studio / Shutterstock.com

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

In late December 2020, the United States initiated the coronavirus disease 2019 (COVID-19) vaccination program with two messenger ribonucleic acid (mRNA)-based vaccines including the BNT162b2 Pfizer and mRNA-1273 Moderna vaccines, as well as one adenovirus vaccine by Johnson & Johnson.

Despite the vaccination program, the emergence of the SARS-CoV-2 Delta variant in 2021 highly dominated the pandemic and, along with waning immunity, resulted in reduced effectiveness of vaccines in the U.S. from 91% to 66%. These factors also contributed to an increasing number of breakthrough infections reported among fully vaccinated individuals.

About the study

The present study analyzed reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections in vaccinated and unvaccinated individuals between May 1, 2021, and August 3, 2021, in the NYULH system.

A total of 1,613 cases of SARS-CoV-2 infection were recorded during the study period, 82% of which were reported in unvaccinated individuals, and 18% were recorded in vaccinated individuals. The researchers obtained high-quality SARS-CoV-2 sequences from 283 unvaccinated and 132 vaccinated individuals.  

Study findings

Demographic analysis showed that the median age in the vaccinated group was 37 years and 42 years in the unvaccinated group, with similar gender distribution in both the groups. The researchers compared clinical and demographic predictors between different variants and found that among the breakthrough group, more than 45% of individuals were asymptomatic and 6% of individuals were hospitalized, all of whom aged more than 50 years and had comorbidities.

Hospitalization rates were significantly higher in the unvaccinated group at 29%, among which the majority were due to COVID-19. Ten individuals required intensive care unit admission (ICU) and seven died due to SARS-CoV-2 infection.

Hospitalizations associated with the Delta variant were significantly lower than those due to the Alpha, Gamma, Iota, and other variants. The death rate recorded was highest for the Alpha variant with four deaths (5.9%), whereas that for the Delta variant was one (0.7%). Delta variant infection was mostly found in younger individuals.

Relationship of clinical, demographic, and genomic data.

Phylogenetic analysis of the SARS-CoV-2 genomes, with respect to the U.S. and global reference sequence, showed that SARS-CoV-2 genomes of the present study covered a wide set of variants with the prevalence of Delta and other variants including the Alpha, Gamma, Iota, Mu, and additional B.1 lineages.

The Delta sequences were more densely packed and had clusters, among which one consisted of the Delta sub-variant AY.25, which had emerged recently and includes spike mutation S112L sequences. Breakthrough infections by the Delta variant were more frequent during the study period, primarily due to B.1.617.2 and AY.25 mutation.

During the initial period of the study, the most reported SARS-CoV-2 cases belonged to the Alpha, Gamma, and Iota variants. Thereafter, at the beginning of June 2021, COVID-19 cases were surprisingly low, which suddenly increased rapidly in late June with the arrival of the Delta variant.

Taken together, the current study reports that the Delta variant had affected unvaccinated and vaccinated individuals comparably. By the end of the study period, the Delta variant had almost fully replaced Alpha, Gamma, and Iota variants.

Conclusions

The researchers investigated the role of genomic mutations and potential sites for the adaptive evolution of the Delta variant in breakthrough infections. The results showed that breakthrough sequences had an average of 35.8 base pair mutations over the full genome and 9.7 amino acid mutations per spike, whereas the unvaccinated group showed an average of 35.6 base pair mutations over the full genome and 9.6 amino acid mutations per spike.

As compared to the Wuhan-Hu-1 wild-type strain of SARS-CoV-2, 168 amino acid changes were identified, among which 115 spike sites in the unvaccinated group and 52 sites in breakthroughs were highly mutated. Besides spike mutation S112L, the F192V mutation in nsp12 and the RNA-dependent RNA polymerase (RdRp) gene were enriched in breakthrough sequences in comparison to unvaccinated controls.

Genomic region-specific mutation analysis revealed that within unvaccinated control sequences, most coding regions had high numbers of mutations. However, in breakthrough sequences, ORF3a (56%) and ORF8 (67%) had higher numbers of sites with enriched mutations.

The researchers merged the present study results with previous study data from 208 breakthrough infections and 1,329 control sequences between February and April 2021. To this end, they found that the pattern of total COVID-19 case numbers over time is comparable to their SARS-CoV-2 sequences in New York State and supports their initiative of sequencing these SARS-CoV-2 emerging variants.

The increase in vaccination rates led to an overall decline in COVID-19 cases. While breakthrough infections by the Iota variant reduced significantly with increasing vaccination, Alpha variant breakthrough infections showed no significant decrease.

Delta variant breakthrough infections showed a significant increase in May 2021 and further increased in a near-linear fashion, both absolute and relative counts. Delta variant infection rates were almost similar in vaccinated and vaccinated individuals.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources