Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA

Abstract

While SARS-CoV-2 vaccines have shown strong efficacy, their suboptimal uptake combined with the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no difference in disease severity between individuals infected with Delta and Omicron variants among the participants in this study, after controlling for other factors, and we found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within 270 days before infection was associated with decreased odds of moderate and severe outcomes, with the strongest association observed at 91-270 days post-vaccination. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Keywords: SARS-CoV-2; disease severity; post-vaccine infection.

Figure 1.. COVID-19 cases from May 2021-May 2022 in Georgia, US.

A. 1,957 Emory Healthcare COVID-19 case mapped by counties in and around Atlanta, GA. B. Percent of population fully vaccinated against SARS-CoV-2 by May 2022 in each state in the United States. Red line represents national average (66.7%). Red bar represents Georgia. C. Proportion of variants circulating in Georgia from April 2021- June 2022. Sequences obtained from GISAID.

Figure 2.. Frequencies of single nucleotide polymorphisms (SNPs) among SARS-COV-2 genome sequences from vaccinated and unvaccinated individuals.

Each point represents a single SNP plotted by its frequency in sequences from unvaccinated individuals (Y-axis) versus its frequency in sequences from vaccinated individuals (X-axis). Data is divided by WHO variant classifications Alpha (A), Delta (B), and Omicron (C). Mutations observed along the diagonal depict mutations observed equally among vaccinated and unvaccinated individuals. Mutations observed moving away from the diagonal represent mutations observed in either vaccinated (X-axis) or unvaccinated (Y-axis) individuals. (D) Frequency of SNPs in SARS-CoV-2 sequences from unvaccinated (top) and vaccinated (bottom) individuals, by genome position (x-axis). In all panels, Alpha is represented by yellow circles, Delta by blue squares, and Omicron by red triangles.