Characterization of COVID-19 Symptoms and Outcomes by Variant Period in the North Carolina COVID-19 Community Research Partnership (NC-CCRP)

Michael E DeWitt

Wake Forest University School of Medicine

Ashley H. Tjaden

George Washington University

David Herrington

Wake Forest University School of Medicine

John Schieffelin

Tulane University

Michael Gibbs

Atrium Health - Carolinas Medical Center

William S. Weintraub

Georgetown University University

MedStar Health Research Institute

John W. Sanders

Wake Forest University School of Medicine

Sharon L. Edelstein

George Washington University


Acknowledgements and Disclosures

The COVID-19 Community Research Partnership gratefully acknowledges the commitment and dedication of the study participants. Programmatic, laboratory, and technical support was provided by Vysnova Partners, Inc., Javara, Inc., Oracle Corporation, LabCorp, Scanwell Health, and Neoteryx. This presentation was supported by the CARES Act of the U.S. Department of Health and Human Services (HHS) [Contract # NC DHHS GTS #49927] and the Centers for Disease Control and Prevention (CDC) [contract #75D30120C08405]. The findings and conclusions in this report are those of the authors. We are grateful to the entire COVID-19 Community Research Partnership Study Group.


The evolution of SARS-CoV-2 during the COVID-19 pandemic has raised interest in the possibility of evolving disease presentation and associated severity since first reports of its emergence in December 20191, especially regarding likelihood of hospitalization.^2 We characterize the evolution of symptoms in those with self-reported SARS-CoV-2 infections and the likelihood of seeking treatment or medical care during different waves of the pandemic.


The NC-CCRP is an observational, longitudinal, multi-site surveillance study representing six healthcare systems in North Carolina. Brief daily electronic survey provided by text or email to obtain self-reported COVID-19 exposures, symptoms, test results, medical attention, receipt of vaccination, and risk behaviors. Demographic information was obtained at baseline.

Statistical methods: * Three variant periods defined: Pre-Delta, Delta, and Omicron (Figure 1).
* Duration of symptoms estimated using linear models adjusted for sex, vaccination, prior infection, and age.
* Calculated proportion of participants reporting each symptom and duration of symptoms.
* Logistic regression models estimated the likelihood of seeking treatment or requiring hospitalization. Estimated marginal mean odds ratios were constructed to examine pairwise differences.


Participants and infections (Table):

  • 37,820 participants provided daily symptom logs, April 2020 – April 2022
  • 5,480 self-reported COVID-19 infections
  • Self-reported re-infections increased from 0.4% during pre-Delta to 2.9% during Delta to 6.3% during Omicron (p<0.001)
  • Self-reported hospitalizations decreased from 4.4% of infections to 0.5% (p<0.001)

Symptoms (Figure 2B):

  • Cough: most frequent self-reported symptom in all waves and increased over time
  • Sore throat increased from 54% during pre-Delta to 62% during Delta to 71% during Omicron
  • The largest change in proportion reporting a symptom was loss of taste or smell which decreased from 55% during pre-Delta to 17% during Omicron (p<0.001)

Treatment (Figures 3A and 3B):

  • Participants more likely to seek treatment during Delta compared with pre-Delta (aOR 1.32 95% CI 1.06-1.64; p=0.014) or Omicron (aOR 1.42; 95% CI 1.21-1.67; p=0.006)
  • Participants much less likely to report hospitalization during Omicron compared with pre-Delta (aOR 0.26; 95% CI 0.10-0.59; p=0.003) or Delta (aOR 0.35; 95% CI 0.18-0.70; p<0.001)


Reduced rates of anosmia and dysgeusia, symptoms previously strongly correlated with pre-Delta infections, consistent with existing literature^3,4
Omicron variant was associated with less seeking treatment or hospitalization Evolution of symptomology to more classical upper-respiratory symptoms with shortened duration and lower rates of hospitalizations compared to Delta and Pre-Delta is consistent with observations of evolving SARS-CoV-2 pathogenesis in which Omicron is associated with lower rates of syncytium formation due to mutations in the spike region associated with use of TMPRSS2^5 Strengths: Prospective, daily logs provide a high degree of clarity into symptoms likely to be associated with infection. Similarly, this study captures symptoms among those who may have had a mild infection and not sought treatment (and thus not be captured in EHR retrospective analysis) Limitations: limited demographic representation and high rates of vaccination in the study cohort


Significant differences in symptom presentation, duration, and risk of hospitalization were detected across the pandemic indicating that continued longitudinal syndromic surveillance could be an important component in measuring disease presentation, outcomes, and prevalence. As the immune landscape changes through vaccination and (re-)infection, understanding breakthrough rates, symptomology and clinical presentation will remain important to distinguish it from other viral infections and provide insight into evolving pathology.


Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5

Twohig KA, Nyberg T, Zaidi A, et al. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study. The Lancet Infectious Diseases. 2021;0(0). doi:10.1016/S1473-3099(21)00475-8

Menni C, Valdes A, Freydin MB, et al. Loss of Smell and Taste in Combination with Other Symptoms Is a Strong Predictor of COVID-19 Infection. Epidemiology; 2020. doi:10.1101/2020.04.05.200484212.

Menni C, Valdes AM, Polidori L, et al. Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study. The Lancet. Published online April 7, 2022. doi:10.1016/S0140-6736(22)00327-0

Meng B, Abdullahi A, Ferreira IATM, et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature. 2022;603(7902):706-714. doi:10.1038/s41586-022-04474-x