Duration of viral shedding and culture positivity with postvaccination SARS-CoV-2 delta variant infections

Abstract

Isolation guidelines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are largely derived from data collected prior to the emergence of the delta variant. We followed a cohort of ambulatory patients with postvaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole-genome sequencing, and viral culture. All delta variant infections in our cohort were symptomatic, compared with 64% of non-delta variant infections. Symptomatic delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR, greater likelihood of replication-competent virus at early stages of infection, and longer duration of culturable virus compared with non-delta variants. The duration of time since vaccination was also correlated with both duration of PCR positivity and duration of detection of replication-competent virus. Nonetheless, no individuals with symptomatic delta variant infections had replication-competent virus by day 10 after symptom onset or 24 hours after resolution of symptoms. These data support US CDC isolation guidelines as of November 2021, which recommend isolation for 10 days or until symptom resolution and reinforce the importance of prompt testing and isolation among symptomatic individuals with delta breakthrough infections. Additional data are needed to evaluate these relationships among asymptomatic and more severe delta variant breakthrough infections.

Keywords: COVID-19; Epidemiology; Infectious disease.

Figure 1. Viral load decay curve in individuals with postvaccination breakthrough SARS-CoV-2 non-delta and delta variant infections.

Trajectory of viral load by PCR from time of index positive test for each study participant with non-delta variant (n = 14) (A) and delta variant (n = 8) (B) PCR-confirmed SARS-CoV-2 infection. Each connected solid line represents a participant. The dashed lines represent the total population mean line of fit derived from a regression equation, including quadratic and cubic terms. The dotted line represents a similar line of fit, but restricted to individuals who remained positive at day 3. Time points denoted with asterisks were viral culture positive.

Figure 2. Kaplan-Meier survival curves demonstrating days from first positive PCR (or from symptom onset if earlier) to negative SARS-CoV-2 viral load and negative culture positivity among the entire sample.

Survival curves for days to undetectable SARS-CoV-2 viral load (A) and viral culture (B) stratified by variant, and survival curves for days to undetectable SARS-CoV-2 viral load (C) and viral culture (D) stratified by duration since completion of COVID-19 vaccination. Observation time begins at the date of positive PCR for asymptomatic cases and date of symptom onset for symptomatic cases.

Figure 3. Scatter plots demonstrating the relationship between days since completion of COVID-19 vaccination and duration of SARS-CoV-2 PCR and culture positivity.

(A) The relationship with duration of PCR positivity, and (B) the relationship for duration of culture positivity. Each point on the graph indicates an individual with postvaccination breakthrough COVID-19 infection (n = 24). Vaccines received are indicated by plot labels as Moderna (M), Pfizer/BioNTech (P), or Johnson & Johnson/Janssen (J). Black solid lines indicated the line of best fit from linear regression models, whereas the gray shaded areas indicate the 95% CI around this estimate. R² and P values are estimates from these models. Green triangles indicate delta variant infections, whereas blue diamonds represent non-delta variant infections.

Figure 4. Kaplan-Meier survival curves demonstrating days from first symptom to negative SARS-CoV-2 viral load and negative culture positivity, restricted to the subsample with symptomatic infection.

Survival curves for days to undetectable SARS-CoV-2 viral load (A) and viral culture (B) stratified by variant, and survival curves for days to undetectable SARS-CoV-2 viral load (C) and viral culture (D) stratified by duration since completion of COVID-19 vaccination.