Duration of secretion of culturable virus in SARS-CoV-2 Omicron (BA.1) infection

To the editors:

The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a shorter incubation time and a higher transmission rate than previous variants.^1.2 Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected individuals in non-healthcare settings from 10 days to 5 days after the onset of symptoms or after the first positive test, followed by 5 days of masking.³ However, the viral decay kinetics of the omicron variant and the duration of culturing virus shedding are not well characterized.

We used longitudinal sampling of nasal swabs to determine viral load, sequencing, and viral culture in outpatients with newly diagnosed 2019 (Covid-19) coronavirus disease.⁴ From July 2021 through January 2022, we enrolled 66 participants, including 32 with samples sequenced and identified as the B.1.617.2 (delta) variant and 34 with samples sequenced and identified as the omicron -sub variant BA.1, including from underlines. Participants who received Covid-19-specific therapies were excluded; All but 1 participants had a symptomatic infection. This study was approved by the Institutional Review Board and Institutional Biosafety Committee of Mass General Brigham, and informed consent was obtained from all participants.

Figure 1. Figure 1. Viral decay and time for negative viral culture.

Panel A shows the viral load decay from the time of the first positive polymerase chain reaction (PCR) test. Viral loads from nasal swabs obtained from individual participants are shown. Each circle or triangle represents a sample obtained on the specified day. The median viral load at each time point for each variant is also shown. LOD indicates the detection limit. Panels B through E show Kaplan-Meier survival curves for the time from an initial positive PCR assay to a negative PCR assay, by viral variant (Panel B) and vaccination status (Panel D), and time from an initial positive PCR assay on a negative viral culture, by viral variant (Panel C) and vaccination status (Panel E). In all panels, the shaded areas indicate 95% confidence intervals. Sequencing showed that all strains of the omicron variant were the subvariant BA.1, including sublines.

The characteristics of the participants were similar in the two variant groups, except that more participants with an omicron infection had received a booster vaccine than those with a delta infection (35% vs. 3%) (Tables S1 and S2 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). In an analysis using a Cox proportional hazard model that adjusted for age, sex, and vaccination status, the number of days from an initial positive polymerase chain reaction (PCR) test to a negative PCR test (adjusted hazard ratio , 0 .61, 95% confidence interval [CI]0.33 to 1.15) and the number of days from a first positive PCR assay to culture conversion (adjusted hazard ratio, 0.77; 95% CI 0.44 to 1.37) were similar in the two variant groups (Figure 1A to 1C and S1 to S3, and Tables S3 to S5). The median time from the initial positive PCR assay to culture conversion was 4 days (interquartile range, 3 to 5) in the delta group and 5 days (interquartile range, 3 to 9) in the ommicron group; the median time from symptom onset or initial PCR positive assay, whichever was earlier, to culture conversion was 6 days (interquartile range, 4 to 7) and 8 days (interquartile range, 5 to 10), respectively. There were no observable differences between the groups in time to PCR conversion or culture conversion by vaccination status, although the sample size was quite small, leading to inaccuracy in the estimates (Figure 1D and 1E†

In this longitudinal cohort of participants, most of whom had symptomatic, non-severe Covid-19 infection, viral decay kinetics were similar to omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and disease severity, we found no major differences in the median duration of viral shedding between participants who had not been vaccinated, those who had been vaccinated but not boosted, and those who had been vaccinated. and strengthened.

Our results should be interpreted in the context of a small sample size, which limits precision, and the possibility of residual confusion in comparisons based on variant, vaccination status and the time period of infection. Although culture positivity has been suggested as a possible proxy for contagiousness,⁵ additional studies are needed to correlate viral culture positivity with confirmed transfer to inform isolation periods. Our data suggest that some individuals infected with the omicron and delta SARS-CoV-2 variants shed a culturable virus more than 5 days after the onset of symptoms or an initial positive test.

Julie Boucau, Ph.D.
Caitlin Marino, BS
Ragon Institute, Cambridge, MA

James Regan, BS
Brigham and Women’s Hospital, Boston, MA

Rockib Uddin, BS
Massachusetts General Hospital, Boston, Massachusetts

Manish C. Choudhary, Ph.D.
James P. Flynn, BS
Brigham and Women’s Hospital, Boston, MA

Geoffrey Chen, BA
Ashley M. Stuckwisch, BS
Josh Mathews, AB
May Y. Liew, BA
Arshdeep Singh, BS
Taryn Lipiner, MPH
Massachusetts General Hospital, Boston, Massachusetts

Autumn Kittilson, BS
Meghan Melberg, BS
Yijia Li, MD
Brigham and Women’s Hospital, Boston, MA

Rebecca F. Gilbert, BA
Zahra Reynolds, MPH
Surabhi L. Iyer, BA
Grace C. Chamberlin, BA
Tammy D. Vyas, BS
Marcia B. Goldberg, MD
Jatin M. Vyas, MD, Ph.D.
Massachusetts General Hospital, Boston, Massachusetts

Jonathan Z. Li, MD
Brigham and Women’s Hospital, Boston, MA

Jacob E. Lemieux, MD, D.Phil.
Mark J. Siedner, MD, MPH
Amy K. Barczak, MD
Massachusetts General Hospital, Boston, Massachusetts

This letter was published on June 29, 2022 on NEJM.org.