Duration of Cultivable Virus Shedding in SARS-CoV-2 Omicron (BA.1) Infection

For the editor:

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

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

Viral decay and negative viral culture time.

Panel A shows viral load decay from the first positive polymerase chain reaction (PCR) test. Viral loads of nasal swab specimens 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 limit of detection. Panels B–E show Kaplan–Meier survival curves for the time from an initial positive PCR test to a negative PCR test, by virus variant (panel B) and vaccination status (panel D), and the time from an initial positive PCR test to a negative viral culture, depending on the viral variant (Panel C) and the vaccination status (Panel E). In all panels, shaded areas indicate 95% confidence intervals. Sequencing showed that all of the omicron variant strains were the BA.1 subvariant, including the sublines.

Participant characteristics were similar in the two variant groups, except that more omicron-infected participants received a booster vaccine than those with delta infection (35% versus 3%) (Tables S1 and S2 in l supplementary appendix, available with the full text of this letter on NEJM.org). In an analysis in which a Cox proportional hazards model adjusted for age, sex and vaccination status was used, the number of days between an initial positive polymerase chain reaction (PCR) test and a negative PCR test (adjusted hazard ratio, 0.61; 95% confidence interval [CI]0.33 to 1.15) and the number of days from an initial positive PCR test to culture conversion (adjusted hazard ratio, 0.77; 95% CI, 0.44 to 1.37) were similar in the two variant groups (Figures 1A to 1C and S1 to S3, and tables S3 to S5). The median time from initial positive PCR test 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 omicron group; the median time from symptom onset or initial positive PCR test, whichever comes first, to culture conversion was 6 days (interquartile range, 4 to 7) and 8 days (interquartile range, 5 to 10 ), respectively. There were no appreciable differences between the groups in the time to PCR conversion or culture conversion according to vaccination status, although the sample size was quite small, which led to imprecision of the results. estimates (Figures 1D and 1E).

In this longitudinal cohort of participants, most of whom had symptomatic and non-severe Covid-19 infection, viral decay kinetics were similar with omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and the severity of disease, we did not find large differences in the median duration of viral shedding between unvaccinated participants, those who were vaccinated but not vaccinated and those who were vaccinated and boosted.

Our results must be interpreted in the context of a small sample size, which limits precision, and the possibility of residual confounding in comparisons according to variant, vaccination status and period of infection. Although culture positivity has been proposed as a possible indicator of infectivity,5 further studies are needed to correlate viral culture positivity with confirmed transmission to inform periods of isolation. Our data suggest that some individuals infected with the omicron and delta variants of SARS-CoV-2 shed culturable virus more than 5 days after symptom onset 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, MA

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, Alta.
May Y. Liew, BA
Arshdeep Singh, BS
Taryn Lipiner, MPH
Massachusetts General Hospital, Boston, MA

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

Rebecca F. Gilbert, BA
Zahra Reynolds, MPH
Surabi 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, MA

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, MA

Supported by grants (to Drs Goldberg, JZ Li, Lemieux, Siedner and Barczak) from Massachusetts Consortium for Pathogen Preparednessa grant (to Dr. Vyas) from Massachusetts General Hospital Department of Medicineand a grant (P30 AI060354, to the BSL3 laboratory where viral culture work was performed) from the Harvard University Center for Acquired Immunodeficiency Syndrome Research.

The disclosure forms provided by the authors are available with the full text of this letter on NEJM.org.

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

Drs. JZ Li, Lemieux, Siedner and Barczak also contributed to this letter.

  1. 1. Abbott S, Sherratt K, Gerstung M, Funky S. Estimation of the test-to-test distribution as a proxy for the generation interval distribution for the omicron variant in England. January ten, 2022 (https://www.medrxiv.org/content/10.1101/2022.01.08.22268920v1). preprint.

  2. 2. Ito K, Piantham C, Nishiura H. Relative instantaneous reproduction number of SARS-CoV-2 omicron variant versus delta variant in Denmark. J Med Virol 2022;94:22652268.

  3. 3. Centers for Control and Prevention of Disasters. The CDC is updating and shortening the recommended isolation and quarantine period for the general population. December 27, 2021 (https://www.cdc.gov/media/releases/2021/s1227-isolation-quarantine-guidance.html).

  4. 4. Siedner MJ, Boucau J, Gilbert RF, et al. Duration of viral shedding and culture positivity with SARS-CoV-2 delta-variant infections after vaccination. JCI Overview 2022;7(2):e155483e155483.

  5. 5. Wolfel R., Corman MV, Guggemos W., et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020;581:465469.

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